Express Pharma (Vol.10, No.20) August 16-31, 2015

VOL. 10 NO. 20 PAGES 64

www.expresspharmaonline.com

Market ‘India is our jumping off point in Asia’ Pharma Technology Review Unsung heroes of pharma industry 16-31 AUGUST 2015,` 40

Sometimes I’m blunt.

But never pointless.

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CONTENTS Vol.10 No.20 AUGUST 16-31, 2015 Chairman of the Board Viveck Goenka Editor Viveka Roychowdhury*

Anudge in the right direction

MARKET

Pg21

Chief of Product Harit Mohanty BUREAUS Mumbai Sachin Jagdale, Usha Sharma, Raelene Kambli, Lakshmipriya Nair, Sanjiv Das

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Bengaluru Neelam M Kachhap Pune Shalini Gupta DESIGN National Art Director Bivash Barua

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PHARMA SALES TO GROW BEYOND $1 TRILLION

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INDOCO REMEDIES PLANS ` 125-CRORE INVESTMENT

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SYNGENE INTERNATIONAL IPO OVERSUBSCRIBED 31 TIMES

Deputy Art Director Surajit Patro Chief Designer Pravin Temble Senior Graphic Designer Rushikesh Konka Senior Artist Rakesh Sharma, Vivek Chitrakar

P14: POST EVENT PHD chamber conducts national conference on ‘Pharma Exports: API Challenges’ in New Delhi

PHARMA TECHNOLOGY REVIEW

Photo Editor Sandeep Patil MARKETING Regional Heads Prabhas Jha - North Dr Raghu Pillai - South Harit Mohanty - West & East

P31: VALUE ADD

Marketing Team Rajesh Bhatkal GM Khaja Ali Ambuj Kumar E Mujahid Arun J Ajanta Sengupta

P33: WHITEPAPER

PRODUCTION General Manager B R Tipnis Manager Bhadresh Valia Scheduling & Coordination Mitesh Manjrekar CIRCULATION Circulation Team Mohan Varadkar

Quality by design

Extractables and leachables from glass

P36: VENDOR NEWS

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UNSUNG HEROES OF PHARMA INDUSTRY

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‘ALFAA UV IS THE UNDISPUTED LEADER IN INDUSTRIAL UV SYSTEMS IN INDIA’

‘INDIA IS OUR JUMPING OFF POINT IN ASIA’

RESEARCH

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FDA APPROVES OTSUKA AND LUNDBECK’S SCHIZOPHRENIA TREATMENT

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EXPERIMENTAL VAGINAL GEL PARTIALLY PROTECTS AGAINST GENITAL HERPES

IKA-Werke bags most innovative medium-sized biz award in Germany

P59: AWARDS Merck Serono awards € 20,000 to Innovation Cup Winners

Express Pharma® Reg. No.MH/MR/SOUTH-77/2013-15, RNI Regn. No.MAHENG/2005/21398. Printed for the proprietors, The Indian Express (P) Ltd. 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 © 2015. The Indian Express (P) Ltd. All rights reserved throughout the world.

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EDITOR’S NOTE

New strategies for growth

A

fter a decade of pain, there are some reassuring signs that the pharmaceutical industry may just be seeing the faint glimmers of light at the end of the R&D pipeline. A recent report from Thompson Reuters shows that 2014 had 46 new molecular entity releases, the highest in a decade. While the higher than usual number could be due to a windfall of delayed releases and approvals, what's really worth noticing is that the quality of releases has changed for the better. For instance, according to the 2015 CMR Pharmaceutical R&D Factbook, one third of 2014 launches were for rare indications, mainly in the oncology arena, with many of these receiving orphan drug status. Phase III launches grew steadily while early development pipelines thinned out, with the industry embracing a 'fail fast, fail cheaply' strategy. Sparse early pipelines could also mean that these companies will need to find replacements once these drugs hit the market.

Most of these strategies are visible in AstraZeneca, the subject of our cover story in this issue. (See story, Getting the science right, pages 1620). Every decade needs new strategies and it will be interesting to see how this business model plays out.

On the domestic front, EU's ban of 700 formulations tested by GVK Biosciences has escalated into a trade dispute, with India's Commerce Ministry calling off trade negotiations due in late August. In what is turning into a 'who will blink first' contest, one wonders at the long term implications of this stand off. India's proposed national IPR policy dues to be released in a few months will see another such tug of war.

India's regulators and regulatory infrastructure desperately need an overhaul if they are to cope with an industry growing at a fast clip. In this issue, we focus on the status of central and regional drug testing laboratories, with a Good Laboratory Practices' special story on how some states and regulators are pushing for change and upgrading their facilities. NABL and WHO pre-qualification certification will go a long way towards instilling confidence in this framework.

Our fervent hope is that other states follow suit sooner than later. (See story, A nudge in the right direction, pages 21-23).

Such a change is already underway at India's IP offices, according to Nirmala Sitharaman,

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Unless regulators feel the same push from the electorate,they will never feel the same urgency to buck up and stay relevant

Minister of State for Commerce and Industry, who at a recent FICCI meet pointed out that the draft IP policy, focuses on stronger enforcement of IPR by increasing the manpower strength in IP offices and reducing the pendency of IPR filings.

Most of the IP offices have gone online and it is hoped that doing away with the manual interface for applications, queries and decisions will speed up decision making.

The July FICCI meet was held to felicitate Micromax on acquiring the 1.25th million international trademark under the Madrid System, and the minister took the opportunity to emphasise that the final draft of the proposed national IP policy was arrived at after a transparent consultative process before being sent to the Union Cabinet for approval. This contention was disputed by academia but all stakeholders are awaiting the final release to see if the government has stuck to its stand to protect India's interests. Going online was a no brainer, a long delayed decision. It is important to realise why the government was able to push this through. The Prime Minister himself has advocated that intellectual property is a means to create jobs and achieve the growth rates he promised the nation when he took office.

His message is reiterated by his ministers down the line, For instance, speaking at the same FICCI meet, Amitabh Kant, Secretary, Department of Industrial Policy and Promotion (DIPP), Ministry of Commerce and Industry, admitted that the key challenge before the country was to attain growth rates of 9-10 per cent year after year for 30 years. “We need to be a nation of job creators where innovation and creativity will be the key driving forces,” he said, underlining the role of India's IP offices and the proposed IP policy in “building Indian brands that can effectively penetrate the global markets.”

The message is very clear: the promise of all round economic growth is the biggest nudge for change. Corporates are answerable to stakeholders and the stock market and therefore are forced to change much faster. Unless regulators feel the same push from the electorate, they will never feel the same urgency to buck up and stay relevant.

VIVEKA ROYCHOWDHURY Editor viveka.r@expressindia.com

MARKET I N T E R V I E W

‘India is our jumping off point in Asia’ Over 370,000 patients in India develop solid tumour based cancers annually, that require comprehensive genomic profiling. Cancer Genetics India launched a solid tumour Hotspot panel based on Next generation sequencing for its biopharma and clinical customers throughout Asia a few months ago. Shalini Gupta finds out more about the company's plans in an interview with Panna Sharma, President and Chief Executive Officer, Cancer Genetics Inc

How big is the DNA-based diagnostic market size globally and that in India?

How much share do you have currently and how much are you targeting in the coming few years in India?

To discuss the diagnostics market, we really have to focus on the portion of the market that is relevant to our company.

The global diagnostics market is worth $17.5 billion, most of which is dedicated to infectious diseases. Cancer is approximately 30 per cent of that number and is fragmented between oncology, equipment manufacturers, and several other areas. We are expecting to capture 10 per cent of that 30 per cent cancer number over the next five to seven years through organic growth and acquisitions.

Do you have presence in other Asian markets too? If yes, which ones? How much does India and these Asian markets contribute to your revenues? Have any particular tests been launched for these markets?

Cancer Genetics International and CG India were established with the objective of offering services to a global community and we are doing exactly that.

Our clients, our partners and our services are global. We have operations in India and China, but the business models for each are different. The India operation is focused on the local market and our goal is to expand this operation significantly over the next 6-12

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months. India is our jumping off point in Asia. We also have an office in Shanghai which services the China-based clinical trials of our US-based biotech and pharma customers.

We plan to expand our China operation where we are actively looking for partners.

What percentage of your current customers are diagnostic labs, doctors, hospitals, pharma companies? Do you see this ratio changing in the future?

Why? What kind of collaborations are you exploring with biopharma and research companies going ahead?

We generally don’t report revenue and percentages in India, but last year 44 per cent of our global revenue came from the clinical business, and 56 per cent from biopharma.

This year we expect clinical to contribute 35 per cent and biopharma 65 per cent. In India, we continue to seek new collaborations that will allow us to advance and further customise the products we are offering in this market.

Collaborations also allow us to access new innovations. One example of these types of collaborations is our partnership with Kamineni Hospital in the cervical cancer testing space. We are also actively seeking partners for our NGS panel for solid tumours.

Why is the DNA-based diagnostic landscape in India

Cancer Genetics International and CG India were established with the objective of offering services to a global community

expanding? What trends do you see?

The degree of interest from clinicians, researchers and patients in India will allow genomic medicine to take the main stage in this market and we are excited to be a part of the democratisation of personalised medicine. One of the biggest trends is the change in the patient’s role in the clinical practice globally. There are a few trends that we’re seeing in the marketplace. Not only are guidelines changing that are affecting researchers and clinicians, but patients are also more aware. They have access to genomic information and want more sophisticated healthcare tools. While both of these things are happening, costs are also coming down rapidly. These three elements are helping the advancement of genomic medicine.

How is the NGS technology panel better than the earlier methods in terms of clinical outcomes? What cost savings does it provide over other regular tests? How would you differentiate yourself from your competitors?

NGS is better because its increased sensitivities result in more comprehensive genomic information being captured.

NGS eliminates any clinical guess work and allows people to receive treatment earlier.

Additionally, fewer samples are necessary, which cuts down on medical costs and time requirements on the patient’s behalf.

While we don’t have significant data regarding overall patient costs for India, there are expectations of cost reductions as we’ve seen in other markets. An example of this is captured in a poster that was presented at the 2015 ASCO conference by our team in collaboration with a major cancer centre in the U.S. The study that was referenced analysed the treatment of renal cancer patients with brand name drug, Sunitinib. The cost of a year of treatment can cost tens of thousands of dollars and treatment for even a trial period can be significant. NGS can help confirm the patient response to the drug, making treatment more efficient in terms of time and costs. We want to make this type of treatment available to all communities. Our company’s vision is founded on innovation—it drives our capabilities and inspires our work. Coupled with our growing global footprint, these are elements that set us apart from our competitors.

Collection of a large library of genomic data gathered from the tests can be used to improve the quality and accuracy of clinical research and discovery efforts. How could this bode for pharma companies? Do you have tieups with pharma companies in the US? We are partnering with the companies that are taking the lead in the personalised treatment space. To this end,

we are now working with seven out of twelve top global pharmaceutical companies including partnerships and collaborations with Gilead, AstraZeneca and Roche. These partnerships are central to our strategy. The pharma industry is changing its approach from blockbuster drug-focused to individualised treatmentfocused and they will fuel the advancement of this approach.

We are fully on board with this and committed to making significant strides in individualised medicine in India. Because laboratory or clinical testing today are largely driven by information, we are currently developing a database in India as different populations have different genomic markers that indicate how cancer will progress or respond to certain treatments.

improving cancer care in this community. The services CG India offers this market place are customised, sophisticated

and are designed with the goal of making personalised cancer care accessible to all through collaborations with local

hospitals such as Kamineni and other partners, to be announced. We are working closely with leading

researchers locally in the government and private sectors. shalini.g@expressindia.com

We are now working with seven out of twelve top global pharma companies including partnerships and collaborations with Gilead, AstraZeneca and Roche This will help us discover and leverage genomic differences with a much higher degree of accuracy and efficiency. We will develop a knowledge base that is not only disease specific, but also local in scope.

What are your future plans for the Indian market?

We are committed to growing our presence in the Indian market, to expanding the use of personalised medicine and to

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MARKET COMPANY WATCH

Pharma sales to grow beyond $1 trillion Forecasts sales to reach $1.3 trillion by 2018 THE INTELLECTUAL Property and Science business of Thomson Reuters, provider of intelligent information for businesses and professionals announced the release of the 2015 CMR Pharmaceutical R&D Factbook, the biopharma industry’s leading resource of global R&D trends. Despite concerns around declines in R&D, the analysis identifies a surge in global sales with 2014’s $1 trillion milestone and forecasts sales to reach $1.3 trillion by 2018. It also reveals a positive shift in new molecular entities (NMEs) with 46 launches in 2014; the highest in over a decade.

The study underscores a

promising industry outlook with increases in sales and NME launches and with shifting trends in R&D pipeline volume and therapeutic areas as evidenced by other key findings.

Diversification increases NME launches: One third of 2014 launches were for rare indications, mainly within anti-cancer. More than 65 per cent were speciality drugs for treatment of anti-cancer, Hepatitis C virus and HIV. Anti-cancer dominates: Anti-cancer development continues to attract the highest amount of investments across all therapeutic areas; with the majority of recent

A promising industry outlook with increases in sales, NME launches and shifting trends in R&D pipeline volume and therapeutic areas

launches receiving orphan drug status from regulatory authorities.

Increase in failing fast and cheaply: Phase III pipeline volumes are steadily growing due to the improved ability to ‘fail fast and cheaply,’ increasing the speed of potentially successful compounds through development.

Since 2003, the CMR Pharmaceutical R&D Factbook has been built in collaboration with leading global pharma companies to assess productivity and to provide insights to strengthen planning and the effectiveness of R&D. It is based on proprietary, primary sources, competitive

intelligence, and public sources covering key trends across the landscape, including R&D pipeline volume, success rates, cycle times, regional comparisons, therapeutic areas, and generics.

“This is an extraordinary year for the pharma. Not only do the critical insights provided by the Factbook challenge negative perceptions, but it demonstrates this industry’s continued commitment to creating and employing innovative solutions to tackle its largest hurdles,” said Basil Moftah, President, Thomson Reuters IP & Science. “” EP News Bureau-Mumbai

GSK Pharma to invest India foils UK firms’s bid to patent use of turmeric,pine bark `1,000 crores at its Bengaluru facility and tea for treating hair loss An attempt by Colgate-Palmolive Co to patent a mouthwash formula made from Indian herbs was also foiled by CSIR-TKDL unit recently INDIA HAS been successful in protecting its traditional knowledge by preventing an attempt made by Europe’s Leading Dermaceutical Laboratory-Pangaea Laboratories, to take patent on a medicinal composition containing turmeric, pine bark and green tea for treating hair loss.

