Express Pharma ( Vol.12, No.16) June 16-30, 2017

VOL. 12 NO. 16 PAGES 68

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'We are currently working with almost all major pharma companies in Asia Pacific'

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CONTENTS MARKET

Vol.12 No.16 June 16-30, 2017 Chairman of the Board Viveck Goenka

SANJEEVANI FOR

Sr Vice President-BPD Neil Viegas

AYUSH

Editor Viveka Roychowdhury* Chief of Product Harit Mohanty BUREAUS Mumbai Usha Sharma, Raelene Kambli, Lakshmipriya Nair, Sanjiv Das, Mansha Gagneja, Swati Rana

AYUSH could be the answer to India's unmet medical needs but only if it is backed by scientific validation and credible evidence | P16

New Delhi Prathiba Raju DESIGN

National Design Editor Bivash Barua Asst. Art Director Pravin Temble Senior Designer Rekha Bisht Graphics Designer Gauri Deorukhkar

P13: PRE EVENT NPME 2017 to be held in Lagos, Nigeria

RESEARCH

Senior Artist Rakesh Sharma, Vivek Chitrakar Photo Editor Sandeep Patil MARKETING Regional Heads Prabhas Jha - North Harit Mohanty - West Kailash Purohit – South Debnarayan Dutta - East Marketing Team Ajanta Sengupta Ambuj Kumar E Mujahid Mathen Mathew Nirav Mistry Rajesh Bhatkal PRODUCTION General Manager BR Tipnis Manager Bhadresh Valia Scheduling & Coordination Ashish Anchan CIRCULATION Circulation Team Mohan Varadkar

P22: INSIGHT

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'WE ARE CURRENTLY WORKING WITH ALMOST ALL MAJOR PHARMA COMPANIES IN ASIA PACIFIC'

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PHARMA PRO&PACK EXPO 2017 TO BE HELD IN HYDERABAD

MANAGEMENT

23

GLOBAL DERMATOLOGY MARKET SET TO BENEFIT EXTENSIVELY FROM PIPELINE BIOLOGICS

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NASH MARKET WILL INCREASE MORE THAN 40 FOLD BY 2026

Let’s move this story forward

P28: UPDATES Sheffield scientist investigates how to stop breast cancer spreading to the bone

26

P33: VENDOR NEWS Coloron opens new technical services lab in Noida

SPORE IS FOCUSSED ON A SPECIFIC ORGAN SITE, SUCH AS BREAST OR LUNG CANCER

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EXPRESS PHARMA

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June 16-30, 2017

EDITOR’S NOTE

Dull Q4FY17 could be a blessing in disguise

A

ccording to a report from CARE Ratings on the corporate performance of Q4FY17, the pharmaceuticals and drugs sector in India, growth in net sales in Q4FY17 de-grew by 0.4 per cent, compared with a healthy growth of 8.8 per cent in Q4FY16. The CARE report, based on a universe of 74 pharma companies, shows that many sectors were worse off. For instance, the electronic consumer durables sector saw a de-growth of 21.7 per cent in the same period. Hospitals and healthcare services, based on a study of 17 organisations, growth in net sales in Q4FY17 grew 10.7 per cent, which is good but not as much as the 16 per cent in the corresponding period a year back.

The reasons for the de-growth in sales of the pharma sector are no secret. Some are specific to the sector, like the increasing span of price control, and the shift of at least some sections of the medical fraternity, to prescribing generics. Most government medical colleges and hospitals have started prescribing generics and this will impact institutional sales of some pharma companies.

Whether this will even out over time, is anyone’s guess. The US market too is shrinking thanks to regulatory-cum-pricing challenges, points out a Q4FY17 preview report from Sharekhan.

Other factors like demonetisation, have impacted all sectors. And the next few quarters

While price control will keep sales revenues much lower than the previous years, demand cannot go below a certain level

will show slimmer growth rates, with the impact of the roll out of the GST kicking in. Pharma pundits predict a couple of months of destocking, which started impacting sales from April, followed by low supplies until they even out.

