Express Pharma December 1-15, 2014 Part I

VOL. 10 NO. 3 PAGES 176

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CONTENTS MARKET Vol.10 No.3 DECEMBER 1-15, 2014 Chairman of the Board Viveck Goenka Editor Viveka Roychowdhury* Chief of Product Harit Mohanty BUREAUS Mumbai Sachin Jagdale, Usha Sharma, Raelene Kambli, Lakshmipriya Nair, Sanjiv Das Bangalore Neelam M Kachhap Delhi Shalini Gupta DESIGN National Art Director Bivash Barua Deputy Art Director Surajit Patro Chief Designer Pravin Temble

ECO-FRIENDLY DRUGS:

DIFFICULT, YET POSSIBLE Besides being patient friendly, pharmaceutical drugs and their manufacturing processes are expected to be eco-friendlyas well.However,the pharma industryhas its own share of problems in doing so | P60

Senior Graphic Designer Rushikesh Konka Senior Artist Rakesh Sharma Photo Editor Sandeep Patil MARKETING Regional Heads Prabhas Jha - North Dr Raghu Pillai - South Sanghamitra Kumar - East Harit Mohanty - West Marketing Team Rajesh Bhatkal GM Khaja Ali Ambuj Kumar E Mujahid Yuvaraj Murali Ajanta Sengupta PRODUCTION General Manager B R Tipnis Manager Bhadresh Valia

P34: POST EVENT Pharmexcil organises technical seminar and international business meet at 6th WAC

WHERE DO WE GO FROM HERE?

51

BRING RESEARCH BACK ON THE AGENDA

Glenmark enrols first patient for phase II trial of GBR 500

54

CT REGULATION IN INDIA: SCIENCE OR SOCIAL JUSTICE?

P66: INTERVIEW

PHARMA LIFE

India on the brink of an opportunity

P58: CLINICAL UPDATES

‘We will launch INSTACOAT 4G at CPhI India 2014’-Suresh Pareek

Scheduling & Coordination Rohan Thakkar

P75: INTERVIEW

CIRCULATION Circulation Team Mohan Varadkar

‘Our customers benefit from innovation in our core technologies’-KV Venugopalan

‘IN INCREASINGLY CROWDED MARKETS LIKE INDIA, A RECOGNISED AND TRUSTED CORPORATE BRAND IS CRITICAL’

29

AUROBINDO PHARMA TO BUY NATROL FOR $132.5 MILLION

30

VENUS GETS MARKETING AUTHORISATION FOR MEROPENEM

33

CPHI INDIA TO RELEASE PHARMA MARKET REPORT

MANAGEMENT

49

P38: OPINION

26

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CIPLA APPOINTS PUNITA LAL AND DR NACHIKET MOR AS INDEPENDENT DIRECTORS ON ITS BOARD

Express Pharma Reg. No.MH/MR/SOUTH-77/2013-15, RNI Regn. No.MAHENG/2005/21398. Printed for the proprietors, The Indian Express Limited by Ms. Vaidehi Thakar at The Indian Express Press, Plot No. EL-208, TTC Industrial Area, Mahape, Navi Mumbai - 400710 and Published from Express Towers, 2nd Floor, Nariman Point, Mumbai - 400021. (Editorial & Administrative Offices: Express Towers, 1st Floor, Nariman Point, Mumbai - 400021) *Responsible for selection of news under the PRB Act. Copyright @ 2011. The Indian Express Ltd. All rights reserved throughout the world.

Reproduction in any manner, electronic or otherwise, in whole or in part, without prior written permission is prohibited.

EDITOR’S NOTE

Looking back, moving forward

S

ometimes, the more things change, the more they remain the same. Express Pharma Pulse was launched in December 1994. Change was in the air: a new edition of the Drug Price Control Order (DPCO) was in the making and companies were also gearing up to evolve from the process to the product patent era, in line with India's commitment to becoming TRIPS-compliant. The Indian government had started taking the first steps towards reviewing the Indian Patent Act of 1970. The turnover of the industry was an estimated ` 8200 crores in 1993/94, which grew to ` 35000 crores in 2003/04.

Fast forward to 2014. Change is once again in the air. Even before Prime Minister Modi and his team took charge, a fresh edition of pricing norms, DPCO 2013, and subsequent orders of the National Pharmaceutical Pricing Authority (NPPA), have changed the dynamics of the pharma industry in India, by increasing the span of price control.

While MNC and Indian pharma unite to protest pricing norms, they are on opposite sides of the fence when it comes to intellectual property rights (IPR). Landmark decisions like the Supreme Court’s rejection of Novartis’ challenge to Intellectual Property Appellate Board’s (IPAB) interpretation of section 3(d) of Indian Patent Act in the imatinib mesylate (Glivec) case, India’s first compulsory license for kidney cancer drug, sorafenib tosylate (Bayer’s Nexavar) mark the evolution of the nation’s patent system.

On one hand Indian companies are acquiring global assets, the latest example being Aurobindo Pharma’s acquisition of Natrol Inc, which is still pending approval. But on the other hand, they continue to be hauled up by the US FDA for GMP non-compliance issues. The strategy to buy US assets to ease entry into world’s largest pharma market is a response to this backlash from global regulators, but this need not be foolproof: the US regulator withdrew approvals given to Ranbaxy for generic Valcyte and Nexium even though it has a facility in the US which is GMP compliant.

The Indian growth story still endures. To be on not to be in India, is no longer a choice, inspite of regulatory roll backs and seemingly populist pricing and clinical trial policies. A PricewaterhouseCoopers (PwC) report projects that the Indian pharma market will touch $74

24 EXPRESS PHARMA December 1-15, 2014

The Indian growth story still endures.

To be on not to be in India,is no longer a choice,inspite of regulatory roll backs and seemingly populist pricing and clinical trial policies

billion sales by 2020. Thus Abbott chose India as the second emerging market (after Brazil) to launch its new corporate identity, underlining the importance the MNC places on this country. (See interview with Paul Magill, Senior Vice President, Chief Marketing Officer, Abbot on page 26) On the IPR front, the pressure to change India’s patent laws continues on various fronts.

For instance, lobby groups like the US-based Intellectual Property Owners Association (IPO) arranged an Innovation Dialog Trip to India from November 16-21, touching first Chennai and then Delhi, reportedly meeting members of the Indian judiciary, IPAB and Intellectual Property offices.

These meetings were obviously laying the groundwork for US Trade Representative Michael Froman’s visit on November 25, when he will lead a US delegation to the US-India Trade Policy Forum (TPF) to be hosted by India’s Ministry of Commerce and Industry (MOCI) in Delhi. Both Froman and Nirmala Sitharaman, Minister of Commerce and Industry, are co-chairs of the US-India TPF. On the face of it, the TPF is a 'follow-through on Prime Minister Modi and President Obama’s commitment ... to deepen our trade and investment relationship’. But discussion and resolution of trade and investment issues as well as IP issues would most certainly top the list. The USTR’s has already launched an ‘out-of-cycle’ review (OCR) of Indian IPR laws and these meetings are clearly using trade as a lever to change Indian patent laws. The first report of the OCR is due to be filed on November 30, and several members of the US Congress are already lobbying for a second investigation in 2015. Will our policy makers succumb?

In our 20th anniversary issue, we invited industry experts to retrospect on some of these issues which we featured in our inaugural issue.

While celebrating our successes, they’ve also analysed our failures and missteps. More importantly, they've suggested the path forward for industry chiefs as well as policy makers. (See pages 36-47; followed by a special section on clinical trials from pages 48-57) The retrospective theme will continue over selected issues going into 2015 as well. How long will these shadows from the past continue to dim the path future?

VIVEKA ROYCHOWDHURY Editor viveka.r@expressindia.com

MARKET I N T E R V I E W

‘In increasingly crowded markets like India, a recognised and trusted corporate brand is critical’ After the hiving off of its proprietary pharmaceuticals business, about half of the new Abbott’s business is either direct to consumers or significantly influenced by them and increasingly in countries where the company is not yet well known. Paul Magill, Senior Vice President, Chief Marketing Officer, Abbott analyses the essense of the company’s new corporate identity to Viveka Roychowdhury

What is the trigger for Abbott’s new corporate identity?

Brand is an investment in growth. Building our corporate identity creates an asset that strengthens our relationships across multiple stakeholders. In increasingly crowded markets like India, a recognised and trusted corporate brand is critical.

People around the world are more empowered to make healthcare decisions for themselves and they care about the companies behind the products they’re using for themselves and their families.

They want to be assured that the company is a good company they can trust. We know from research that twothirds of consumers check labels to see what company is behind a brand and more than 50 per cent do research on the company. In emerging economies — like India — healthcare services and products are often paid outof-pocket by the consumer, which means consumers consider attributes beyond clinical benefit in the buying decision, such as the

26 EXPRESS PHARMA December 1-15, 2014

reputation of the company or recommendations of friends and family. As our focus increases on India, it’s critical that we work to build a recognised corporate brand here.

The change you see now has its roots in the company’s separation almost two years ago of the proprietary pharmaceuticals business into a completely different company called AbbVie. The new Abbott consists of four businesses — nutrition, diagnostics, medical devices and branded generic pharma — of roughly equal size. The new Abbott is also increasingly consumeroriented, with about half of our business either direct to consumers or significantly influenced by consumers.

How does it differ/diverge from the original values and mission when the company was started 125 years ago?

Abbott’s new corporate identity builds upon our 125year heritage and begins a new chapter that fully expresses what Abbott is

As our focus increases on India, it’s critical that we work to build a recognised corporate brand here

about, championing the enabling power of health and celebrating what people at all stages of life can achieve at their healthiest.

At a fundamental level, the DNA of Abbott does not change. Our core values remain the same. Our focus on science and innovation is still our guiding star. Abbott has always been about delivering the enabling power of health to people at all stages of life.

What is changing is the way in which we are telling our story. Abbott has historically relied on the strength of our diverse and high quality products to tell our story. It’s a strategy that served us well in the past but today’s global marketplace is changing faster than ever before, demanding new and innovative ways to connect with consumers.

As more and more of our business goes direct to the people who use our products, and to countries where our company is not yet well known, it’s more important than ever before that we have a highly recognisable and

meaningful identity which speaks to our company’s purpose. In this way, people around the world can know who we are, what we stand for, and what Abbott means to them because many of them will be touched by an Abbott product at some time in their lives. Our new brand positioning ‘Life. To The fullest,’ embodies our continued focus on the enabling power of health.

Are these triggers restricted to Abbott or are they a reflection of global trends? If yes, what are these trends?

Abbott has been one of the world’s most successful companies for more than a century because it has continually transformed itself to meet the changing needs of patients and consumers and to tackle society’s most significant healthcare concerns.

Today, 70 per cent of Abbott’s business comes from countries other than the US. Be it the strong growth of emerging economies, the outof-pocket nature of the

customer in these economies, or that consumers are vastly better informed about healthcare than ever before, we look to understand, anticipate and adapt to these trends.

One trend in particular that we see in most countries of the world is the shift in how people think about health.

Health is no longer just about treating disease. It’s not just about ‘patients and pills,’ it’s about people living healthily, so they can open up possibilities in their lives.

There’s an increasing recognition that when we are at our healthiest, we can unlock all that life has to offer.

Health is the great enabler of doing more, achieving more and experiencing more in life.

About half of the company’s product portfolio is now directly consumer-facing.

How will this re-branding transform into new strategies (marketing and other wise) on the ground for the company’s employees (sales force, etc)?

At a product level, marketing strategies that are decided by the businesses will continue. You will continue to see the Abbott ‘A’ on our products.

What really changes is the

Abbott’s diversified healthcare businesses are well positioned to help play a big part in improving health and wellbeing in India

manner in which people will experience Abbott’s corporate identity. You will see associations with events which illustrate and demonstrate the core purpose and character of Abbott, for example, our sponsorship of the recently concluded TEDx Gateway in Mumbai. The TED movement is all about making great ideas accessible and sparking conversation with a belief in the power of ideas to change attitudes and lives. For more than 125 years, Abbott has been doing exactly that – inspiring breakthroughs in health that would lead to people living longer and

better lives.

India also represents one of our largest employee bases outside the US, and employee engagement is critical to corporate identity. Corporate identity provides a North Star for employees, helping to align the organisation and fuelling further pride in the company.

So we began by unveiling the new corporate identity to our employees, before unveiling it externally.

The new identity will also be leveraged across the businesses whenever we are talking about ‘all-Abbott’ and want to reflect our purpose and contributions as a company.

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EXPRESS PHARMA

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December 1-15, 2014

MARKET

In terms of sales, which are the most important emerging markets for Abbott?

Strategically, India, Brazil, Russia, China and the Asia/Southeast Asia and Latin America regions are among the important markets and regions for Abbott, globally. 40 per cent of Abbott’s sales come from emerging markets.

With emerging markets proving to be growth drivers for most sectors, including the pharma/healthcare sector, how does Abbott plan to translate the new brand values into practice

in India?

Abbott’s focus is on building the new identity globally through strong engagement with a number of stakeholders, told through compelling stories and experiences. While consumers are at the centre of the company’s new brand identity, the effort goes beyond consumers to other stakeholders, including making Abbott even more attractive to top talent across the world.

This is not a traditional marketing campaign, but rather we’re investing in a number of different expressions and sponsorships that speak to

different aspects of what ‘Life. To the Fullest’ means to

VISIT US AT CPhI INDIA 2014, 2-4 DECEMBER 2014, MUMBAI

STALL NO. G28 (HALL NO.1)

our different audiences.

For example, in 2015, we’ll

be supporting runners as the first-ever title sponsor of the World Marathon Majors.

This underscores Abbott’s commitment to helping people be proactive in their approach to health and wellness and experience all that life has to offer.

Specifically in India, in October 2014, we began revealing our new corporate identity to our employees and then to external audiences though the TEDx Gateway sponsorship, our refreshed Abbott India website (www.abbott.in), as well as visible outdoor signage and print advertising. This is just the beginning, expect to see us even more

visible next year.

Kindly comment on the opportunities and challenges of doing business in the pharma/healthcare space in India.

We see the changing healthcare space as an opportunity. In increasingly crowded markets (businesswise) like India, a recognised and trusted corporate brand is critical.

Abbott’s diversified healthcare businesses are well positioned to help play a big part in improving health and wellbeing in India. viveka.r@expressindia.com

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MARKET

COMPANY WATCH

Aurobindo Pharma to buy Natrol for $132.5 million Emerges as the highest and best bidder to acquire the Californiabased company AUROBINDO PHARMA USA, Aurobindo Pharma’s 100 per cent subsidiary, has emerged as the highest and best bidder to acquire California-based Natrol and other affiliate entities, under a process to be finally approved by the United States Bankruptcy Court for the District of Delaware.

Under the auction process, Aurobindo USA emerged as the highest and best bidder with a bid of $132.5 million to acquire the assets of Natrol with an agreement to take on certain liabilities. Aurobindo USA believes that Natrol is an excellent strategic fit and provides the right platform for creating a fully-integrated OTC platform in the US and in other international markets. Natrol, which manufactures and sells nutritional supplements in US and other international market, provides Aurobindo with strong brand reputation and presence in a variety of attractive supplement markets, proven performance in the mass market, health food and speciality channels, existing longterm relationship with key distribution and retail partners addressing a broad range of consumers and an effective growth strategy to expand market penetration.

The acquisition is subject to final approval by the US Court and other statutory approvals as may be required, including any termination of the waiting period or approval under the HSR Act, and closing conditions as per the Asset Purchase Agreement.

EP News Bureau – Mumbai

EXPRESS PHARMA

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December 1-15, 2014

MARKET

Venus gets marketing authorisation for Meropenem Meropenem is a last-resort drug of the carbapenem class of antibiotics which is used in intensive care units (ICUs) of hospitals VENUS REMEDIES has achieved yet another landmark by getting marketing authorisation from Switzerland for its generic product meropenem.

The company has got this approval from Swiss drug authority Swissmedic through its German subsidiary Venus Pharma GmbH for meropenem 500 mg and 1 g injections.

“With plans to launch this product early next year through our partner Swiss Pharma GmbH Zurich, we will be able to capture 10 per cent share in the meropenem market of Switzerland,” said Venus Remedies Chairman and Managing Director Pawan Chaudhary.

Being among the first few companies to receive marketing authorisation from Switzerland for this drug, Venus enjoys a distinct advantage. “The marketing approval for this critically important antibiotic has once again proved the company’s R&D capabilities and its expertise in developing world-class products with regu-

latory might. It will help us strengthen our portfolio in the Swiss market,” said Chaudhary.

Meropenem is a last-resort drug of the carbapenem class of antibiotics which is used in

VISIT US AT CPhI INDIA 2014,

2-4 DECEMBER 2014, MUMBAI

STALL NO. G28 (HALL NO.1)

intensive care units (ICUs) of hospitals. The global annual sale of meropenem, which stood at $1,879 million in 2012, is estimated to grow at a compounded annual growth rate (CAGR) of 7.5 per cent to reach around $2,100 million in 2014-15.

The drug is used in the

treatment of severe bacterial infections like pneumonia, broncho-pulmonary infections in cystic fibrosis, complicated urinary tract infections, complicated intraabdominal infections, intraand post-partum infections, complicated skin and soft tissue infections and acute bacterial meningitis.

Venus Remedies has secured more than 40 marketing authorisations for meropenem throughout the world from countries like the UK, France, Germany, Saudi Arabia, Australia and Italy, among others.

With this marketing approval from Switzerland, the company is expecting to generate good revenue in the coming year.

Venus is already selling meropenem in various European Union (EU) and non-EU markets, and is in the process of extending its footprint and sales operations in other markets like Spain, Australia and South Africa through strategic tie-ups.

EP News Bureau – Mumbai

US FDA committee votes against Novartis' multiple myeloma lead FDA not bound to follow Committee's guidance its review of LBH589 NDA NOVARTIS ANNOUNCED that the US Food and Drug Administration's (FDA) Oncologic Drugs Advisory Committee (ODAC) did not recommend the investigational compound LBH589 (panobinostat), a pan-deacetylase (panDAC) inhibitor, for patients with previously treated multiple myeloma when used in combination with bortezomib and dexamethasone.

The committee's vote will be considered by the FDA in its review of the LBH589 new drug application (NDA), but the FDA is not bound to follow the committee's guidance. The final decision regarding US approval is made by the FDA. However, Novartis believes that the compound has the potential to be an important treatment option for multiple myeloma patients and indicated that it will continue working with the FDA on a path forward.

According to a press release from the company, data

Final decision regarding US approval is made by the FDA presented at the meeting included two clinical studies evaluating LBH589 in combination with bortezomib and dexamethasone for patients with relapsed or relapsed and refractory multiple myeloma: a phase III randomised, double-blind, placebo-controlled, multicentre global registration trial called PANORAMA-1 (PANobinostat ORAl in Multiple MyelomA) and a phase II US multicentre, single-arm, open-label study called PANORAMA-2.

EP News Bureau – Mumbai

Glenmark receives final ANDA approval for Omeprazole DR capsules It is a generic version of Prilosec by AstraZeneca GLENMARK GENERICS has been granted final approval for its abbreviated new drug application (ANDA) from the United States Food and Drug Administration (US FDA) for omeprazole delayed release capsules, their generic version of Prilosec

by AstraZeneca.

Omeprazole DR capsules are

30 EXPRESS PHARMA December 1-15, 2014

indicated for the short-term treatment of active duodenal ulcer in adults. The approval is for the 10, 20, and 40mg strengths of Omeprazole. According to IMS Health sales data for the 12 month period ending September 2014, Omeprazole garnered annual sales of approximately US $520 million.

Omeprazole DR capsules are used in short-term treatment of active duodenal ulcer in adults Glenmark’s current portfolio consists of 94 products

authorised for distribution in the US marketplace and 72

ANDA’s pending approval with the US FDA. In addition to these internal filings, GGI continues to identify and explore external development partnerships to supplement and accelerate the growth of the existing pipeline and portfolio.

EP News Bureau – Mumbai

MARKET

India pharma companies well positioned for global growth Failure to comply with the stringent quality requirements in developed markets is a key risk GROWTH FOR Indian pharma companies is likely to get a boost as countries are increasingly focusing on affordable healthcare. However, failure to comply with the stringent quality requirements in developed markets is a key risk, reveals a report by Standard & Poor’s, ‘Indian Pharmaceutical Companies Have a Global Opportunity, If They Conquer Compliance Issues.’

“Expansion into developed markets, especially the US, is positive for the credit profiles of

Indian pharma companies. The market’s size and the absence of price controls are likely to support the revenue growth and profitability,” said Vishal Kulkarni, Credit Analyst, Standard & Poor’s.

The growth prospects are particularly high for Indian companies in the speciality and complex generic drugs segment in the US. Most of these companies have a limited presence in this segment, but we expect them to gradually move up the value chain. Compliance with

To subscribe: bpd.subscription@expressindia.com

Growth prospects very are high for Indian firms in speciality and complex generic drugs segment in US

regulations is a key requirement for Indian pharma companies to realise their growth potential, the report notes. Failure on this front would seriously hurt creditworthiness. It could lead to disruptions in production, import bans, remediation costs and above all reputational and litigation risks. The largest 10 Indian pharma companies are much smaller in terms of revenue than their global generics peers.

Indian companies’ R&D focus will continue to help them

build a sustainable product pipeline. Standard & Poor’s expects the role of Indian companies in M&As in the global pharma market to be moderate to marginal. Their acquisitions are likely to be measured against the backdrop of elevated valuations, longer integration periods, problems with operational synergies, and the managerial bandwidth required to reap benefits from such acquisitions.

EP News Bureau – Mumbai

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December 1-15, 2014

MARKET

Merck Serono launches web-based software for people with MS The software is available in six additional countries MERCK SERONO, the biopharmaceutical division of Merck, announced the expanded launch of its updated electronic injection device, the new RebiSmart, for the self-administration of Rebif (interferon beta-1a), the company's disease-modifying drug used to treat relapsing forms of multiple sclerosis (MS), along with its new first-of-its-kind web-based software platform, Msdialog.

Following an initial launch in 14 countries in May, MSdialog and the new RebiSmart device are now also available to people with MS and their healthcare team in Spain, Greece, Hungary, Israel, Chile and Colombia.

People with MS can selfinject Rebif with the new RebiSmart, place the device in its transmitter and wirelessly send treatment data – injection times and doses – to the secure MSdialog server, where it is stored and available to be reviewed by people with MS and their health care providers. People with MS who use MSdialog can choose to receive email or SMS reminders to take their medication, and, along with their nurses, use MSdialog in between visits with their physician to track adherence and report health related outcomes.

MSdialog will allow people with MS to engage in the management of their disease by asking them to complete periodic health report questionnaires based on short forms of published instru-

32 EXPRESS PHARMA December 1-15, 2014

ments and standard scales, such as the Multiple Sclerosis Quality of Life Inventory (MSQLI) and the Multiple Sclerosis International Quality of Life (MusiQoL) questionnaires.

“People with MS often cite a lack of adequate technology tools to help them effectively engage with their healthcare team in between and during consultations, and in my own practice, I’ve

VISIT US AT CPhI INDIA 2014,

2-4 DECEMBER 2014, MUMBAI

STALL NO. G28 (HALL NO.1)

seen first hand the need for tools to help capture important information that could influence care decisions,” said Dr Peter Rieckmann, Head of the Neurology Department at Bamberg Academic Hospital at the University of Erlangen in Germany.

Dr Steven Hildemann, Chief Medical Officer, and Head of Global Medical Affairs and Global Drug Safety at Merck Serono said, “With the introduction of MSdialog, we are offering a unique digital technology to provide people with MS a management system that can help them create a more open dialogue with their healthcare

team. Following a successful launch in May, we are thrilled to offer this new management solution in additional countries and look forward to receiving regulatory approval in more countries in the near future.”

RebiSmart was the first injection device in MS that records the date, time and dosage of each injection so that an accurate dosing history can be discussed with a patient, allowing physicians to monitor and improve patient adherence to therapy.