Traditional Knowledge Digital Library (TKDL), a unit of Council of Scientific and Industrial Research (CSIR), located the patent application filed at European Patent office by Pangaea Laboratories and filed pre-grant opposition along with prior-art evidences from TKDL,

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proving that turmeric, pine bark and green tea, are being used as a treatment for hair loss, since long in Indian systems of medicine like Ayurveda and Unani. A PIB release stated that the UK-based company had filed the patent application at European Patent office in February, 2011. CSIR-TKDL Unit had filed evidences from TKDL on January 13, 2014 after the patent application got published on website, pursuant to which the patent application is finally deemed to be withdrawn by the applicant on June 29, 2015.

Recently, CSIR-TKDL Unit

has foiled an attempt of Colgate-Palmolive Company to patent a mouthwash formula containing herb (NutmegJayaphal) extract used in Indian traditional systems of medicine to cure oral diseases, at European Patent office.

CSIR-TKDL, headed by Dr Archana Sharma, submitted proof in the form of references from ancient books in this case, which said the herb and its extracts of Myristica Fragrans were historically used for oral diseases in Indian systems of medicine.

EP News Bureau-Mumbai

The facility will be operational by 2017 GLAXOSMITHKLINE Pharmaceuticals’ (GSK India) greenfield manufacturing facility at Bengaluru, having an installed capacity of over nine billion tablets and capsules per year, will be operational by 2017, according to a report in PTI. The company said that it has decided to create a new greenfield manufacturing site at Vemgal near Bengaluru, to be operational by 2017. Initially, the site will supply a range of solid dose form products. Reportedly, the unit will have an installed annual capacity of over nine billion

tablets and capsules to supply in the local market. The new site, which represents up to `1,000 crores in investments, will be the first greenfield pharma site GSK has built across the globe over the past 10 years. The state-of-the-art site will be the first factory designed for the new GSK production systems.

GSK India is also upgrading the Nashik site by investing in infrastructure across all areas with special focus on good manufacturing practices (GMP), safety and sustainability.

Its Nashik facility has completed enhancement of the existing Eltroxin facility in safety standards. The unit is ready to launch new products in Bactroban creams early next year.

EP News Bureau-Mumbai

MARKET

Indoco Remedies plans ` 125-crore investment Posts net profit of `20.3 crores as compared to `18.7 crores for the preceding Jan-Mar quarter INDOCO REMEDIES has planned an investment of `125 crores for expansion of its sterile ophthalmic facility at Goa and for setting up a greenfield API facility at Patalganga. The investment will also cover an additional pilot plant for finished dosages at Goa, said Suresh Kare, Chairman, Indoco Remedies.

Addressing shareholders at the 68th annual general meeting of the company, Kare said, “This investment, in sync with the Government of India’s ‘Make in India’ initiative, will be funded through a mix of debt and internal accruals”.

Stating that the company is on a high growth trajectory, Kare pointed out that Indoco’s domestic formulation business was 14.7 per cent as per AWACS data of March 2015, surpassing the industry average of 13.3 per cent.

“Top three brands of the Company, Febrex Plus, Cyclopam and Sensodent-K feature amongst the top 500 brands in the Indian pharma market. During the year, the company launched 19 new products across various therapeutic segments.

Going forward, the company will continue to launch around 20 new products every year. The company has re-structured the marketing divisions to sharpen the pattern of coverage of different doctor specialities and have added around 500 MRs, taking the total MR strength to 2800,” Kare said.

During the year, the company received US FDA approval for its sterile ophthalmic facility for the third consecutive time.

With this approval, all the three finished dosage and two API facilities are now USFDA approved.

EP News Bureau-Mumbai

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August 16-31, 2015

MARKET

Ananth Kumar inaugurates modernised general tablet section of IDPL,Gurgaon plant IDPL, Gurgaon plant has been upgraded at the cost of `3 crores as per 'Revised Sch -M' requirement and has obtained GMP certificate THE UNION Minister of Chemicals & Fertilizers, Ananth Kumar, inaugurated the modernised general tablet section of IDPL, Gurgaon plant.

The Minister of State for Chemicals & Fertilizers Hansraj Gangaram Ahir and Secretary, Department of Pharmaceuticals, Dr VK Subburaj were also present on the occasion. IDPL is one of the Central Public Sector Enterprises under the Department of Pharmaceuticals, engaged in manufacturing and marketing a large number of medicines for the masses.

According to a PIB release, General tablet section of IDPL, Gurgaon plant has been upgraded at the cost of `3 crores as per 'Revised Sch -M' requirement and GMP certificate has been obtained. After modernisation, IDPL, Gurgaon plant will be able to launch new products in the field of diabetes, oncology, NSAIDS, Antibiotics3rd Generation, nephrology and cardiology, as well as other

Kumar said that providing affordable and good quality medicines to the masses of the country is important and the public sector undertakings have an important role to play segments of lifestyle diseases at affordable prices.

Kumar said that his department is working on the ‘MakeIn-India’ mantra and this unit of IDPL is a step in that direction.

He assured government’s full support in enhancing the efficiency and productivity of the public sector undertakings.

Kumar said that providing affordable and good quality medicines to the masses of the country is important and the public sector undertakings have an important role to

play as they are not driven by profit motives and serve public interest. He assured that the public sector undertakings will not be sold. Instead, a model will be developed for leveraging their assets to make them financially sustainable.

The minister said that a task force will be set up soon to look into all these aspects. He said that his ministry is working in close coordination with other concerned departments of the Government of India and the state governments as ‘Team

India’ for attaining health security. The minister said that Jan Aushadhi will be revamped soon. He informed that pharma cluster, pharma parks and medical devices parks are also a step in this direction.

Ahir said that the government will provide support to IDPL in enhancing its production and its modernisation to enable it to regain its past glory.

Dr VK Subburaj said that besides affordability and availability, quality of the medicines is also important. He said the government is taking policy initiatives so that more and more Indian pharma companies become compliant to the WHO quality standards.

He also said that the drugs provided by IDPL and other public sector undertakings will facilitate in smooth functioning of the government’s programmes and help provide access to people of good quality medicines.

EP News Bureau-Mumbai

and faculty exchanges and may include a site at Purdue Research Park,” the statement further said.

Biswas said that the longterm research partnership will help accelerate innovative drug development and manufacturing excellence.

“The long-term research partnership augurs well for DRL’s philosophy of providing access to innovative, high-quality medicines to global patients at affordable cost,” he added.

AJANTA PHARMA has received final approval for its three Abbreviated New Drug Application (ANDAs) by US FDA for Montelukast tablets, 10 mg, Montelukast sodium chewable tablets, 4mg and 5mg and Montelukast oral granules.

Montelukast sodium tablets, 10 mg, the generic version of Singulair tablets

by Merck, is indicated for treatment of prophylaxis and chronic treatment of asthma and to relieve symptoms of seasonal and perennial allergic rhinitis in patients two years of age and older.

Montelukast 4mg chewable tablets are suitable for two to five year-old patients while Montelukast 5mg chewable tablets are available for patients from six to 14 years of age. Montelukast oral granules are specially appropriate for patients of 12 months of age and older.

For the 12 months ending June 2015, Montelukast tablets, chewable tablets and granules had sales of approximately $237 million, $87 million and $31 million respectively, according to IMSHealth. Ajanta intends to launch these products shortly.

The approval of the Montelukast product family is part of an ever-growing portfolio that Ajanta Pharma has developed for the US market. Including these three ANDA approvals, Ajanta now has five approved ANDAs and another 20 ANDAs under approval with FDA.

EP News Bureau-Mumbai

EP News Bureau-Mumbai

DRLand Purdue varsity in drug research MoU To forge a strategic partnership in a range of research areas and novel technologies in the field of pharma processes and product development THE US-BASED Purdue University has signed a Memorandum of Understanding (MoU) with Dr Reddy’s Laboratories (DRL) to strengthen pharma research and development, as reported in PTI. According to a statement issued by the University, the intent of the MoU is to forge a strong strategic partnership in a range of research areas and novel technologies in the field of pharma processes and product development.

Suresh Garimella, Executive Vice-President for Re-

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search and Partnerships, Purdue, and his counterpart Amit Biswas, Executive VicePresident and Global Head of Integrated Product Development, signed the MoU. Reportedly, the MoU will advance the ‘Purdue Moves’ drug discovery initiative to translate basic research into life-changing treatments.

“Purdue has tremendous strength in pharma drug discovery and development research, but we need additional partners to help translate our discoveries through

the delivery of a medicine or technology,” Garimella said.

“The partnership with the Indian drug maker combines strengths that could lead to world-changing research,” he added.

Areas of planned collaborative research and education include targeted drug delivery, manufacturing technology, scale-up of pharmaceutical operations, process engineering, and research and development methodologies and technology.

“The collaboration will include student engagement

Ajanta Pharma gets approvals for three ANDAs

MARKET

Syngene International IPO oversubscribed 31 times The IPO is an offer for sale (OFS) by Biocon of a part of its shareholding in Syngene SYNGENE INTERNATIONAL’S (Syngene) Initial Public Offering (IPO) has been oversubscribed 31 times based on the electronic bid file available on the websites of Stock Exchanges. The Qualified Institutional Bidders (QIBs) subscription stood at 51.47 times while the non-institutional investor subscription was at 90.24 times. The retail subscription was 4.77 times.

The issue opened for subscription on July 27 and closed on July 29, 2015. The IPO is an offer for sale (OFS) by Biocon of a part of its shareholding in Syngene.

Commenting on the successful subscription to the IPO, Kiran Mazumdar Shaw, Chairperson Biocon, said, “We are indeed overwhelmed with the response to the IPO, and I would like to thank the public for reposing their confidence in the differentiated story of Syngene. Am confident that together we will deliver value for all stakeholders in the times to come. This value unlocking will also augur well for Biocon’s stakeholders.”

Peter Bains, Chief Executive Officer, Syngene said, “We are pleased with the favourable response of investors to Syngene’s IPO. We believe this reflects strong confidence in Syngene’s differentiated strategy, capabilities to support its growing customer base and its future growth prospects.”

The price band for the offer was fixed between `240 and `250 per equity share of `10 each. The Anchor Investor bid period was on July 24, 2015 and the company allocated 60 lakh equity shares to Anchor Investors at a price of `250 per equity share.

The equity shares being offered are proposed to be listed on the BSE and the National Stock Exchange of India after completing the requisite listing formalities.

EP News Bureau-Mumbai

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MARKET POST EVENT

PHD chamber conducts national conference on ‘Pharma Exports: API Challenges’in New Delhi Policy makers disclosed initiatives, policies and schemes for betterment of the pharma sector Usha Sharma New Delhi DEPARTMENT OF Pharmaceuticals (DoP) has declared 2015 as ‘Year of Active Pharmaceutical Ingredients’ (API) and to give added impetus for growth, recently, Progress Harmony Development (PHD) chamber recently organised a national conference on ‘Pharma Exports: API Challenges’ in New Delhi. The conference discussed various issues being faced by the pharma industry where policy makers disclosed initiatives, policies and schemes for betterment of the pharma sector.

The conference was attended by key industry stakeholders and policy makers. Nishant V Berlia, Chairman, Health Committee, PHD Chamber, in his speech, gave a broad scenario of the Indian API industry and issues associated with it.

Boujdaria Jamel, Charge D’ Affairs, Embassy of Tunisia shared a brief note on pharma companies located in Tunisia and business opportunities for the Indian pharma companies.

Sudharshan Seneviratne, High Commissioner of Sri Lanka talked about the potential presence of the Indian pharma companies in Sri Lanka. He informed that the Sri Lankan Government is providing subsidies to set up new units in that country. He highlighted that the Sri Lankan population is facing tragic kidney failure issues and everyday15-20 people die in the country, due to the disease.

Dr VK Subburaj, Secretary, Department of Pharmaceuticals, Ministry of Chemicals and Fertilisers, Government of India, said that land is a big constraint for the pharma industry in our country, whereas, China provides easy availability of land and electricity at affordable

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rates. In order to overcome this situation, the government is looking for better business opportunities where the environment is more conducive. The Government of India is determined to see that the Indian API sector is self sufficient. The current situation of the Indian API industry is very challenging, but the government is in the process of formulating various policies, seeing a huge potential in the small and mid sized companies.

Subburaj also mentioned that there is a need to strengthen small and mid-sized API manufacturing units and financial assistance will be provided for the same besides working on the pharma technology upgradation scheme. He also informed that schemes have been introduced for the benefit of clusters. “We have already launched various schemes for innovation in the sector. Indian pharma companies should concentrate on innovations and also focus on disease profile which has immense business potentials in the long run for eg; Alzheimer, Parkinson’s etc. Companies should invest on research programmes in a dynamic manner so that the sector can show promising growth,” added Subburaj.

Replying to an Express Pharma query on when the policy on bulk drugs by the Ministry of Chemicals & Fertilisers, Government of India will be out, which was targeted in March 2015, Subburaj replied that the technical work process of the policy is almost ready and is awaiting for some responses from the stakeholders. It will soon be introduced for the industry. He said, “We are going to have discussions with the Bulk Drugs Manufacturing Association (BDMA) and identify challenges associated with it.

Dr VK Subburaj, Secretary, Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, addressing the PHD Chamber Conference on Pharma Exports: API Challenges

Hansraj Gangaram Ahir, Minister of State, Ministry of Chemicals and Fertilizers, addressing the conference

We have already opened national bulk drug research centre in Hyderabad where we will find out the new process which can produce cost-effective drugs ” Subburaj informed that today only 14 to 15 per cent Indian pharma companies are following global standards, which is quite negligible in the global scenario. Today our people (Indian population) are not quality oriented, but look for cost effective things, whereas our sector (pharma) cannot follow the same parameters. The pharma sector needs to have affordable drugs with high quality parameters.

While signing off, Subburaj assured the industry that various secretaries of government bodies related to the pharma sector are keen to work together in resolving the issues. Besides these, the government will also conduct international meetings between governing bodies of various countries, take part in exhibitions, organise industry meets to reach out and understand global requirements and boost exports.”

Hansraj Gangaram Ahir, Minister of State, Ministry of Chemicals and Fertilisers, Government of India urged the pharma industry to help the government in its initiatives. He also

assured the industry that the government is not going to become an obstacle in its growth path and will support the industry.

Ahir talked about issues being faced by the clinical research industry and urged the industry to follow the path which is being practised globally. “In future we will hold meetings between the health ministry and industry associations,” Ahir said.

Replying to a question raised

by Express Pharma on the delay in opening Jan Aushadhi centres across India, Ahir informed that it is easy to begin any programme but core challenges need to be maintained without any break. There are issues due to shortage of drugs for certain disease profile. However, the policy is ready and under review and there are plans to launch 1,000 stores on September 15, this year.