The dipping sales revenues and other factors like continued negative rulings from global regulators, have naturally seen pharma stocks taking a beating. But like domestic sales absorbed the demonetisation shock, the sector will ride out the GST roll out. But the challenges in the US market are proving too bitter to swallow. US FDA remediation actions are taking longer to be resolved while price collusion charges by the US Department of Justice, have seen a sharp correction in stock prices from their highs in FY2016, points out the Sharekhan report.

The silver lining is that no one believes this lull will last. Sharekhan continues to remain positive on the long-term prospects of the Indian pharma sector, and is advising investors to stay selective.

The reasons are obvious. Medicines come under the non-discretionary expenses category, so while price control will keep sales revenues much lower than the previous years, demand cannot go below a certain level. One hopes that the pharma companies are using the downtime to fix the long-term issues more permanently this time.

VIVEKA ROYCHOWDHURY Editor viveka.r@expressindia.com

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MARKET I N T E R V I E W

‘We are currently working with almost all major pharma companies in Asia Pacific’ Sylvia Hii, Founder & VP – Marketing, Digital A Plus Group of Companies in an interaction with Usha Sharma, elaborates on the immense opportunities provided by digital service providers within the pharma industry

What is the business potential of digital communication within the pharma sector and how fast is the market growing?

There is a huge potential for digital communication in the pharmaceutical sector as evidenced by the robust growth year-onyear. This is the only industry which has withstood recession and political turmoil.

Global spending on medicines is expected to reach $1.2 trillion by end of 2017, according to a recent report by the IMS Institute for Healthcare Informatics. With increased competition and cost cutting and with more customer getting text savvy (use of smart phones and Internet), the market is skewed towards digital engagement. Digital communication is not only between pharma and doctors, but it is a three-way communication where all the stakeholders are involved giving ample opportunity for all the digital service providers in this industry.

What services do Digital A Plus offer to pharma companies? Do you also cater to other sectors?

Digital A Plus strives towards empowering its customers with all possible offerings that will add value to their business/service/life. The offerings can be mainly categorised into business promotion (marketing support to the pharma companies), medical training (to the medical field force), HCP education, and patient education and awareness. Although most of our offerings are skewed towards business promotion, recently patient education is gaining rapid momentum.

Recently, the PM announced that medical practitioners should prescribe generic medicines. According to you how will this impact market dynamics ?What role will DigitalAPlus play in this change?

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Our services to pharma companies includes training, marketing and patient education outputs. We do not specifically cater to specific brand or generic and it would depend on the client for which we are working on and their objectives and marketing directions. We do see increase in the medical communication of generic drugs as well. With this we expect shift in the market dynamics with more generic coming through the bio-equivalence study and pricing also playing a major role in the prescription habits.

Till now how many pharma dedicated projects have been executed and which are they? How many are in the pipeline? Who are your major pharma clients?

In the past five years, we have executed at least 2000 projects to various clients like MSD, AstraZeneca, Sanofi, Novartis, Cipla, Torrent, SunPharma, DRL, Allergan, Takeda, Eisai, Mundipharma & etc. The projects extend from a simple print leaflet to complex 3D output via virtual reality or augmented reality. Projects like, pharmacists engagement portal for all mobile devices, theme-based social media campaigns for women’s health and men’s health related, Ipad gamifications for doctors and internal sales training, annual email marketing end-to-end solutions for multiple brands etc. We are also undertaking bulk html programming projects from pharma companies since we are certified content partners for CLM platforms like Veeva, MI Touch and Viseven Group. We have been continuously improvising to cater the everhungry requirement in the space of digital. We are currently working with almost all the major pharma companies in Asia Pacific including few regional ones.

How much do pharma companies invest in

MARKET digital marketing than traditional marketing?

According to you, how much should a company invest while contemplating for digital marketing?