The new RebiSmart offers updates to the original device, including a larger screen, new interactive onscreen guide and signals to help patients through the injection process, graphical display of treatment adherence and a transmitter for wireless data transfer. The new RebiSmart is used with Rebif multidose cartridges, each of which contains one week's worth of medicine. Individually adjustable comfort settings give patients more flexibility with injection duration, speed and depth, helping minimise discomfort and pain.

The new RebiSmart and MSdialog were first available in the United Kingdom, France, Italy, Switzerland, Ireland, Austria, Finland, Portugal, Germany, Belgium, Canada, Denmark, Luxembourg, Netherlands and Sweden as of May 2014, and further launches will follow in 2015.

EP News Bureau – Mumbai

Govt bracing up to popularise traditional medicines Healers expressed anguish that traditional treatment systems in India were not getting their due recognition INDIA’S ANCIENT medicinal systems are being given a ‘newlook image’ as part of the new government’s effort to popularise them without losing their essence, said Union Tribal Affairs Minister Jual Oram.

Such a concerted exercise will specially benefit rural India where people largely rely on local herbal doctors, said Oram while inaugurating a two-day Traditional Healers Meet in the national capital as part of the Sixth World Ayurveda Congress (WAC).

“Deliberations are on with experts and practitioners ensure that such a plan benefits the country’s huge number of villages,” Oram told a gathering of healers, who called upon the government to give accreditation to deserving traditional healers.

The minister expressed optimism that the meet would facilitate exchange of ideas between practitioners of different branches of ancient medicines.

“The outcome of the deliberations would further enable the government to chart ways on empowering Ayurveda and traditional Indian treatment systems,” added Oram, himself a tribal leader.

Bengaluru-based scholar Darshan Shankar said in his keynote address that the healers’ fraternity had two suggestions before the government to strengthen traditional cure in India.

“One is a scheme that would ensure a home-level network of use of herbal medicines. The

A gathering of healers called upon the government to give accreditation to deserving traditional healers other is fast and prompter accreditation of healers by a competent body of experts,” said Prof Shankar, who is Vice Chancellor of Institute of Trans Disciplinary Health Sciences and Technology (ITDHST), Bengaluru.

Prof Ritu Priya of Jawaharlal Nehru University, Delhi, stressed the need for bridging a gap between traditional and modern medicines in presentday India. Healers from the South, West, Central and NorthEast India at the meet expressed anguish that traditional treatment systems in India were not getting their due recognition even as they formed the basis for modern medicine.

ITDHST’s Prof G Hariramamurthi welcomed the gathering.

EP News Bureau – Mumbai

MARKET

PRE EVENT

CPhI India to release pharma market report CPHI INDIA, organised by UBM Live, will be releasing a comprehensive India pharmaceutical market report at CPhI India 2014, to be held from December 2-4, 2014 in Mumbai.

The report, conducted with the help of research partner Global Business Reports, will include thought-provoking analysis from key industry players, e.g. Cipla, Piramal, Sun, Lupin, Aurobindo and Biocon, Government bodies (IBEF/Pharmexcil) and explore new growth areas emerging across the country.

The CPhI India report will feature a robust analysis of the Indian pharma market and include significant contributions from 98 companies and all major Indian manufacturers, evaluating conditions for both foreign and domestic companies.

Printed copies of the detailed report will be available at CPhI India along with a media-ready version produced and launched to media at the event, including an overview of trends contained within the full report.

CPhI India will take place at the Bombay Convention and Exhibition Centre, Mumbai (India) and is expected to be attended by nearly 30,000 industry executives from over 95 countries.

CPhI will co-locate with P-MEC India, ICSE India and BioPh. A series of technical seminars will take place throughout the show, providing detailed insights into current trends, issues and developments surrounding the pharma community, alongside the CPhI Pharma Awards India.

Another initiative is CPhI Global Angels charity campaign, launched earlier at CPhI Worldwide. It is designed to call on the pharma community to lend its support to this global charity that is transforming disadvantaged communities around the world.

EP News Bureau-Mumbai

EXPRESS PHARMA

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December 1-15, 2014

MARKET

POST EVENT

Pharmexcil organises technical seminar th and international business meet at 6 WAC Partners with 6th World Ayurveda Congress for the third time, sees 55 overseas delegates from 20 countries PHARMACEUTICALS Export Promotion Council of India (Pharmexcil) recently organised a technical seminar and international business meet during 6th World Ayurveda Congress (WAC). Pharmexcil, with the active support of Ministry of Commerce, Govt of India, organised the seminar and meet at Pragati Maidan, New Delhi.

The technical seminar created awareness for manufacturers and exporters of herbal and AYUSH products on the certifications issued by various organisations which are mandatory/useful for exporting traditional/herbal health products.

Sudhanshu Pandey, Joint Secretary, Ministry of Commerce & Industry, Govt of India, was the chief guest for the technical seminar. Eminent speakers from Star -K Kosher, Halal India, USP India, ECOCERT, and NSF International delivered presentations during the seminar. Officials from Department of AYUSH, Bala Prasad, Joint Secretary and Dr Geetha Krishnan graced the event as guests of honour.

Industry leaders from the AYUSH sector actively participated in the seminar.

The international buyer seller meet saw 55 overseas delegates from 20 countries representing the traditional medicine industry (including herbals, AYUSH, dietary supplements, and nutraceuticals) and Food and Drug officials (FDA).

It also saw participation from 150 Indian delegates. The participating countries were Bahrain, Bangladesh, Bolivia,

34 EXPRESS PHARMA December 1-15, 2014

Vardhan; Nilanjan Sanyal, Secretary, Department of AYUSH, Government of India and Dr Jaya Kumar of World Ayurveda Foundation.

Modi said that the biggest challenge to Ayurveda comes from people who have dedicated their life to it. They too do not trust it fully, he said. Seeking to dispel the notion of Ayurveda

Sudhanshu Pandey, Joint Secretary, Ministry of Commerce & Industry, Government of India, New Delhi addressing the gathering. Also seen in the picture are (L-R) Raghuveer Kini, Executive Director, Pharmexcil India; Dr Geetha Krishnan, Secretary General, World Ayurveda Foundation; Dr PV Appaji, Director General, Pharmexcil India; Ashutosh Gupta, Chairman, Pharmexcil India; and Bala Prasad, Joint Secretary, Department of Ayush, Ministry of Health & Family Welfare, Government of India

VISIT US AT CPhI INDIA 2014, 2-4 DECEMBER 2014, MUMBAI

STALL NO. G28 (HALL NO.1)

Overseas delegates from 20 countries were present during the valedictory session

Canada, Egypt, Ghana, Iraq, Kazakhstan, Kyrgyzstan, Malaysia, Mauritius, Nepal, Philippines, Rwanda, Singapore, Sri Lanka, Sweden, Ukraine, the US, and Uzbekistan.

Ayurvedic and herbal products and powders, extracts, ayurvedic formulations and herbal formulations, dietary supplements, neutraceuticals and functional foods were displayed. Overseas delegates

expressed their satisfaction at being provided a unique platform to meet a good number of Indian manufacturers and exporters supplying a wide variety of herbal extracts and Ayurvedic formulations.

Drug regulatory officials from Egypt, Iraq and Nepal were also present at the business meet. The event provided an opportunity for Indian companies, especially

small and medium companies, to have face-to-face interactions/ network and understand the regulatory practices in these countries.

The Council also participated in Arogya Expo and organised a 'Exporters Pavilion'. The valedictory session organised by the Department of AYUSH was graced by Narendra Modi, Prime Minister of India; then Health Minister, Dr Harsh

and allopathy being competing streams of medical science, the PM described Ayurveda as a way of life. He said that a disease can be cured by allopathy; and if a person adopts Ayurveda, he can ensure that he remains healthy and free of disease.

The PM also said that it is essential for Ayurveda to reach people in a simple, effective way. For this, the modes of treatment should be better packaged. He added that space has to be created in international medical and science publications for articles on Ayurveda but the effort for this has to come from the practitioners and researchers of Ayurveda.

EP News Bureau-Mumbai

EVENT BRIEF DECEMBER 2014 - MAY 2015 6

Bio-Invest in Gujarat

BIO-INVEST IN GUJARAT Date:December 6, 2014 Venue: Mahatma Mandir, Gandhinagar, Gujarat Summary: Government of Gujarat will organise ‘BioInvest in Gujarat’, which will be supported by the Department of Science and Technology (DST), Gujarat State Biotechnology Mission, Govt of Gujarat (GSBTM), Association of Biotechnology Led Enterprises (ABLE) and KPMG. The event will see worldrenowned scientists, senior government administrators and industry leaders.

Approximately 500 attendees are expected to participate that will provide an ideal forum for business networking and exchange of ideas. Anandiben Patel , Chief Minister, Gujarat will inaugurate the event. Dr K

8

Vijay Raghavan, Secretary DBT and DST (Government of India) will give the keynote address. Sir John Burn from Institute of Human Genetics, UK, Prof Ken-ichi Arai, Chair Programs Committee, Biotech Japan, Dr S Ayyappan, Secretary, DARE & DG ICAR, Dr Harkesh Mittal, Secretary, TDB and Dr Renu Swarup, Managing Director, BIRAC besides other CEOs are likely to participate in the event.

The sessions will cover healthcare, agriculture, industrial biotech, innovation and will be addressed by eminent speakers from public organisations and private companies. Top officials from the Government of Gujarat will discuss the facilities and incentives being provided to companies for setting up their businesses in the state.

Asia Pharma Expo-2015

13

PHARMA Pro & Pack Expo 2015

Contact details: GSBTM Dr Madhavi Joshi Mob: 9978441233 ABLE Dr Anil Chauhan Mob: 9871632688

and the US are likely to participate.

Contact details: Tel: +91 7940008233/ 53 Mob: +91 8000481114 Email: ceo@GPEexpo.com Website: www.asiapharma.org

ASIA PHARMA EXPO-2015

PHARMA PRO & PACK EXPO 2015

Date: January 8-10, 2015 Venue: Bangabandhu International Conference Centre, Dhaka, Bangladesh Summary: Bangladesh Association of Pharmaceutical Industries will host international exhibition on South Asian Pharmaceutical industry, Asia Pharma Expo2015. The exhibiting companies from more than 26 countries across the world are expected to participate. The expo will be accommodating 400 booths to the exhibitors. Major OEM suppliers from Asia, Europe

Date: May 13-15, 2015 Venue: Mumbai Exhibition Centre, Mumbai Summary: PHARMA Pro & Pack Expo 2015 will be organised by IPMMA. 20,000 pharma trade professional/ decision makers and 250 industry majors will exhibit their technologies/ services.

Visitors’ profile include biotechnology specialists, plant management, CEOs, engineers, technocrats and scientists, policy makers, diplomats and foreign commercial corp,

compliance, process engineering, corporate management, procurement department, custom manufacturing/ marketing services, purchase officers, equipment suppliers and distributors, quality assurance/ quality control, maintenance engineering, R&D professionals, manufacturing/ production engineering, regulatory officers, operations management, validation, packaging engineering, vendor development, pharmacists.

Contact details: Indian Pharma Machinery Manufacturers’ Association 52, 1st floor, Suyog Industrial Estate LBS Marg, Vikhroli (West) Mumbai – 400 083 Tel: +91 22 6561 9272/ 2578 6007/ 2685 5108

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cover ) 1 9 9 4 - 2 0 1 4 Express Pharma Pulse to Express Pharma

C E L E B R A T I N G

20 Y E A R S

As we mark Express Pharma’s 20th anniversary, experts retrospect on some of the topics we featured in our inaugural issue, analyse the achievements and deliberate on the way ahead

India on the brink of an opportunity | 38

INSIDE Ranjana Smetacek

36 EXPRESS PHARMA December 1-15, 2014

The biotechnology environment | 40 Dr Anil Chauhan

(

THE MAIN FOCUS

Wake up call for Indian pharma | 46 Dr Gopakumar Nair

James C Greenwood

Dr PM Murali

Forging India’s bioeconomy | 42 EXPRESS PHARMA

37

December 1-15, 2014

cover ) OPINION

India on the brink of an opportunity On Express Pharma’s 20th Anniversary, Ranjana Smetacek, Director General, Organisation of Pharmaceutical Producers of India (OPPI) rewinds to the milestones of the past two decades, but concludes that even though much has been accomplished, more remains to be done

2

0 years are not a long time in the history of a nation, but the events of the last two decades have shown that much can be accomplished by way of dismantling some of the debilitating features of an old order and replacing them with revitalising new ones. It would be instructive to rewind to the early 1990s: the introduction of the Patents Act in 1970 mandated process patents for drugs and saw a boom in the domestic generic drugs industry which thrived on “reverse engineering” and the tweaking of production processes. The government’s policy focus was on promoting import substitution and domestic production with a view to enhancing the affordability of drugs. On the down side, there was an exodus of research-based pharmaceutical companies and huge damage was caused to India’s potential as a base for R&D. The opening up of the economy in 1991 had a salubrious effect on the pharma industry as well as the broader healthcare sector. In the last 20 years, a number of significant changes have taken place that cumulatively have the potential to deliver greater economic growth and superior healthcare by promoting and protecting innovation. Liberalisation meant that India began to fall in line with in-

38 EXPRESS PHARMA December 1-15, 2014

Cover story from Express Pharma Pulse, December 1, 1994, page 1

ternational best practices and global trading norms. The adoption of a system of product patents and legal protection, through Trade-Related Intellectual Property Rights (TRIPS), provided greater encouragement to the innovation driven industry. Since 2005 the patent

regime in India has allowed the patenting of drugs by virtue of being signatory to TRIPS. These moves helped see the return of international investors to the Indian market.

However, even though much has been accomplished, much remains to be done before India

can be considered welcoming of innovation that can contribute meaningfully to transforming the healthcare sector and help our pharma industry fully realise its enormous potential.

The government is committed to making India one of the world’s leading destinations for end-to-

RANJANA SMETACEK, Director General, Organisation of Pharmaceutical Producers of India (OPPI)

end drug discovery and innovation by the year 2020. Although India has achieved the distinction of being the world’s number one supplier of low-cost generic medicines, a combination of misguided government policy and shortsighted business practices has crippled our efforts to become a drug discovery and innovation powerhouse, while jeopardising our access to export markets due to serious issues relating to quality.

Five years ago, the then President declared this to be India’s “decade of innovation”. However, we have since lost sight of a critical fact: protecting innovation means protecting our innovators and creators, attracting world-class R&D, and creating and sustaining high quality jobs through robust protection of intellectual property (IP) rights.

Today, we excel at developing copies of off-patent drugs, but we lag far behind comparable member nations of the World Trade Organisation (WTO) in new drug development. India has some of the finest minds available for research. It has a well-developed pharma industry that can ably support R&D. But for many complex reasons, we have not realised our potential to lead in R&D. Sometimes, IP protection is seen as a barrier to healthcare access, but the truth about healthcare access and affordability is more complex.

( Critical dimensions of healthcare access A recent study by the IMS Institute for Healthcare Informatics – Understanding Healthcare Access in India: What is the Current State? – defines four critical, interrelated dimensions of healthcare access.

These components are: physical accessibility and the location of healthcare facilities; availability and capacity of needed resources; quality and functionality of service required for patient treatment; and affordability of treatment relative to a patient’s income.

The study calls for an integrated approach to healthcare infrastructure in the country that would ensure delivery of the actual therapy in a cost-effective manner to all stakeholders. Such an approach, it said, could result in a 40-45 per cent reduction in out-of-pocket expenditures for both outpatient and inpatient treatments.

Any efforts to improve healthcare in India must take note of the fact that urban residents, who make up 28 per cent of India’s population, have access to 75 per cent of the health infrastructure in India. They have access to 66 per cent of the country’s available hospital beds, while the remaining 72 per cent who live in rural areas have access to just one-third of the beds. The distribution of healthcare workers, including doctors, nurses and pharmacists, is highly concentrated in urban areas and the private sector.

The 72 per cent patients in rural areas face a major challenge just in terms of the physical reach of any healthcare facility. They must travel more than five kilometers to access an inpatient facility, 63 per cent of the time. Difficulty in accessing transportation options and the loss of earnings, as a result of travel time, lead to treatment being deferred, or facilities selected that may be closer but are not cost-effective or bestsuited to patient needs. This is particularly true for patients

EXPRESS PHARMA

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December 1-15, 2014

suffering from chronic ailments.

Then there is the high ab-

senteeism of doctors at rural centres in many states in India and major gaps in the quality

THE MAIN FOCUS

and availability of even basic medical care, apart from what is essential for serious illness.

Finally, there is the question of continued on 44

cover ) OPINION

The biotechnology environment The recent changes in the Government seems to have excited the industry but the real test will be to see if the enthusiasm translates to action on the ground, cautions Dr Anil Chauhan, Director, ABLE

I

ndia, Bangalore and biotechnology have come a long way in the past 20 years. The biotech industry that was just about emerging internationally and in India in 1994 has now transformed into an industry that is growing in double digits as compared to the overall pharmaceutical market. At this point, biologics contribute about 15 per cent of the global pharma market which is edging close to a $1 trillion. As the population ages the market share of biologics is bound to increase since biotech drugs are the better remedy for cancers, rheumatoid arthritis and other age-related diseases.

The biotech industry in India is approximately $5 billion but had the regulations been more supportive, the biotech industry could have been in the range of $ 7 to 8 billion by now.

Being a high investment industry, investors in the biotech domain need to be aware of any obstacles before they invest. Apparently, Indian and international investors have been hesitant to invest in India for want of clarity on matters related to IPR, environmental permissions, market perceptions, role of NGOs, etc. It comes as no surprise that India has been rated 147 out of 189 countries in the ‘ease of doing business’ in a recent World Bank report.

Globally, investment in biotech has seen its highs and

40 EXPRESS PHARMA December 1-15, 2014

News clip from Express Pharma Pulse, December 1, 1994, page 2

lows but this past year has been a blockbuster as far as the IPOs are concerned. The momentum does not seem to be abating.

However, investment in the Indian biotech sector has been anaemic at best.

Challenges and opportunities The recent changes in the Government seems to have excited the industry but the real test will be to see if the enthusiasm translates to action on the ground. If the clinical trials and crop field trials situation re-

mains unresolved and sub-judice, development of new drugs and biotech varieties will remain confined to labs. Similarly, frequent delays in obtaining permissions, patent challenges, compulsory licenses or price controls also do not bode well for innovation and growth.

Transparency, timeliness, predictability are key issues that need to be resolved. The emphasis of the Government on ‘Make in India’ needs to be supported by world-class infrastructure, a rational licensing and approval system, time-bound clearances,

improvements in quality control and assurance. Another important driver is the availability of human resources for all phases i.e. from early discovery to development. There appears to be a gap in the skills availability and requirement at most levels.

Attempts are being made to fill the gap through finishing schools at the entry level to encouraging Indian researchers and professionals abroad to return to work in India. However, a more basic and wider effort needs to be made to fulfil the future requirements.

DR ANIL CHAUHAN, Director, Association of Biotechnology Led Enterprises

India’s success in vaccines production and supply to the developing world has been a great achievement and that lead is expected to continue. Biosimilars are the new developing opportunity that has seen Biocon, Dr Reddy’s Laboratories, Intas Biopharmaceuticals and Wockhardt develop and market biosimilars. In addition to the biologics, genomics will be a second driver that enables personalisation of treatment. Several innovative companies like Strand Life Sciences, Molecular Connections, Mapmygenome, Bigtec Labs operate in this space. In the coming years other opportunities will be those biotech sub-sectors that utilise India’s existing strengths in IT to develop large scale Big Data capacities and to leverage India’s engineering skills to widen the medical tech space. Manufacturing is another big-ticket item that Association of Biotechnology Led Enterprises (ABLE) has been trying to push.

ABLE had submitted a white paper to the PMO in December 2012 suggesting that the Government of India spend atleast ` 5000 crores to ramp up the manufacturing infrastructure.

The recent push by the new government for manufacturing in India is a welcome development.

In the agriculture biotech space the success of BT cotton in the past decade has transformed rural lives in the cotton growing states. A much bigger

( opportunity awaits several other crops. The current government needs to push for adopting well tested traits in food crops as well. This will help improve India’s food security and the nutritive value of crops while simultaneously protecting the environment.

Unlike the pharma sector that is dominated by large MNCs, biotechs are relatively small in size. The world over, the paradigm is to develop a whole ecosystem of start-ups that serve to keep the Innovations coming in at a rapid pace. Silicon Valley is home to a huge number of start-ups with thousands added each year. The Indian government is trying to promote a similar model and it may well trigger a spurt of growth. Since start-ups need to be sustained to carry on for some years before they enter the real world, funds need to be available from private sources. At this point this is a real challenge. Suggestions have been that the start-ups be allowed to tap the stock markets even though they do not have revenues.

ship Talks in various cities and towns that included Coimbatore, Jaipur, Chandigarh and

Dharwad. These centres were chosen with an intention to make the programmes more in-

EXPRESS PHARMA

41

December 1-15, 2014

clusive. In 2012, ABLE developed an ambitious roadmap for the Indian biotech industry tar-

geting a size of $100 billion by 2025.

Continued on page 45

Consistent investments has ensured that our products are recognized worldwide for their quality and efficiency.

QUALITY EXCIPIENTS FOR THE

PHARMACEUTICAL INDUSTRY EXCIPIENTS

ABLE’s role ABLE has been advising its members and the government on various issues. One of the most important programmes that it structured is the Biotechnology Entrepreneurship Student Team (BEST) event, supported by the Department of Biotechnology (DBT) of the Government of India. In 2014, the 6th Edition of BEST was held in October. The format involves shortlisting 20 teams (four to five students each) from over 150 teams on basis of theirproposals and the best teams are selected and awarded on basis of their business plan presentations. Thus each year BESTsparks an Innovative spirit in 100 bright youngsters.

ABLE plans to scale up efforts in the coming years.

ABLE has conducted similar regional – NEST- in North East India in the past and is currently partnering with BIRAC for Stimulating Bio-Entrepreneur-

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cover ) OPINION

Forging India’s bioeconomy Without the support of its government, the Indian biotech industry may not be able to achieve its high potential, say James Greenwood, President and Chief Executive Officer, Biotechnology Industry Organization and Dr Panchapagesa Murali, President, Association of Biotechnology-Led Enterprises

T

he Indian biotechnology industry is on the cusp of entering a new era when it can provide significant economic growth and development to the people of India and around the world.

India already has many of the necessary ingredients needed in order to grow its bioeconomy, such as a talented and enthusiastic scientific workforce. However, not all the ingredients are in place in order for the country to reach the next level.

In 2012, the Association of Biotechnology-Led Enterprises (ABLE) laid out an ambitious goal of growing the Indian bio-economy from its present $ 5 billion to more than $100 billion by 2025. This call to action was quickly picked up by Government officials and others who saw the potential benefits of a strong and vibrant biotech industry in meeting the needs of Indians in regards to medicine, food, fuel and environment.

This challenging yet attainable goal would place India’s biotech industry on par with India’s information technology industry in terms of numbers of high-paying jobs and in terms of revenue. For this to happen, India must address some fundamental areas of policy and regulation, and take steps towards creating an environment that encourages, not discourages, investment by innovators.

42 EXPRESS PHARMA December 1-15, 2014

JAMES GREENWOOD, President and Chief Executive Officer, Biotechnology Industry Organization

DR PANCHAPAGESA MURALI, President, Association of Biotechnology-Led Enterprises

News clip from Express Pharma Pulse, December 1, 1994, page 5

The current size of the biotech industry is approximately $5 billion. In order to reach the goal of $100 billion, we need a dual focus on entrepreneurship and innovation.

At the moment, India has a limited number of biotech companies. In order to reach its potential, India needs to encourage the development of many more, by tearing down the barriers to new investment and improving the overall climate for business. About $4-5 billion in investment is needed on an annual basis for the next four years to realise

the industry’s goal for growth.

Furthermore, the country needs to encourage more academic researchers to become entrepreneurs, taking their ideas from the laboratories to the products, in the process creating many new jobs for India.