Anil Khaitan, Chairman and Managing Director, Sunil Healthcare raised issues being faced by the Indian API industry and put forth various benefits being offered by the Chinese Government. He urged the government to enhance the industry with various benefits and to open innovation funds, which will help small and mediumsized pharma companies.

BR Sikri, Director, Auronext Pharma, touched upon the key points like anti-dumping law, showing leniency to the audit process of Chinese plants, a fast track system for clearance, positive working environment at government offices for the betterment of the industry.

Kiran Kalia, Director, NIPER Ahmedabad highlighted the need for the academia and industry to move forward together in scaling up research projects. u.sharma@expressindia.com

EVENT BRIEF AUGUST-SEPTEMBER 2015 25

Asia Labex

2

ASIA LABEX Date: August 25-27, 2015 Venue: Pragati Maidan, New Delhi Summary: Asia Labex is an international exhibition and conference on laboratory, analytical, biotech and diagnostic instruments and consumables. Around 200 plus exhibitors from 15 countries, 1800 brands will take part in the event. 20 seminar topics will be discussed in the expo and seminar.

Contact details Fenza Exhibitions Building No. 21, 3rd Floor, Behind Samrat Restaurant, Outram Lines, GTB Nagar Delhi 110009 Email: info@asialabex.com Tel: +91-11-45088781 / 45088782

PharmaLytica 2015

Summary: SCM Confex, the biggest conglomerate of supply chain and logistics professionals from global

pharmaceutical and chemical companies, will focus on creating a robust infrastructure for end-to-end

10

6th Annual SCM Pharma Summit

supply chain solutions. The organiser for the event is UBM. Contact details UBM India

E-mail: suvidha.shetty@ubm.com Web: http://globalformulation.com

PHARMALYTICA 2015 Date: September 2-3, 2015 Venue: HITEX Exhibition Centre, Hyderabad Summary: PharmaLytica conference is the knowledge forum where topics in analytical, outsourcing, laboratory, scientific and biotechnology sector will be discussed. The event will see a congregation of 200 leading local, regional, and international exhibitors.

Country pavilions from China and Korea will be set up.

Contact details Jayesh Kanaskar Project Head jayesh.kanaskar@ubm.com T: +91 22 61727162 | M: +91 9819586780 Yogita Panchal Project Manager E: yogita.panchal@ubm.com T: +91 22 61727510 | M: +91 9930027424

6TH ANNUAL SCM PHARMA SUMMIT Date: September 10 - 11, 2015 Venue: Novotel Mumbai Juhu Beach

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www.merckmillipore.com

cover )

GETTING THE SCIENCE RIGHT The ‘no pain, no gain’ mantra seems to be finally putting the $25 billion AstraZeneca on the road to recovery, as it continues to prune sites and sell off once prized R&D assets to finance the promising leads entering phase II/III trials.

Bracing for further revenue erosion due to patent expiries, UK’s largest pharma company is betting on emerging markets like India before revenue from new products kick in.

Sanjay Murdeshwar, Country President and Managing Director, AstraZeneca Pharma India believes getting the science right is as important as expanding accessibility to patients. Will the company recover lost ground?

BY VIVEKA ROYCHOWDHURY

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THE MAIN FOCUS

T

he last few years have been a painful transformation of AstraZeneca as it right-sized its R&D, chose its focus areas and fought off an aggressive takeover bid. As it sells off research leads in non-core areas to shore up its balance sheet and finance a dozenodd new molecular entities (NMEs) either at registration or entering Phase III, the most expensive stage of trials, the Anglo-Swedish company is still not out of the red.

In an overview of this year’s first half yearly global revenues announced on July 30, the company revised its prior FY2015 total revenue guidance from mid-single digit to low single-digit per cent. This is a small victory but will this sustain? The slight improvement in topline growth came due to externalisation deals worth more than half of the total revenue of $12.4 billion, which was up one per cent.

Caprelsa (vandetanib), a rare disease therapy was the latest molecule which was divested to Genzyme/Sanofi in late July, which netted AstraZeneca $300 million; $165 million as an upfront payment for the global rights to sell and develop the molecule, and up to $135 million as milestone payments after further development and sales.

Like most pharma MNCs, AstraZeneca's revenues fell hard off a steep patent cliff, and the company took longer than most to arrest the slide. Its antipsychotic medication Seroquel went of patent in 2012, while 2014 saw two big revenue earners, Nexium, its blockbuster acid-reflux medication and Symbicort, for COPD and asthma, fall off the cliff. 2016 will see another hit, with Crestor, a cholesterol lowering medication due to lose its patent.

AstraZeneca’s peers have also gone through the same process of looking for ways to improve R&D productivity. Increasing demand by payers and regulators for greater evidence of comparative effectiveness of medicines also increases development times and costs. In terms of geographies, Japan and emerging market (EM) regions were also given a thrust.

(See box: AstraZeneca’s plans for its six key growth platforms) Over the last two years, R&D was consolidated to three locations: Cambridge, UK; Gaithersburg, US; and Mölndal, Sweden. All three locations are in close proximity to globally recognised bioscience clusters with strategic global R&D centres, allowing for closer interaction with scientists both within and outside AstraZeneca. Two autonomous biotech units, MedImmune and Innovative Medicines and Early Development (IMED) were created as well as a clinical development group called Global Medicines Development (GMD).

In mid 2013, the company chose Sanjay Murdeshwar to head their EM strategy in India as country president and managing director, AstraZeneca Pharma India Limited (AZPIL). Murdeshwar, who was then based out of the US, and had spent 17 years at Bayer, with stints at the headquarters in Germany, as well as Philippines and Singapore, was also looking to head back home to attend to family commitments.

The AZPIL opportunity attracted him because the company was going through a transformation, to evolve to the next level and he felt the company’s new CEO had taken some “very interesting decisions as to what and where the company wanted to be perceived as a pharmaceutical company,” recounts Murdeshwar.

The company has had a long innings in India, starting out as Astra India in 1979, headquartered in Bangalore, predating the 1999 merger between the Swedish Astra and British Zeneca.

Short term pain ...

Rebuilding a blueprint

Plummeting revenues led to a realignment in the company’s priorities, a change of course credited to Pascal Soriot, who joined in October 2012 as CEO, after stints at Roche and Genentech. With a new tagline of 'What science can do', the company went back to the drawing board and changed their way of looking at science.

Clearly, R&D had to show what it could do in the market, else it faced an existential crisis. The AstraZeneca management decided to focus on a few core areas (down from a total 13 areas of research/business): Oncology, Respiratory, Inflammation and Autoimmunity (RIA) and Cardiovascular Metabolic Diseases.

Very clearly, AstraZeneca realised that unlike a number of companies, including some pharma MNCs which had a branded generics play, what worked for them was science. “Science is at the core of what we do and therefore we resumed investing back into research substantially,” says Murdeshwar. He admits that AstraZeneca may have had a relatively “dry pipeline” for a reasonable period of time. Given the lack of promising drug candidates, the company decided to stay away from generics. He explains this risky stance saying,“If you put science and patients at the core of what you do, then a company takes very different decisions.”

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cover ) The management’s decision to prune its portfolio had a lot ramifications in terms of the follow on decisions. For instance, since diabetes was identified as one of the growth platforms, AstraZeneca became a lot more ‘proactive’ in the diabetes space, buying out BristolMyersSquibb stakes in their joint business.

Similarly, the second area of focus was respiratory diseases, in which the company started acquiring assets to make up for revenue loss due to Symbicort going off patent. For instance, in July 2014, the company paid $875 million up front, and along with milestones up to $2.2 billion, for the rights to Almirall’s respiratory business and inhalation device subsidiary. In another bid to retain its strong presence in this therapeutic category, the company paid $600 million for Actavis’ respiratory drugs portfolio this March.

AstraZeneca’s vulnerability due to falling sales attracted an aggressive takeover bid from Pfizer, spanning November 2013 to May 2014. Pfizer’s bid faced flak from shareholders and UK politicians who worried that the merger would result in job losses and cuts in research spends. Though one major factor driving Pfizer’s interest was to turn Pfizer into a UK-based company and reap tax inversion benefits as well as cost savings due to merged operations, the long drawn out battle was also proof that AstraZeneca’s choice of focus areas and strategies to excel in these areas were steps in the right direction.

Cardiovascular and metabolic diseases was another focus area as well as oncology.

Thanks to some of the very good choices made in Phase I and Phase II by the company’s R&D leaders, the company today has very clear candidates in its oncology pipeline. Overall, AstraZeneca today has 16-17 candidates in its Phase III pipeline, which as Murdeshwar points out, “Two years ago, we didn't believe this would happen. It is very unusual,” and a complete sea change after the pipeline transformation.

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... for long term gain He underlines the importance of science in this turnaround with an example. AstraZeneca had a very good ovarian cancer molecule in Phase 1. But when they started testing the molecule, they realised that the peak potential (patient population which would benefit from the candidate) was only $500-600 million. For most global pharma companies this would be too small a peak sale point but the AstraZeneca CEO decided to go ahead, with the rationale that it did not matter how big that product was, in terms of revenues. What mattered was that it was really going to fundamentally change some patients’ lives. The molecule Lynparza is for BRCA-mutated advanced ovarian cancer, which went on to become a huge talking point, thanks to Angelina Jolie, who was also detected with the same mutation. Murdeshwar cites another similar example: AZD9291 (EGFR), for lung cancer, again with a genetic marker to it.

This seems to be a milestone in the way the company started to evaluate its R&D leads; marking a shift from a single-minded focus on revenue potential to the idea that R&D programmes should be seen in a longer timeframe, as investments in a certain way of doing science. As treatment, especially for cancer, becomes more personalised, targeted patient pools will reduce but today, many pharma companies are actively looking at serving the needs of these smaller patient groups. The extra science and technology which goes into these treatment regimens actually acts like an entry barrier reducing competition. The company intends to increase their emphasis on novel science, such a personalised healthcare, expecting half their launches to be with a companion diagnostic by 2020.

But research is a cash guzzling business, where will the revenue growth come from to fund these programmes? Murdeshwar is pragmatic when he says, “Of course we would like to grow. We have growth platforms of emerging markets, and Japan,

The last two years have been about clarifying what are our growth platforms in India SANJAY MURDESHWAR country president and managing director, AstraZeneca Pharma India

which are our two big platforms because other countries would see some patent erosion. But you’d also like to have scientific leadership. Once you put science as the technological differentiation for our company, then our choices are clear.”

Today, two years after the pipeline transformation, the management’s efforts to build a sustainable, durable and more profitable company seem to be bearing fruit. The next phase of their strategy, will most probably see their transformed R&D organisation accelerate revenue growth and sustainability. The company will continue to build on their EM strategy. The move to diversify their portfolio will see an increasing focus on biologics (already 50 per cent of the pipeline) and devices, as well as a balance of primary and speciality care increasing the profitability of the business.

AstraZeneca has tasted success in its efforts to monetise their science-led strategy, through collaboration, out-licensing and divestment deals.

For example, the company has an alliance with Eli Lilly to codevelop and commercialise their

BACE inhibitor, AZD3293, in Alzheimer’s disease. The second major deal is the co-commercialisation agreement with Daiichi Sankyo in the US for Movantik, which launched in March for opioid induced constipation;, The deal earned the company $200 million in upfront externalisation revenue included in Q1 2015 total revenue.

A third strategic collaboration is the one with Celgene to develop their immuno-oncology portfolio in blood cancers.

The India play With EM regions identified as one of the six growth drivers, Murdeshwar is tasked with expanding the company’s access to as many patients as possible. Referring to the vision highlighted on AstraZeneca’s Open Innovation website, ‘to deliver 10 new molecules over the next seven years, and to touch the lives of 200 million patients every year by 2025,’ he points out, “We are measuring our success both by the number of patients as well as the number of molecules we bring out. We believe that by doing so, all our stakeholders, from patients, the physician commu-

nity as well as shareholders, would obviously gain. This core idea has driven the India strategy as well, with AZPIL aligning itself as much as possible to the global pipeline.”

As he points out, India has huge unmet medical needs in the company’s disease focus areas. There are 65 million diabetic patients in India and unfortunately growing by the day. In the respiratory area, India has 45 million patients in the asthma-COPD space. Its the same reality of unmet medical needs in the CVD space while in the area of cancer, the company has its work cut out in terms of creating diagnostic markers, creating the infrastructure etc in preparation for future marketing authorisation for AZ’s oncology portfolio.

The global shift in priorities will also ‘change the DNA of AZPIL as well and this is what we are currently going through,’ he says. Currently, AstraZeneca in India is involved in clinical trials with five molecules in therapeutic areas such as oncology, diabetes, respiratory, and infection. In addition to that, at present, clinical trials in the areas of CKD associated anemia, cardiovascular risk reduction, and oncology are under preparatory stage.

Resizing R&D Less than a year after he joined AZPIL, the following January, the India operations got a rude wake up call, when it was announced that the R&D centre in Bangalore would be shut down.

Since AstraZeneca had decided to withdraw from the infectious diseases space, its antiinfectives R&D centre at Waltham was hived off into a separate biotech company. As AZPIL’s Bangalore R&D centre, Avishkar, focused on anti-infectives with a tropical disease slant, the company had to shut this down as well.

A statement from AZPIL on the closure of the site explains that although they no longer engage in ‘in-house’ research activities in India, AstraZeneca continues to make their compound library available through ‘open innovation’ partnerships and

( also provide expertise that can help advance medical research programmes. Over the years, Avishkar had become a nucleus of Bangalore’s life science ecosystem and the statement commits to ‘developing distinctive science, including research into Neglected Tropical Diseases (NTDs), worldwide and in India. ... To help local science to build on this legacy we have taken steps to ensure that our earlystage NTD portfolio will continue to progress by supporting the establishment of a new, ‘not for profit’ organisation in Bangalore called ‘FINDER’ - The Foundation for Neglected Diseases Research. We have also committed to a substantial contribution of scientific equipment from the site to the National Centre for Biological Sciences (NCBS). The equipment will become part of a

core NCBS facility open to the entire R&D community in Bangalore.’

If India, as part of the EM block, is identified as a growth driver, wasn't it counterproductive to shut down research into infectious diseases like TB, etc, where India and other developing/tropical nations, have huge patient populations with unmet medical needs? Murdeshwar clarifies that though the Bangalore R&D centre was shut down, the company retained one of the leads in the TB programme. It continues research in the infectious disease area at Boston, so infection remains an area of focus, but its going to be opportunistic.”

Explaining this strategy, he says that besides the three main areas (cardio-metabolics, cancer, and respiratory), the company

The company has tied up with DRL for a distribution agreement for saxagliptin and its fixed dose combination with metformin and with Sun Pharma for Brilinta/ ticagrelor

THE MAIN FOCUS

may not invest too much in the other two areas (infection/vaccines and neurosciences) but if there are very interesting molecules which can be built on, they are opening to partnering in this area. In the second area termed ‘emerging market diseases’, like typhoid etc, Murdeshwar says that the company is willing to create open research platforms and patent pools with a lot of their R&D work done so far, so that other interested R&D centres or players can take the lead on what interests them and move it ahead if they find it economically viable and they have the technology. The TB molecule from the shut down Bangalore facility is now part of this open source initiative.