Most pharma companies have realised the importance of digital marketing and takes the lion share of their budget. At the moment, they are allocating between 20 per cent – 30 per cent of their budget to work on digital marketing campaigns. The focus has also shifted from outbound marketing to inbound marketing. It is natural in traditional media to reach out to a generally broad, public to draw people’s attention to your product or service. With digital media, it enables consumers to proactively seek out for your products or company and come to your digital marketing channels willingly. However, traditional marketing includes F2F is most appreciated by most doctors even now due to the emotional connect. The actual spending on digital would again depend on the brand and company direction.

Although the budgets are slightly skewed towards the

digital side. To be very frank, in India at the moment, pharma companies are not contemplating for investing in the digital marketing campaigns, they are trying out new ideas almost every other days. The digital budget will definitely becoming 80 – 90 per cent in the next three to five years.

Are Indian pharma companies reluctant to adopt digital communication?

No, there is a huge transformation in digital spending, we could see that almost all the major Indian pharma companies have endorsed digital marketing with investing high on different tools. Most companies have been using tablets or iPAD as part of general communication tool to the doctors.

What challenges do you foresee for pharma digital communication? What solutions would you suggest?

Healthcare or pharma sector is governed by strict regulations and legal restrictions. This makes it more challenging in delivering the

marketing/educational services in digital format. We cannot apply the regular policies of advertising, educating or consulting. Each communication has to undergo multiple levels of reviews and approvals. This delay and limits the scope of creativity and innovation. However, the challenge and key to success lies in how you quickly and efficiently adapt to this environment.

It is important to include all stakeholders at every stage of planning and execution, especially medical and legal, regulatory department.

Imparting training to the field force who are executing the output is also important.

Recently, there have been news about Ransomware attacks. What precautionary measures would you suggest to avoid malware attacks?

Most of the digital communication done for pharma companies are not hosted on public domain but on firewall protected servers.

Also, they are hosted on devices where internet usage is minimal or protected. Further,

those which are hosted on public domain such as portal, website, we follow policy which can safeguard the content and secure servers to protect from any malware attacks.

A few Indian pharma companies have created platforms which are connected with patients, for eg: DRL's Purple Health.

How can pharma companies go for better patient engagement activities in respect to patient safety and compliance issue?

Patient education content needs to be de-branded and not intended for promoting the brand but to manage disease and quality of life. Pharma companies need to frequently update with relevant content and make it more interesting and engaging. This could be in the form of games, Q&A, using kiosk machine, reminder application etc.

Presently, the company has its presence in Malaysia, Singapore and China. Are there plans to foray into new geographies?

Currently, we are focusing on

these geographic including India, however, we are planning to expand to remaining Asia Pacific countries and the Middle East in the next two years. However, this again would depend on the market dynamics, company policy, direction and need for engaging newer customer.

Tell us about the company's future plans for next three years?

Pharma is the only sector that will never slow down, as health cannot be compromised. With rapid growth of pharma, innovative, cost-cutting, effective digital trends in terms of personalised apps, AR, VR and social media marketing is the future. We are also planning transform ourselves into an institution that not only caters to the need of individualised pharma companies, but also enables the pharma and healthcare stakeholder as well as patients to provide quality services and care and improve overall quality of life respectively. u.sharma@expressindia.com

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MARKET PRE EVENTS

NPME 2017 to be held in Lagos,Nigeria The expo will be held from August 30-31 to September 1, 2017 4TH NIGERIA Pharma Manufacturers Expo 2017 (NPME 2017), an international exhibition on pharmaceutical industry, will be held at Lagos, Nigeria from 30-31 August to 1 September, 2017. The expo will attract more than 150 exhibiting companies and nearly 3,500 pharma trade professionals from Nigeria, Ghana, Mali, Chad, Cameroon, EQ Guinea, Central African Republic, Senegal, The Gambia, Ivory Coast, Niger, Burkina Faso, Benin amongst others.

NPME 2017 will provide an unique platform to showcase pharma processing machineries (tablet/ capsule/ liquid/ injectables/ ointment/ dry syrup), packaging machineries, packaging materials and consumables, API, bulk drugs etc NPME 2017 is being jointly organised by the Pharmaceutical Manufacturers Group of

Manufacturers’ Association of Nigeria (PMG-MAN) and GPE EXPO.