Separately, India needs to re-emphasise its commitment to innovation and introduction of innovative biotech products. Significant resources are rightly focused on manufacturing biotech products, particularly biopharmaceuticals, at lower costs in or-

der to ensure widespread affordability. While admirable, this is an extremely competitive space and will not likely bring in significant revenue and thus not contribute greatly to the growth that India is looking for. An equal if not greater emphasis should be placed on developing new products for the global marketplace. By doing so, companies in India will be in a position to attract new investment capital and generate substantial amounts of new revenue.

In such a manner, India will realistically reach its goal of

creating a $100 billion industry.

Because our two organisations, the Biotechnology Industry Organization (BIO) and ABLE, see the potential that can result from collaborating, we teamed up last year, to produce a comprehensive report on the Indian biotech industry entitled “Accelerating Growth: Forging India’s Bioeconomy”. In order to reach the goal of a $100 billion bioeconomy, the country needs a working plan and this report was designed to provide such a guide. The goal was to provide the new Indian Government, led by Prime Minister Narendra Modi, with a road map for the nation’s biotech industry, identifying the major areas that require attention. Based on research and interviews with Government and industry stakeholders inside and outside India, the authors covered a range of topics, such as intellectual property, regulatory environment, tax and investment policies, and technology transfer.

Biotech, like other industrial sectors, requires an ecosystem to nurture and sustain it. In the case of biotech, this ecosystem requires sub-

( stantial input and assistance from the Government of India, at both the Central and State levels. Biotech operates in a highly regulated environment. Numerous government policies, rules and regulations are at play, influencing every single aspect of the industry, from research and development, through regulatory approvals, taxation and finance, all the way to government procurement. These policy concerns go well beyond the mandate of any one ministry or agency. Rather, multiple ministries need to work together towards a common goal.

The biotech industry in India faces challenges that, like the country itself, are diverse and complex. We see evidence of slow growth in the sector tied directly to matters of policy and associated regulatory practices, for example clinical research. The government should take steps to speed the regulatory process, increase investment in the sector, attract multinational biotech companies, improve the business environment, and encourage innovation. However, doing so will require visionary leadership within government, coordination among agencies, public education, and steps to ensure government investments or policies are not stymied by unwarranted bureaucratic measures or the unintended consequences and costly delays of court rulings.

For India to compete globally, attract investment, and enjoy the economic benefits that its strength in biotech can bring, it needs to align itself with global standards in these areas. Below are some of the highlights taken from the report: ◗ The Government of India should focus on improving its regulatory agencies and processes to regulate the biotech industry in a transparent and consistent manner, giving patients and con-

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December 1-15, 2014

sumers confidence in the biotech products they purchase, and providing compa-

nies with a stable, predictable, and level playing field. Furthermore, India should har-

THE MAIN FOCUS

monise its regulatory processes and requirements with those of other countries.

◗ Tax and investment policies should be reformed such that the necessary investments in

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cover ) infrastructure can be made. ◗ India should provide forums that foster partnering opportunities, and take steps to address concerns about the protection of intellectual property and other policies, laws, and business practices that impede partnering activity. ◗ The current intellectual property system in India is being perceived as an impediment to the development of the Indian biotech industry.

Using the patent system as a mechanism to control drug pricing forestalls making the difficult decisions about necessary investment in the healthcare system, but does not deal with the underlying

issues. ◗ Technology transfer from academic and government laboratories to industry should be encouraged, and researchers should have access to training to be successful entrepreneurs. ◗ The Government should exert leadership in the national debate about the appropriate uses of agricultural biotech based on a thorough social and scientific assessment of an appropriate incorporation of biotech into Indian and global food security.

India has the potential to be a powerhouse and a favoured destination for the global biotech industry. To achieve this vision, and reach

its goal of a $100 billion industry, the country must have the right mix of policies, regulations, and business environment to attract global investors. Without the support of its government, the Indian

biotech industry may not be able to achieve its high potential and the world will not benefit from what could be Asia Pacific region’s dominant biotech hub.

This report can provide

the central government and various states with thoughts on where they should focus their energies in the coming months and years. At the urging of India’s new leadership, India is entering a new era of governance and regulation.

Efficient and effective governance, coupled with a regulatory system anchored in global standards, is needed in order to provide the necessary underpinnings to allow Indian companies to compete on the global stage. In this manner, policymakers can help the Indian bioeconomy grow and thrive, in turn providing the economic, health and other benefits that India and its people richly deserve.

The OPPI has urged the Department of Pharmaceutic als to make the UCPMP a statutory code.This will inspire confidence among patients and demonstrate India’s commitment to a high level of ethics and compliance

code if needed.

The OPPI has urged the Department of Pharmaceuticals to make the UCPMP a statutory code, in the best interests of both patients and the industry. This will inspire confidence among patients and demonstrate India’s commitment to a high level of ethics and compliance. A statutory code would work as a ready reference and guide in pharma marketing. Of course, its success would depend on the cooperation of the Medical Council of India and the Indian Medical Association.

OPPI members follow a stringent Code of Pharmaceutical Practices, which is based on the code of the International Federation of Pharmaceutical Manufacturers and Associations.

India is widely recognised as a regional superpower and must say goodbye to the adage that most Indian families are just one illness away from poverty. We in the pharma industry are ready to partner with the government and join forces to help make that his-

toric transition to guaranteed health security for all. OPPI remains committed to supporting the nation’s healthcare objectives, collaborating with the Indian Government and other stakeholders to find sustainable solutions; solutions that balance the need for innovation with the necessity for more accessible medicines, within a robust IP environment. A holistic approach is needed to expand healthcare in India and OPPI believes the pharma industry can form part of the solution.

We support the Indian government’s quest for more accessible and affordable medicines and welcome a more comprehensive dialogue between private and government stakeholders. Inclusive healthcare is critical to our nation’s future. Through concerted efforts - whether through CSR, research and development (R&D), Public Private Partnerships or other initiatives - the healthcare system in India can be improved to equal that of other countries in East and South-East Asia.

To reach its goal of a $100 billion industry, the country must have the right mix of policies, regulations, and business environment to attract global investors

continued from page 38

India on the brink ... the cost of medicines. Across public and private facilities, and for chronic and acute diseases, medicines account for more than 60 per cent of patients’ total out-of-pocket expenses for outpatient treatments, and 43 per cent for inpatient treatments. Interestingly, this share of expenditure for medicines has not increased since 2004 for inpatient treatments, and has decreased for outpatient treatments. Low insurance penetration – and current insurance plans do not cover drug costs – has not helped.

Need equitable access for optimal care Overall, the statistics highlight the conundrum India faces. The healthcare system needs to ensure equitable access in rural and urban areas for optimal preventive and curative care.

On the one hand, there is a lack of access to healthcare, while on the other there is a greatly expressed concern about affordable healthcare. The key to healthcare access is proximity to healthcare facilities, a robust

44 EXPRESS PHARMA December 1-15, 2014

health infrastructure, easy access to medicines, adequate and efficient resources in government facilities, competent medical personnel and a well-developed distribution network.

This requires higher investments in health infrastructure development, focusing on universally available primary healthcare facilities for individuals and families at grass-root levels in the community. This is where the government must step up, in terms of developing the health infrastructure in India, across all the identified dimensions.

Make UCPMP a statutory code Finally, we must insist on ethical marketing, to ensure that patients are prescribed only those medicines they truly need. The government issued the Revised Draft Uniform Code of Pharmaceutical Marketing Practicies (UCPMP) in 2012, as a voluntary code for the Indian pharma industry with the intent to review it down the road and make it a statutory

(

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continued from page 41

The biotechnology...

This was welcomed by the industry and also accepted by the Government as a long-term goal.

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Showing its support to the Government, ABLE impleaded and was included as a co- respondent in a case filed in the SC court by an NGO against the Government of India attempting to place a ban on field testing of GM crops.

ABLE also showcases the strengths of India’s public and private sector by participating in international biotech events.

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cover ) OPINION

Wake up call for Indian pharma Unless Indian pharma companies wake up to the new “patent challenge” regime, they could “miss the bus”, opines Dr Gopakumar G Nair, Chief Executive Officer, Gopakumar Nair Associates

I

t is time for Indian pharma industries to wake up and take note of the emerging patent litigation scenario in India.

Patent litigations in India in past five years or more have taken India closer to US in ex-parte injunctions and duration of individual patent cases pending in High Courts even though India can be proud (?) that we have longest pendencies of patent suits in India. Indian patent law provisions for challenging patents and patent applications have been applauded and appreciated by third world countries and NGOs while MNCs and developed countries have decried and denounced these provisions.

After a patent has been granted in India, there have been various options for an “interested person”, to challenge the validity of the patent. Firstly, a post-grant opposition could be filed in the Patent Office within one year of grant. Secondly, a revocation petition could be filed in the Intellectual Property Appellate Board (IPAB) any time after grant, before expiry, of the patent.

Thirdly, if anyone is sued for infringement, that person could file a counter claim for invalidation in the High Court. These provisions having been supported by specif-

46 EXPRESS PHARMA December 1-15, 2014

DR. GOPAKUMAR G. NAIR, Chief Executive Officer, Gopakumar Nair Associates

their mind to the “quality” of the patent or the strength and validity of the claims in evaluating “prima facie case” in patent infringement suits, prior to granting “ex parte” injunctions or even hasty grant of injunctions after preliminary hearing. Thereafter, most cases involving infringement suits remain pending for five or more years, even without “framing of issues” leave alone commencement of arguments. Such cases are pending in courts substantially related to pharma patents.

Invariably, the sued (defendant) party, files a suit of “counter claim for revocation/invalidation” invariably in all cases. However, after the latest judgement of the Supreme Court in Aloys Wobben vs. Yogesh Mehra (The Enercon Case) (Civil Appeal No. 6718 OF 2013), this opportunity to file counter claim for revocation will no more be available if the same party has already filed (failed or pending) for revocation either through post-grant opposition or through a revocation petition in IPAB. News clip from Express Pharma Pulse, December 1, 1994, page 8

ic sections of the Patents Act (1970), such as Sec. 25(2), Sec.64, Sec.104 and Sec.107, they were being considered parellelly and independently.

From June 2014 onwards, this scenario is changing drastically. Unless the pharma industry wakes up to the new “patent challenge”

Pre-grant opposition: The first and best option regime, one could “miss the bus” !

Unfortunately, unlike rest of the world, the Indian judiciary appears to be not applying

The “first and best option” for pharma competitors is, therefore, timely filing of a pregrant opposition. Only 1-2 per cent of Indian patent applica-

(

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tions are subjected to pre-grant opposition. This is primarily because most pharma companies do not “watch” the details of the pending patent applications in the official website published by the Indian Patent Office, every Friday of the month (www.ipindia.nic.in).

It is, henceforth, imperative for Indian pharma to keep watching and taking note of pending patent applications with a view to file pre-grant oppositions after publication in official patent office website and before grant of the patent.

The advantages of filing pregrant opposition are many. Firstly, this is the cheapest option com-

filed by “any person”, not necessarily by an interested person. Therefore, it is possible for a third party individual to file the pre-grant. The grounds have to be selected from (a) to (k) under Sec. 25(1). Supporting evidence such as prior art, product in the market or arguments/affidavit in support should accompany the pre-grant opposition. Since, of late, pre-grant oppositions have also assumed “civil proceedings” format in written submissions, reply statements and rejoinders, it is advisable to involve a professional in-house or external patent attorney while filing pregrant oppositions.

Success rates in pre-grant op-

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positions are high in India. This is primarily because only vulnerable and weak patent applications are subject matter of pre-grant filings. Subject to doing the “home work” of evaluating the vulnerability of the invention in the patent application, pre-grant oppositions are the “best-bet” in a patent defense strategy.

The details of the relevant Supreme Court Judgement are available on http://supremecourtofindia.nic.in/outtoday/ac67181 3.pdf. A summary of the case is available in the JIPR (The Supreme Court Clarifies Indian Patent Invalidity Proceedings) by Neeti Wilson (http://nopr.niscair.res.in/bitstream/123456789/29510/1/JIPR%20 19%285%29%20358-360.pdf) .

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Only vulnerable and weak patent applications are subject matter of pre-grant filings.

Subject to doing the “home work” of evaluating the vulnerability of the invention in the patent application, pre-grant oppositions are the “best-bet”in a patent defense strategy pared to revocation or challenging invalidity during enforcement proceedings or infringement suits.

The cost benefit is almost 1:100.

Secondly, not succeeding in a pregrant opposition does not bar the same opponent from opting for one of the three options for revocation, thereafter. Thirdly, filing a pre-grant opposition reasonably ensures “quality checks” at the patent office, because a pre-grant opponent helps the Patent Controller/Examiner by providing inputs, which may escape the notice of the patent office. In most cases, pre-grant opposition also provides additional “breathing time” for the opponent to plan further strategies till grant of a patent, which is likely to be infringed.

Pre-grant opposition can be

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MANAGEMENT

CLINICAL RESEARCH What does the next 20 years hold for clinical research in India? Express Pharma presents some perspectives and sugestions for policy makers

48 EXPRESS PHARMA December 1-15, 2014

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INSIGHT

Clinical research in India:

Where do we go from here?

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A policy promoting clinical research and innovation needs to be supported by action at various levels opines Suneela Thatte, President, Indian Society for Clinical Research (ISCR)

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I

n recent times, there have been encouraging reports in India around new discoveries and more effective treatment for unmet medical needs made possible through clinical research done in the country. Even as we celebrated the success of clinical trials for the first indigenous vaccine for rotavirus, the renowned Tata Memorial Hospital announced at a symposium in Goa that clinical research had contributed to mortality rates for breast cancer dropping significantly in the last 20 years in particular. Yet elsewhere the irony wasn’t lost when media reports mentioned that the quest for a vaccine for dengue had been stymied in India due to a challenging regulatory environment for clinical research or when the father of a child suffering from Pompe disease spoke of his desperation to find a trial in India his daughter could participate in. The reality is that, under current conditions, sponsors are turning away from doing clinical research in India. In a few years from now, we will see the real impact of the current environment when several new medicines and potentially superior therapies will be out of reach of Indians simply because no clinical research was conducted in the country. In 2005, when the decision was taken to remove the phase lag for

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SUNEELA THATTE, President, Indian Society for Clinical Research (ISCR)

clinical trials in India, the rationale was so as to ensure that India would not lag behind in access to new medicines. Today, the clinical research environment in the country is unfortunately far away from that vision for research and innovation.

One does not need to overemphasize the importance of clinical research in the drug development process which is long, expensive and complex. It takes an average of 10-15 years for a new medicine to be developed for human use. It is only through clinical research that one can determine the safety and effectiveness of a new drug or treatment

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MANAGEMENT

or an existing one being used in a new way. The genetic makeup and profiles of people has a significant role to play in how their bodies respond to therapeutic intervention which is why a multi-ethnic, multi-racial population like India needs clinical research. Besides, India has a sixth of the global population and a fifth of the global disease burden. The Government of India working group on Disease Burden (communicable and non-communicable diseases) for the formulation of the Twelfth Five Year Plan (2012-2017) referred to the triple burden of disease that India has: ◗ Communicable diseases like TB, leprosy, vector borne diseases, water-borne diseases, zoonotic diseases and vaccine preventable diseases ◗ Emerging non-communicable lifestyle diseases like cancer, cardiovascular diseases ◗ Emerging infectious diseases like Ebola virus, SARS, H1N1.

All these factors make a compelling proposition for sponsors to conduct clinical research in India and yet in the last two years most have chosen not to.

The factors that triggered this development are all too familiar now. In January, 2013, through a gazette notification that took the clinical research fraternity by surprise, CDSCO brought into effect new compensation guidelines that had a far reaching impact on the conduct clinical of clinical research in India. Ill thought through and prompted by misguided activism and judicial developments, these guidelines were the beginning of a series of landslide developments in the regulatory environment that were compounded by unpredictable approval timelines and a spate of unannounced site inspections by teams who were ill equipped and had little or no GCP training.

Today, almost two years later, not much has changed in the regulatory environment.

Although there have been attempts by regulators to review several of the challenging reg-

50 EXPRESS PHARMA December 1-15, 2014

ulations through a multi-stakeholder collaborative approach and a commitment that change will come sooner than later, the key issues that stakeholders across the clinical research spectrum continue to face are: ◗ Irrational and unbalanced compensation guidelines ◗ Unpredictable review and approval process ◗ Myopic operational orders such as mandatory across the board audio visual recording of informed consent, limiting the number of trials an investigator can conduct at a given point in time and limiting the distribution of clinical trial sites.

So where does India go from here? Assuming that the regulators recognise that there is an urgent need to fix the roadblocks that today challenge clinical research and are committed to introducing guidelines based on ethics and the principles of science (as has been stated at recent public events), there is still a lot that needs to be done. A policy framework for clinical research has to be an integral part of the Government’s health agenda for the country for it is only through clinical research that we will be able to find newer and more effective treatment to treat our growing and unique burden of diseases.

Assuming that regulators recognise the urgent need to fix roadblocks that challenge clinical research and are committed to introducing guidelines based on ethics and the principles of science, there is still a lot that needs to be done A policy promoting clinical research and innovation needs to be supported by action at various levels: ◗ Rational regulations: Regulations and guidelines developed through a multi

stakeholder consultative approach that are based on science and highlight a commitment to patient safety, ethics and confidentiality in line with per globally accepted practices There are situations unique to India like literacy, socio economic considerations and social cultural norms which must also be taken into cognizance in the development of guidelines so that no one is denied the right to participate in research because of these challenges as with audio visual recording of informed consent for instance. ◗ Capacity building: We need more trained resources within CDSCO to ensure the smooth roll out and governance of clinical research in the country.

Guidelines will remain guidelines with good intent unless there is operational guidance and trained staff to ensure their implementation. ◗ Accreditation: To address the concerns that have been raised about the conduct of clinical research in India, we should have an objective system to accredit investigators, sites and ethics committees.

The accreditation should be provided by an independent third party and reviewed at periodic intervals. ◗ Infrastructure develop-

ment: If we want to grow clinical research in the country and ensure a healthy balance of research across geographies, the Government needs to invest in better infrastructure particularly at government run hospitals and institutions. It is unfortunate that many patients do not have the option of participating in clinical research in many areas of our country because sites are ill equipped and investigators not trained in clinical research. ◗ Public education and awareness: Misreporting and sensationalism of clinical research in India has created fear and suspicion amongst the public at large. A key requirement is public education and awareness not just about clinical research in general but also about the rights and responsibilities of those who participate in a clinical trial.

We need to create an environment where patients have the confidence and trust that their participation in a trial is to their benefit. ◗ Transparency and Openness: We are in a situation where there is a crisis of confidence.

Greater transparency and openness by the regulators will go a long way in restoring trust amongst various stakeholders.

There was much hope held out for patients in our country when clinical research began to grow in India in the 1990s and indeed in the last few years we have seen several life saving drugs being introduced. We are all patients and beneficiaries of better and more effective medication made possible through clinical research. It is likely that there will be a downward trajectory in new medicines introduced in India over the next few years but regulatory will and intent through speedy action can change this…as well as a demand from stakeholders across the clinical research spectrum for the right to better healthcare and treatment.

MANAGEMENT

INSIGHT

Bring research back on the agenda The country has a responsibility towards the health of its citizens that translates to creating an enabling environment, advocates Dr Shoibal Mukherjee, independent professional and research consultant

W

ith more than 300 million disability adjusted life-years (DALYs) lost due to disease and premature death, India has, by far, the highest dis-

ease burden in the world â&#x20AC;&#x201C; China is a distant second with about 200 million.

Communicable and non-communicable diseases are equal contributors to the countryâ&#x20AC;&#x2122;s

To subscribe: bpd.subscription@expressindia.com

disease burden, each accounting for 40-45 per cent, while injuries make up the rest. The country has a responsibility towards the health of its citizens that translates to creating

an enabling environment for investments in healthcare and goal-directed research in health technologies. With its track record of recent successes, the domestic pharma industry,

DR SHOIBAL MUKHERJEE, Independent professional and research consultant

together with foreign investment in this sector, can play a pivotal role in turning the situation around if given the right incentives and a conducive regulatory environment.

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52 EXPRESS PHARMA December 1-15, 2014

IMPACT ON INDIA’S SHARE OF RESEARCH IN ASIA Number of New Trials Registered

The world pharma market is worth approximately $1 trillion.

Of this, about $600 billion is sales of patented products and approximately $250 billion is global generics. In the last 20 years the domestic pharma industry has competed successfully in the generics space, capturing about 6 per cent of the market share (excluding domestic sales), amounting to approximately $15 billion in exports.

While there is still potential for India’s share of the global generics sales to grow further, a section of the domestic pharma industry now stands poised to enter the much bigger patented products market. The challenge in getting the best value for investments in innovative research, which drives the discovery and development of patented pharmaceuticals, lies in the capital intensive nature of drug development, particularly the clinical research component which consumes 60-70 per cent of the cost and time required to commercialise a new medicine.

Indian companies would have a clear advantage over competitors in other countries if they could leverage the significant local cost advantages in research.

Commercial successes can help build expertise and capacity in research that could be leveraged to address local disease burden.

The training and development of personnel in cutting edge research in a growing pharma sector would be crucial to building an ecosystem for health technology research that would be available for application to the country’s health needs.

However, domestic regulatory hurdles have now made it impossible for the domestic industry to benefit from its locational advantage. Moreover, the country has been unable to sustain foreign investments in this sector, with repeated instances of research facilities being closed down and foreign entities announcing discontinuation of research projects in the country.

Far from fostering an environment to support front-line research at a globally competitive scale, these developments have

500 450 400 350 300 250

Taiwan China India Korea Japan

200 150 100 50 0 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014

US Na onal Ins tutes of Health, ClinicalTrials.gov Database. 2014 1H annualized.

led to an attrition of research capacity and a reversal of growth in research capability. Employment opportunities in the health technology research and development sector have contracted sharply and job losses are plaguing this knowledge intensive high-potential domain.

Lost ground From 2010 onwards India has witnessed heightened activism and, at times, media sensationalism targeting clinical research.

Consequent actions, led by Parliament and the Supreme Court, have put pressure on the government and regulators, resulting in a slew of new regulations around clinical trials. While these regulations have been well-intentioned, their consequences were not well thought-through, and have not augured well for clinical research in the country, with upstream damage to the climate for innovative pharma research and downstream damage to the long-term future of pharma innovation in India.

Chief among the flurry of regulations introduced in 2013 has been GSR 53(E) of January 30, 2013, on compensation for clinical trial participants deemed to have been “injured” during the course of their participation. This regulation is not in

line with practices anywhere else in the world. Moreover, the quantum of compensation proposed by the government is out of proportion to that paid in the context of other types of injury that trigger compensation payments in the country. The assumption that the cause of an individual adverse event occurring during the course of a clinical trial can be reliably determined prior to completion of the trial is flawed. Typically, such causal relationships can only be determined after a statistically large enough number of patients have been exposed to the medicine through multiple clinical trials or after the medicine has been marketed. Regulatory delays have also taken a toll on research capacity investments in the country. Clinical trial approvals have plummeted from 529 in 2010 to just 73 of 207 applications received in 2013. The length of delays has extended beyond 12 months, jeopardising project timelines. Requirements such as dictation of the type and geographical distribution of sites by the regulatory authority, the elimination of non-institutional ethics committees, and demands for commercial commitments prior to approval of research projects have made India unviable as a global research

destination. Consequently, the forward intention of clinical projects and research funding to be directed to India has fallen by 65 per cent from its base in 2010. India’s share of clinical trials among the top 5 countries in Asia has fallen from 20 per cent in 2010 to 8 per cent in 2013 and its ranking in Asia has fallen from third to fifth. Further deterioration in these figures is expected in 2014. Reforms in clinical trial regulation will be meaningless in the absence of significant clinical research activity in the country.

The impact of the research policy has been injurious to all stakeholders. Patients, the most prominent beneficiaries, have lost the option to participate in clinical trials. To many patients with life-threatening diseases running out of conventional options, clinical trials provide a last affordable chance of cure or palliation. Thousands of patients across the country have benefited from participating in clinical trials over the past decade, and some have spoken of their experiences on national television and other fora. Cancer patients have regularly sought clinical trials in the face of resistance to conventional therapy. Others who have lost out to bad policy include research employees and

fresh life-science graduates seeking employment as research units close down and fresh hiring comes to a halt. Hospitals that set up research units and employed research staff are unable to sustain their investments, and academic intramural research has become unviable.