Making India count But Murdeshwar has an uphill

task as he strategises to climb the rankings in India’s hyper competitive and fragmented pharma market. He admits, “We are at a cusp. The last two years have been about clarifying what are our growth platforms in India as well as what are not.”

The company is now set to fire on at least two fronts, with two pivotal deals signed in June.

It tied up with Dr Reddy’s Laboratories for a distribution agreement for saxagliptin and its fixed dose combination with metformin, in Type II diabetes and with Sun Pharma for Brilinta/ticagrelor.

In the June MAT AIOCD Pharma Trac rankings, AZPIL is ranked at 36, but he can take satisfaction that it grew fastest (35.4 per cent) amongst the 31-40 ranked corporates, which made it the fastest growing pharma

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cover ) MNC in June as well. The company made its entry into the ` 500-crore club and one of its key brands, Brilinta, in the CVD space, notched one of the fastest growth rates in the Top 300 brands.

Besides Brilinta in the CVD space, the respiratory therapeutic area is also going to be another important growth area, with Symbicort. According to him, the company can do much better with this product as we did not spend time defining the science, technology and need of such a product to Indian patients. The company took a price cut of 40-50 per cent on this product. “That's the three things we're going to look at: cutting-edge science, accessible to as many patients as possible and therefore how do we make that happen,” he summarises.

With two deals in place, is AZPIL scouting for more such distributorships with Indian companies in other areas of the product basket, to make it a volumes games? Logically the next deal should be in the respiratory range, but Murdeshwar laughs off such speculation saying, “At the end of the day, what is important is our strategy to make innovative products as accessible to as many physicians and patients as possible and if we need help to achieve this goal, we will look at partnerships but if we decide we don't need help, we'll do it alone.”

Besides fighting for market share, the company has also had its fair share of legal problems like the recent compulsory licensing bid by Lee Pharma. On another front, the parent company has made two unsuccessful attempts to delist the Indian entity; in 2004 and 2010. An offer for sale (OFS) in 2013 was stalled when a SEBI investigation found that a single group of investors, through six entities, subscribed to 94.02 per cent of the shares offered by AZPIL through the OFS. In an order dated June 24, 2014, SEBI ‘suspected concerted/coordinated action of AZP AB and Elliott group’ (a foreign institutional investor) in order to facilitate the delisting of AZPIL. In order to protect the interests of retail in-

20 EXPRESS PHARMA August 16-31, 2015

ASTRAZENECA'S PLANS FOR ITS SIX KEY GROWTH PLATFORMS 1.BRILINTA – To deliver Brilinta’s potential as a cardiovascular medicine, with plans for market leadership in the US and worldwide, and further clinical studies 2. DIABETES – To maximise the potential of their broad innovative non-insulin antidiabetic portfolio to transform patient care in diabetes 3. RESPIRATORY – To maximise the opportunity of their ‘end-to end’ strengths in medicines, pipelines and devices to transform patient outcomes in asthma, COPD and IPF 4. EMERGING MARKETS– Refocusing efforts on innovative medicines; accelerating investment in EM capabilities, with a focus on China and 15 top markets; broadening reach through multi-channel marketing; and transforming capabilities to support new products, for eg. market access and patient affordability 5. JAPAN – Building on the company's

vestors, SEBI directed the stock exchanges to monitor the delisting process closely. The company did not give an update on the delisting process as the matter is still subjudice.

The long-term picture EM markets growth was 18 per cent in Q12015 and growth normalised in Q2 (+9 per cent) in line with long-term view. The respiratory grew at +30 per cent, driven by Pulmicort and Symbicort, Brilinta (+80 per cent), diabetes (+88 per cent), driven by Forxiga and Onglyza and Oncology (+18 per cent) Though the company does not break out country wise revenue figures, he emphasises that EM revenues have been growing quite substantially, with China obviously as the big growth driver. India is very clearly an important growth platform player in this geography but much depends on how the company can address and access as many patients as possible.

Thus India seems to be a volumes play, but with the expanding the span of price control, is it tougher for pharma MNCs, when compared to other EM

oncology franchise and working to maximise success with launches across the diabetes portfolio and with Symbicort, Nexium and Crestor 6. ONCOLOGY - Became the sixth growth platform in January 2015; several potential submissions in 2015 to 2016; expected to contribute largest proportion of pipeline-driven revenue growth and potential to grow to quarter of sales by 2023

countries? Murdeswar doesn't think so, saying, “I don't believe so, at least not for us. All our patented innovative products available in the India market are around 70 per cent discounted to their prices in developed markets. So we are bringing it at a price point where we will hopefully create as much accessibility as possible. At the end of the day, it will come down to the science. Globally too we are restructuring ourselves around getting our science right.”

This philosophy drives other decisions. For instance, of the 1200 people in AZPIL, 40-45 are in the medical division. Globally too, of the 57000 employees globally, 1200 are in science-related functions.

According to Murdeshwar, they presently have one of the biggest medical teams in India, all 40-45 MBBS-qualified doctors out in the field, involved in medical education. Clearly, with the choice between hiring more MRs or more staff in the medical department, the company has made its choice. And this is driven by its product range. For instance, he reasons that the level of discussions on BRCA

mutated ovarian cancer would have to be more scientific than a sales pitch.

So also in the diabetes space, Forxiga, which was launched this May, is an SGLT2, a very new and different class of molecules, which is slightly counterintuitive to current practice. As he explains, conventionally, the presence of sugar in urine is considered a sign of diabetes and treatment strategies focused on bringing the sugar levels back to acceptable levels with medication, lifestyle changes etc. But with SGLT2s, the mode of action is that (excess) sugar should pass out through the urine. So the type of interactions the company's medical education staff will have with clinicians would be beyond current text book knowledge, more cutting-edge latest research.

This needs a different level of preparation. For instance, the diabetes educators are based at and certified from Bangalore’s St John’s Hospital, so that they interact with patients and clinicians, in order to get the technical knowledge to have such a conversation. Summing up, he says, “If this is going to be the

differentiator, then this is a good differentiator.”

Differentiation in the clinician community will be tough, as competition is high in these areas and the disadvantage of narrowing focus is that the risk is higher. Murdeshwar says, “We look at this as an opportunity to study how these molecules work in Indian patients with Indian diets and lifestyles.”

According to him, for instance, Forxiga works on very clear areas of fat adiposity, i.e. the fat around the waist, which is a big problem in Indian and Asian patients. So the molecule is seemingly tailored made for the Indian/ Asian genetic makeup/pool. “We still have a long way to go before we understand how this molecule will address the characteristics of an Indian diabetic metabolism.

This will be our differentiator and we will keep building on this.

Which is why we need more staff on the medical and clinical side. That is how the future will be and how we need to be ready.

We certainly are on the way to get there, but I must confess it is a long way,” he admits.

With Crestor due to go off patent in 2016 patent loss will continue to eat into AstraZeneca's global revenues quite substantially. Is the company on track to replace the revenue loss from these patent losses? He concedes that there will be one to two years of sluggish growth in the years when the blockbusters go off patent, but is confident that revenues will pick up as the new molecules hit the market.

His lodestone is the publicly announced ambition to improve the lives of 200 million patients globally and be a $50 billion company in 2025. On the revenues front, the company is currently about half way there, at $25-26 billion. “In India, we need to touch the lives of 8-10 million patients in the next 4-5 years.

From a patient, an unmet need perspective as well as a science perspective, we have very good science and the legs to develop these significantly in India and give physicians a choice,” he signs off. viveka.r@expressindia.com

GLP SPECIAL

Anudge in the right direction National government-run laboratories are responsible for approving the availability of new drugs in the market.Yet, very few of them are NABL-accredited and many of the non-accredited ones fall way below the global standards. There is an urgent need to improve these labs with qualified staff and technical assistance which is lacking as of now, to prod them on the way to progress

BY USHA SHARMA

T

he Indian pharmaceutical industry is the leader in supplying affordable generic medicines to the world.

It has got the highest number of US FDA approved manufacturing facilities outside the US which highlights its capability to deliver affordable healthcare to many nations.

Commenting on the capabilities of Indian pharma companies, SD Joag, Ex Secretary General, Indian Pharmaceutical Association says, “India is the largest producer of essential medicines for management of high-burden diseases in developing countries and speciality drugs to developed countries, both in terms of finished formulations and active pharmaceutical ingredients (APIs).

However, the quality of medicines produced in India is frequently under scrutiny the US FDA, UK MHRA, ECA, TGA and WHO will always remain keen to monitor the consistency of quality medicines and regulatory compliance of Indian pharma manufacturers while producing the medicines.”

For the last one and half years, Indian pharma companies have increasingly been pulled up on for the quality front from different countries' regulators. There have been an increase in warning letters and 483's, which impacted the pharma export largely. Dr Ajit Dangi, President and Chief Executive Officer, Danssen Consulting mentions, “While India

CDSCO Laboratory at West Zone, Mumbai

has acquired the distinction of being a reliable source of quality medicines at affordable prices, we have a long way to go as far as consistently producing acceptable quality medicines as shown by the US FDA import alerts and 483s for over dozen large Indian pharma companies in the last few years.”

Explaining the root cause for such an alarming stage and underlying the need for qualified laboratory system in India, Dangi attributes, “The US FDA laboratory forms the back bone of any drug quality issue which the drug manufacturer face. These labs, with few exceptions, more often than not, lack adequate number of trained analysts, sophisticated analytical instruments and accreditation from organisations like National Accreditation Board for Testing and Calibration of Laboratories (NABL).

Another important issue is that of data integrity of results

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produced in such labs.”

Criticality of NSQ drugs Globally, the Indian pharma industry has shown a tremendous growth and has been recognised as ‘Pharmacy of the World’ but the regulatory agencies in the country have not been able to keep pace with this progress. For several reasons, India is being questioned for its quality. Is it because there is a lack of understanding related to the process or is there other reasons?

The Drugs Act (Amendment) 2008 defines only three categories of drugs under section 36AC namely. spurious, misbranded and adulterated.

Dangi informs, “The lack of proper definition for not of standard quality (NSQ) drugs often results in genuine and licensed manufacturers being penalised under the above three categories. Quite often, a standard quality drug manufactured by a licensed manu-

facturer fails in potency or physical appearance (discoloration, chipped tablets etc. ) due to improper storage or poor supply chain during distribution.” (For more details on NSQ drugs, see story http://www.financialexpress.com /article/pharma/managementpharma/redefining-nsq/89009/) Dr Raman Mohan Singh, Director, Central Drugs Testing Laboratory, Mumbai, Ministry of Health and Family Welfare, Government of India says, “Analysing the criticality of the issue, the Department of Health, Ministry of Health and Family Welfare decided to define NSQ drugs and proposed necessary changes in Section 36AC. The government has formed a committee under the leadership of Dr Surinder Singh, Former DCGI. Across the country, more than 45,000 samples were collected for assessing and measuring the quality and assigned to six central and two state level

The need of the hour is therefore to strengthen the capacity of selected GMP inspectorates and medicines testing laboratories in India to enable them to meet international standards SD Joag Ex Secretary General, Indian Pharmaceutical Association

The US FDA laboratory forms the back bone of any drug quality issue the drug manufacturer has to face Dr Ajit Dangi President and Chief Executive Officer, Danssen Consulting

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GLP SPECIAL

In present scenario, I have not seen such activities where we have exchanged technical assistance in the global sphere. If we do not get the training and exchange programme globally which is being expected, then how are we going to strengthen our parameters and be at par with global standards Dr Raman Mohan Singh Director, Central Drugs Testing Laboratory, Mumbai, Ministry of Health and Family Welfare Government of India

The major concern of the government laboratories is its ability to handle the volume of work in their respective state. This leads to too many samples waiting for analysis and thereby incapacitating inadequate storage archival and documentation TS Jaishankar Managing Director, Quest Life Sciences

22 EXPRESS PHARMA August 16-31, 2015

laboratories namely Central Drugs Testing Laboratories (CDTL) in Chennai, Kolkata, Kasauli, Regional Drug Testing Laboratories in Chandigarh, Guwahati, Hyderabad and state laboratories in Maharashtra and Gujarat respectively.”

Initially, the committee planned to conduct the tests in private as well as governmentrun laboratories which are NABL accredited. Singh further says, “The committee decided to accomplish the NSQ project in three to four months through tender process. However, when the quality analysis of those private NABL accredited labs was carried out in , the committee realised that certain required parameters not being followed and hence decided to do all the tests in the central and state-run laboratories. We have received 5000 samples which will be submitted before the end of this year besides our routine tests. Earlier, we used to conduct 25003000 tests in a year, which has been doubled now.”

He informs that two months backs the Indian Pharmacopoeia Laboratory (IPL), Ghaziabad, had received the WHO pre-qualified QCL certification which is the first government laboratory which has obtained this certification.

Following the steps of IPL, Singh is gearing up for the Mumbai lab as well. Presently, the CDTL, Mumbai is conducting tests of various samples like import / export samples from airports / port trusts, registration samples, new drugs samples from DCG(I) office, Zonal Survey samples from Zonal and Sub Zonal office of CDSCO, legal samples (Form 18) through central drug inspector, medical devices samples, proficiency testing samples, CGHS samples and other miscellaneous samples. He informs that presently the lab received more than 5,200 samples under drugs survey for drugs safety India through NIB, Noida under the directions of Ministry Health & Family Welfare through CDSCO for checking the NSQ / spurious drugs moving in the country. The analysis of these samples is going on

CDSCO Laboratory at West Zone, Mumbai

simultaneously with war footing on time bound manner.

Singh informs, that “We are in the process of applying NABL accreditation and later we will go for the WHO pre-qualified QCL certification in CDTL, Mumbai.

Singh while replying as to how such accreditation and recognition will be beneficial to the industry says, “With the NABL (ISO / IEC 17025:2005) accreditation, we will be in a position to call our lab a globally recognised one which will assure all quality measures.”

TS Jaishankar, Managing Director, Quest Life Sciences shares his insights and says, “The Tamil Nadu government undertakes regularly testing of samples out of every supply made to pharma medical stores. The major concern of the government laboratories is its ability to handle the volume of work in their respective states. This leads to too many samples waiting for analysis and thereby incapacitating inadequate storage archival and documentation.”