NPME 2017 will provide an unique platform to showcase pharma processing machiner-

ies (tablet/ capsule/ liquid/ injectables/ ointment/ dry syrup), packaging machineries, packaging materials and consumables, API, bulk drugs, additives, excipients, pharma finished products, formulations lab reagents, glassware and equipment, analytical, R&D equipment and biotech instruments, environment control equipment and services, utilities products and services, turn-key contractors, project consultants etc.

EP News Bureau

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MARKET

PHARMAPro&Pack Expo 2017 to be held in Hyderabad The exhibition which is to held from September 21-23, 2017 will offer immense business opportunities to national and international pharma buyers as well as machinery manufacturers PHARMA PRO&PACK Expo 2017 co-located with IndiaLAb Expo 2017 / Analytica Anacon 2017 will be held between 2123, September, 2017 at HiTEX, Hyderabad, India. It is expected that more than 450+ exhibitors will be participating and around 18,000 trade visitors and serious buyers will attend the exhibitions.

India is said to be the next ‘Pharma Capital’ of the world.

With stringent regulatory environment within the country, pharmaceutical companies are meeting the highest quality standards which are at par with international regulatory standards. Meeting high standards of quality is only possible with a robust pharma processing and packaging machinery system as well as its ancillaries available at the doorsteps for the Indian pharma manufacturers at a highly competitive cost.

According to Rattan Singhania, Trustee, Indian Pharma Machinery Manufacturers’ Association (IPMMA), PHARMA Pro&Pack Expo exhibitions creates numerous

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The exhibition remains a healthy trade domain for every exhibiting company with equal opportunity of growth and meets all the trade attendees at the show business opportunities for Indian pharma machinery manufacturers within the country as well as in the overseas markets, due to the vast number of trade visitors who visited the shows from India and abroad. The exhibition also provides a strong business platform to even a smallest entrepreneur to display his technical skills to national and international pharma buyers.

Moreover, the exhibition remains a healthy trade domain for every exhibiting company with equal opportunity of growth and meets all the trade attendees at the show.

Such international trade events happening at our doorsteps play most impor-

tant roles to nurture the domestic business of pharma machineries and lab equipment manufacturers. It encourages solution providers to grow their business in a fair and transparent trade-ecology. With the launch of this exhibition, PHARMA Pro&Pack Expo in its first year (the year 2013) emerged as the largest most resourceful Indian pharma machinery exhibition in this sub-continen. Over period of time, it scaled up to accommodate more number of national and international pharma machinery manufacturers and solution providers in bigger way, added Singhania.

Looking to the response to

the previous editions of PHARMA Pro&Pack Expo exhibitions from the industry, Mahendra Mehta, President, IPMMA and CEO, Parle Global Technologies said, “The 2017 edition of PHARMA Pro&Pack Expo will be the fifth edition, which would be beneficial in line with the Make-in-India programme initiated by the current government. At the same time, it is very interesting to have foreign buyers alongside the national buyers inspecting our products.” Speaking about the quality of products made

by Indian pharma machine manufacturers, Mehta informed that seeing is believing and when you showcase and demonstrate the working of your products to buyers at the show, the product speaks for itself. As far as the quality of the exhibit machines are concerned, there are distinct improvements over the past editions of the show.

The exhibitors have also turned more responsive when compared with the past editions.

EP News Bureau

PharmaTech Expo 2017 to be held in Ahmedabad THE SIXTH edition of PharmaTech Expo 2017, an International Exhibition on Pharma Machinery, Lab & Packaging Equipment is scheduled on 3-5, August 2017 at Gujarat University Convention Centre, Ahmedabad, Gujarat.

The three-day long event is an important platform for showcasing the latest innovation and technologies throughout all phases of the product lifecycle, focusing pharma manufacturing and processing technology, pharmaceutical systems and services.