The globalising segment of the domestic pharma industry has been disadvantaged the most as the impact on research comes at a time when many companies are on the threshold of initiating major clinical development programmes for novel intellectual property assets. The cost of these programmes is likely to escalate by multiples as trials that could have been undertaken at home now have to be conducted abroad. Economic viability and commercial strategies have to be reconsidered. Significant loss of competitive advantage, at both enterprise and national levels, is inevitable.

Recommendations The current state and trajectory of growth in health technology research and development is not compatible with India’s aspiration to emerge as a global hub for pharmaceutical research. Nor is it in line with India’s position among the leading economies of the world and its need to address its massive disease burden in a self-sufficient manner in the years to come. It is therefore imperative that appropriate policy changes be made to rectify the situation, and to encourage and incentivise investment in health research and development while ensuring that regulations support the highest level of quality and ethics in research activities.

The following recommendations aim to draw a road map to meet this imperative:

Short term requirements Of immediate concern is the shrinking of established capacity in clinical research and the diversion of research funding by local and international investors to other countries of the region.

Early reversal of the prevailing

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sentiment and regaining the confidence of the investor community will require the following regulatory initiatives to be undertaken with sincere followthrough: â&#x2014;&#x2014; Time-bound review of all applications The regulatory agency should set benchmarks for turnaround time of clinical trial applications with an attempt to turn around primary applications in 3 months and secondary applications in 2 weeks. Metrics should be measured and publicly reported for each application. Clear and cogent reasons should be stated in writing to the applicant in case of rejections, which should be based on accepted scientific and ethical principles. â&#x2014;&#x2014; Rationalisation of compensation regulations In absence of breach of law/rules, no-fault compensation regulations should apply strictly to study-related injuries (study drug and any study-specific investigation or procedure). The quantum of compensation should be rationalised to approximate the level of payments made by the Government of India in case of accidents and calamities. Medical negligence should be treated as in routine practice. â&#x2014;&#x2014; Removal of arbitrary restrictions Hard restrictions, such as on choice of sites, number of trials per investigator, and mandatory video recording of patients, should be relaxed. Sponsors should be free to choose any site that has not been debarred due to misconduct. A system of audits and inspections should ensure compliance to published regulations. Graded action, including possible debarment, should be taken against noncompliant sites. Video recording should be encouraged, but qualified exemptions should be permitted.

If the above initiatives are taken, publicised, and sincerely followed through, it is likely that sponsor interest in making research investments in India can be revived in the short term.

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Long-term imperatives More will have to be done to sustain biopharma research activ-

ity in the country over the long term and take the country to a leading position in applied clinical

research in the region. Some of the suggestions below have been a part of the vision of previous

committees and expert panels.

They are reiterated here with Continued on page 57

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INSIGHT

CTregulation in India: Science or social justice?

Mark Barnes, JD, LLM Faculty Co-Director, Multi-Regional Clinical Trials Center at Harvard (Harvard MRCT), Lecturer, Harvard Law School, Partner, Ropes & Gray LLP and Dr Barbara Bierer, MD, Faculty Co-Director, Harvard MRCT; Professor of Medicine, Harvard Medical School and Brigham and Women’s Hospital opine that using the clinical trial context to promote a social or political policy agenda in India may sacrifice scientific integrity in the service of social justice

C

linical researchers in India and the pharmaceutical and biotechnology industry are well aware of the various restrictions and regulations imposed by the Supreme Court and the Ministry of Health since early 2013. These restrictions and regulations include, among other things, a requirement for audio and visual recording of all informed consent discussions in clinical trials; mandatory provision by trial sponsors of “ancillary care” for medical conditions experienced by clinical trial participants even if those conditions are unrelated to the trial; and most importantly, mandatory compensation for all injuries experienced by clinical trial participants that are “related to” their participation in a trial. These measures have, quite predictably, imposed large new costs and additional uncertain future liabilities on the planning and conduct of clinical trials in India, and have caused a fall-off in interest among both sponsors and investigators, with clinical trial approvals declining from about 500 in 2012 to about 70 in 2013 and 150 anticipated in 2014.

When one considers the

54 EXPRESS PHARMA December 1-15, 2014

causes of the adoption of these measures, one sees – in the media reports, the opinions of the Supreme Court, and in public statements – a repeated concern that citizens of India may be enrolled in clinical trials without appropriate and fully informed consent, and once enrolled, may be harmed with no compensation provided for the injury. The response to these concerns has produced measures that, we believe, are overly broad and do not surgically and precisely address the real risks to subjects.

Mandatory audiovisual recording of informed consent discussions was mandated for all participants, not for those who either are at some defined disadvantage (e.g., illiterate, decisionally impaired) or for those who wish to be recorded in this way.

Instead, this broad mandate includes every consent procedure for every trial, independent of re-

ligious and cultural preferences, the sensitivity of the disease being studied (e.g. HIV, mental illness), the social norms of the community, and the degree of privacy desired by the participant.

Similarly, the requirement that compensation be paid to any participant who has suffered an injury “related to” the trial seems sensible – until one looks further at the definition of “related to,” which is broad enough to encompass even injury from being run over on a busy road or injury from antecedent illness.

Why should the sponsor of a clinical trial be required to pay for the expenses of heart problems suffered by a participant enrolled in an oncology drug trial, when the heart problems preceded that person’s entry into the trial? Why should a sponsor be required to pay for the lifetime medical care of

breast cancer when the study addressed only the effective treatment of multi-drug resistant tuberculosis?

The overbreadth of these requirements, and how poorly tailored they are to achieve the specific goal of protecting clinical trial participants from risks directly caused by trials themselves, leaves one wondering whether the regulatory authorities fully comprehend the clinical trial process and the nuances of complex medical and biological processes. One further wonders whether what animates these measures may be less a concern for specific justice in individual cases than the goal of righting social wrongs and achieving social justice, unrelated to but prompted by clinical trial experiences. Achieving social justice and a more just allocation of social resources may be completely laudable – even de-

The best of social justice intentions can adulterate science, by establishing, in law, false links between apparent causes and ill effects

MARK BARNES, JD, LLM Faculty Co-Director, Harvard MRCT,Lecturer, Harvard Law School, Partner, Ropes & Gray LLP

DR BARBARA BIERER, Faculty Co-Chair, Harvard MRCT, and Professor, Harvard Medical School

sirable – as social or political policy, but unconsciously using the clinical trial context to promote this agenda threatens to corrupt science and to undermine health, with results that may create more social distress than social justice.

To understand the threat here, take the example of compensation mandated for injuries “related to” a trial, and the current regulatory definition of “related to” that is so broad as to include nearly anything adverse, from any cause, that may happen to a clinical trial participant.

While the social justice result of such a mandate for compensation may be to transfer some defined amount of financial resources from companies, nonprofit organisations and academic medical centers that sponsor trials to people – often poor or of modest means – who participate in trials, the specific concepts used to operationalise this financial transfer do nothing

MANAGEMENT

but distort critical scientific concepts.

In clinical trials, the efficacy of a new drug, device or vaccine, and their safety profile, are being actively investigated and tested.

Assessments of both safety and efficacy are, in turn, largely dependent on the clinical results, good and bad, and the carefully monitored adverse effects of the test agent. But sick and ill patients enrolled in trials experience many adverse health events. Most of them, typically, are related to the underlying illness that the test agent is meant to treat and not to the test agent; other bad health events are due to intervening causes that have nothing to do with the test agent or with the underlying disease – such as falling off a motorbike or drowning in rough seas.

In order to assess what adverse health effects are actually caused by a test agent and not by other factors, best practices in clinical trials (and international clinical trial standards) call for each investigator and the trial sponsor to analyse each adverse effect or unanticipated problem for its potential for having been caused by the test agent, and to record that probability finding in the clinical trial record, which is then reviewed by the ethics committee and ultimately presented to drug and device control authorities to support an application for approval of the test product. To assess causation, different variables must be carefully considered, such as the proximity in time between administration of the product and the appearance of the adverse condition, and similar patient experiences with other products whose mechanisms of action are similar to those of the test product. To understand a test agent’s efficacy and safety, therefore, the assessment must adhere closely to objective data, and make judgment based on facts, not sentiment or on an understandable desire to assist an afflicted individual.

Yet these recent compensation regulations, in order to assure that injured participants get some compensation and as-

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sistance, require that compensation be given only when injuries are “related to” a trial, when in reality, “related to” is defined so

broadly as to include nearly every bad event in the life of a trial participant. The result is that in India, when a trial con-

cludes and the data are analysed, it may appear as though there have been multiple compensated injuries that were

“related to” the trial, when in fact, the adverse health effect was unrelated to the trial or the test product.

MANAGEMENT

There is no current method to compensate individuals for humanitarian reasons, independent of a finding of relatedness of the injury to the trial.

Thus, the law and regulation— in order to achieve a beneficial social justice purpose— threaten to contaminate the reporting and scientific causality assessment of these health conditions. CDSCO may not be able to ignore multiple compensated injuries in a trial, when considering a new drug for approval. And attorneys who seek to sue drug companies for injuries allegedly caused by an approved marketed drug will reference evidence from injuries compensated during the trials of the drug (because they were found

“related to” the drug being tested) to establish that injuries after marketing were also caused by, or related to, that drug.

Finally, because of these multiple compensation events for injuries “related to” the trial and the test drug, the safety profile of drugs tested in India will appear more problematic than in the rest of world, leading to the conclusion that there are biological, genetic, or environmental differences in the Indian population that might explain the adverse event profile, when in fact there is no difference.

Forever after, the mistaken conclusion will be that specific trials must be conducted on Indian populations powered to detect differences, when in fact the

The best of social justice intentions can adulterate science, by establishing, in law, false links between apparent causes and ill effects

faulty regulatory framework— not biology—undergirds the findings.

In this way, the best of social justice intentions can adulterate science, by establishing, in law, false links between apparent causes and ill effects. The paramount concern here is that India, which has every human potential to become a world leader in science, not allow its laudable commitment to social justice inadvertently to be implemented under false concepts, the predictable effect of which will be to adulterate scientific discourse and hinder science itself.

In this case, the danger has come in the guise of clinical trial compensation regulations, but this risk could appear in regula-

tions related to, for example, scientific funding, technology export controls, or intellectual property. In this recent experience, a regulation quickly drafted, without nuance or refinement, misleadingly has labeled all injuries in a trial as “related to” or caused by the trial.

If this shows us anything, it is that legal concepts should follow and respect science and not contradict it; social justice goals ought to be overt, explicit and appropriately defined and not embedded in unrelated or only tangentially related regulations and laws. In short, honesty in science, accuracy in scientific terminology, reasoning, evidence and integrity must be respected, or else science itself will be at increasing risk in India.

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Continued from page 53

Bring research back on ... some specificity. ◗ Restructuring of regulatory agency The regulatory office needs to be restructured particularly in terms of number, qualifications and experience of staff. Induction of a regular head of the agency, preferably with seniorlevel regulatory experience at one of the world’s leading agencies would be desirable. Other technical officials should be laterally inducted on the basis of experience and technical competence. ◗ Functioning of regulatory agency The functioning of the regulatory agency should be based on detailed operating procedures. Databases should be maintained using the latest information technology, particularly for active sites, active trials, and adverse events. A system of online submissions and e-governance should be put in place. ◗ Technical pre-consultation A system of formal technical pre-consultation and scientific advice should be put in place for applicants to receive regulatory guidance following best practices at the world’s leading regulatory agencies. ◗ Enforcement apparatus A system of regular inspections of clinical research sites, ethics committees, and research organisations should be put in place with thorough training and clear operating procedures for inspectors. Regulations against fraud, data manipulation and misreporting should be instituted. ◗ Guidance for sites The regulatory agency should provide guidance to sites that can subsequently form the basis for an accreditation system. At a minimum these should cover standards for operating procedures, documentation systems, facilities for trial participants, patient awareness, trial access and recruitment guidelines.

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RESEARCH

CLINICAL UPDATES

Glenmark enrols first patient for phase II trial of GBR 500 The company out licensed Vatelizumab (GBR 500) to Sanofi for all indications in 2011 GLENMARK HAS enrolled first patient in a multi-centre phase II clinical trial to evaluate Genzyme’s investigational infusion therapy vatelizumab in patients with relapsing remitting multiple sclerosis (RRMS). The trial, called EMPIRE, is designed to assess the efficacy of vatelizumab vs. placebo in RRMS patients. The safety, tolerability and pharmacokinetics of vatelizumab will also be assessed.

Multiple sclerosis is a chronic inflammatory demyelinating and neuro degenerative disease of the central nervous system (CNS). Uncontrolled inflammation within the CNS leads to inflammatory damage that is associated with demyelinating lesions and neuro

degeneration in patients with MS. Vatelizumab is a humanised monoclonal antibody that targets VLA-2, a collagen-binding integrin expressed on activated lymphocytes. The mech-

anism of action of vatelizumab is not known, although it is hypothesised to block VLA-2 on activated immune cells, leading to interference with collagen-binding in areas of inflam-

mation, and thus may reduce the inflammatory cascade in MS. Genzyme is developing vatelizumab in MS in partnership with Glenmark Pharma-

ceuticals. In addition to its marketed therapies, Genzyme has an MS R&D pipeline focused on investigational treatments to address unmet needs for relapsing and progressive forms of MS through research in selective immunomodulation, neuroprotection and remyelination.

Commenting on the progress with GBR 500, Dr Michael Buschle, President of Biologics and Chief Scientific Officer, Glenmark Pharmaceuticals said, “We are excited about the commencement of this trial and are pleased with the continued progress of our partnership with Sanofi/Genzyme.”

EP News Bureau-Mumbai

US FDAvotes against Novartis’LBH589 compound (ODAC) did not recommend the investigational compound LBH589, a pan-deacetylase inhibitor, for patients with previously treated multiple myeloma when used in combination with bortezomib [*] and dexamethasone NOVARTIS ANNOUNCED that the US Food and Drug Administration's (FDA) Oncologic Drugs Advisory Committee (ODAC) did not recommend the investigational compound LBH589 (panobinostat), a pandeacetylase (pan-DAC) inhibitor, for patients with previously treated multiple myeloma when used in combination with

58 EXPRESS PHARMA December 1-15, 2014

bortezomib[*] and dexamethasone.

The committee's vote will be considered by the FDA in its review of the LBH589 new drug application (NDA), but the FDA is not bound to follow the Committee's guidance. The final decision regarding US approval is made by the FDA. "We are disappointed by this

voting outcome and believe the results from our clinical trials provide strong evidence to support LBH589 as a potential first-in-class treatment option for multiple myeloma, a cancer where an unmet patient need exists," said Bruno Strigini, President, Novartis Oncology.

"We will continue to work with the FDA as it completes its re-

view of the US application."

Data presented included two clinical studies evaluating LBH589 in combination with bortezomib and dexamethasone for patients with relapsed or relapsed and refractory multiple myeloma: a phase III randomised, double-blind, placebocontrolled, multicenter global registration trial called

PANORAMA-1 (PANobinostat ORAl in Multiple MyelomA) and a Phase II US multicenter, single-arm, open-label study called PANORAMA-2[1].

Reference (*)Trade name Velcade registered to Millennium Pharmaceuticals, Inc. (1) Novartis LBH589 ODAC Briefing Book.

Study confirms positive safety profile and effectiveness of Pradaxa in atrial fibrillation patients The FDA Medicare analysis is based on patient data from elderly patients enrolled in Medicare THE US Food and Drug Administration (US FDA) Medicare analysis of 134,000 atrial fibrillation (AF) patients treated with either Pradaxa (dabigatran etexilate) or warfarin in a general practice setting, was published in Circulation. The FDA authors conclude that dabigatran was associated with a significantly reduced risk of ischaemic stroke and intracranial bleeding, a significantly increased risk of major gastrointestinal bleeding and a significant survival benefit compared with warfarin in eld-

erly patients with non-valvular AF. The FDA study confirms findings of the RE-LY study in 18,000 patients, which led to the approval of Pradaxa for stroke prevention in AF worldwide.

The FDA Medicare analysis is based on patient data from elderly patients enrolled in Medicare. The FDA study included patients who started treatment for dabigatran or warfarin for non-valvular AF between October 2010 and December 2012 and were older than 65

years.

The detailed results of the analysis showed: ◗ Fewer ischaemic strokes due to blood clots with Pradaxa (20 per cent less than with war-

farin) ◗ Fewer intracranial bleeds with Pradaxa (66 per cent less than warfarin) ◗ Survival benefit with Pradaxa (14 per cent better than warfarin) ◗ No difference in major bleeding between Pradaxa and warfarin ◗ No difference in acute myocardial infarction between Pradaxa and warfarin ◗ More gastrointestinal bleeding with Pradaxa (28 per cent more than warfarin)

The US FDA had explicitly stated, “Pradaxa provides an important health benefit when used as directed.”

“The results of the US FDA Medicare analysis clearly confirm that the positive safety and efficacy profile observed in the clinical RE-LY study was also achieved in real world general practice”, commented Professor Jörg Kreuzer, Vice President Medicine Therapeutic Area Cardiovascular, Boehringer Ingelheim.

Source: Business Wire

CPHI INDIA 2014 SPECIAL

COVER STORY

ECO-FRIENDLY DRUGS:

Difficult, yet possible Besides being patient friendly, pharmaceutical drugs and their manufacturing processes are expected to be eco-friendly as well. However, the pharma industry has its own share of problems in doing so

BY SACHIN JAGDALE

60 EXPRESS PHARMA December 1-15, 2014

C

hemicals are inevitable constituents of almost all drugs. Though these chemicals are regularly checked for their controlled side effects on the human body, their adverse effects on the environment perhaps never get the due attention.

Scientifically and technically strong pharma operators know this fact very well.

However, things are taking time to change, sometimes due to compulsions of the business and sometimes due to lack of alternatives.

Role of catalysts Use of a catalyst is considered unavoidable in the drug manufacturing process. However, catalysts like palladium are not only expensive for the company but also harmful for

the environment. So, is there a need to find an alternative to catalysts as a step towards making drug development eco-friendly? According to experts, contrary to popular belief, catalysts are not polluting agents apart from few exceptions. In fact, catalysts can aid in reducing environment pollution.

Pravin Herlekar, Chairman, Omkar Chemicals, says, “Use of catalysts is a must in many drug manufacturing processes. There are alternate processes without the use of a catalyst. However, they would lead to more complex issues related to effluents. Catalysts are primarily used to improvise on the yields of the desired product, minimise by-products, expedite kinetics of the reactions and minimise efflu-

Use of catalysts is a must in many drug manufacturing processes. There are alternate processes without use of catalyst.

However, they would lead to more complex issues relating to effluents Pravin Herlekar Chairman, Omkar Chemicals

ents. There are new generation catalysts such as chiral catalysts and nanotechbased catalysts which make use of common metals such as cobalt, nickel, copper, etc. as against costly materials like palladium. However, they are process specific and cannot be applied in general.

But one must say that use of a catalyst helps in reducing environmental issues.”

A chemical research scientist, speaking in his personal capacity, echoes Herlekar's views. According to him use of catalysts is a must. He says, “As of now catalysts are unavoidable.

Catalysts avoid all routes that other chemicals would take as reagents. Use of a proper catalyst is very important. Different types of catalysts can be used for one

reaction. However, yield and selectivity of the desired product will change with the catalyst. Catalyst with the best yield and selectivity must be used. Next step is the optimisation of process parameters.

In the pharma industry, optimisation is mostly avoided due to urgency or lack of time in product development, very rapid product changes, unawareness or negligence.

Catalysts are unavoidable, but must be used wisely. I do not think there is any research to avoid catalyst. In fact, catalysts are the best candidates to do the job with maximum yield selectivity and minimal waste.”

Replacing stoichiometric methods with catalyst would be a good eco-friendly option, opines a spokesperson from BASF. “The key to more

CPHI INDIA 2014 SPECIAL

eco-friendly processes in fine chemicals manufacturing is the substitution of classical organic syntheses employing stoichiometric amounts of inorganic reagents with cleaner, catalytic alternatives. The E factors (by waste per kg product) of chemical processes increase dramatically on going downstream from bulk to fine chemicals and pharma products, mainly owing to the use of stoichiometric methods,” informs BASF's spokesperson. He adds, “The concept of atom efficiency is a useful tool for rapid evaluation of the amount of waste generated by alternative processes. To make processes more atomefficient and decrease the E factor, catalysts are key to success. For example, the Presidential Green Chemistry Awards show examples of catalysts being used for making processes more eco-friendly.

A good starting point for the use and impact of E-factor calculations and the role catalysts can make in this is: Pure and Applied Chemistry, 2009, 72 (7), p.1233-1246 by R.A. Sheldon.”

Companies can more effectively treat effluents to ensure they are properly disposed off Vijay Ramanavarapu Corporate Development, General Manager, Granules India

Drug design Though changing drug design is an option mulled over by scientists, developing 'benign by design' drug is hardly possible. Understandably, why would a company think about sacrificing drug qualities that keep it active and stable for the sake of environment?

BASF spokesperson says, “If this is referring to the production process of a specific drug we can state the following: a trend is observed towards replacing stoichiometric reagents by catalysts to make processes more cost efficient and eco-friendly. If the statement is referring to changing the chemical structure of a pharma compound, making a statement by BASF is more difficult and better answered by pharma companies.

However, it is known that changing the design of a

62 EXPRESS PHARMA December 1-15, 2014

pharma compound has an impact on the pharmacological effect and typically cannot be considered for existing pharma products.”

Herlekar opines, “The drug required for a particular disease is designed after considering its efficacy, extent of side effects, affordability, etc.

Once the drug is designed, we have to select the most cost effective process for manufacturing the same. This can be done by adopting the best available processes of synthesis, while keeping in mind the final targeted cost of drug. A suitable route of synthesis should be chosen to address the issues relating to the environment.”

Dealing with effluents Water is the largest receptor

of pharma effluents. Drug residues excreted by the pharma manufacturing plants linger in water bodies for months or even years. The challenging part is that the effects of these residues are hard to isolate and sometimes poorly understood. According to reports, anti-depressants like Prozac might disrupt frog development. Consumption of fish containing harmful chemical may prove fatal to human life as well. So effluents remain one of the biggest hurdles in making drugs ecofriendly.

Vijay Ramanavarapu, Corporate Development, General Manager, Granules India, says, “Companies can treat effluents more effectively to ensure that they are properly disposed of. Proactive compa-

nies can install zero-liquid discharge (ZLD) systems to ensure that all water is treated on-site and can be safely used for other applications such as garden water. While many Indian companies aren’t being proactive right now, we feel that in the future, successful companies will focus on how to minimise their environmental impact due to increasing emphasis on sustainability.

Many companies, in particular, Western-based customers, are increasingly using environmental sustainability as a selection criteria when picking a new supplier.” He adds, “While researching new methodologies, pharma companies need to ensure the end product is still the same and the impurity profile of the product doesn’t change. Any

major changes including different raw materials will require regulatory approvals from agencies such as the US FDA which will take time for a company to receive. At Granules India, our R&D has actively been working on green technologies that will reduce our carbon footprint.

We believe this will not only give us a cost advantage but also improve our overall sustainability efforts.”

While developing pharma processes, chemists hardly make prior discussions with chemical engineers, complains a chemical engineering expert.

He explains, “Chemist's target is to get the product, yield does not matter to them. Process engineering and intensification must be done. The use of statistical techniques like design of experiments in process development and optimisation is also lacking. Effluents will be produced, but E-factor can be very low if process (reaction and workup) is well optimised.”

The most cost effective processes may lead to serious environmental issues while the most eco-friendly processes may lead to high cost of production. “We have to strike a balance wherein we optimise both these factors,” stresses Herlekar.