Approaching global standards In order to meet the global regulatory requirements, the Central Drugs Standard Control Organisation (CDSCO), a national regulatory authority is striving to equip its personnel and systems as per the global standards. The Indian regulatory body had announced to conducted several workshops to train/update their drug regulators in collaboration with the US FDA, Gujarat FDCA with UL. According to an industry source, Drug Information Association (DIA) conducts an annual meeting of their worldwide members for a minimum

of three days in one of the major cities in the US. Members who take part in the meeting are normally from academia, companies, regulatory bodies and pharmacy students. It is an accepted body of a neutral status and thus provides a neutral platform for all the regulatory experts from various countries to interact and exchange views on regulatory advancements on the global front. It is invariably attended by US FDA, EDQM, EMA and other regulatory authorities of various countries who mingle with these prominent people and exchange ideas and update themselves every year.

The source informs that unfortunately Indian regulators do not seem to be present in numbers. More so, we have not seen any decision maker participating in this international forum except for India programmes. Hence, a good number of opportunities are lost scaling up the knowledge and utilise useful decisions for the countries’ regulatory system.

As a result there is big void which exists in terms of the actual methodical regulatory requirements. This is seen and felt conspicuously in our regulatory personnel.

The source also informs that, one gets exposed to various training modules available at these fora which could be used to train regulatory officials. Several small meetings were held on these training areas by WHO authorities along with European Pharmacopoea Authories (EDQM) and EMA. In fact these global regulatory authorities have been suggesting that Indian pharma associations should provide modules for training wherein these authorities will pitch in their expertise.

Singh answers on set expectations from Indian regulators as well as international bodies, and says, “In present scenario, I have not seen such activities where we have exchanged technical assistance in the global sphere. If we do not get the training and exchange programme globally which is being expected, then how are we going to strengthen our parameters and be at par with global standards to recoginise our facilities internationally?”

“Most of the government state-run laboratories are only conducting primary tests in labs and do not have high-end sophisticated instruments required for critical analysis.

There is hardly any interaction between the government and industry-run laboratories which results in lack of awareness on GLP practices. Since laboratories have to decide on the end results, the government should ensure primarily that all the state-run laboratories are accredited for GLP by NABL or equivalent or even higher international regulatory bodies,” says Jaishankar.

Dangi reciprocates, “The Maggi episode has opened a Pandora's Box on the status of government laboratories and their working techniques.

While the primary responsibility of producing good quality medicines consistently lies with the manufacturer, regulatory bodies like the FDA need to provide stringent oversight to guard the public health.”

Joag emphasises, “The drug testing laboratories should also be supported with the provision of reference standards at affordable price. The Indian pharma industry is totally dependent on USP / BP /EP reference standards which are very expensive. There is enough expertise and talent in our country to produce these reference drug standards or impurity standards. The Indian government should exploit this possibility to support the pharma industry. The API industry and the government will have to work hand in hand for achieving this need.”

Joag further says, “The government should also recognise the need of sophisticated

GLP SPECIAL CAPACITIES OF TESTING LABORATORIES UNDER CDSCO* Labs Actual Capacity (approximately) CDL. Kolkata 3,316 CDTL, Mumbai 2,774 CDTL, Kasauli 3,564 CDTL, Hyderabad 579 CDTL, Chennai 1,633 RDTL, Chandigarh 2,207 RDTL, Guwahati 1,680 Total Testing Capacity of All Labs 15,753 Source: (CDSCO website) *Data based on Financial Year 2013-2014 ()

instruments for the evaluation of quality compliance. These instruments are not produced in our country and hence compelled to import these by paying huge money. The regulatory quality requirements are changing fast and upgrading of instruments to meet such requirements is inevitable. The government can support the industry by giving exemption on taxes as the conversion of foreign currency is always on the upsurge.”

Joag says, “However, states like Gujarat, Karnataka and Maharashtra are equipped themselves as per global standards. Dangi highlights, “Food and Drugs Control Administration (FDCA), Government of Gujarat under the able leadership of FDCA Commissioner, Dr Hemant Koshia, has made commendable strides in upgrading the entire administration collaborating with CDSCO, US FDA and US-based training organisation UL. FDCA in Gujarat has a well equipped mobile laboratory to check on counterfeit drugs is a unique initiative. We need more and more FDA labs in the country to emulate FDCA in Gujarat. The need of the day is to have skilled regulators understanding the global requirements of quality compliance in terms of purity, efficacy and safety of drugs and the drug testing laboratories equipped with not only sophisticated instruments but with skilled operators.”

Joag feels, “A capacity building programme for GMP inspectorates and control laboratories should be drawn up, aimed at establishing quality management systems and building staff competence to operate at all international standards. The focus will be on supervisory activities (inspection and laboratory testing) related to the manufacture and quality control of drugs and formulations. Attention should be specifically paid to generic medicines. The capacity building programme should be a regular activity of the CDSCO and state drug control authorities. At the end of every such programmes, the performance should be checked with international standards by informal audits.”

Joag suggests, “The programme could be made mandatory to all drug control departments in India and the drug testing laboratories for strengthening the skill development infrastructure at both inspection and analytical levels. Aimed at empowering the drug regulators and the analysts working in drug testing laboratories with similar regulatory knowledge and analytical skills as offered to the US FDA officials, the CDSCO

should soon equip its drug inspectors with relevant areas of current Good Manufacturing Practices (cGMP) through online training or skill development workshops.”

Dangi says, “Many FDA laboratories which have reasonable amount of sophisticated analytical instruments find maintenance and calibration as major problems.

Since these instruments have a working life of about five to seven years, availability of spares, after sales service after the guarantee period is over is quite a challenge. It is not the funding which is always the problem. Under the World Bank's capacity building programme, funds to upgrade such labs are available.”

Indian pharma companies are facing a dual problem in not maintaining a qualitydriven process as well as keeping records.

Joag opines, “It has also been observed that the foreign regulators are more conscious about documentation and data integrity while auditing the manufacturing units in India. Moreover, the current complex system of drug regulation is unable to provide users with sufficient assurance that the medicines produced comply with international pharma standards and have issued warning letters even to the leading and multinational Indian companies. Is it not an alarming situation?”

Joag highlights, “Compliance with good manufacturing practice and qualified laboratory testing are essential for the production of quality medicines and independent control. The improved performance of GMP inspectors and official drug control laboratories in India could therefore make a significant contribution to verify the quality of medicines, irrespective of whether these are intended for export or for domestic use.”

Joag concludes and says that the quality of medicines produced in India and the reliability of its system for supervision of manufacturers are of great interest to the global regulatory and public health communities. It is therefore considered that the project will be able to elicit support from many regulatory authorities. The need of the hour is therefore to strengthen the capacity of selected GMP inspectorates and medicines testing laboratories in India to enable them to meet international standards.

Jaishankar suggests, “Government laboratories should be accessible to all tier-II and tier-III cities of each state as well.” u.sharma@expressindia.com

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RESEARCH RESEARCH UPDATES

FDAapproves Otsuka and Lundbeck’s schizophrenia treatment Data from clinical trials showed that brexpiprazole was less likely to cause akathesia, a common side-effect of anti-depressants that leads to distress and restlessness THE US Food and Drug Administration approved Danish drugmaker H Lundbeck A/S and Japan’s Otsuka Pharmaceutical's Rexulti, an anti-psychotic drug used to treat schizophrenia.

The drug, brexpiprazole, was also approved as an adjunctive therapy for major depressive disorder (MDD), a serious psychiatric condition that can lead to persistent feelings of sadness, frustration or anger, the health regulator said. Otsuka Pharmaceutical is a unit of Otsuka Holdings.

The agency based its decision on seven clinical trials, three of which examined the drug’s effect on schizophrenia and four testing it as an adjunctive therapy for MDD. The drug, which will be available in the US in early August, comes close on the heels of Johnson & Johnson getting FDA approval for a longer-acting version of its schizophrenia treatment. Schizophrenia is a chronic, severe, and disabling brain disorder that can cause delusions and hallucinations. It affects about one per cent of Americans, according to the National Institute of Mental Health. At its worst, MDD can lead to suicide, with almost one million lives lost every year, according to the World Health Organization Data from clinical trials showed that brexpiprazole was less likely to cause akathe-

24 EXPRESS PHARMA August 16-31, 2015

sia, a common side-effect of anti-depressants that leads to distress and restlessness. The approval comes at a good time for Otsuka, a unit of Otsuka Holdings. The company’s US patent for a similar anti-psychotic, Abilify, which is sold by Bristol-Myers Squibb Co in the US, expired in April.

Abilify was one of Otsuka’s main revenue drivers. It raked in $2.29 billion worldwide in 2013 before sales fell 12 per cent the following year, according to Bristol-Myers’ quarterly report.

The FDA, in April, allowed four companies, including Israel’s Teva Pharmaceutical Industries, to begin producing generic versions of Abilify for mental illnesses such as bipolar disorder and schizophre-

nia. Otsuka said late last year that it would buy US-based Avanir Pharmaceuticals for about $3.5 billion in its biggest-ever deal to expand its portfolio of neurological drugs before Abilify’s patent expired.

Consensus forecasts from industry analysts point to annual sales of $1.4 billion for brexpiprazole by 2020, according to Thomson Reuters Cortellis, the life sciences division. Other promising schizophrenia drugs in development include Vanda Pharmaceuticals Inc’s Fanapt, which was found effective in a relapse study last month, and Alkermes' aripiprazole lauroxil, which the FDA will decide on in August.

Reuters

Insulin patches could replace injections for diabetics Smart insulin patch can sense the blood sugar level and release insulin at the right time only once the blood sugar goes up A JOINT North Carolina State University and University of North Carolina research project aims to replace insulin injections with an insulin patch.

Dr Zhen Gu, a professor at the schools’ Joint Department of Biomedical Engineering, says the work aims to make administering insulin autonomous for patients.

“Basically we developed this kind of so-called smart insulin patch, which can sense the blood sugar level and release insulin at the right time only once the blood sugar goes up. And the insulin can be quickly released from the patch. Meanwhile once the blood sugar level goes to a normal range, less insulin is released or is just inhibited. Basically this kind of smart insulin patch is not only smart, it is also painless,” Gu says.

For the 21 million Americans diagnosed with diabetes and the more than 387 million world-wide affected by the disease, insulin injections and attached insulin pumps could become things of the past. Gu and others at the lab found a

way to fit more than 100 microneedles onto the patch, which is less than the size of a dime. Each microneedle is filled with insulin and enzymes that can tell when blood sugar levels change.

“Basically we designed this kind of material a polymerbased material, which can be sensitive to blood sugar level changes,” Gu says. “We are trying to mimic the functioning of the beta cells or the vesicles inside the beta cells and they can disrupt once the blood sugar goes up and release insulin quickly.” Currently the patch works for up to nine hours, according to a recent study, but Gu hopes they can design it to last for several days.

This measure, Gu says, will decrease the chance of human error when administering insulin shots, which he says can be imprecise both in location and in the amount of insulin injected.

Administering too much insulin can induce hypoglycaemia when blood sugar levels fall too much. In the worst cases, it could result in death.

The patch has been tested on mice and other animals and so far the results are promising, Gu says.

"We are proud of our technology and we really want to translate it as fast as possible.

Currently, we are working with our collaborators and testing it on animals like mini pigs in a study. If this mini pig study successfully demonstrates it, we will move to the human being testing immediately,” Gu says.

Reuters

Experimental vaginal gel partially protects against genital herpes Women who used tenofovir gel, the annual rate of infection with the genital herpes virus was 10.2 per cent versus a rate of 21 per cent for women who used a placebo gel AN EXPERIMENTAL vaginal gel containing a drug used to treat the AIDS virus could prevent half of cases of genital herpes, according to a study done in South Africa.

Among women who used tenofovir gel, the annual rate of infection with the genital herpes virus, known as herpes simplex virus type II or HSV-2, was 10.2 per cent versus a rate of 21 per cent for women who used a placebo gel. If the gel were to be approved and manufactured, and "if a woman was concerned about acquiring herpes simplex virus type II, this would be the best protection available," Chief Author Dr Salim Abdool Karim of the Centre for the AIDS Programme of Research in South Africa said.

"The problem is, right now it's not available. And taking tenofovir tablets instead of the gel doesn't have the same benefit," he said. "You see some protection with tablets, but the levels of protection are much lower."

HSV-2 virus infects about one in five sexually active adults worldwide, or about 417 million people aged 15 to 49 years old, the study team writes in the New England Journal of Medicine. The virus is the most common cause of genital ulcers, and in South Africa, the estimated infection rate is 50 per cent to 60 per cent. Throughout Sub-Saharan Africa the rate is thought to be as high as 80 per cent in women and 50 per cent in men. Condoms provide the best protection, but even that is limited because the virus can be shed and acquired by other parts of the groin not shielded by a condom, Karim said.

Oral tenofovir is used to prevent and treat HIV. The test of its ability to protect against genital herpes was grafted onto an existing study, which ultimately demonstrated that the gel reduced the odds of getting HIV by 39 per cent.

Among the 422 women enrolled in the herpes study, half were given applicators with the drug-infused gel and the rest were given a placebo gel. They were told to

HSV-2 virus infects about one in five sexually active adults worldwide, or about 417 million people aged 15 to 49 years old insert the gel within 12 hours before they expected to have sex and as soon as possible within 12 hours after sex. The women were tracked for an average of 18 months.

The study results indicate that topical tenofovir can reduce HSV-2 acquisition by almost half, said Dr Connie Celum, Director of the International Clinical Research Center, University of Washington in Seattle.

"This is significant, given the lack of other interventions to reduce HSV-2 acquisition other than condoms," said Celum, who was not connected with the study. The drug worked best among women who used the gel religiously.

When drug levels in the vagina were high, the annual rate of herpes-2 infection was less than six per cent compared to almost 16 per cent when there was no detectable tenofovir in the vaginal fluid. The study did not detail side effects, although an earlier report available online says the drug can increase the risk of mild diarrhoea.

"Because it's in the gel formulation, it leads to very high levels in the genital tract and very low levels in the blood, so very little is absorbed and you get very limited side effects," Karim said. "We did see a slight increase in mild diarrhoea and it wasn't statistically significant."

Reuters

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RESEARCH

Molecular tinkering doubles cancer drug’s efficacy By surrounding molecules of paclitaxel with self-assembling spheres composed of amino acids, the Duke team doubled tumour exposure to the drug compared to Abraxane while simultaneously reducing its effects on healthy tissue RESEARCHERS HAVE packaged a widely used cancer drug into nanoparticles, more than doubling its effectiveness at destroying tumours. The drug paclitaxel has been used for decades to fight breast, ovarian, lung and other cancers. But its effectiveness has been limited by its small molecular size and insolubility in water — properties that allow the body to clear the drug too quickly, reducing its accumulation in tumours.