He adds, “Pharma effluents may certainly be chemical-free and there are ways and means to do so. Such effluents can be treated by making them neutral, followed by adjusting their levels of biological oxygen demand (BOD), chemical oxygen demand (COD), etc. They can be further processed in multiple effect evaporators, RO plants, incinerators, etc. and the water obtained can be recycled back into the process. However, all these operations add to the cost of the product and the market must accept and sustain the same.”

There are many research activities which are still at

the conceptual stages. For e.g.

Developing drugs with photodegradable properties.

These drugs would be light sensitive and would decompose once exposed to light in the waste treatment plant.

Possibilities of adding temporary stabilisers to the drug which would break off only after arriving inside the body are also being explored.

Financial hurdles As mentioned earlier, becoming eco-friendly is an expensive option and pharma companies would require a hefty balance sheet to invest in the same. Under tight market conditions, raising additional

money is seen as a business eroding step by the pharma industry. Unless going green coincides with some other profit-making measures, convincing drug manufacturers to implement eco-friendly methods looks difficult. â&#x20AC;&#x153;In India, most the drug manufacturing is being done in the SME sector and these units do not have the requisite financial strength as well as the space required for exhaustive treatment facilities. One way to come out of this situation is to have government support in promoting larger CETPs in the industrial areas wherein the government can subsidise the cost of process-

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Going green should coincide with some other profit-making measures to convince drug manufacturers to implement eco-friendly methods

ing effluents,â&#x20AC;? says Herlekar.

Becoming eco-friendly should be the joint venture between the pharma industry and the government. Financially strong MNCs can afford to invest extra money for new developments, however, for majority of the Indian drug manufacturers, government's subsidy would prove helpful.

Subsidy could be on buying machinery to treat effluents or to provide lands for effluent treatment at nominal costs.

Government can also reward a company with the most ecofriendly record.

ble yet difficult to achieve dream. Any successful drug is a result of years of effort, research and investment.

Changing these drugs, their manufacturing/research set up overnight, is obviously not very practical for pharma companies as they offer solutions that suits their financial requirements. Moreover, treating human beings first gains priority over caring for the environment. However, both humans and the eco-system are part of a cycle where they are interdependent.

Damage to one of the entities would surely affect the other.

The way forward Eco-friendly drugs is a possi-

sachin.jagdale@expressindia.com

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December 1-15, 2014

serving with the

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CPHI INDIA 2014 SPECIAL

I N T E R V I E W

‘We will launch INSTACOAT 4G at CPhI India 2014’ Suresh Pareek, Managing Director, Ideal Cures reveals his strategies and expectations from the CPhI India 2014 show, in an interaction with Viveka Roychowdhury What have been the major launches from Ideal Cures in the past year?

Last year Ideal Cures launched two new products and a mobile application. The products launched included INSTAMODEL, the ready-touse extended release material custom formulated for each molecule like Metoprolol, Metformin, and Diclofenac etc.

INSTAMODEL is a brand new concept in the excipient industry and an Ideal Cures initiative to make the first in this product range.

The other product launched was INSTAMASK, yet another ready-to-use concept for taste masking of bitter active ingredients. Both product launches received excellent response. Both these products are doing well in India as well as the international market.

What is the strategy for CPhI India 2014? Are there new launches, services etc?

The strategy for CPhI India, 2014 is to meet customers from around the world. For this we are inviting our area managers and other senior persons from international regions to join us.

Last year we opened a lab in Istanbul, Turkey and this year we opened a representative office in Tel Aviv, Israel. We already have an office in Milan, Italy since the last five years.

Representatives from these countries will join us at CPhI India this year.

This year we will also

66 EXPRESS PHARMA December 1-15, 2014

launch the 4th generation of coating material brand named as INSTACOAT 4G. INSTACOAT 4G is the innovation which will sent competitors back to labs.

INSTACOAT 4G is designed to meet the requirement of continuous coaters, large scale auto coaters like 67 and 72 inches as well as conventional coating machines.

INSTACOAT 4G will reduce coating time by 50 to 70 per cent.

Along with this, another product which we will be showcasing is sugar fast coating. In terms of technical advancement, it is meant to save time and improve process finishing for products that are still being sugar coated.

Although no new launches are available for sugar coated products, the sole reason for us to develop this product is to help and support the companies that are still making such sugar coated products.

Both these products are dedicated to the worldwide pharma industry, as a contribution by Ideal Cures towards reduction of carbon footprint.

How is the mobile app launched last year doing?

Any more digital services aids in the pipeline?

The InstacoatLab mobile app has been very well received by the industry.

Many customers have used our app to to save costs and

time. Many other features like colour guide and country wise regulatory guide serve as ready reckoners. We recently launched the app in the iOS version and will be launching the BlackBerry and Windows version soon.

We will also be adding brand new features to the app this coming year.

know, was of the previous central government and there was a lot of uncertainty. In spite of that, at Ideal Cures we achieved a growth rate of 24 per cent. In our case, film coating systems are our prime business and this is the one which is growing the fastest.

Other excipients like neutral spheres, cooling compound,

The strategy for CPhI India, 2014 is to meet customers from around the world. For this we are inviting our area managers and other senior persons from international regions to join us CPhI has been a good platform to launch new products, network with existing customers and meet new customers

In terms of global sales, which geographies are Ideal Cures’ focus areas?

Our focus for global sales is Asia as well as Europe until next year and then we will be moving to other geographical areas. In Europe, we already have one office in Milan, Italy and by next year we have plans to have two more offices in Europe. Similarly, we will have increased focus in the Asian countries as well.

What has been the growth rate of the company in this fiscal over the last? Which categories are growing the fastest?

Last fiscal year, as we all

and taste masking compositions are catching up and showing good growth rate.

In the years to come, new products should do a lot of value addition to us.

What are your expectations from CPhI India 2014?

CPhI has been a good platform to launch new products, network with existing customers and meet new customers. We also wish to achieve new product launches which help us understand the trends in the industry. As usual we expect the show to be good. viveka.r@expressindia.com

RET® control-visc

Way ahead in pharma solid dosage form coating technology

The Magnetic Stirrer for Scientists

Ideal Cures has put a lot of emphasis on energy savings while launching the 4th generation tablet film coating system. An outlook by Suresh Pareek, Managing Director, Ideal Cures, Saryu Pareek, Sr Vice President – Corporate, Ideal Cures and Laxmikant Sadafule, Vice President – Sales and Marketing, Ideal Cures Baran uses IKA® equipment

T

he prospect of climate change is alarming and is widely attributed to global warming. This calls for an action to conserve energy and maximise output with minimum input. Individuals and companies are putting a lot of emphasis on energy savings, it not only saves money but also our planet As a part of the initiative to conserve the environment, Ideal Cures has launched the 4th generation tablet film coating system, which reduces the process time drastically and at the same time utilises less energy which certainly helps to reduce CO2 emission.

History tells us, the first coating of solid pharmaceutical dosage forms began in around the 9th century B.C. with the Egyptians. During the initial days, the solid dosage form was called as ‘Pill’, a spherical hand-shaped (pill) which contains active ingredient, sugar and other diluents. The other excipients that were used for coating were sugar, talc and gelatin. Silver and gold were also used. Many of these coatings proved to be impervious to acid attack in the digestive tract; as a result, the pill never released its active drug completely and was thus ineffective.

The candy industry was the first to develop and enhance the art of coating.

The first sugar coated pills was produced in Philadelphia, US, in 1856.

The enteric coating system was developed in the 1880’s. In 1953, the first

Phil S. Baran Ph.D. Recipient of MacArthur Genius Grant

SURESH PAREEK, Managing Director, Ideal Cures

Patented

Safety. Power. Intelligence.

Strongest and safest magnetic stirrer in its class with integrated weighing function and torque trend indication

SARYU PAREEK, Sr VP – Corporate, Ideal Cures

For more information, Please go to www.ika.com/RET

LAXMIKANT SADAFULE, VP – Sales and Marketing, Ideal Cures

compression coated tablet was introduced and 1954 saw the first film coated tablet being marketed.

The coating technology primarily

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IKA®-India Private Limited 814/475, Survey No.129/1, Mysore Road, Kengeri 560060 Bangalore, Karnataka, India Tel. +91 80 26253900 · +91 80 26253925 Fax +91 80 26253901 info@ika.in · www.ika.in

designed

to work perfectly

CPHI INDIA 2014 SPECIAL

has three components coating material, solvent system and machineries used for the coating.

Components in coating evolution Initially, pharma companies developed coatings in house, but slowly the trend for ready-touse film coating caught on due to increased productivity, efficiency and time savings. One of the most popular polymers for coating has been hydroxy propyl methyl cellulose (HPMC). Various reasons for its popularity are safety, tried-tested for a long time, film strength and its film forming property. Initially, low viscosity of HPMC E-15 was the most popular polymer for inhouse coating system. With HPMC E-15, the challenge was the coating process time because of five to eight per cent solids in non-aqueous solvent systems. As productivity started becoming a concern the ready-mix concept was preferred by the companies. This concept reduced product development time, enhanced consistency in coating, simplified inventory management and also had other advantages. Ideal Cures launched their first ready mix product in year 1999 with the first generation coating material brand named INSTACOAT. The next step was launching the second generation coating products with combination of different polymers including low viscosity HPMC grade and with different combination of polymers like HPMCHPC, HPMC-Polysaccharides.

After the formulation of multi component systems, the next generation of film forming polymer came up: polyvinyl alcohol (PVA). PVA is a film-forming agent produced by the hydrolysis of polyvinyl acetate. An alkali metal or inorganic acid is used as a catalyst in methanol, ethanol or a mixture of ethanol and methyl acetate, to accelerate the hydrolysis of polyvinyl acetate to yield polyvinyl alcohol (PVA).

PVA is used as film forming

68 EXPRESS PHARMA December 1-15, 2014

Conventional pan

Spraying process with INSTACOAT 4G

Ideal Cures launched their first ready mix product in 1999 with the first generation coating material brand named INSTACOAT. The next was the second generation coating products with combination of different polymers

Autocoaters

Continuous coater

agent in a number of pharma formulations. INSTACOAT EHP 250, an optimised instant release film coating formulation based on PVA brought revolution in pharma coating. INSTACOAT EHP 250 can be applied on the tablets with a solid content of up to 25 per cent, which is a major step towards achieving highly efficient film coating processes. Besides the increased solid content of the formulations, other properties, like reduced permeability of water vapour or oxygen through a film, have also been achieved.

Another important component in coating technology is the solvent system used. Historically solvents like acetone, benzene, carbon tetrachloride, chloroform, IPA, MDC etc. have been used in pharma coating process. As the regulatory requirements started getting stringent, organic solvents were avoided due to its disadvantages like safety, carcinogenicity etc.

Then first choice for non-aqueous solvent which were widely used in past was the combination of Isopropyl alcohol (IPA) and methylene chloride. Next, methylene chloride was eliminated and the concept of hydroalcoholic coating system evolved and came to be used widely with different ratios.

Currently, the preferred choice for a solvent is only aqueous.

The reasons for this being safety, cost benefit and a reduction in carbon footprints.

Machinery revolutions have played an important role in the evolution of coating system. It was started with the conventional coating pan with external air blower and external exhaust system. Looking at the productivity demand, different sizes of conventional coating pans were introduced like 30, 36, 40, 42 inch etc. There was a huge demand for the machines which could produce good quality, consistent coating along with in-

creased productivity, then the generation of autocoaters came into existence with different capacity, which were completely closed side vented pans fully automated. The bigger pan size available in autocoater were 67/72 inch, still there was a demand for high productivity and the latest innovation we have is the continuous coater, the machine in which feeds the core tablets from one end and the cores are coated before they reach the other end.

The coating process consumes a lot of energy and this energy consumption takes place during the following phases. They are inlet air, heating the tablets, heating the machine, heating the solution, during evaporation of the solvent, process loss, exhaust air, during pan rotation, room HVAC system.

Thus each of these steps generates heat and causing CO2 emission. Reduction in

time required for each of these processes is to have higher solid content coating product requiring less time on the coating cycle.

With an increasing emphasis on optimisation of process times and energy consumption, the 4th generation of film coating product was developed targeting an improved coating efficiency. An example of this new generation is INSTACOAT 4G, which is obtained by layering polyvinyl alcohol on a plasticiser backbone. Due to the lower viscosity compared to all previous film coating materials, INSTACOAT 4G can be applied in concentrations of 35 â&#x20AC;&#x201C; 40 per cent.

The beauty of this product is that one doesnâ&#x20AC;&#x2122;t have to go for any special or new equipment.

This product can work in any machine like conventional coating pan, autocoaters, continuous coating machine, bottom spray for pellet coating etc.

There is absolutely no need for any additional investment.

If we compare the process time with the conventional coating products from other suppliers which offer products from 11 per cent solid content up to 25 per cent solid content INSTACOAT 4G at 35â&#x20AC;&#x201C;40 per cent solid levels, almost reduces the process time by half. Due to low process time the total energy consumption required is drastically reduced to half, which in turn saves money, lowers CO2 emission and increases the capacity of the plant. INSTACOAT 4G is the perfect fit for high volumes and where there is time constraints for tablet coating.

The pharma industry has the opportunity to use the INSTACOAT 4G to save the money and also to reduce the CO2 emission. Ideal Cures is dedicated to save the environment by helping its customer by providing the economical and ecological value added products which helps them to grow and increase profitability.

INSIGHT

Lipases: industrial biocatalysts for production of pharma intermediates and fine chemicals Bhalchandra K Vaidy, and Sandeep Bijamwar in this article describes applications of lipases in pharma and fine chemical industry

T

he past decade has witnessed a heightened interest in exploring potential of enzymes for industrial organic synthesis.

Chemically enzymes are proteins and functionally they are catalysts of biological systems (biocatalysts).

Being catalysts, enzymes accelerate the rate of reaction by decreasing the energy of activation.

The high selectivity and specificity of enzymes make them valuable catalysts especially for synthesis of pharmaceuticals and fine chemicals, where the demand for enantiomerically pure molecules is continuously increasing [1].

BHALCHANDRA K VAIDYA Research Scientist, Advanced Enzyme Technologies

Advantages of enzymes: ◗ Efficiency: Enzymes are far more efficient than chemical catalysts.

The initial reaction rates of enzymatic (biocatalytic) transformations are roughly 1010 to 1020 times higher than that of chemo-catalysed reactions. ◗ Selectivity: Enzymes exhibit exceptionally high chiral (enantio-) and positional (regio-) selectivities.

Thus, the tedious blocking-deblocking steps which are commonly required for asymmetric chemo-catalytic reactions are not required in biocatalytic transformations. ◗ Specificity: Enzymes are specific

SANDEEP BIJAMWAR Business Head - Healthcare API, Advanced Enzyme Technologies

for certain chemical compounds (substrate specificity); which avoids side reactions and formation of unwanted by-products. ◗ Work in mild reaction conditions: Enzyme-catalysed reactions are generally carried out under mild conditions (of pH, temperature, pressure etc.) that mitigate common problems like isomerisation,

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CPHI INDIA 2014 SPECIAL

racemisation or epimerisation of the product. ◗ Green catalysts: Enzymes are regarded as ‘green catalysts.’ They are completely biodegradable and therefore do not cause environmental pollution. Moreover, enzymatic processes are less hazardous, less polluting and consume less energy than conventional chemo-catalytic processes, especially those which use heavy-metal catalysts.

Classification of enzymes Enzymes catalyse enormous range of reactions. They are increasingly found to transform almost any reaction of organic chemistry. According to the report of the first Enzyme Commission in 1961, enzymes are classified into six classes depending upon the type of reaction they catalyse [1]. The six classes of enzyme and corresponding type of reactions are summarised in Table 1.

Among the six classes of enzymes, hydrolases have a major share in industrial biotransformations particularly in resolution of racemic compounds and in asymmetric synthesis of enantiopure chiral compounds.

Hydrolases are relatively stable enzymes and their catalysis do not require co-factor. One of the most extensively utilised enzymes of hydrolase class is lipase.

Lipases (triacylglycerol ester hydrolase, EC 3.1.1.3) are important enzymes in biological systems, where they catalyze the hydrolysis of triacylglycerol to glycerol and fatty acids. Besides their natural substrates, lipases are capable of catalysing a wide range of non-natural chemical compounds.

Depending on the nature of substrate and reaction conditions, lipases catalyze a wide range of enantio- and regio-selective reactions such as hydrolysis, esterifications, transesterifications, interesterification, aminolysis and ammoniolysis (Fig. 2). Due to their catalytic versatility, li-

70 EXPRESS PHARMA December 1-15, 2014

Fig 2: Lipase catalyzed reactions

pases have emerged as a unique industrial biocatalyst in pharmaceutical, fine chemical, food and flavouring and recently in cosmetics and perfumery industries [2].

Lipases are ubiquitous in nature and are produced by several plants, higher animals, and microorganisms. Microorganisms have shorter life-span, are easy to cultivate by fermentation and easy to manipulate genetically. Hence, most of commercial lipases are from microbial sources.

We at ‘Advanced Enzymes’ manufacture and export enzymes to the various applications for last 50 years. Our lipases are robust biocatalysts useful for industrial organic syntheses of pharmaceutical building blocks and fine chemicals. Our lipases are available in soluble and immobilised preparations. The immobilised lipases are support-bound and therefore can be recovered from the reaction mixture and can be reused for repetitive biotransformation cycles.

Lipases for pharma and fine chemical industry

The role of chirality in efficacy and safety of drugs has been thoroughly identified and implicated globally by pharma companies as well as concerned regulatory agencies. As a consequence, the production of single enantiomers of active pharmaceutical intermediates (APIs) has become increasingly important in pharma industries.

Besides pharma, the ‘chirality’ is receiving attention particularly in agrochemical, perfumery, flavour and dye industries [3]. Being stereo-selective, lipases play a significant role in production of enantiopure intermediates. Representative examTable 2: Applications of lipases in synthesis of APIs and fine chemicals (4-8)

TABLE 1: CLASSIFICATION OF ENZYMES Number

Enzyme class (EC)

Type of reaction

1

Oxidoreductases

Catalyse oxidation-reduction reactions

2

Transferases

Catalyse transfer of specific groups such as methyl, amino, acyl, glycosyl or phosphate from one substance to another

3

Hydrolases

Catalyse hydrolytic cleavage of C-C, C-O, C-N and other bonds

4

Lyases

Catalyse cleavage of C-C, C-O, C-N and other bonds by elimination

5

Isomerases

Catalyse isomerization reactions

6

Ligases

Catalyse joining of two molecules

ples of APIs and fine chemicals which are synthesised by lipase catalysed biotransformations are listed in Table 2.

Conclusion Enzymes (biocatalysts) are increasingly used in industrial organic synthesis. Lipases are eco-friendly, stereo-selective biocatalysts. They exhibit broad substrate specificity and catalytic versatility.

Moreover, lipase catalysed biotransformations are simple, do not require co-factor and are easy to scale-up. As a result, lipases have emerged as important industrial biocatalysts especially for production of enantiopure drug intermediates and fine chemicals.

The current trends of industrial manufacturing viz. ‘green synthesis’ and ‘sustainable development’ suggest that the commercial utilisation of lipases in pharma and fine chemical industries will continue to expand in years to come.

Furthermore, the recent technological developments in large-scale DNA sequencing, protein expression systems and enzyme engineering methods will foster the industrial utilisation of lipases, and also other enzymes by in large.

References: 1 Bommarius, A.S.; Riebel, B.R. Biocatalysis: Fundamentals and appli-

cations. Wiley VCH, Weinheim, 2004.

2 Vaidya, B.K.; Ingavle, G.C.; Ponrathnam, S.; Kulkarni, B.D.; Nene, S. Immobilization of Candida rugosa lipase on poly(allyl glycidyl ether-coethylene glycol dimethacrylate) macroporous polymer particles.

Bioresource Technol., 99 (2008) 3623-3629.

3 Caner, H.; Groner, E.; Levy, L.; Agranat, I. Trends in the development of chiral drugs. Drug Discov.

Today, 9 (2004) 105-110.

4 Anderson, E.M.; Larsson, K.M.; Kirk, O. One biocatalyst-many applications: The use of Candida antarctica B-lipase in organic synthesis.

Biocatal. Biotransform., 16 (1998) 181-204.

5 Fernandez-Lafuente, R. Lipase from Thermomyces lanuginosus: Uses and prospects as an industrial biocatalyst. J. Mol. Catal. B: Enzym., 62 (2010) 197-212.

6 Liljeblad, A.; Kallinen, A.; Kanerva L.T. Biocatalysis in the preparation of the statin side chain. Curr. Org. Chem., 6 (2009) 362-379.

7 Patel, R.N. Synthesis of chiral pharmaceutical intermediates by biocatalysis. Coord. Chem. Rev., 252 (2008) 659-701.

8 Ghanem, A. Trends in lipase-catalyzed asymmetric access to enantiomerically pure/enriched compounds. Tetrahedron, 63 (2007) 1721-1754.

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COMPANY PROFILE

Synokem Pharmaceuticals: One-point contact for every need

S

ynokem Pharmaceuticals is a professionally managed fast growing pharmaceutical company having over three decades of manufacturing and marketing experience. The company is based in the National Capital Region and has a current turnover of `300 crores. The company has two new ultra modern plant at Haridwar, Uttarakhand which falls under the (100 per cent excise free zone and one per cent CST Zone). The company has been accredited with ISO9001:2000 . It is a WHO,( cGMP Certified) unit with total quality management and in house testing laboratory.

The company's success is the result of focusing on the clients' top priorities such as quality products, ontime delivery, competitive rates and unparalleled responsiveness. The company is able to cater to the needs of the clients in a better way through its own packaging unit viz. Synokem Packaging. Synokem manufactures more than 500 pharma formulations products in the form of tablets, capsules, liquid orals, ointments and sustain release preparations.

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ABHINAV ARORA, Director, Synokem Pharmaceuticals

JM ARORA, Managing Director, Synokem Pharmaceuticals

There is a dedicated hormonal facility wherein hormonal preparations are manufactured.

1

Abbott

2

Ajanta pharmaceuticals

3

Alembic

4

Aristo

5

Alkem Laboratories

6

Bharat Serum Vaccines

7

Cipla

8

Cadila

9

Emcure Pharma

10

Eris Life Sciences

11

Fourtts India

12

Galpha Labs

13

Glenmark Pharmaceuticals

14

Intas Pharmaceuticals

15

Indoco

16

Lupin

17

Mankind Pharma

18

Macleods Pharmaceuticals

19

Medley Pharmaceuticals

20

Meyer Organics

21

Molekule Pharma (Plethico)

22

Micro Labs

23

Ranbaxy

24

RPG Life Sciences

25

Sun Pharma

26

Torrent Pharma

27

Troikaa Pharmaceuticals

28

Wallace Pharma

29

Zydus

30

Wockhardt

Synokem plans to start its operations in Sri Lanka, Myanmar, Thailand, Cambodia, Vietnam, Laos, Philippines, Malaysia, Indonesia, Singapore, LAC (Latin American Countries), CIS and African countries Synokem has also ventured into exports. The countries where it plans to start its operations are Sri Lanka, Myanmar, Thailand, Cambodia, Vietnam, Laos, Philippines, Malaysia, Indonesia, Singapore, LAC (Latin American Countries), CIS and African countries. It has also tied up with Indian pharma companies to supply for their exports requirements.

The company manufactures pharma formulations for companies of national repute.

Visit us at Hall 1 (IP 036) & Hall 2 (Stall T7) at CphI India 2014

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P-MEC INDIA 2014 SPECIAL

P-MEC INDIA 2014 A preview of products and services, analyses and insights

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I N T E R V I E W

‘Our customers benefit from innovation in our core technologies’ Waters Corporation is a leading laboratory technology provider that offers innovative analytical instruments to assist scientists in reaching their scientific goals, increase productivity, and earn laboratory-based organisations a higher return on their investments in research, development, and quality control. In an interaction, KV Venugopalan, President, Waters talks about the company's plans, projects in the pipeline, challenges and opportunities in the industry and more, with Usha Sharma

Waters provides researchers of complex diseases with unparalleled analytical tools to make breakthrough discoveries. Can you elaborate on this?

Waters’ portfolio of LC, MS, and informatics solutions supports discovery, research and development, and commercialisation in the life science and pharmaceutical industries for small and large molecule therapeutics. These include, but not limited to – proteomics, biomarkers studies, metabolomics, lipidomics, MALDI imaging, medicinal chemistry, regulated bio-analysis, drug metabolism and pharmacokinetics (DMPK), methods development, impurities analysis, natural products analysis, quality control (QC), process analysis, amino acid analysis, oligonucleotide, RNAi analysis, etc. As blockbuster drugs come off patent, the generics industry is poised to make a difference in people’s lives all over the world by providing access to medication that they previously couldn’t access or afford. With advances in analytical technology such as UPLC, and the USP’s initiative to likewise modernise compendial methods, generic pharma organisations are in a

stronger position than ever to upgrade laboratories and improve productivity, efficiency, and be more confident in product quality using Waters platform solutions. Waters India plays a significant role in ANDA submissions, process and product development, quality control and assurance and regulatory compliance in all major companies in India.

The company offers its services to almost all sections of the pharma industry.

Which are more complicated and why? How can the complications be overcome?

The challenge facing any laboratory technology provider is always to stay ahead of the industry by anticipating and preparing for every change in requirements — whether it is a scientific challenge, an engineering problem or regulatory challenges. Indian pharma industry has multiple opportunities and challenges.

While India has the maximum number of US FDA approved plants outside the US and gets about 37 per cent of all the ANDA approved every year, we also get the maximum number of warning letters due to increased regulatory activities.

Increasing price competition

To subscribe: bpd.subscription@expressindia.com

very unique in that sense. We conduct regular training and education programme to create awareness about quality systems and procedures, provide compliant ready products and help improve productivity to remain competitive. Our regular training programmes also assist them in managing high level of attrition without impacting quality and productivity.

We will be showcasing a couple of our latest technologies during this exhibition from other generic companies, high rate of attrition, lack of trained manpower, etc. are some of the major challenges facing the industry in India and therefore the suppliers like us.

Waters India has initiated many programmes to support the Indian industry and we are

How strong is the company’s research pipeline? Which are the new areas that the company plans to explore and how soon?

From introducing the first commercial HPLC system to the first UPLC system or the first computer based-data system to the ion mobility mass spectrometry system, Waters has always been the innovation leader in the industry. Our latest introductions include Ultra Performance Convergence Chromatography and QDa mass detector which is the smallest and easy to use MS detector designed for a chromatographer.

Let me also say a few words about another breakthrough technology from Waters, the iKnife. Generally when surgeons remove tumour tissue

they try to leave a ‘margin’ of healthy tissue to ensure all the cancer is removed. Sometimes this means the patient has to remain under general anaesthetic for another 30 minutes or so while tissue samples are sent for analysis to check if the margin is clear.

Even then, it is still possible that some cancerous tissue remains and the patient has to undergo further surgery to remove it. Now, a new technique based-on an ‘intelligent knife,’ called the ‘iKnife,’ promises to remove the need for lab analysis and the accompanying delay and it also helps avoid repeat surgeries.

The iKnife is a combination of an established technology called electrosurgery that was invented in the 1920s and a new technology that is still emerging, called rapid evaporative ionization mass spectrometry (REIMS) introduced by Waters.

How many products have the company developed? Which of them is your blockbuster product and why?

Waters is the only company in the industry which designs, manufactures and supports all products that is sold, whether it is an LC system, MS systems, Continued on page 78

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INSIGHT

Laboratory facilities for the future The art of designing laboratories for the future is to establish and nurture meaningful connections among people, whether in offices or laboratories, by creating strategically located, dynamic, technology-enhanced environments where people would want to be a part of such environments.

An insight by Archana Sohoni, Laboratory Architect, Arena Consultants

L

aboratories are becoming more flexible and digitally connected. The future of science facilities is also being shaped by the growing pressures of commercial and environmental sustainability. The building economic pressures and the desire to achieve immediate return on investment (ROI), the process of planning and designing of laboratory facilities is accelerated. The accelerated project schedules require additional effort to maintain quality. Moreover, it is observed that the design concepts of a laboratory are revisited.

Today, the laboratory design process is characterised by a 'more, faster, smarter' approach. Companies are keen on maximising funds in a short time frame. The focus is more on developing leaner processes for delivering projects and leveraging technology like building information modelling (BIM).

Functionality, space, safety, and flexibility have been identified as the four most desired characteristics of a laboratory.

These four characteristics are interconnected and changing one of these features affects the others. While functionality and safety are never compromised, there is often a tendency to sacrifice space and flexibility due to budget constraints. Typically, reducing space is the simplest and quickest way to reduce cost.

Informal meeting areas, open lounges and other spaces that

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enhance collaboration and interaction have been continually thought of ‘waste of space’ as space within a research facility.

To build or renovate Many times institutions and corporations take more conservative approach to facility development, by way of renovation work thus leading to a fewer new construction projects.

Clients are seen to be risk averse and want to know whether new facilities or renovation projects will meet their vision and strategic business goals. The problem is that these buildings can be eight, 10 even 50 years old, basically out of date and many times unsuitable to set up laboratory infrastructure. Yet, the outcome need not be negative. Limitations of avail-

able space, forces the designer to look at various options and layouts. It also gives an understanding of how spaces can be adapted to new requirements and make systems work more efficiently. Nevertheless, each facility is different. Hence, the company stakeholders must identify the useful life expectancy target for the facility upfront, so that a proper feasibility study can be conducted and correct solutions can be derived. A fresh new facility construction versus renovation decision is dependent on many factors such as location, cost, schedule and flexibility. If location of the site is a priority, then renovation may be the only choice. If expansion or operating costs are paramount, then relocation or building a new fa-

cility is the key. The most expensive part of renovating a research facility is downtime.

Flexibility Flexibility is hard to define, but reducing a facility's flexibility may mean the loss of spare engineering capacity and space for anticipated growth. Many owners say they want future flexibility, however, lack the understanding to define what 'flexibility' means? The concept of flexibility has different meaning to different people. Functionality and flexibility together are design qualities that allow a facility to do more in less space.

Sharing a single space between two or more departments is a space-saving method that is relatively easy to recognise during planning process but it is also possible that a single space be planned that will serve multiple functions.

The need for flexibility Collaborative, interdisciplinary facilities that support and promote the sharing of equipment, technology and resources are growing in popularity. Researchers want to modify their laboratories quickly, inexpensively and without facilities personnel.

However, it has to be thought of and planned as an approach early in the design process or else adopting it at a later stage can be fairly expensive.

Strategies to build flexible, collaborative research environments include the use of casework systems that are easily

ARCHANA SOHONI, Laboratory Architect, Arena Consultants

moveable, limiting fixed elements in the laboratories and containing hazards in the smallest workable area. Movable and height-adjustable laboratory benches with only minimal services are the norms in the interior of laboratories. Flexible engineering services—supply and exhaust air, water, electricity, voice/data, and vacuum systems—are important to labs.

Labs must have easy connects/disconnects at the walls and ceiling to allow for fast, affordable fixation of equipment.

The engineering systems may need to be designed to enable fume hoods to be removed or added, to allow the space to be changed from a lab environment to an office and then back again, or to allow maintenance of the controls outside the lab.

‘Service columns’ is a concept where all utilities and electrical cabling can be dropped down from the ceiling. The user can easily connect the equipments and can use the bench space effectively.

In addition to the initial demands, at least an additional 25 per cent should be considered for future expansion. Space should be allowed in utility corridors, ceilings, and vertical chases for future HVAC services, plumbing, and electrical needs. Service shutoff valves should be easily accessible, located in a box in the wall at the entry to the lab or in the ceiling at the entry. All pipes, valves, and clean-outs should be clearly labelled to identify the contents, pressure, and temperature.

Sustainability Sustainability has become a laboratory standard, as there has been considerable awareness among the stakeholders on lifecycle operational costs and the move towards green building. Laboratory owners now expect more efficient and sustainable buildings. Planning objectives are set to achieve US Green Building Council goals of Leadership in Energy and Environmental Design (LEED) Silver, LEED Gold, or even LEED Platinum for their facilities.

In India, CII spearheaded the Green Building movement in India - 2001. We also have LEED-India Green Building Rating system-2007, the National Building Code, MoEF guidelines, Energy Conservation Building Code of the BEE, National GLP Compliance Monitoring Authority- 2002 and TERI guidelines.

Research facilities particularly those involving chemicals, biologics and nanotechnology are expensive to build and operate given the requirement for large volumes of outside air for ventilation. A typical laboratory uses five times as much energy and water per square foot as a typical office building, due to large numbers of containment and exhaust devices, number of heatgenerating equipment, intensive ventilation requirements including 'once through' air, research laboratories form the most energy demanding facilities.

Most laboratory owners are aware that the utilities loads and oncethrough air requirements can make designing an energy-efficient laboratory a challenge. However, demand-based

systems and more efficient engineering cannot only yield operational savings, but also reduce design difficulty. Highperformance and low-flow fume hoods and air and lighting monitoring systems are examples. Occupancy sensors on fume hoods can reduce airflow when the laboratory is unoccupied. Isolating chemical fume hoods in hot zones reduces the overall volume of air required for safe operation.

HVAC is the most complicated and expensive aspect of laboratory engineering. While chilled beams are being increasingly used abroad, as a means of addressing ventilation and heat loads, India is yet to adopt this concept and technology due to various limitations and factors. Chilled beams have proven effective in maintaining lower air change rates per hour and reducing sizing of ductwork and central air handling equipment in comparison to the traditional chillers and heat recovery wheels.

Technologies that reduce artificial lighting levels have become more common. Ceiling-mounted occupancy sensors use both passive infrared and ultrasonic sensors to turn off the lights when the laboratory is unoccupied. In contrast incorporating exterior window shading and glazing on the exterior faรงade of laboratory building has now become more prevalent for both comfort and sustainability. Daylight sensors, capture the intensity of ambient light from windows and modulate the lux levels in response to the natural sunlight entering the building.

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Virtual labs A significant amount of change has occurred in the past 10 years primarily in the US and Europe to utilise the computer more for 3D simulation, data crunching and to allow meetings to occur in real time around the world on flat screens. Many of the researchers have teams in multiple locations around the world to capitalise on funding, expertise, and focus within a country, company, or campus. Virtual spaces are now evolving where a person can be sitting in a lab in Europe and talk to their research team across the globe

as easy as getting a cup of coffee from the break room. Speed to market is getting more rapid each year with most institutions working faster than ever.

While this is the scenario worldwide, the picture on domestic front is quite different.

Collaborative spaces Collaboration is the latest key word in present-day type of working. It is highly influenced by younger generation coming from contemporary academic institutions where students are exposed to brain storming and team work. Many times research labs are designed to con-

sidering multi-function types of work within the same lab. Academic labs too are interdisciplinary and rarely designed solely for one discipline. Thus the trend is toward more collaborative and less private space.

Typically these spaces are designed outside the labs, yet having proximity to lab areas, to encourage spontaneous and higher interaction. They are clubbed with breakout areas and are equipped with writing boards/ pin-up boards etc.

These spaces are designed as informal spaces unlike conference or meeting rooms thus opening an avenue for open discussions

and sharing. These spaces are designed with lot of thoughts and environment such that the userâ&#x20AC;&#x2122;s feel comfort and relaxed.

Way forward The interior of a laboratory has an amazing influence on the creativity and productivity of the scientists. The art of designing laboratories for the future is to establish and nurture meaningful connections among people, whether in offices or laboratories, by creating strategically located, dynamic, technology-enhanced environments where people would want to be a part of such

environments.

Architects have always been expected to balance the needs of stakeholders to create spaces that are aesthetically and functionally effective in addition to be economical. Global warming has added a new facet of making sustainable environment and an added responsibility to the designers. Quite often during the design phase of a laboratory, priority is given to functionality and aesthetics are overlooked. The aesthetical challenges in laboratory design can be taken up as an opportunity to create an environment which is motivating.

Continued from page 75

â&#x20AC;&#x2DC;Our customers benefit from... data and informatics solutions or columns and sample preparation products. Being the pioneer and innovation leader in the industry, majority of our products are trendsetters and have contributed significantly to our success. Waters Acquity UPLC systems, Alliance HPLC systems, Empower Chromatography Data Management systems, Nugenesis SDMS systems, Oasis sample preparation systems, Synapt HDMS Ion Mobility Mass Spectrometry systems, etc. are only few examples of our blockbuster products. They are blockbuster products not only because of their significant contribution towards our sales but also being disruptive technology that changes the way scientists and chemists perform analysis and achieve results.

What is the USP of your product?

Laboratories require performance, reliability, and workflow consistency.

Whether a newly manufactured HPLC system,

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or one that is several years old, robustness, precision and reproducible results are essential to provide not only consistency, but also exceptional confidence in the analytical work flow, year after year. Waters strives to provide innovative technological solutions, products, and services to our customers by attaining a keen understanding of their needs and requirements. And our systems exceed the expectation of all our customers by helping them improve their performance, productivity and reliability of results.

Waters also offers services to the clinical research arena, however, growth in the Indian clinical research industry is not so alluring at present?

What is your say on this?

The market has been challenging for the past couple of years. However, the situation is fast improving with clearly defined rules and regulations for obtaining permissions and conducting clinical trials in India. India

Waters strives to provide innovative technological solutions, products, and services to customers continues to offer attractive destination for clinical studies for many reasons including large pool of patients, strong clinical infrastructure, etc. It is only a matter of time before we regain our dominant position in this sector.

Which new technologies will be launched at CPhI India 2014? Will they be cost effective?

Waters products are always cost effective as we focus our design on improving laboratory productivity, efficiency, throughput and

overall performance. We will be showcasing a couple of our latest technologies during this exhibition.

IonKey - An ionKey/MS System adds the power to perform multiple analyses on limited sample volumes with increased sensitivity and ease of use.

QDa - ACQUITY QDa Detector is a mass detector built around the needs of analytical scientists for chromatographic analysis.

Robust, reliable and requiring no sample adjustments, it integrates with your current LC, ACQUITY UPLC, UPC2 and purification systems. For the first time, any analytical scientist can consistently generate the highest quality mass spectral data, routinely without the need for any special training or expertise thus eliminating any need to contract out and wait for results from specialist analytical service laboratories.

UltraPerformance Convergence Chromatography (UPC2) is a broad-based, complementary

analytical platform that is taking its place alongside LC and GC as one of the three essential separation technologies for modern laboratory analysis.

What is your road map for the next two years?

Better technology furthers better science. Waters continually pushes the limits of scientific possibility, helping our customers to reach their goals every day. Through constant collaboration with the scientific community, our customers benefit from innovation in our core technologies: separation and analytical sciences, mass spectrometry and laboratory informatics. Separately, or together, our solutions contribute to our customersâ&#x20AC;&#x2122; enduring business and scientific success. We will continue to introduce innovative products to the market every year at the same time ensuring that our infrastructure is strengthened in India to provide superior support to all our users. u.sharma@expressindia.com

P-MEC INDIA 2014 SPECIAL

INSIGHT

Handling static charge at pharmaceutical manufacturing Static charge is a small variable which affects the quality of the product indirectly. One needs to understand what it is and how it can be eliminated or avoided. An insight by Ramesh Sahu, Product Manager, Skytech Systems (I)

P

harmaceutical industries use high qualityoriented process to ensure that a full proof quality product comes out with very minute degree of tolerance which is allowable.

There are many external factors which affects the final quality of the product.

Nowadays, the concept of QbD and PAT is being implemented in pharma manufacturing process which help to eliminate these variables at its generation point itself.

Static charge is also a small variable which affects the quality of the product indirectly, so we should understand what it is and how it can be eliminated or avoided. Static current can also have a major impact on human safety and is a health hazard. It can even cause an explosion as well.

Figure 1

80 EXPRESS PHARMA December 1-15, 2014

Static electricity is a major cause of fire and explosions in many industries handling flammable liquid. The hazard of electrostatic spark ignition of flammable vapour can be minimised by taking actions to limit the accumulation of electrostatic charges to safe values.

Primary importance is the proper bonding and grounding of equipment and containers.

In addition, charge accumulation in liquids must be limited, in many instances, by controlling the rate of charge generation and/or the rate of charge dissipation.

What is it and how it gets generated?

Static electricity is an imbalance of electric charges within or on the surface of a material.

The charge remains until it is able to move away by means of

an electric current or electrical discharge. Static electricity is named in contrast with current electricity, which flows through wires or other conductors and transmits energy.

A static electric charge is created whenever two surfaces contact and separate, and at least one of the surfaces has a high resistance to electrical current (an electrical insulator). The effects of static electricity can be demonstrated by the spark as the excess charge is neutralised when brought close to an electrical conductor (e.g. a path to ground), or a region with an excess charge of the opposite polarity (positive or negative). The familiar phenomenon of a static shock, more specifically, an electrostatic discharge–is caused by the neutralisation of charge.

The most common genera-

tors of static electricity are processes involving flammable liquids. Static electricity is generated by liquids flowing through pipes and in mixing, pouring, pumping, filtering or agitating liquids or solids. The rate of generation is influenced by the conductive of the liquid or solids, the amount of turbulence in the media, the interfacial surface area between the flowing material and other surfaces, liquid velocity and the presence of impurities.

Some specific locations where static electricity is generated are: ◗ Material transport system In piping systems the generation rate and the subsequent accumulation of static charge is caused due to the function of the flow rate, velocity, pipe diameter and pipe length.

RAMESH SAHU Product Manager, Skytech Systems (I)

◗ Filling operations The turbulence experienced in filling operations, caused by large flow rates, splashing or free-falling liquid and solids, greatly increases the charge accumulation above the level generated in piping systems. ◗ Separation There are many separation operations being implemented.

Vibrating system is one among them which causes the generation of static electricity. ◗ Filtration Filters, because of their large surface area, can generate as much as 200 times the electrostatic charge generated in the same piping system without filtration.

Pharma manufacturing have come across many operations in line with the above categories wherein it is prone

to generate static electricity for e.g. ◗ Liquid handling systems. ◗ Solvent dispensing ◗ Vibro-sifters ◗ Fluidised bed drier ◗ Powder transmission ◗ Mixing and processing reactors Some of the processes are discussed below

Solvent dispensing The various process including the transportation of the liquid from one process to other or solvents storage yard and dispensing of the same as and when required is the major area where this static current can cause even an explosion. So better interlocking is necessary because of the flammability nature of the solvent.

Static charge accumulation is a function of the resistance of the path by which charges dissipate within a liquid. The dissipation of static electricity is dependent on a property of the liquid known as ‘conductivity.’

Some flammable liquids have very low conductivities and tend to accumulate static charges.

The chances of static build-up may lead spark explosions, fires, property damage and injury to workers. Occupational Safety and Health Administration (OSHA) has regulation for these liquid dispensing systems to ensure the processes being safe enough for men at work and the environment.

While OSHA does not prescribe how, but it dictates when and where static grounding and bonding procedures must exist. For e.g. when unloading or loading bulk carriers such as tanker or tank trucks or transferring flammables in small barrel, OSHA 1910.106(F)(3)(iv) talk about the static protection.

Sec. 1910.106(f)(3)(iv) (a, b &c) Static Protection.

■ Bonding facilities for protection against static sparks during the loading of tank vehicles through open domes shall be provided: ◗ Where Class I liquids are loaded, or ◗ Where Class II liquids or Class III liquids are loaded into vehicles which may contain vapors from previous cargoes of Class I liquids ■ Protection as required in (a) of this subdivision (iv) shall consist of a metallic bond wire permanently electrically connected to the fill stem or to some part of the rack structure in electrical contact with the cargo tank of the tank vehicle.

■ Such bonding connection shall be made fast to the vehicle or tank before dome covers are raised and shall remain in place until filling is completed and all dome covers have been closed and secured.

Although the generation of static electricity cannot be eliminated, its rate of generation and accumulation can be reduced by adopting a proper dissipation system with real time control will eliminate the possible explosion. There are various manufacturers who provide such interlocking systems which monitor and control the rate of generation and dissipation of the static charge. A typical block schematic diagram (Figure 1) of such system is being indicated here, courtesy GE Advanced Sys-tek, Vadodara.

Vibro sifter

Static charge accumulation is a function of the resistance of the path by which charges dissipate within a liquid

Vibro separators are circular gyratory screens used to separate solids from solids and liquid from solid. Vibro sifter consists of specially designed motor mounted vertically at the center of the base plate of the screen. The screen is in between feeding hopper and bowl. The material is fed on to the centre of top screen. The undersize material passes rapidly through the screen during its travel to the periphery. The oversize material gets continuously discharged through

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a tangential outlet. This is achieved by specially designed vibratory motor along with eccentric top and bottom weights.

Rotation of the top eccentric weights creates vibration in the horizontal plane which causes material to move across the screen cloth to periphery increasing the horizontal throw, causing oversize material to discharge at a faster rate. The bottom eccentric weight rotates below the centre of mass creating tilt on the screen giving vibration in vertical and tangential plane. Adjustment of the quantum and relative position of the top and bottom weight permits control of amplitude and material flow patterns. Rugged springs placed over the circular motor base amplifies the vibration.

Due to the vibration the friction between the screen and the product material static current is being generated in the body of the shifter. Unless the product is flammable in nature the it will not lead to an explosion but it has a great impact on the operator around it, once the operator gets in contact with any conductive part of the

82 EXPRESS PHARMA December 1-15, 2014

Powder transmission

shifter he/she gets the electric shock. To avoid such unpleasant situation it has to be properly grounded and on real time it should be monitored and controlled. The static current grounding device should be integrated for monitoring and control of the process.

Powder transmissions are being done by any of the following methods like conveyors, gravitational flow or flow through a pipeline with dry air. In case of gravitational flow and pneumatic conveying the friction caused between the powder and wall generates the static electricity at both ends i.e. at pipeline and the product. So the pipeline and the collecting bin should be properly grounded so that the static current generated is dissipated properly. Same grounding system (used in case of Vibro sifter) can be deployed to control the static charge generated in the system.

Fluidised bed drier Drying is a process of removal of liquid from solid products with the help of heat. Various process of drying is being implemented. Drying is a function of contact area, between the drying media and the product.

Currently, fluidised bed drier is popular across powder drying application because of it high efficiency and the fast process.

Normally an initial moisture content upto 20 per cent is ideal but materials with higher initial moisture content can be dried successfully.

In fluid bed drying, heat is supplied by the fluidisation gas, in some cases the heat also being supplied by heating plates or tubes which are immersed in the fluidised layer.

These fluid beds are designed to dry powder particles where the residual moisture

Conclusion

content is higher than what is wanted in the final powder. Hot drying air is distributed through specially designed perforated plates on which the powder particles/agglomerates are resting.

Static charge generated due

to the powder or granules which gets fluidised inside the dryer unit should be dissipated with proper grounding system otherwise it will also create unpleasant situation as explained in the above application like operator safety etc.

Static charge generation is a common phenomena for any flowing or vibrating mechanism. Where there is friction between two independent surfaces there is static charge generated. Generation of static charge canâ&#x20AC;&#x2122;t be fully eliminated but can be controlled. Best way to handle such static charge is by planning a better dissipation methodology with controlled automation to it.

PROFILE

Neomachine Mfg Co: A leader in automatic coating technology

K

olkata-based Neomachine Mfg Co was started in 1973 with an objective of manufacturing all types of pharmaceutical machinery.

For a decade, the company catered to the requirements of the Indian pharma companies in injectable, liquid, tablet, capsule and ointment sections machinery.

‘While catering to this market segment, Neomachine happened to come across a Kolkata-based pharma producer, who were envisaging problems in film coating of tablets. Until then, the tablets were being coated in conventional pans, which were not only causing health hazards to the coating personnel, but was also a time-consuming process. Inspired by this opportunity, Neomachine started the process of developing an automatic coating machine in the right earnest.

After, two years of research and development, the first ‘Neocota, Automatic Coating System’ was manufactured in 1984.