Many molecular packaging systems have been developed to deliver the drug while counteracting these effects, with a protein-bound version of the drug called Abraxane currently the leading therapy. But Ashutosh Chilkoti, Professor and Chair of the Department of Biomedical Engineering at Duke University, thought his team could do better. By surrounding molecules of paclitaxel with self-assembling spheres composed of amino acids, the Duke team doubled tumour exposure to the drug compared to Abrax-

ane while simultaneously reducing its effects on healthy tissue. This kept mice with tumours alive significantly longer and, in some cases, completely eradicated the tumours.

The big difference between Abraxane and the Duke approach is the types of molecular bonds that are formed. In Abraxane, the paclitaxel is physically surrounded by albumin, a common blood protein.

In the new packaging system, multiple copies of the drug are chemically bonded to an amino acid polypeptide, forming a water-soluble nanoparticle with

the drug hidden in its core.

These nanoparticles are highly soluble in blood and are the perfect size to penetrate and accumulate in tumours where they take advantage of a tumour’s acidic environment.

Jayanta Bhattacharyya, Senior Researcher in Chilkoti’s lab and first author on the paper said, “The chemical bonds holding the polypeptide cage together are stable in blood, but dissolve in a tumour’s lower pH levels. This delivers the drug directly to the tumour and helps prevent it from randomly absorbing into healthy tissue, re-

ducing side effects.” To test their system, Chilkoti, Bhattacharyya and their colleagues used two groups of mice. The first group had human breast cancer growing in their own mammary glands. While none of the mice treated with Abraxane survived past 85 days, most of the mice treated with the new packaging system survived past 100 days. A second group of mice had human prostate tumours growing under their skin. Similarly, while they did not survive past 60 days when treated with Abraxane, every single mouse treated with the new packaging system survived past 70 days, with some experiencing a complete cure.

As the mortality rates suggest, the Duke technology showed a higher concentration of paclitaxel in the tumours with more staying power than Abraxane, while simultaneously showing much lower levels throughout the rest of the mice’s bodies.

EP News Bureau-Mumbai

‘The pill’prevents womb cancer: Study Researchers said an estimated 400,000 womb cancer cases had been prevented by use of the pill in wealthy countries the past 50 years USING AN oral contraceptive, often referred to as ‘the pill’, gives long-term protection against womb cancer and the longer it is used the greater the reduction in risk, scientists said. In an analysis of all available evidence, the researchers said an estimated 400,000 womb cancer cases had been prevented by use of

26 EXPRESS PHARMA August 16-31, 2015

the pill in wealthy countries the past 50 years, including some 200,000 in the last decade.

“The strong protective effect of oral contraceptives against endometrial cancer which persists for decades after stopping the pill means that women who use it when they are in their 20s or even

younger continue to benefit into their 50s and older, when cancer becomes more common,” said Valerie Beral, a professor at Britain’s Oxford University who co-led the study.

For their study, published in The Lancet Oncology journal, Beral’s team pooled data on 27,276 women with endometrial cancer in 36 studies from

North America, Europe, Asia, Australia and South Africa -using virtually all the epidemiological evidence ever collected on the effect of oral contraceptives. They found that for every five years on the pill, the risk of endometrial cancer reduces by about a quarter.

Reuters

MERS vaccine shows promise in animals AN EXPERIMENTAL vaccine for the deadly MERS virus has shown positive results in animal testing, bringing researchers a step closer to a human vaccine regimen.

A two-step regimen of experimental vaccines against Middle East Respiratory Syndrome (MERS) prompted immune responses in mice and rhesus macaques, according to US National Institutes of Health scientists who designed the vaccines. Vaccinated mice produced broadly neutralising antibodies against multiple strains of the MERS coronavirus (MERS-CoV), while vaccinated macaques were protected from severe lung damage when later exposed to MERS-CoV. The findings suggest that the current approach, in which vaccine design is guided by an understanding of structure of viral components and their interactions with host cells, holds promise for developing a similar human MERS vaccine regimen.

Currently, no licensed vaccines are available for MERS, a disease that first appeared in 2012. The research team was led by Barney S Graham, WingPui Kong, and colleagues at the National Institute of Allergy and Infectious Diseases' Vaccine Research Centre.

The investigators used structural information about a viral protein called the spike (S) glycoprotein, which MERSCoV uses to enter cells, to design a number of experimental vaccines that they administered to mice in a two-step regimen involving an initial ‘priming’ injection followed several weeks later by the same or a different 'booster' vaccine.

PTI

PHARMA TECHNOLOGY REVIEW

Unsung heroes of pharma industry Chemical engineers have been significant contributors to Indian pharma’s success story, yet they have been denied their much-deserved share of recognition

By Sachin Jagdale

R

ising competition in domestic and global markets, accompanied by highly stringent regulatory norms have made it necessary for the pharma industry to shorten drug development time without compromising on quality. Since, chemicals are unavoidable constituents of drug development processes, chemical engineers have key roles to play in this scenario. Industry experts consider chemical engineers vital to the success that’s been achieved in scaling up the drug development process in India and across the world.

Priceless contribution Chemists have always been seen as the face of the pharma sector. Yet, on many occasions, chemical engineers are the ones who are supporting them from behind the scenes as they possess experience in multiple disciplines like mathematical modelling, reactor design, equipment design, scale up phenomena, safety analysis, rate and equilibrium processes, reaction rate analysis, fluid dynamics etc. Though pharma industry

is not the largest employer of chemical engineers, the contribution of the available lot of engineers to the drug manufacturing companies cannot be ignored.

“Pharma industry requires continuous R&D to develop different products and molecules. This requires a lot of primary work on pilot plant/bench scale for developing the most feasible and economical process to get best conversion and yield. Chemical engineers play an important role using scale up techniques to arrive at plant scale model with optimised power utilisation and achieve same results as found in pilot scale,” informs Prakash Purandare, Consulting Chemical Engineer

Role in reducing drug prices Pharma industry is always under pressure to reduce drug prices. In a pricesensitive market like India, this issue becomes even more pertinent. If the pharma industry manufactures drugs in an economical way, it will definitely help to avoid hassles while deciding the price of the final product. This is where chemists can rely upon

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PHARMA TECHNOLOGY REVIEW chemical engineers.

The common observation is that many life savings drugs are very costly. But, actual manufacturing costs could be much less. However, according to Purandare, drug prices are not just dependent on manufacturing cost, but rather on its technology cost, monopoly of product and its demand and supply.

He informs, “Chemical engineers have a major role in utility cost reduction and developing innovative ideas. Heat recovery is a very common, simple approach to reduce utility/fuel cost. From a chemical engineer’s point of view, manufacturing cost, mainly utility cost, can be reduced by studying different heating/cooling time cycles for peak utilisation of available utilities. Operations can also be staggered for best utilisation of equipment/utilities.

Hot water/steam/hot air generation via waste heat is very common. But it may not be a strange idea to cool reactors/process coolers with other process media. Solvent recovery has always been a major contributor to cost reduction. Most of the solvent recovery plants in pharma industry are batch operated.

There is huge cost saving in both initial and running costs if converted into continuous.”

He adds, “Major cost reduction would be to convert water

Chemists have always been seen as the face of the pharma sector.Yet, on many occasions, chemical engineers are the ones who are supporting them from behind the scenes as they possess experience in multiple disciplines like mathematical modelling, reactor design, equipment design, scale up phenomena, safety analysis, rate and equilibrium processes, reaction rate analysis, fluid dynamics etc cooled coolers with air-cooled finned tube coolers wherever possible. This will dramatically reduce not only initial installation piping, insulation and civil cost but also maintenance cost on circulation pumps, valves etc. Pharma manufacturing till today is manually operated at different stages, being batch plants. But, many manual operations can be switched over to maximum possible automisation. Transfer times are a key area to be looked at where lot of valuable production time is wasted. It can be improved by enhanced conveying methods.”

There are a few more ways through which chemical engineers can help minimise the drug prices. They can opti-

mise reaction condition to minimise raw materials and maximise product. Process intensification is also very important which allows maximum yield of product, simple process with lesser unit operations and less waste generation.

A chemical scientist from a reputed petrochemical company in India, on the condition of anonymity, opines, “Chemical engineer has a crucial role to play when chemists develop a process and it is not possible to scale up some of the steps.

His suggestions should be taken during process development from engineering perspective. Chemical engineer's involvement is useful in getting optimum process.”

In the quest of due recognition Despite the long list of services that chemical engineers offer to pharma companies, they often do not receive their due in the industry. Why is it so?

“Pharma plants are mainly operated batch wise and have multi-purpose facility. Once a plant is installed and process is stabilised, chemical engineers may not have a significant role other than monitoring day-today operations. However, there is huge potential on heat recovery, innovative unit operations and utility optimisation where chemical engineers can put their expertise and improve on production cost,” explains Purandare.

Pharma companies are

mainly dominated by the chemists who have an expertise in chemistry. However, as per experts, big players in pharma do have separate technology transfer or scale up divisions. On the other hand, a very common observation is that medium and small scale companies generally do not employ chemical engineers and hence processes there are mostly unoptimised and give less product. Sometimes lack of knowledge and ignorance also make chemists to not involve chemical engineers in the processes.

Conclusion The Indian pharma industry is in the transition phase. Its ambitious plans of making a shift from generic to innovation driven industry need to be backed by skills of chemical engineers. The petrochemical industry is the biggest employer for the chemical engineers.

Surprisingly, the Indian pharma industry, which is third largest by volume in the world and also one of the leading chemical-dependant industries, employs negligible number of chemical engineers. For its own good, it's high time for the Indian pharma sector to become more appreciative of the role of chemical engineers in its progress and growth. sachin.jagdale@expressindia.com

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services introduced by your organisation for our various sections: Pharma Ally (News, Products, Value Add), Pharma Packaging and Pharma Technology Review sections. Related photographs and brochures must accompany the information. ❒ Besides the regular columns, each issue will have a special focus on a specific topic of relevance to the Indian market. ❒ In e-mail communications, avoid large document attachments (above 1MB) as far as possible. ❒ Articles may be edited for brevity, style, and relevance. ❒ Do specify name, designation, company name, department and e-mail address for feedback, in the article. ❒ We encourage authors to send their photograph.

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PHARMA TECHNOLOGY REVIEW I N T E R V I E W

‘Alfaa UV is the undisputed leader in Industrial UV systems in India’

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Alfaa Biopure Series UV systems help provide bacteriologically safe water of the highest possible standards and systems as demanded by regulatory bodies such as US FDA quality procedures, including current Good Manufacturing Practices (cGMP).

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Since water quality plays a critical role in the manufacture of pharma products, (90 per cent of the product is water) it needs to be bacteriologically pure at all times, especially during the process.

Normally it takes 48 hours to know if the water is safe (bacteriologically), by which time the batch is already manufactured. In effect it becomes a post mortem to know if a batch has

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Can you explain the concept of a microprocessor controlled water purifier?

The user-friendly digital controller provides extensive functionality and data logging capabilities. It can be easily interfaced to SCADA systems to extend functionality. It helps the customer know how many hours the UV lamp has been used and when it is due for replacement. This ensures that the customer replaces the lamp at prescribed intervals.

Coupled with the UV Monitor,

30 EXPRESS PHARMA August 16-31, 2015

(which is the online validation tool), it ensures that the water quality meets its requirements with reference to the absorption coefficient (transmission of UV). It also detects whether the UV intensity has gone down due to low voltage; low or high water temperature; or ionic salts which absorb UV. In short, the digital controller, coupled along with the UV intensity monitor, is vital to help the customer know the proper functioning of the UV system.

Who are your pharma clients?

Practically every company in the pharma and bio-pharma industry relies on Alfaa UV for disinfection of process water.

Some prominent pharma players like Dr Reddy’s Laboratories, Johnson & Johnson, Cipla, Ranbaxy, Alchem, Wokhardt, Smithkline Beecham, Bayer, and Sun Pharma are satisfied Alfaa UV

Practically every company in the pharma and biopharma industry relies on Alfaa UV for disinfection of process water users, amongst several others, and have installed our purification systems across most of their manufacturing plants.

What is your market share in India?

Alfaa UV is the undisputed leader in industrial UV systems in India with a market share of

70 per cent. In the pharma sector Alfaa UV’s market share is as high as 90 per cent.

What percentage of your revenue comes from the Indian market?

80 per cent of our revenues come from the Indian market.

Exports are growing at a rapid pace too.

How will you differentiate yourself from your competitors?

We are the only company to provide UV systems which have been designed from ground up to specifically cater to the high purity water distribution loops in pharma manufacturing units. The systems are optimised to provide high UV doses in an extremely small footprint utilising high output UV lamps.

The Biopure Series UV Systems incorporate unmatched features such as online UV dose, sanitary vessel

and sensor design, remote lamp operation, dual remote feedback to plc, plus many more sophisticated and advanced features for total safety, reliability and real time monitoring during the process.

Apart from this, an excellent service backup throughout India ensures that the downtime for the systems is the least, and that the systems function at their peak.

Besides the pharma industry, which are the other industries you cater to?

Alfaa UV systems are the preferred choice of the food and beverage industry, marine foods, mineral water, poultry, distilleries, cosmetic industry, bulk drugs, hospitality sector, paint industry, automobile industry, hospitals, construction industry, and in the recycle and reuse of waste water, across all industries and commercial complexes. sachin.jagdale@expressindia.com

PHARMA TECHNOLOGY REVIEW VALUE ADD

Quality by design Dr Philippe Solot, Chief Executive Officer, AICOS Technologies emphasises on experimental design with the software package Stavex to achieve best results while developing a pharma product

QUALITY BY design means to design a process from its development onwards so as to avoid the later occurrence of major problems, shall it be during the scale-up or the production. A pharmaceutical product has been developed with a lot of effort, the formulation is correct, even the authorisation of FDA is available — and then, at the scale-up, the desired API dissolution profiles cannot be achieved anymore.

The support team of the company Glatt is often confronted with such scenarios. It supports its customers from the selection of the appropriate technology to the development of the final production process, as it has been the case in the example just described. The pharma product consisted of modified release (MR) pellets.

The pellets are spray-coated, whereby the second last layer controls the dissolution dynamics (Figure 1). The API delivery should be pulsatile and occur after eight hours.

Unfortunately, many factors influence the product quality. Some effects may be predictable (e.g. yield or agglomeration rate) but one cannot really predict how the agent release will behave depending on the process parameters.

Common problems with the processing of modified-release coatings, which are like here based on aqueous dispersions, are in particular due to the stickiness of the coating materials as well as to the adjustment of the optimal film forming temperature. The expert team at Glatt takes a systematic approach. Overall, a pro-

duction process should be designed in such a way that it is reliably reproducible and as robust as possible against process fluctuations. And therefore the scale-up process should run as fast and as easy as possible – and with a manageable number of experiments. For a commercial production, attention should be paid not only to the product quality, but also to an efficient and hence economical production method. This is why Glatt makes a point of evaluating and testing all possible problems already during the process design, even for product and process development at a small scale. In case something has to be corrected later on, the effort is much higher.