During the last three decades, Neomachine manufactured and marketed more than 550 machines, out of which 100 machines were exported to the different countries like the US, Australia, China, Jordan, Yemen, the UAE, Uganda, Kenya, Sudan, Cyprus, Saudi Arabia, Austria, Brazil, Bangladesh, etc.

Neomachine, a professionally managed organisation now has two manufacturing units in Kolkata, which are equipped with state-of-the-art equipment like fabrication, machining, assembling, finishing and other related jobs. The company has been strictly following all the quality control guidelines during manufacturing. The bought-out items are inspected at the manufacturers’ works periodically.

The company has a dedicated team of engineers for providing erection and commissioning and prompt after-sales service to the clients.

The in-house R&D facility is abreast of the latest technology upgra-

ANUP MAITRA Managing Director, NEOMACHINE

dation and the latest developments in ‘coating technology.’ This helps in continuous improvement of the product.

Neomachine also provides DQ/IQ/OQ/PQ Qualifications for automatic coating system and are in the process of getting CE Certification.

Over the years, the company has gained vast experiences in manufacturing ‘Automatic Coating System’ by interacting with various Indian and multinational pharma and confectionery units based in India.

Products like Cadbury India’s fastmoving product ‘Gems’ and Parke Davis’ ‘Chicklets’ are coated in the systems manufactured by Neomachine.

The company also impart aqueous and non-aqueous film coating and sugar coating technology to clients, who need the same expertise.

Neomachine also supplies Hepa Filter for filtration of incoming drying air and Mobile Bed Wet Scrubber for purification of exhaust air for the companies that need these items.

Neomachine, being a single-product company, manufactures various models of Neocota. The automatic Coating Machine, gained vast experience in coating technology since the last two decades. Neocota is designed to comply with current US FDA and other international legislation as well as anticipated trends. The improved and flexible design enables Neocota to perform in national and overseas environment without any system modification.

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I N T E R V I E W

‘In India, we are considered to be one of the best and trusted brands in the industry’ Debasish Roy, MD and Subhasish Roy, CEO, The United Engineering Company (UEC) spoke to Express Pharma about the current state of pharma packaging industry in the country Today, after five decades in pharma-machinery manufacturing industry, how has UEC positioned itself?

In the last five decades, UEC has developed more than 30 kinds of indigenous pharmaceutical machinery and we are continuously upgrading ourselves. From the early 60’s of the last century, UEC has become a major house of the import substitute in pharma machinery though we are much aware of high-speed machine from the first world country and also stiff competition from low valued machines from our neighbouring countries, UEC machines still hold their own position. In India, we are considered to be one of the best and trusted brands in the industry. ‘UNITED’ machines also cut a niche for itself in the international markets. We are growing as a brand day-by-day.

In the Indian pharma industry, automatic ampoule filling and sealing machine means UEC. Which machines are in your product basket for small volume and large volume parenteral manufacturers?

UNITED Automatic Ampoule Filling & Sealing (AFS) machines are widely accepted in the market, not only in India but also overseas.

They are the most reliable and efficient machines available in the market, adhering to all the current manufacturing practices, technologies and automation. We have various models of our AFS machine

84 EXPRESS PHARMA December 1-15, 2014

and paper labels suitable for round and flat bottles. These machines are manufactured as per the latest manufacturing techniques and automation.

Debasish Roy

Subhasish Roy

having various outputs and dosing system to cater to the customer’s need.

Apart from our AFS machines, our product list offers ampoule and vial washing, automatic liquid filling, automatic rubber dispensing and pressing, and, automatic sealing machines for vials, both in automatic and semi-automatic models. We also manufacture automatic labelling machines for ampoules and vials both for paper and sticker labels. Our latest inclusion being the external cleaning and drying machine for ampoules and vials, has made our brand a one stop solution for our clients.

These machines are available in models with different outputs.

All the UNITED machines are manufactured with equal expertise and are accepted and appreciated in India as well as in abroad for their quality, efficiency, performance and the fact for these being ‘value for money’ products. Our customer support team also plays an important role in making our brand trustworthy.

ments for your bottling line of machines?

Apart from our pilot scale and automatic linear line of machines for bottles, we have introduced a total range of rotary machines for bottles, which includes UNITED ARBW —Automatic Rinsing Machine which can handle 30 ml to 450 ml in the same machine and can clean the container with both water and air. The ‘ARBW’ has five different models depending on the speed.

UNITED 'RBFS' Automatic monoblock bottle filling and capping machine which has three different models with a newly developed special UNIZIGMA head for pet bottles.

For non-metallic caps we have introduced a special 'Pick and Place unit' and 'Magnetic Screw Capping Head', to maintain a certain torque as required by the customer.

Inline with the above high speed labelling machines, we manufacture high speed labelling machines for sticker

What are the latest develop-

The company had introduced ‘UNICOATA’, automatic coating machine lately. Tell us more about the machine.

Where is ‘UNICOATA’ used?

‘UNICOATA’ was introduced by UEC quite a few years back and has had a remarkable response. It is a complete range of solutions for automatic tablet coating. It provides the user with best and uniform coating results with simple operation, yet equipped with the latest technology.

'UNICOATA' maintains an international standard and is a 'No-Frill', easy to use machine and excellent results. Around 60 machines have already been installed including 'Multiple installations' in Iran, the US and Bangladesh.

Maintaining strict ‘quality control’ parameters, is an important element in today’s pharma production business.

How is UEC conforming to the quality guidelines?

UEC has a QC Team, who are responsible of all the raw materials. Apart from DQ, IQ and OQ, UEC's QC team are responsible for physical and chemical testing of raw material from reputed testing houses.

Most of the

machine parts of UEC are made from CNC or VMC and are hardened depending on the quality of the material, procurement of appropriate raw materials from the right place.

Which pharma companies use UEC machines?

It is very hard to name a few of the companies in India as we are catering to the needs of most of the pharma companies.

Besides, we are providing our machines to leading names in Bangladesh like Opsonin Pharma, Renata (previously Pfizer Bangladesh), Drug International, Hamdard – Bangladesh, Pharmadesh Lab, Kemiko Pharma, Incepta Pharma, Essential Drugs and several others.

Do you export these machines and to which countries?

We have a strong foothold in the overseas market and have exported to countries like Bangladesh, Iran, Nairobi, Nigeria, Bolivia, Sri Lanka, Sudan, South Korea, Indonesia, Malaysia, Mauritius, Chile, the US, Canada, the UAE, Nepal.

Presently, we are looking to extend our horizons to the European and other markets.

What are your future plans?

Being into business for more than five decades, we have a lot of things to do, a lot of targets to achieve and explore different avenues. Turning every unturned stones and being better than the best is the motto for the future.

P-MEC INDIA 2014 SPECIAL

The UEC: Leaders in pharma packaging machinery manufacturing since 1963

T

he United Engineering Company (UEC) with the brand name 'UNITED' is known for being the pioneer and commander in packaging machinery manufacturing in India.

UEC, which was started in 1963 by GD Roy, from the beginning, attained a high reputation in providing machines and services of highest standards with utmost care. With the founder's innovative ideas and unmatched leadership qualities, UEC crossed various boundaries in different fields of work.

Initiating the business with

Founder: GD Roy (R)

solutions for parenterals (ampoules and vials), UEC has diversified its business into the bottle packaging sector and has also mastered in providing machines for automatic tablet coating. UEC also provides customised solutions for its customers.

With a vision to provide the best pharmaceutical manufacturing technology, UEC has also ventured into different industries such as distilleries, cosmetics, foods and beverage, paints, chemicals, home care, office and student stationery and others.

The company has also expanded its footprints abroad in a large way. Today, 'UNITED' machines are exContinued on page 87

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INSIGHT

Optel Vision’s innovation in carton serialisation: Flying carton tracker The benefit of Optel Vision’s unit is its ability to minimise downtime by quickly integrating into any installation so less production time is lost

O

ptel Vision’s Flying Carton Tracker (FCT), is a cutting-edge technology bringing carton handling and printing to a whole new level. The FCT is a revolutionary ultra-compact, high-speed carton handling solution with advanced inspection and fully controlled ejection.

This a stand-alone unit allow printing and inspection on cartons with the ability to reject any single carton on the fly.

Gripping the carton from the top, this unit is installed over an existing line without cutting or modifying the line layout. The system can handle a wide range of carton sizes with speeds of up to 400 cartons per minute. The unit can be either mobile or fixed into position and can be integrated just after a cartoner or at the end of the production line. This system can be fed automatically or manually by operators.

The benefit of this unit is its ability to minimise downtime by quickly integrating into any installation so less production time is lost. Changeovers are now very fast with only two simple adjustments. The ability to run a large range of carton sizes increases the line agility between various products.

“We wanted to offer a flexible and cost-effective solution that will decrease downtimes by quickly implementing directly on any packaging line

FEATURES Ultra compact module Quick to install and validate Speed up to 400 cartons / min Zero inch line extension

86 EXPRESS PHARMA December 1-15, 2014

without the need of a table or conveyor to hold the cartons,” says Louis Roy, President, Optel Vision.

While the printing and inspection on the cartons is done in a continuous motion without stopping the item, a camera ensures that the printed information is of good quality otherwise it will be retained and rejected at the top of the machine.

Other inspections are also possible such as dimensional measurement of the item, verification of pre-printed information or bar code grading.

◗ Pre-position and hold carton perfectly ◗ Print the datamatrix and human-readable codes ◗ Verify and grade the printed information ◗ Eject faulty carton ◗ Carton handling device ◗ Print batch information (Lot, Exp, etc) ◗ Print serial number (Datamatrix) ◗ Flexible printing and camera head positioning ◗ Laser, inkjet and HP Coder supported ◗ Datamatrix verification and

The system can handle a wide range of carton sizes with speeds of up to 400 cartons per minute Hence, serialised datamatrix print quality is critical to allow the products traceability from the plant to pharmacy.

Considering carton quality variability and different formats, it is important to ensure the on-line print process meets print quality requirements and flexibility.

If your line is already equipped with proper carton handling devices, our PharmaProof line solution will handle the print verification, bar code grading and serial number commissioning.

In case your line does not allow precise carton printing, Optel Vision offers this two very flexible solutions which will:

grading ◗ Carton tracking and ejection ◗ Alarm control ◗ Tool-less changeover ◗ Servo motor bottom/top belt control ◗ Speed of up to 400 PPM ◗ Compact and mobile machine ◗ RFID capability ◗ Addition of any other inspection Optel Vision is committed to innovate and answer the challenging demands of its customers. We are proud to bring new flexible solutions to the packaging industry for pharma companies.

To see the live demonstration, Visit Optel Vision Booth: Hall 5, K12 or visit www. flyingcarton.com

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The UEC: Leaders in pharma packaging... ported to more than 21 countries across the globe namely the US, Canada, Bolivia, Nigeria, Kenya, United Arab Emirates, Iran, Sri Lanka, Bangladesh, Malaysia, Indonesia, Vietnam, Korea and others.

UEC puts in a lot of effort for their research and development and strives to provide the best and optimised solution to its customers. By virtue of dedication and continuous hard work of their R&D team, 'UNITED' machines provide technically advanced solution for its customers.

Presently, UEC is having its head office at Kolkata. It has three manufacturing units in West Bengal, covering an area of over 10000 sq ft. UEC is having another office at Mumbai along with a service station.

The United Engineering Company has been honoured by the prestigious ‘Innovator’s Award’ from the Indian Pharmaceutical Congress for their innovation and development.

Today, at UEC, machines are equipped with the latest technology. For its customers, UNITED machines are cost effective but are guaranteed with the highest quality, optimum production and ensured unconditional service.

UEC is equally focused on being a corporate citizen. It has never shirked the responsibility of the society and has always been an active participant in numerous social events which help in uplifting the quality of living of the deprived.

With almost every pharma formulation manufacturer being an 'UNITED' machine user coupled with over 50 years experience, UEC commits in becoming better than the best in the near future.

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REVOLUTIONARY. NOT ONLY IN CONCEPTS. Solutions for your investment project.

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We combine professional engineering with in-depth technology expertise. We support you from the initial idea to turnkey production with our comprehensive advice and reliable product management. You benefit from flexible and reliable engineering solutions from one source. In projects of pharmaceutical, biotech, food, feed, chemical or related industries.

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Glatt. Integrated Process Solutions.

P-MEC INDIA 2014 SPECIAL

I N T E R V I E W

‘Our turnover will soon hit the `1-billion mark’ Stability chambes play an important role in the pharmaceutical space. Newtronic has developed full range of products and caters the demands of its customers. NM Mehta, Managing Director, Newtronic Lifecare Equipment shares the company’s corporate plans with Usha Sharma

What are Newtronic’s plans’ for the future?

We are setting up our second manufacturing facility at Umbergaon. This facility will help us to achieve our goal to the next level and meet the growing market demands.

In our commitment to create customer value at all times, our R&D team continues to innovate with a primary and unstinted focus on reducing the carbon footprint of our products.

How big is the Indian stability chamber market and how fast is it growing?

Though significantly big, we still feel that the Indian stability chamber market is still at its nascent stage.

With most of the mulitnational pharma companies choosing India over China as a cost-effective destination for stability operations, the market is well poised to get bigger. Adding to that is the growing demand of the domestic pharma companies to launch their products in other countries and therefore meet the regulatory market compliance norms.

What role does stability chambers plays in pharma

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industry?

It plays a critical role.

Stability testing and stability analysis has become an important criteria for regulatory bodies these days to ascertain the efficacy and market-worthiness of drug products and drug substances. Degradation of a product prior to its expiry period not only results in failure of therapy but may also result in patient’s death in some of the cases.

Any discrepancies arising out of stability analysis can delay the approvals for the pharma companies to commercially launch their drug product.

What percentage of the market has been captured?

In the domestic market, our market share is approximately 65-70 per cent and growing steadily at 25 30 per cent per year.

Our international sales has grown at a whopping 100 per cent in the last two years.

With installations of more than 6000 chambers, almost all the leading pharma companies are our customers today.

How many products are in the pipeline and when do you plan to launch them?

We will soon launch the ultra-low deep freezer series.

These products will achieve º temperatures as low as -80 C. One of the USPs of these freezers is that they will seamlessly integrate with ICDAS - NEWTRONIC’s 21 CFR Part 11 ready software.

Thereby with features of data logging, realtime and comprehensive alarms, audit trails, data trending, ecomments and e-signatures, the customer benefits from a product that complies to the regulatory markets.

Our service team spans across all the major pharma hubs of India and globally across 37 countries

What services do you provide to your clients?

Our service programmes are quite comprehensive in nature. It ensures that the customer sees Newtronic as a one-stop solution provider for all the stability requirements. We offer all kinds of after-sales support and services. Chamber commissioning, qualification, documentation (DQ, IQ, OQ, PQ), comprehensive and noncomprehensive AMC programmes, calibration/validation, chamber upgradations and refurbishing, audit support are some of our offerings in this area.

Our customers (international-based

customers) are also greatly benefited by our online support programme, an efficient medium to diagnose and resolve any software programme related issues as well as carry out periodic upgradations.

Our service team spans across all the major pharma hubs of India and globally across 37 countries.

Stability testing is 24/7 and any breakdowns will require the users to file deviations – something that everyone wishes not to!

Undoubtedly, after-sales support and service is at the core of our business. They are the most important parameters for the customers to measure our success and their satisfaction levels in using our products.

We take pride in the fact that our service support has been greatly appreciated by our customers and majority of them have rated it as fast and effective.

What trend do you see in the market and how fast can Newtronic gain from this opportunity?

Clearly the trend is growth-oriented and very bullish. Under the leadership Continued on Page 91

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‘We plan to achieve ` 5-bn turnover by 2020’ Sandip Mhatre, Managing Director, Thermolab Group reveals details of the company’s upcoming strategies and new offerings to Usha Sharma

In the next three years, Thermolab will celebrate its golden jubilee. What are your plans?

Golden Jubilee year shall be the half way mark to reassess our ambitious target of achieving ` 5 billion turnover by 2020.

Tell us about the company’s ongoing activities?

Thermolab Group’s activities include: ◗ Thermolab Scientific Equipments is engaged in manufacturing of stability chambers (walk-ins and standalone), BOD incubators, cooling cabinets, ovens, vacuum ovens, deep freezers (walk-ins and standalone), autoclaves and other related equipment. ◗ Thermolab Testing Services is a NABL accredited company engaged in in-house and onsite calibration and validation of plant, machinery and equipment with various parameters like temperature, relative humidity, time, pressure, vacuum, pH, conductivity etc. ◗ Thermolab Sales and Services is engaged in installation, maintenance, validation, annual contracts, upgradations, modifications and supply of spares for all temperature and humidity controlled equipment.

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◗ Thermolab Analyticals is engaged in product sample storage and analytical testing for stability studies of pharma, biopharmaceuticals and drug substances. ◗ Thermolab Healthcare is having three divisions of food, nutraceuticals and cosmetics, offering unique lifestyle products which are made from selected natural ingredients.

Any new services in the offing?

We are already providing 20 0 8 celsius and -20 celsius chambers, standalone and walk-in types, for cold chain maintenance of medicinal products. We are now poised to enter the fruits and vegetables (F&V) sector for 'Farm to Fork' cold chain services under the guidance of National Centre for Cold-chain Development (NCCD). Unlike storage of medicines which are in packed conditions, (F&V) handling is challenging as the materials are live and we need to take care of oxygen, carbon dioxide, ethylene and other atmospheric molecular ingredients present in the storage environment. NCCD along with Cemafroid, France recently arranged a training programme in Paris in cold chain management where Thermolab represented the industry sector.

Our recent innovations reduced connected electrical load to almost one fourth bringing down running costs significantly

Which is your block buster product?

Stability testing chambers and BOD incubators continue to be top on our sales charts as we are arguably the only one offering precise temperature and relative humidity conditions warranted by international standards and guidelines. Our recent innovations reduced connected electrical load to almost one fourth bringing down running costs significantly. Last year, we lunched Biological Safety Cabinets and Unidirectional Air Flow System (formerly called as Laminar Air Flow) targeting the healthcare sector.

Indian hospitals and dispensaries are notorious for spreading uncontrolled infectious diseases due to bad air management. In laboratories where human body fluids and other materials are tested, our biological safety cabinets are used for containing potentially pathogenic organisms. With insurance companies stressing on certain environmental conditions as pre-cursor for accreditation of hospitals, we feel that our clean air division will see faster growth in coming years.

How competitive is the market?

Client expectations have

escalated proportionately. The audit requirements have become more stringent.

However, due to constant upgradations, we manage to stay on the top. Current data integrity issues are being faced by many pharma manufacturers related to untrustworthy software and alleged data manipulations. We have recently commissioned one of the largest stability testing storage areas for a multinational company at Vishakhapatnam and the facility has received approval from US FDA inspectors.

The market will see competition from China in the coming years and we are ready to meet the challenges.

How has I-Mark recognition helped Thermolab to accelerate its growth?

I Mark is a prestigious achievement for us. It has given us the confidence of meeting global design standards.

What is the company's target for the present financial year?

Our target is 40 per cent which is more than the last year. As things stand today, we may overshoot our target by March 2015. Last year we have seen a growth of 25.6 per cent. u.sharma@expressindia.com

Superior excipients meeting your formulation challenges

Continued from Page 88

‘Our turnover... of the new government, the world is looking at India as the number one destination for investment and growth.

Newtronic is an established brand and a player in the field of stability testing. With our ability to understand and act quickly on customer expectations coupled with an aggressive and customeroriented workforce, we believe we are ready to bag most of the opportunities in the market today, especially the challenging ones.

What is the strength of your workforce and do you plan to expand it?

DI-CAFOS ® TRI-CAFOS ®

exports division have set targets to tap into newer geographies such as Russia, South Africa and other such emerging markets.

Along with a solid customer base, we have also nurtured the aftersales-support in these countries.

During the last fiscal what was the company’s turnover and how much it is projecting to earn from the current fiscal?

Our turnover will soon hit the `1billion mark. Indeed, it will be a proud moment for all of us at Newtronic. The sweat and toil in the past three and half decades is reaching a much desired milestone.

I take this opportunity to thank each

We have expanded our presence in more than 37 countries now. Our international presence is largely in the Middle-East and Far East countries. In this fiscal, our exports division have set targets to tap into newer geographies such as Russia, South Africa and other such emerging markets

Accelerated disintegration time

Increased tensile strength

Improved tableting performance

Reduced tablet size

Protection We have a workforce of 200. It includes the team at our headoffice-cum-plant in Mumbai, at our second upcoming plant in Umbergaon as well as our sales and services team spread all across India and abroad. This workforce is likely to grow by another 15-20 per cent in the coming months.

How large is your international presence and which markets do you plan to tap?

Every organisation seeks to increase its growth beyond the land of its origin. We have expanded our presence in more than 37 countries now. Our international presence is largely in the Middle-East and Far East countries. In this fiscal, our

and every one within the industry who has been instrumental in this landmark achievement.

of water-sensitive APIs

Tell us about the company’s expansion plans.

We have set aggressive expansion plans this fiscal. Expansions are planned not only in the manufacturing facility at Umbergaon but also in other areas. We are doubling our number of branch offices across India. Our sales and services teams are also getting beefed up. We are expanding to other geographies and with our new range of products. So overall, it is going to be an exciting journey for the Newtronic family.

Enhanced powder flow

u.sharma@expressindia.com

Chemische Fabrik Budenheim KG EXPRESS PHARMA

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pharma@budenheim.com www.budenheim.com

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INSIGHT

Viscosity and rheology of topical semisolids Viscosity is a property of fluid that depends on the conditions of measurement. An outlook by Dr Phalguni Naik, Application Support Manager, Brookfield Advanced Application Laboratory

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reams, gels and suspensions comprise the largest part in the pharmaceutical industry.

Viscosity and rheology are monitored for quality control, consistency and pharmacopoeial regulations during formulation of ointments and gels. However, material’s viscosity is not a single value, rather viscosity is a property of fluid that depends on the conditions of measurement, for example, the rate of deformation (shear rate), etc.

The value of Newtonian fluid is one in which the viscosity does not change with shear rate and time. The best example of Newtonian liquid is water. For non-Newtonian fluid, viscosity is a function of shear rate and time and may increase or decrease with respect to shear rate and time. An example of non-Newtonian liquid is viscosity of topical semi-solids.

Topical suspensions are liquid preparations that contain solid particles dispersed in a liquid medium intended for application to the skin. Some suspensions are classified as lotions, ointments, gels, creams and pastes. Viscosity decreases with increase in shear rate (rubbing action means increased shear rates); while viscosity regains after shearing stops.

This is called ‘Thixotropy’ and can be evaluated from thixotropic loop by

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The value of Newtonian fluid is one in which the viscosity does not change with shear rate and time. The best example of Newtonian liquid is water. For non-Newtonian fluid, viscosity is a function of shear rate and time and may increase or decrease with respect to shear rate and time cone plate rheometers with 1-2 ml of samples.

Rheological properties such as viscosity and thixotropy of semi-solid dosage forms can influence their drug delivery. Viscosity may directly influence the diffusion rate of the drug.

Therefore, the product flow behaviour must be monitored at the time of its application.

This also helps to monitor batch-to-batch consistency.

Most topical semisolids, when applied on the surface of the skin, show non-Newtonian behaviour. The structures formed within semisolid drug products during manufacturing can show a wide range of behaviours, including shear thinning, viscosity, thixotropy and irreversible or reversible structure damage.

Brookfield R / S Cone Plate Rheometer with CFR 21 compliance is a good option to measure viscosity and rheology of topical semisolids.

A number of rheological

properties play an important role in determining how a material behaves as it moves from storage to handling environment and vice-versa. For example, the force or stress required to initiate flow (yield point) of fluids and semi-solid products plays a significant role in the shelf-life, storage, transfer, packaging and end-use performance of those materials.

Why to measure rheology properties?

The success of the product formulation in the market depends on the end-use performance. The correct formulation of these ingredients allow topical gels and creams to easily flow out of the container (yield stress), which ensures no sedimentation of solid particles during storage, stability (zero shear viscosity) and good spreadability (shear-thinning) on the surface. This helps in uniform coating of the gels on the skin surface for medicinal

use and controlled drug delivery. The modulus gives information on stiffness of the product.

All these quality parameters are related to rheology properties, determined by Cone Plate Rheometer. Based on this rheometric technique, one could predict quality monitoring and behaviour of topical semisolids in the end use performance.

Experimental The data was obtained by Brookfield R/S Cone Plate Rheometer on viscosity and flow behaviour / rheology properties of topical semisolids.

The sample required is 2 ml.

Result: DI Thixotropy The test setting was done as follows: Step 1: Shear Rate ramp 0 to 200 / second for 60 seconds.

Step 2: Shear Rate ramp

DR PHALGUNI NAIK, Application Support Manager, Brookfield Advanced Application Laboratory

from 200 to 0 / second Result: 68.9224 [Pa / S].

Thixotropic fluids are generally dispersions; but when they are at rest, they construct an intermolecular system of forces and turn the fluid into solid, thus, increasing the viscosity.

In order to overcome these forces and make the fluid turn into a liquid again and which may flow, an external energy strong enough to break the binding forces is needed. Thus, as above a yield stress is needed.

Once the structures are broken, the viscosity is reduced when stirred until it receives its lowest possible value for a constant shear rate. The viscosity of thixotropic fluids is time dependent, i.e. once shearing is stopped and the fl uid is at rest, the structure will be rebuilt.

This will inform about the fluid possibilities of being reconstructed.

D.II. Viscosity and yield stress The yield stress is important for pharma products in determining the shelf life, stability and the ease of application for the end-use performance.

Yield stress is defined as the minimum force (Stress) required to initiate flow and can be measured on Brookfield Controlled Stress Rheometers model RS Cone Plate.

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Controlled stress Rheometer like Brookfield R/S Plus Cone Plate Rheometer provides a more sensitive measure of this yield stress. The yield stress is related to the level of internal structure in the material which must be destroyed before flow can occur. This is very important to design optimum torque for dispensers and dosing pumps to increase the process efficiency.

both liquid and solid properties within the same material. The majority of pharma materials are ointments, creams, pastes and gels — all semi-solids.

To understand these complex flows, commercial medical gels, shampoos and cough syrup were tested using the Controlled R/S Cone Plate Rheometer.

Rheology of gels

This is important for the physical performance of the product when used by the consumer. Most ointments are intended to be thick when standing to prevent them from flowing away from the

Pharma and cosmetic gel materials range in consistency from fluid to solid. Semisolid products are the most difficult materials to characterise rheologically because they combine

Differentiation among different formulation of gels

intended area of use. High viscosity at near zero shear rate characterises this behaviour; thus determining the yield stress value quantifies this desired property. Ointments are also engineered to be easy to apply when rubbed. This is known as shear thinning behaviour. Both characteristics of yield and shear-thinning can be easily characterised using only a small volume of 1 ml of the sample with Brookfi eld R/S Cone Plate Rheometer.

Brookfi eld R/S Rheometer with cone spindle CP 75-1 enables low to high shear rate measurements with only 0.5 ml of sample material. The

temperature control of the plate is easily accomplished by connecting to circulating water bath.

However, a continuous shear rate programmed viscosity test clearly demonstrates significant differences between the two. The entire measurement time was 6.5 minutes. While both samples exhibit shear thinning behaviour, sample 1 showed a significant loss of viscosity as a result of shearing action, while sample 2 showed minor viscosity loss. Loss of viscosity due to shearing action is termed thixotropy. Such tests allow the pharma manufacturer to adjust formulations to consis-

tently achieve the desired product performance.

Conclusion Thus, it can be seen that Controlled Stress Rheometers like Brookfi eld R/S Cone Plate Rheometer is capable of measuring and comparing rheology properties of pharmaceutical gels and topical semi-solids in a very short time.

Abbreviations CFR = Code of Federal Regulation cP = Centi-Poises Pa.s = Viscosity in Pascal. Seconds [Pa.s = 1000 cP] R / S= Shear Rate / Shear Stress

Waters PATROL UPLC process analysis system bags Frost & Sullivan award PATROL represents best-in-class product quality and reliability for real-time chromatographic analysis of in-process samples

W

aters Corporation has received the 2014 Product Innovation Award for PATROL UPLC Process Analysis System from Frost & Sullivan in the Global Process Liquid Chromatography market.

Since it was first introduced in 2004, ACQUITY UltraPerformance Liquid Chromatography (UPLC) pioneered a new category of chromatographic performance with the commercialisation of sub-2-μm (micron) particle columns engineered in tandem with advanced instrumentation and fluidics modules to deliver superior performance at higher pressures. In 2010, Waters expanded the scope of its UPLC technology to process environ-

Since it was first introduced in 2004, ACQUITY UltraPerformance Liquid Chromatography (UPLC) pioneered a new category of chromatographic performance with the commercialisation of sub-2-μm (micron) particle columns engineered in tandem with advanced instrumentation and fluidics modules to deliver superior performance at higher pressures ments by launching the PATROL UPLC Process Analysis System based on ACQUITY UPLC Technology.

“On behalf of the employees of Waters, we are honoured to receive this recognition from such a respected organisation

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like Frost & Sullivan,” said Rohit Khanna, Vice President of Worldwide Marketing and Informatics, Waters Division.

“The PATROL UPLC Process Analysis System provides our customers, for the first time, the combination of automation

and UPLC together for direct online connection to their processes with real-time UPLC analysis.”

Janani Balasundar, industry analyst at Frost & Sullivan, noted, “With a perfect mix of technological expertise and ex-

tensive market experience, Waters has helped its customers reap an abundance of benefits by optimising process operations with strict conformity to existing regulatory standards.

The PATROL UPLC Process Analysis System is most often used in applications in research and development, quality control, and process engineering."

Balasundar continues “PATROL UPLC combines a unique blend of functionally rich attributes, which includes speed of analysis, ability to generate calibration curves for quantitation of different analytes, and availability of an automated barcode reader; this distinguishes Waters Corporation’s systems in the market.”

EP News Bureau-Mumbai

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Donning by design: Sterile cleanroom gowning evolves to help minimise contamination risk Damon Larkin, Product Marketing Leader, Cleanroom Apparel, Kimberly-Clark Professional, in this article addresses the importance of process protection in cleanrooms via the appropriate cleanroom suit. It provides an overview of the sterile cleanroom apparel category and defines key areas for improvement. Also, it introduces a new concept for sterile cleanroom gowning to help minimise the problems associated with current technologies

I

n the pharmaceutical industry, the investments needed to bring a product to market are staggering. In fact, it is widely reported that the fully capitalised cost to develop a new drug can range from $800 million to nearly $900 million.

The steep price of product rejects and recalls makes it crucial to ensure high product yields by maintaining strict cleanroom cleanliness and sterility. That is one of the reasons that the US Federal Drug Administration (FDA) mandates that any product that is injected, or used in the eyes or on open wounds must be sterile, i.e., free from viable microorganisms. That is because, if contaminated with microorganisms, these pharma products can adversely harm patients.

Microorganisms introduced into a cleanroom environment need only three things to grow: moisture, food and temperature – all of which exist in a cleanroom. Consequently, all incom-

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ing air, water, chemicals, and materials must be filtered or sterilised to meet high standards of purity and microbiological control, so as not to contaminate processes or products in production. Also to be ‘filtered,’ in a sense, is the cleanroom operator, who, most will agree, is the dirtiest thing to enter a cleanroom.

Consider the following ◗ One square inch of hand surface has an average of 10,000 microorganisms. ◗ Every square inch of the human body has an average of 32 million bacteria on it. ◗ Every minute of the day, people lose about 30,000 to 40,000 dead skin cells off the surface of their skin. ◗ Even when stationary, people generate approximately 100,000 particles of 0.3 microns or greater. On the move, this rises to approximately five million.

Keeping the operator’s dirt and germs out of the sterile

cleanroom environment and away from sensitive products and processes is the main objective of the sterile cleanroom suit. The suit needs to protect the environment from viable particles such as bacteria and yeasts, and non-viable particles such as hair, dead skin cells, and dandruff. To that end, it is critical for cleanroom operators to select cleanroom suits that provide not only the highest levels of inherent sterility, but also the greatest chances of maintaining that sterility through the gowning process.

Sterile cleanroom suits: An overview Although there are no federal regulations for sterile cleanroom garments used in the pharmaceutical industry, guidance for the industry is available from The Institute of Environmental Sciences and Technology (IEST), which publishes a recommended practice IESTRP-CC003.3, “Garment Considerations for Cleanrooms and

P-MEC INDIA 2014 SPECIAL

Other Controlled Environments.” The recommended practice provides guidance for the selection of fabric, garment construction, cleaning and maintenance of cleanroom garments and testing of cleanroom apparel for use in aseptic and non-aseptic cleanrooms.

While cleanroom garments can either be disposable or reusable, according to industry analysts, most sterile facilities will opt for disposable garments due to contamination concerns relating to reusable garments returned from laundering facilities. In some companies, disposables may be used at some locations and reusables at others.

This can depend on the classes of the various cleanrooms at different locations. Disposable garments may be easier to manage from a cost standpoint as well, since the price for reusable garments often carry ‘hidden’ charges such as delivery and pick-up fees (and related energy surcharges), lost/unused garment charges, laundering and sterilisation charges, and more.

For the past 40+ years, disposable cleanroom suits have been made from flashspun polyethylene fabric. According to industry analysts, flash-spun polyethylene provides filtration efficiency for sub-micron sized particles and microorganisms and is suitable for light splash protection from non-hazardous liquids.

Disposable suits also can be made from spunbond-meltblown-spunbond (SMS) fabric, which has outer layers of spunbond polypropylene for strength and cloth-like comfort, with middle layers composed of a matrix of microfibers, which creates a torturous path for fine particles and liquids.

Reusable cleanroom suits are typically made from woven polyester-blend fabrics, which may degrade after multiple laundering and sterilisation cycles. Most operators in a sterile cleanroom environment in the pharma industry will wear three

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While cleanroom garments can either be disposable or reusable, according to industry analysts, most sterile facilities will opt for disposable garments due to contamination concerns relating to reusable garments returned from laundering facilities to four disposable suits in a day, each suit being worn for two to three hours at a time. Often, cleanroom protocol dictates that garment changes must be made each time the cleanroom is re-entered. Once discarded, these suits can be incinerated, or they can be re-purposed through a garment recovery service that will take the used garments and sell them back into non-sterile applications.

Cleanroom garments in the US may be sterilised via several methods, including gamma irradiation, e-beam sterilization and ETO sterilisation. Gamma sterilisation is widely considered to be the most cost-effective method. The desired Sterility Assurance Level (SAL) for garments to be used in sterile pharma manufacturing is 10-6,

which translates into a one-in-amillion probability of a garment being non-sterile. Once sterile, cleanroom suits must be packaged in a way that this sterility is maintained throughout handling, transportation and storage.

Sterile gowning: Room for improvement Ask any cleanroom operator and chances are that he or she will find something about sterile gowns that could be improved. In fact, Kimberly-Clark Professional did just that, spending the better part of two years interviewing cleanroom operators, visiting them in their workplaces and evaluating the features and functions of traditional sterile cleanroom gowns to identify areas in which

there was potential room for improvement.

Key findings of that research ◗ The sterile cleanroom gowning process takes between five and 10 minutes for the vast majority of cleanroom operators. ◗ Almost one-third of cleanroom operators indicate that cleanroom coveralls are the most difficult part of the sixstep gowning process, and that donning coveralls takes an average of 30 per cent of the entire gowning process time. ◗ Cleanroom operators are disposing of an average of 10 per cent of their sterile cleanroom garments every week due to exterior contamination dur-

ing the gowning process. ◗ Most new cleanroom operators need 30 hours of initial training on cGMP donning procedures before they are allowed in the cleanroom itself, and an average of sixhours of ongoing training each week. ◗ More than 50 per cent of cleanroom operators reported garments ripping out orbillowing due to poor fit. ◗ One-third of cleanroom operators report being unsure of their garment’s sterility due to the appearance of its packaging. ◗ Approximately 87 per cent of cleanroom operators would consider switching to a new garment if it was more comfortable and offered less risk of contamination.

The issue of garment comfort was also addressed. Scientific research in the workplace has revealed that a moderate variation in body temperature can greatly reduce concentration and increase risk-inducing behavior. Workers unable to maintain a thermo-neutral zone, or comfort zone, have a higher tendency to become injured and need time off from work, thus reducing productivity. In fact, more than 40 per cent of cleanroom operators polled during Kimberly-Clark’s research report employees need to exit the cleanroom due to overheating on a regular basis.

Inside R&D: Designing a new gowning approach A multi-functional product development team at Kimberly-Clark Professional set out to design a new approach to sterile gowning that would eliminate the problems identified during the company’s research.

The resulting Clean-Don Technology provides the following features: ◗ A patent-pending snap technology that features built-in snaps which gather up legs and arms to lower the risk of the garment touching the floor, then automatically re-

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◗

◗

◗

◗

lease as the garment is put on.

This eliminates problems associated with traditional cleanroom garments, in which the garments’ arms and legs typically dangle freely as the operator dons the garment, thus increasing the chance that those dangling arms and legs may touch the floor, thus contaminating the garment.

This problem with traditional garments is particularly acute with individuals who are on the shorter, yet portlier side, meaning they often have to go up one garment size and therefore would have an even more difficult time keeping the longer dangling arms and legs of the garment from touching the floor.

An innovative inside-out fold pattern that presents the inside of the garment as the package is opened, reducing the risk of touching and contaminating the outside of the apparel.

A highly visible blue line along the inside of the garment that signals the proper place to grasp while gowning, helping workers avoid touching the exterior of the garment.

Thumb loops that help keep the garment from riding up the arm and help to maintain the glove/garment interface.

A unique process to package the new garments for sterility assurance. The technology uses a vacuum seal process to allow the breathable SMS fabric to be sterilised with Gamma irradiation. The unique look and irradiation indicators on each package help to confirm irradiation and sterility.

A roomy design that is less likely to rip out than ANSI minimums since it provides 12 per cent more chest room and six per cent longer body length. At the same time, the garments’ elastic waist and back reduce loose-fitting material that could contact work surfaces or billow out, forcing air to exit the garment at its extremities.

◗ An SMS (Spunbond Meltblown Spunbond) material that provides a cloth-like feel and is 25 times more breathable than TYVEK. Sharing and evaluating the new garment and donning concepts with cleanroom operators were crucial to ensuring the new approach was successful. Testing of the Clean Don Technology with cleanroom operators found the following: ◗ 93 per cent of operators preferred the heavy vacuumsealed package for providing greater sterility assurance.

Operators also said they would have no problems stacking the heavily vacuumed packages. ◗ 86 per cent of the operators prefer the coverall’s thumb loops to hold the sleeves in place. ◗ 86 per cent of operators felt the blue stripe would lower the risk of contamination that would result from touching the outside of the garment or contacting a nonsterile surface, and would help facilitate aseptic gowning. Operators estimated that the disposal of coveralls contaminated during the donning process would be reduced by 52 per cent with the new garment and donning concept.

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◗ A full 100 percent of operators agreed that the arm and leg snaps would help prevent contamination during the gowning process and that the overall approach would provide better compliance in maintaining sterility. ◗ A full 100 percent of operators thought the material felt more like cloth than the leading competitive sterile cleanroom coverall, which was largely described as “hot, sweaty and platic-feeling.” ◗ 93 percent of operators felt the new coverall design would provide greater ease of training. The average estimated time saved in the donning process among all operators studied was approximately one minute.

Validation and training: Inculcating the new approach One of the necessary steps when validating a new sterile cleanroom gown is to carefully review the garment’s certification. Be sure to ask the garment supplier for the following: Certificates of conformance These verify that a specific product lot conforms to all specifications before the lot is released. Physical characteristics

should be tested in accordance with relevant ASTM standards.

Particles should be tested in accordance with relevant IEST standards.

Certificates of irradiation These document the minimum and maximum dosage of irradiation that a product received. Look for sterilisation validation documentation that confirms that the doses have been verified, the loading patterns were sufficient, and that the process is audited on a regular basis.

A variety of functions will need to be involved in the approval process for a new cleanroom gown. First, safety must approve the use of a new product. Each local safety officer must ensure that the product will not violate any EPA or OSHA regulations or permits.

Any changes to processes are also concerns for regulatory personnel, as they may impact the company’s FDA license. After acceptance by safety and regulatory, Quality must be included and will play a key role in testing and accepting the new product or process. Quality assurance personnel are involved in reviewing all of the procedures and process records, testing the product to ensure its sterility, and approv-

ing the final selection based on the data. The Quality Control organisation will inspect all incoming sterile products, policing the environment and reporting the result. The purchasing department is the final step in the process and often provides rubber-stamp approval for ordering the products already accepted by the other players.

Most pharma companies will conduct a new garment validation process for three to nine months, during which time the new garments would be worn in a controlled area, though not necessarily in the actual cleanroom in which the garment is designed to be worn.

In many pharma companies, a new sterile gown also will need to undergo testing on three lots before validating and approving it. In some cases, a change to the standards of practice for that environment will also be required. Many users will assess a garment’s sterility on-site by using contact plates or swabs containing a nutrient media. To formally validate gamma- or e-beam-irradiated garments for sterility assurance levels, use ANSI/AAMI/ISO 1137-1994 ‘Sterilization of Health Care Products – Requirements for Validation and Routine Control – Radiation Sterilization’ and ANSI/AAMI/ISO 11737-1-1995 “Sterilization of Medical Devices –Microbiological Methods – Part 1: Estimation of Population of Microorganisms on Products.”

Validating a new sterile cleanroom garment is not a task to be undertaken lightly. However, when a new approach to sterile gowning can help improve the gowning process, reduce opportunities for operator error, and minimise the risk of contamination, it provides a strong incentive for pharma companies to consider switching.

For further details or clarification please contact us: avinash.vhanakaware@kcc.com |+91 9850 570 212

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INSIGHT

Optimising the viscosity test Robert G McGregor, General Manager, Global Marketing, Brookfield Engineering Laboratories, gives an outlook about the type of instruments to be used while evaluating â&#x20AC;&#x2DC;thickerâ&#x20AC;&#x2122; materials that do not flow readily

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&D has the responsibility for developing test methods that qualify materials for acceptability in manufacturing. The physical property that addresses flow behaviour is viscosity, which is a measurement of resistance to flow. For liquids this seems reasonably obvious, but for semi-solid materials, like margarine, butter, jams, etc. the word 'spreadability' may seem more appropriate.

Observing and quantifying the way in which materials change shape during deformation is all part of the viscosity measurement world.

The question is what type of instruments to use when evaluating these 'thicker' materials that do not flow readily.

Standard bench top viscometers and rheometers use a rotating spindle immersed in the fluid to make the viscosity measurement. (See Figure 1).

Resistance to rotation at different speeds is measured as discreet torque values and converted mathematically into scientific units called 'centipoise'. The resulting graph from this test looks like the display on the instrument in Figure 1. Viscosity values are recorded on the y-axis vs. rotational speeds on the x-axis.

Non-Newtonian materials exhibit a decrease in viscosity as rotational speed increases.

This type of flow behaviour is referred to as 'pseudoplastic' or 'shear thinning.'

Non-flowing materials present more of a challenge when measuring viscosity be-

Figure 1: Brookfield DV3T Rheometer uses rotating spindle to measure viscosity

Figure 2: Brookfield RS Soft Solids Tester with Vane Spindle for Non-flowing Materials

cause the spindle digs a hole when rotating in place. Once the material moves away from the spindle, it does not recover

and leaves a void in the space adjacent to the spindle. Viscosity readings decrease quickly and there is no practi-

Figure 3: Stress vs. time graph for two butters tested with Vane Spindle at 0.5rpm

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ROBERT G MCGREGOR, General Manager, Global Marketing, Brookfield Engineering Laboratories

cal way to record data that is meaningful. Choosing a different spindle geometry is the solution.

The vane spindle shown on the instrument in Figure 2 offers several advantages. It can be immersed directly into the material without disturbing the sample structure. The material that is trapped between the vanes represents fresh sample that can be tested without prior shearing history.

The type of instrument shown in Figure 2 is a controlled stress rheometer. It offers the dual capability of either applying a defined torque to the spindle or rotating the spindle at a defined speed. The former mode of operation is useful in determining the force to initiate flow while the latter characterises both the initial

Figure 4: Stress vs. time graphs for comparison of spreadable butters to margarine

P-MEC INDIA 2014 SPECIAL

force and the viscosity or resistance to movement once flow begins. Using the latter method provides two pieces of comparative data in a quick test that can be used to qualify products.

In a controlled speed test at low rpm, say 0.5 rpm, the spindle measures increasing resistance to movement as rotation commences.

The recorded stress climbs to a peak value called the 'yield stress' because it represents the initiation of flow behaviour for the material. Figure 3 shows the graph for this type of test on traditional butter and a newer spreadable version of the same product. The slope of the lines after flow commences give an indication for the viscosities of the respective products since it indicates their different resistance to movement at the same rate of spindle rotation.

The same test can be used to compare butters to margarine for spreadability. Figure 4 shows the same test on three different products. The behaviour of the butters exhibits a gradual flow transition around the point of yield stress whereas the margarine has a sharp drop off after start of flow. This reflects a more brittle structure in the margarine which manifests as less resistance to spreading the margarine once movement begins. Butter 1 clearly shows higher yield stress and viscosity values compared to butter 2 and might therefore represent a premium brand.

If the controlled torque capability of the rheometer is used and held at a constant value close to the yield stress of the material, the creep behaviour can be measured. This characterises the ability of materials, such as jams and icings, to hold their shape under constant load, such as gravity.

This type of test is important for applications where the appearance of the material is important to the customer. An-

Figure 5: Brookfield CT3 texture analyser with cylinder probe measuring gelatin sample

Figure 6: Spreadability test fixture used with texture analyser

Figure 7: Force vs. distance graph for spreadablility of butter and margarine

other example is maintaining structural integrity of jams and icings used as fillers in cakes and pastries, so that oozing does not occur. Holding shape is the desired property in all cases.

An alternative approach for making these types of measurements is with a texture analyser as shown in Figure 5. This device moves a probe into the test sample at a defined rate of penetration.

Measurement of spreadability

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is accomplished using the fixture shown in Figure 6 with the cone-shaped probe moving at 1mm/sec into the container of test material. The resistance to penetration is recorded as a force measurement in units of grams by the instrument, both as a function of time and displacement. The distance which the probe penetrates into the sample is defined by the user.

There are several advantages to this method:

◗ The test sample can be kept in its original package or container if desired. ◗ Material is not disturbed prior to testing. ◗ Work expended to penetrate or flow the sample is quantifiable. ◗ Removal of the probe can measure the adhesive property of the material, i.e. its ability to cling to the probe as it retracts.

Figure 7 shows the graphical data for a typical spread-

ability test on butter and margarine. The peak force quantifies the hardness of the sample. The slope of the curve up to the peak force is a measurement of 'stiffness' and will change if the speed of penetration for the probe is adjusted.

The area under the curve leading up to the peak force is a measurement of the work done to penetrate the sample.

The margarine exhibits softer behaviour compared to the butter throughout the test.

Given the two available methods for measuring highly viscous, non-flowing materials — rheometer with (cone) VANE spindle and texture analyser with cone probe — is one better than the other? The data from both types of tests are valid and represent quantifiable ways to measure hardness/firmness and spreadability. The bottom line is that both methods work acceptably, are easy to execute, and require similar prep and cleanup. The ability to mathematically calculate the work done with the texture analyser gives an added piece of information. Repeatability may be comparable with either method, but is best confirmed through testing of the material in question.

Of importance to the lab manager is the cost to purchase the equipment and the training of personnel. Both instruments have been available in the market place for many years and are used by general industry. While R&D may use the software for initial material characterisation, the QC lab can use either instrument in standalone mode and report values for yield stress or hardness respectively.

So it really boils down to preference. In labs with sufficient resource, it is normal to find both devices employing test methods similar to the above. Perhaps now is the time for your lab to investigate these test techniques and improve the QC testing on your 'soft-solid' product.

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