DR PHILIPPE SOLOT, Chief Executive Officer, AICOS Technologies

The spray pressure for the coating liquid, however, has no noteworthy effect on the product quality ‘API release’ Figure 1: Wurster fluid bed process toproduce modified-release pellets

DISSOLUTION PROFILES FROM A MULTIFACTORIAL DESING STUDY

Figure 2: Dissolution profiles for the experimental conditions analysed. The blue curves lie within specifications for the pulsatile API release of the modified-release pellets after eight hours

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PHARMA TECHNOLOGY REVIEW Efficient approach using design of experiments First, the critical limits of the production processes are evaluated in preliminary experiments. The aim is to be able to choose the parameter setting in the subsequent optimisation experiments in such a way that all experiments are feasible. There are some parameters like the system or nozzle configuration, for which the effect can be estimated in advance. However, in the present case, four factors remain, the influence of which on the future quality of the pharma product is critical and requires a thorough analysis.

The volume of the fluidised air flow influences the product fluid bed and the atomisation pressure influences the yield as well as the agglomeration behaviour. The inlet air temperature and the spray rate of the coating liquid influence in turn the stickiness of the coating layers. It is now necessary to examine how these factors are linked to each other.

For the closer examination, design of experiments comes into play. If the number of experiments should not escalate out of control, a systematic simultaneous variation of several factors of influence is only possible with the support of a software. Due to the easy handling, the well comprehensible analysis reports and the clear project documentation, Glatt has decided on the software package Stavex of Aicos Technologies.

One only has to input the response variables and the factors, and the software then proposes an experimental design, in this case with 19 experiments. Already this small design allows to analyse the influence of all four factors and of their interactions and to identify optimal settings.

In the case that various experimental designs are possible, these are automatically evaluated and presented with comments by Stavex. The user can simply follow the proposal of Stavex and choose the design recommended. Another option can also be taken. At this point like at many others, it is possible to modify the procedure according to individual priorities.

32 EXPRESS PHARMA August 16-31, 2015

Figure 3: 4D-graph generated by Stavex. X-axis: fluidised-air volume, y-axis: product temperature, z-axis: inlet air temperature; the response variable “API release after eight hours” is coded in colour. The colour scale ranges from two per cent (red) to 65 per cent (violet). The target value is 10 per cent. The area concerned (orange) is represented separately (right picture) in form of an iso-surface

For a commercial production, attention should be paid not only to the product quality, but also to an efficient and hence economical production method may lead to an even better behaviour.

Overall, in the case presented, one obtains that it is advantageous to work with a high fluidised air flow at moderate temperatures (Figure 3). The spray pressure for the coating liquid, however, has no noteworthy effect on the product quality ‘API release.’ The system, and therefore the product quality, thus react sensitively to changes in the factor settings.

Experimenting in a planned and controlled way

Figure 4: Experimental effort during various phases of a process development project of Glatt. By applying early targeted Design of Experiments the experimentation at production scale can be reduced to a minimum

In the application just described, all factor ranges could be defined quantitatively. For the software, however, qualitative factors (e.g. type of nozzle 1 to 5) constitute no obstacle. A further specialty of Stavex is the handling of mixture factors, i.e. of factors that have to sum up to 100 per cent or 20 mg. Stavex even allows several mixture classes, which is in particular useful in galenics.

Practical restrictions like “at a high temperature the spray pressure has to be increased” or alternative factors (either filler 1 or 2, either batch size 35

kg with a drying time of one to two days or 40 kg with a drying time of one to three days) can very easily be taken into account.

Optimisation of the dissolution dynamics In order to examine the dissolution behaviour of the API contained in the pellets, one registers its release curve. The API release is characterised by the corresponding values, obtained after 6, 8, 10 and 12 hours, as well as by the value t50 per cent. Besides, response variables can also be specified qualitatively.

Such a qualitative value can be the integrity of the coating film.

In order to appreciate globally, the compliance to specifications of several response variables, a so called desirability function can be defined in Stavex. In this way, an optimal compromise setting can be determined automatically. Figure 2 represents dissolution profiles obtained with different experimental settings. Those dissolution curves that fulfill the specifications are marked in blue. However, the optimum calculated by Stavex can be different, since another combination of factor settings

The combination of the experience and the expertise of the process developers at Glatt with a powerful design of experiments system like Stavex allows a fast and efficient process optimisation. If the quality is already ensured at the design phase, unpleasant surprises during the scale-up can be avoided.

Figure 4 shows, using a typical project of Glatt, how the scale-up process can be run with very little effort by applying early design of experiments.

Moreover, this methodology, the controlled and planned experimentation, enables to gain advanced knowledge of products and processes. In the project described, the influence of the parameter setting on the agglomeration behaviour as well as on the dissolution kinetics could in particular be examined and clarified in detail.

PHARMA TECHNOLOGY REVIEW WHITEPAPER

Extractables and leachables from glass Dr Bettine Boltres, Product Manager, Pharmaceutical Tubing, SCHOTT, Germany in this white paper, touches on a risk-based approach of the evaluation and describes important facts to consider when assessing extractables and leachables from glass OVER THE past years the increased development of biopharmaceuticals is making ever higher demands of the packaging components. The biologically developed drug formulations growing in the areas of therapeutic proteins, vaccines and monoclonal antibodies exhibit much higher sensitivities towards any foreign substances and changes in environment than the chemical drugs do. Additionally the liquid formulations containing surfactants, salts and chelating agents coupled with ever lower drug levels placed a global focus on the interactions between the formulation and the packaging material and thus the whole container closure system.

Determination of potential extractables and / or leachables became part of the process validation when filing new drug applications.

Both the EU and the US regulations state, “Equipment shall be constructed so that surfaces that contact components, inprocess materials, or drug products shall not be reactive, additive, or absorptive so as to alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements”[1] [2] [3]. This regulation applies to all materials including metals, glass, and plastics. A good introductive overview can be gained from a BPSA publication[4]. Other recently published guidelines reflect the increased focus: USP <232> and ICH Q3 for “elemental impurities” and USP <1663> and <1664> for extractables and leachables [5] [6] [7] [8].

Polymers are considered to have a high potential interaction with the product. However, other materials, often considered to be inert, such as glass or stainless steel, were shown to release substances into the drug

formulation.

The FDA’s Final Report on Pharmaceutical cGMPs for the 21st Century — A Risk-Based Approach[9] provides clear guidance on utilising scientifically sound, risk-based approaches to pharmaceutical cGMP requirements. Basically a risk-based approach means that drug container closure systems should not be evaluated according to the same procedure but on an individual basis. Furthermore, it is recommended to initiate this as early as possible in the development process when changes can be addressed more easily. Effective science- and risk-based assessments are best done from a foundation of comprehensive process knowledge, which is key to quality by design principles[10] [11] [4] . Starting with a risk-based approach at a very general level throughout the whole medical drug product range there is already a difference in the degree of concern and the likelihood of interactions of the drug with the container.

Oral tablets having a small manner of interaction with the packaging material pose just little concern whereas injectables having a high exposure to the primary packaging material surface pose the highest concern.

Focusing on injectables there are also several factors influencing the risk of creation of extractables and leachables. The highest risk is posed by a large volume medicine that is administered on a daily basis and is coming from a storage packaging material.

Table 2 shows a very structured risk-based approach.

In order to set up a compatibility study the definitions have to be clarified even more so as they have changed over the past years due to a gain in experimental knowledge.

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DR BETTINE BOLTRES, Product Manager, Pharmaceutical Tubing, SCHOTT, Germany

● Oxygen ● Silicon ● Boron ● Sodium ● Calcium, ● Aluminum ● Hydrogen

TABLE 1: DEGREE OF CONCERN AND LIKELIHOOD OF INTERACTION FOR COMMON CLASSES OF DRUG PRODUCTS [2] Likelihood of drug container interaction Degree of concern

High

Medium

Low

Highest

Inhalation aerosols and solutions; injections and injectable suspensions

Sterile powders and powders for injection; inhalation powders

None

High

Ophthalmic solutions and suspensions; nasal aerosols and sprays

none

None

Low

Topical or oral solutions and suspensions

Topical or oral powders

Oral tablets and capsules

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PHARMA TECHNOLOGY REVIEW Extractables Components of a certain packaging material that are released during a certain stress test procedure (e.g. aggressive solvents, exaggerated conditions of time and temperature).

Extractables are determined by exposing components or systems to conditions that are more severe than normally found in a biopharmaceutical process, typically using a variety of solvents at high temperatures. The goal of an extractable study is to identify as many compounds as possible that have the potential to become leachables [10].

Leachables Components of the container closure system that are migrating into the drug formulation during usual production process and storage. Up to now it was believed that leachables are a subset of extractables. Nowadays, it has become more clearly that there is a possibility of the occurrence of leachables that are not detected by the usual extractables screenings e.g. because they form under special and different conditions between the drug formulation and some material components. It is thus not recommended to rely solely on extractables data.

It is important to keep in mind that the concentration of a leachable in the final drug product is not as important as the dosage that is accumulated by the patient. The acceptable concentration of a leachable is higher for a 1 mL injection than for a 1000 mL transfusion. In other words, the concentration of the leachable in the 1 mL injection could be 1000 times higher and achieve the same dosage of the leachable (Table 2). Therefore, when addressing leachables from processing materials, the concentration measured during a leachables test must be translated to a final dosage level in the drug product [10].

Whether or not extractables and leachables are present at a level that might cause safety concerns should be reviewed by qualified toxicologists. As for the quality of the product it is important to know the potential leachables because some compounds can also affect product efficacy and stability.

However, to address these

34 EXPRESS PHARMA August 16-31, 2015

TABLE 2: RISK ASSESSMENT FOR LEACHABLES RELATED TO DOSAGE ACCUMULATED BY THE PATIENT [10] Factor

Low risk

High risk

Dose-related

Dosage volume Dosage frequency

1 ml Once per incident (acute)

1000 ml Daily (chronic condition)

Process-related

Contact area per volume of drug product

Large bag, filter or connector

Small bag

Contact time

Minutes (transfer tubing or connector)

Months (storage bag)

points it is most important to possess an in depth knowledge about the whole process and its interacting parameters.

Borosilicate glass has a distinct and known composition with a defined set of potential extractables and leachables.

In general borosilicate glasses consist of the following elements: ◗ Silicon ◗ Oxygen ◗ Boron ◗ Aluminum ◗ Sodium, potassium ◗ Calcium, magnesium, barium Depending on the type and manufacturer this can vary. For light protection iron and titanium or manganese are added.

As the nature of potential extractables and leachables from glass is known the amount being released from the glass is rather the question. However, this question can be neither be answered easily nor generally. As often the case for glass interactions it depends on a lot of different simultaneously occurring factors.

These factors are among others: ◗ Glass composition ◗ Converting process: Flames and temperatures, burner gases, climatic conditions, materials that are in contact with the glass during formation, like steel or tungsten parts; washing, drying, annealing oven ◗ Container size / volume ratio (concentration of extractables and leachables decreases with increasing container size due to a smaller surface area which is in contact with the solution) ◗ Pretreatments: Surface treatments can significantly change the appearance of extractables and leachables ◗ Rubber components: They can interact with a glass component ◗ Drug product: pH value, complexing agents, buffers, solvents,

salts ◗ Storage and transportation conditions; time, temperature, humidity, impact of light ◗ Pharmaceutical process: washing process, drying, sterilisation process, stopper material Borchert et al. describe an extractables study in their paper performed on borosilicate glass containers[12]. They were monitoring different elements as well as the pH shifts and the total extractables. As a solvent they used unbuffered (pH 4.0, 6.5, 8.0.

9.5, 10.4) and buffered (pH 8.0, 10.0) aqueous solutions. The containers they used were from different global suppliers both tubing and molded. All glass components could be found in different concentrations. In addition rubber components could be identified as well (Na, Ca, Mg, Zn, Ti).

Bohrer performed the glass grains test using solutions of some inorganic salts like NaCl, KCl, CaCl2, MgCl2, NaHCO3, NaH2PO4, KH2PO4, sodium gluconate, citric acid and glucose.

She also found the whole variety of glass components in the solution in a range of 8.8 to 33 ppm for silicate, 0.9 to 6.9 ppm for borate and 0.5 to 2.4 ppm for aluminum and confirmed that the basic solutions of NaHCO3 and gluconate extracted the highest amount of glass components[13] [14].

As easily visible evaluating processing and packaging materials for extractables and leachables requires co-operation between vendors and end-users and a commitment to utilise the best science possible within a risk-based framework.

Additionally it becomes clear that a summation of the individual extraction values of each packaging material does not lead to a complete picture.

Rather it is necessary to per-

● Al Aluminum ● B Boron ● Ba Barium ● Ca Calcium ● Cl Chloride ● F Fluoride ● Fe Iron ● K Potassium ● Mg Magnesium ● Na Sodium ● Si Silicon ● Ti Titanium ● Zn Zinc

form the studies on the final product container closure system in order to receive realistic values.

References [1] European Comission of Glass, "Good Manufacturing Practices, Medicinal Products for Human and Veterinary Use," 2010.

[2] FDA, „Guidance for Industry.

Container Closure Systems for Packaging Human Drugs and Biologics,“ 1999.

[3] US Government Printing Office, "Equipment construction," CFR, Code of Federal Regulations, Food and Drugs, Title 21, p. Part 211.65, 2010.

[4] BPSA, "Recommendations for Extractables and Leachables Testing Part 2: Executing a Program," BioProcess International, vol. 6, no.

1, pp. 44-53, 2008.

[5] USP 36, NF 31, Chapter <232>, Elemental Impurities - Limits, United States Pharmacopeia, 2013.

[6] ICH Q3D, Guidlines For Elemental Impurities, International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use, 2013.

[7] USP 36, NF 31, Chapter <1663>, Assessment of Extractables associated with Pharmaceutical Pacakging / Delivery Systems, United States Pharmacopeia, 2013.

[8] USP 36, NF 31, Chapter <1664>,

Borchert et al: Reaction of different elements on borosilicate glass containers

Assessment of Drug Product Leachables associated with Pharmaceutical Packaging / Delivery Systems, United States Pharmacopeia, 2013.

[9] FDA, Pharmaceutical cGMPs for the 21st Century - A Risk-Based Approach, Final Report, 2004.

[10] D. Bestwick und R. Colton, „Extractables and Leachables from Single-Use Disposables,“ Bd. 7, Nr. S1, pp. 88-94, 2009.

[11] BPSA, „Recommendations for Extractables and Leachables Testing, Part 1: Introductin, regulatory Issues and Risk Assessment,“ BioProcess Int., Bd. 5, Nr. 11, pp. 36-44, 2007.

[12] S. J. Borchert, M. M. Ryan, R. L. Davison and W. Speed, "Accelerated Extractable Studies of Borosilicate Glass Containers," Journal of Parenteral Science & Technology, vol. 43, no. 2, pp. 67-79, 1989.

[13] D. Bohrer, „Containers,“ in Sources of Contaminantion in Medicinal Products and Medical Devices, 1. Hrsg., John Wiley & Sons, Inc., 2013, pp. 185-227.

[14] D. Bohrer, P. C. do Nascimento, E. Becker, F. Bortoluzzi, F. Depoi and L. M. de Carvalho, "Critical Evaluation of the Standard Hydrolytic Resistance Test for Glasses Used for Containers for Blood and Parenteral Formulations," PDA Journal of Pharmaceutical Science and Technology, vol. 58, no. 2, pp.

96-105, 2004.

PHARMA TECHNOLOGY REVIEW INSIGHT

Coming soon: New qualityregulations worldwide for botanical materials Dilip Charegaonkar, Managing Director, Anchrom Enterprises (I) talks about the effectiveness of HPTLC to know about the chemical fingerprint of a botanical material extract

PHARMACOPOEIAS of the US, Europe, the UK and others have decided to add 'HPTLC fingerprint' as a mandatory test for 'identification of materials of botanical origin' and for 'fixed' oils (i.e. vegetable oils).

An established chemical analysis method, High Performance Thin Layer Chromatography (HPTLC) , gives an idea about the chemical fingerprint of an extract of a botanical material, without identifying the chemicals present.

HPTLC 'fingerprints' are unique too and not only establish the identity but also ensure the presence or absence of adulterants, substitutes, similars etc. Since materials of botanical origin are extremely complex, the HPTLC identification test is designed, both to ensure the identity of product by multiple ways of evaluation and the absence of adulter-

DILIP CHAREGAONKAR, Managing Director, Anchrom Enterprises (I)

ants, substitutes etc. HPTLC was chosen as the method of choice because it is extremely simple to perform, yet gives a lot of information about the sample at a low cost. A proper fingerprint can also be used for quantification of 'chemical marker' substance(s) which is usually done to determine commercial value, in the Western world, markers cannot be used for identification. Sophisticated instrumentation is required for HPTLC analysis, which meets the regulatory and good laboratory practices (GLP) requirements.

'Botanical origin' obviously refers to herbal medicines, spices, essential oils, and numerous foods such as vegetable oils, dried fruits, saffron, tea, coffee, natural colours etc. This makes it a very relevant test, especially for our exports worldwide.

India should prepare itself to meet this new requirement by creating HPTLC fingerprints. After August 1, a foreign buyer can ask for a fingerprint of e.g. basmati rice to distinguish it from long grained rice. We need to aggressively safeguard our interests in the worldwide markets, especially for our traditional exports by studying these regulatory changes and creating suitable HPTLC fingerprints proactively.

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PHARMA TECHNOLOGY REVIEW VENDOR NEWS

IKA-Werke bags most innovative medium-sized biz award in Germany Award presented at the German SME Summit in Essen IKA-WERKE KG has been recognised as one of the most innovative medium-sized businesses in Germany at the German SME Summit in Essen.

'Top 100' mentor Ranga Yogeshwar honoured the company with the seal of approval: IKA-Werke is 'Top 100 Innovator' for the third time in a row and in 2015, reached second place in the category for companies with over 250 employees.

The company, based in Staufen im Breisgau, employs over 800 people at eight locations on four continents.

President and Owner, René Stiegelmann is always coming up with new ideas. He allots 70 per cent of his working hours to innovation activities. "We

set high standards for the functionality and durability of our products. That is why we constantly strive to improve on what we have achieved,” explains Stiegelmann.

Since customer requirements can be very specific, the company needs highly customised innovation processes.

For example, if customers cannot find a suitable solution in the

existing IKA product portfolio, they can contact the customising centre. In this department, engineers will assess the feasibility of a customer request.

Processes can be realistically simulated and presented to the customer on a small scale by using one or more of the several pilot systems. In the Application Support Lab, customers can learn more about the devices suitable for their applications or experiments. Good ideas and their rapid implementation are a key competitive factor for us.

This is why we invest a great deal of time and money in our innovation management processes. As part of this, we rely on the wealth of ideas that come from all of our employees. I

would like to thank them all for helping us achieve the 'Top 100 Innovator' award,” explains Stiegelmann.

The 'Top 100' seal of approval is awarded after a two-stage review process developed by Dr Nikolaus Franke and his team from the Institute for Entrepreneurship and Innovation at the Vienna University of Economics and Business Administration.

Analysts investigate the innovation management processes and their success using over 100 parameters across five categories.

The decision on which mediumsized company is awarded the ‘Top 100’ seal of approval is solely made by the analyst panel.

EP News Bureau-Mumbai

Exco InTouch granted US patent for mDNA technology mDNA is an automated management tool that identifies, distributes and manages patients and their mobile device interactivity in clinical and healthcare programmes EXCO INTOUCH, provider of digital patient engagement and data capture solutions for clinical research and healthcare providers, has been granted a US Patent corresponding to its mDNA technology.

It is an automated management tool that seamlessly identifies, distributes and manages patients and their mobile device interactivity in clinical and healthcare programmes.

Reportedly, mDNA provides study managers, sponsors and healthcare providers with effec-

36 EXPRESS PHARMA August 16-31, 2015

tive control over the environment in which patients interact with mobile data capture services, thereby offering device management benefits for traditional, fully provisioned clinical trials. In addition, by managing each patients’ interactions within defined parameters, mDNA overcomes the perceived barriers to the adoption of bring your own device (BYOD) in clinical trial and healthcare settings.

Through its ability to identify the patient device in use and manage the system response accord-

ingly, mDNA ensures consistency of display and content in a BYOD environment, thereby enhancing the familiarity and usability of mobile technology for each participant.

In addition to these benefits, mDNA facilitates the remote maintenance and update of eCOA (electronic Clinical Outcome Assessments) and ePRO (electronic Patient Reported Outcomes) solutions. Furthermore, mDNA manages and protects personally identifiable information (PII), creating

unique identifiers for each user and removing the requirement for PII to be stored within the system. This provides confidence in the management of data which is fully compliant with data security and regulatory guidelines including EU data protection, Safe Harbor and HIPAA. Tim Davis, Chief Executive Officer and Founder, Exco InTouch said, “We are excited by the addition of the US patent for our ground-breaking mDNA technology to our mar-

ket leading patient engagement portfolio.”

He further said, “With the granting of this patent, we look forward to continuing to bring its wide ranging benefits to bear for patients, sponsors and healthcare providers, and leading the industry in providing secure and engaging mobile solutions that improve the patient experience in clinical research and healthcare programmes.”

EP News Bureau-Mumbai

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PHARMA LIFE AWARDS

Merck Serono awards € 20,000 to Innovation Cup Winners Merck Serono Innovation Cup 2015 awards novel idea for a new innovative hypoxia activated prodrug approach for the treatment of cancer

MERCK SERONO, the biopharmaceutical business of Merck, recently announced the winners of the 2015 Innovation Cup – a programme that underscores the company’s commitment to developing the next generation of biopharmaceutical talents and discovering promising approaches to new medicines. An oncology team, consisting of PhD and post-doctoral researchers, won the Innovation Cup trophy and € 20,000 for their idea to create an innovative hypoxia activated prodrug approach for the treatment of cancer.

The members of the 2015 Innovation Cup Winning Team are Francis Hunter from University of Auckland, Wang Shan from Tsinghua University, Jia Lin from Tsinghua University, Kshitij Srivastava

from German Cancer Research Center (DKFZ), Heidelberg, Sotirios Sotiriou from University of Geneva, Oliver Thorn-Seshold from LMU München, Arne Sutter, the coach.

During a week-long Innovation Summer Camp, 31 participants gathered to learn the essentials of drug discovery and development in a highly stimulating and competitive environment. Working together in six teams of high diversity, students generated new ideas in the areas of oncology, immuno-oncology, autoimmune diseases, chemo- and bioengineering, medical devices/electronic health and innovations for emerging markets, receiving guidance and support from Merck Serono coaches to turn their ideas into business plans.

To subscribe: bpd.subscription@expressindia.com

At the end of the week, teams presented their proposals to a jury consisting of senior Merck managers and external experts.

Dr Ulrich Betz, Department Head Innovation & Entrepreneurship Incubator at Merck Serono, initiator and manager of the Innovation Cup said, “For the fifth year in a row, we are excited to work with bright young students from around the world to uncover the next great innovation in medical science. Participants are given the opportunity to work with Merck Serono professionals and to learn how drugs are successfully discovered, developed and brought to market to benefit patients in need.”

EP News Bureau-Mumbai

Lauras Labs’CEO gifts ` 1.5 crore grant to ISB Dr Chava is an alumnus of the ISB's founding PGPMAX class AN ALUMNUS of the the Hyderabad-based Indian School of Business's (ISB) founding class of Post Graduate Programme in Management for Senior Executives (PGPMAX), Dr Satyanarayana Chava, Chief Executive Officer, Laurus Labs has agreed to contribute a monetary grant through his company, to enhance the quality of teach-

“ISB alumni are our brand ambassadors and standard bearers. They contribute to the school through 'Work, Wisdom and Wealth'.

Chava is an inspiration for all of us. He has created a very successful business, and is passionate about contributing to social causes.

On behalf of the ISB community, I thank him for his generosity.”

This is his second contribution to his alma mater, with his earlier contribution aimed at supporting the ‘Technology Commercialisation Programme’ for scientists at ISB. An MoU was signed on July 21, 2015, between Laurus Labs and ISB ing and research by funding ` 1.5 crore spread over three years.

This is his second contribution to his alma mater, with his earlier contribution aimed at supporting the ‘Technology Commercialisation Programme’ for scientists at ISB. A Memorandum of Understanding (MoU) was signed on July 21, 2015, between Laurus Labs and ISB represented by Chava and Ajit Rangnekar, Dean, ISB respectively.

Speaking about the collaboration, Rangnekar said,

Chava, who has track record of 26 years in the pharmaceutical industry, especially in research and development, manufacturing and business development, considers this an investment in the future through ISB. "It is my belief that the value of any great institution like ISB comes from three angles – its faculty, its students and the learning environment that it provides. We decided to invest in the first and contribute to building the faculty,” he commented.

EP News Bureau-Mumbai

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PHARMA LIFE APPOINTMENT

SIRO Clinpharm appoints Dr Vatsal Shah as COO Vatsal will be responsible to ensure seamless delivery of SIRO’s integrated services SIRO CLINPHARM has appointed Dr Vatsal Shah as the Chief Operating Officer, who has been with the company for over three years. Vatsal will be located at the company headquarters in Mumbai, and, as a new COO, he will be responsible to ensure seamless delivery of SIRO’s integrated services of clinical operations, medical writing, clinical data management, biostatistics and programming, pharmacovigilance, and clinical trial supplies management.

With over 18 years of experience encompassing all clinical research services across diverse industry spaces of pharmaceutical companies, CROs and KPOs,

Vatsal was a key member to create and lead one of India’s largest medical writing teams in his stint with Novartis, as well as with SIRO, the most notable and major feats the industry has seen in the country.

Dr Gautam Daftary, Founder and Chairman, SIRO Clinpharm said, “It was only natural to have Vatsal lead SIRO’s operations given his achievements and his vision for the company. I am elated that he has taken over this new responsibility, and the team is very excited to see the change he has in store for us. I am assured that under his distinct leadership and direction, the entire team of SIRO will soar to

He has over 18 years of experience encompassing all clinical research services across diverse industry spaces of pharmaceutical companies greater heights of success worldwide.”

Vatsal said, “SIRO is ready to embark upon a new trajectory and I’m thrilled to lead the company to its next phase of innovation with operational excellence.

In this age of revolutionary technology and dynamic clinical re-

search and marketing needs, SIRO hopes to achieve service brilliance in the form of flexible solutions, upgraded know-how and domain excellence, laced with project management and governance to ensure delivery success.

EP News Bureau-Mumbai

OBITUARY

Dr Suniti Solomon,pioneer in HIVresearch and treatment in India,passes away She set up the first voluntary testing and counselling centre and an AIDS Research Group in Chennai while serving at the Madras Medical College DR SUNITI SOLOMON, whose team was the first to document evidence of HIV infection in India in 1986, recently died at her residence in Chennai. A pioneer in treating HIV patients since the 80s at a time when many physicians were reluctant, she founded the first voluntary HIV testing and counselling centre, YR Gaitonde Center for AIDS Research and Education (YRG CARE), a premier HIV/AIDS care and support centre, in Chennai.

She was also the Professor of Microbiology at the Madras Medical College.

At a time when the international journals had been writing

60 EXPRESS PHARMA August 16-31, 2015

a lot about the HIV outbreaks in the world in 1980s, it was the six blood samples she collected from female sex-workers sheltered at a government home in Mylapore that sent first shockwaves of the deadly virus in India. Samples initially tested positive were sent to Christian Medical College (CMC) in Vellore as the facility for ELISA test was only available there in mid-80s. Later, samples were sent to the Johns Hopkins University in Maryland, US for further confirmation. The first findings of the deadly virus, in Tamil Nadu, was even read out in the state legislative assembly.

She set up the first voluntary

testing and counselling centre and an AIDS Research Group in Chennai while serving at the Madras Medical College and Government General Hospital as a Professor of Microbiology.

She was also a member of the National Technical Team on women and AIDS and a member of the advisory board of International AIDS Vaccine Initiative-India, member of the Scientific Committee of the National AIDS Research Institute, Pune, Government of India, a permanent member on the Microbicides Committee of the Indian Council for Medical Research (ICMR) and member of the Asia Data Safety Monitoring Board of the Division of AIDS, NIH, USA. A pioneer in public health and HIV related studies, she was part of several pioneering HIV research studies including

the US National Institute of Mental Health’s multi-country HIV/STD Prevention Trial, the US National Institute of Allergy and Infectious Diseases’ HIV Prevention Trial Networks, NIH award that will measure stigma in healthcare settings in Southern India, and a Phase III study of six per cent CS GEL, a candidate microbicide of CONRAD. She also served as the President of the AIDS Society of India.

Among her colleagues and specialists, she is always remembered as a doctor who dared to deal with HIV at a time when many physicians were reluctant to enter that field.

EP News Bureau-Mumbai

REGD.WITH RNI NO.MAHENG/2005/21398 REGD.NO.MH/MR/SOUTH-77/2013-15, PUBLISHED ON 5TH & 20TH EVERY FORTNIGHLY & POSTED 6-7-8 & 21-22-23 OF EVERY FORTNIGHLY. POSTED AT MUMBAI PATRIKA CHANNEL SORTING OFFICE.

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