According to industry estimates approximately 35-40 per cent of India's pharmaceutical machinery is produced in Gujarat. This strong growth prospects of the pharma exports segment and growing demand from the domestic market, will further fuel the growth in the overall pharma machinery sector.

Experts are of the opinion that there is a strong local and global opportunity for Gujarat in the manufacturing of pharma machinery, given its strong and well-established engineering sector. Express Pharma is the media partner for the event.

EP News Bureau

MARKET EVENT BRIEF AUGUST TO SEPTEMBER-2017 3

21

PharmaTech Expo 2017

PHARMATECH EXPO 2017 Date: August 3-5, 2017 Venue: Gujarat University Convention Centre, Ahmedabad, Gujarat Summary: The 6th Edition of PharmaTech Expo 2017 will be Gujarat’s largest pharma expo and will be concurrently held with ‘Labtec’ & ‘Track & Trace’ Expo 2017. The focus will be on pharma machinery and equipment manufacturing sector and pharma packaging. More than 150 exhibitors from across the country participated in last year’s event.

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Decision makers from sectors like hospitals, diagnostic labs, oil and petroleum, chemical, cosmetics and government departments will meet at the tradeshow. The event will be supported by Ministry of Science & Techn-ology, Government of India.

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cover ) SANJEEVANI FOR

AYUSH

AYUSH could be the answer to India's unmet medical needs but only if it is backed by scientific validation and credible evidence

BY LAKSHMIPRIYA NAIR

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(

{

Om Sarve Bhavantu Sukhinah Sarve Santu Nir-Aamayaah | Sarve Bhadraanni Pashyantu Maa Kashcid-Duhkha-Bhaag-Bhavet |

THE MAIN FOCUS

}

May all become happy, may all be healthy (free from illness), may all see what is auspicious, may no one suffer in any way.

T

his Sanskrit prayer is also a goal that India has been striving to ensure for its citizens and enabling universal healthcare access (UHC) is a pivotal step towards achieving this noble objective. Yet, it remains a distant dream due to unequal health access, threat of existing and emerging diseases, lack of trained medical professionals and rising costs of healthcare.

The patient-centric approach of India’s alternative and traditional systems of medicines that comprise Ayurveda, Yoga & Naturopathy, Unani, Siddha & Sowa-Rigpa and Homoeopathy (AYUSH), has led the government to look at them as a panacea to India’s public health challenges.

Spurred by the belief in the potential of AYUSH to alleviate the crises within Indian healthcare, the government has been trying to promote and popularise alternative systems of medicine with an aim to integrate it with modern systems of medicine.

However, despite myriad actions to promote and popularise AYUSH, it hasn’t taken off the way it was expected to.

A health survey conducted by National Sample Survey Office (NSSO) in 2015 revealed that ‘inclination towards allopathic treatment was prevalent (around 90 per cent in both the sectors). Only five to seven percent usage of ‘other’ including AYUSH was reported both in rural and urban area.’

Clarion call for evidence So,

what’s

hindering

the

growth of AYUSH and preventing its widespread acceptance?

In answer to this question, experts and industry veterans cite various reasons on all fronts: education, research, clinical practice, industry, and regulation.

But, all of these are interconnected and seems to be linked to one mammoth hurdle: lack of scientific validation and evidence.

This has often led to the rampant misuse of herbal and traditional medicines and thereby the negative outcomes are often reported. Though traditional medicines have been in use for a long time, there has been limited quality control and negligible documented evidence of their safety and effectiveness. This, in turn, has negatively impacted the development of regulations and legislation in this arena. Hence, building trust in the traditional medicine systems through validated data and irrefutable evidence has emerged as an urgent need to leverage the true potential of these systems.

Are clinical trials the answer?

Fortunately, paying heed to the increasing clamour for evidence-based AYUSH, regulators and the government have been mulling over measures, systems, policies and processes to ensure better documentation and validate the drugs and practices of these alternative systems of medicine. Clinical trials for AYUSH drugs is one of them.

In 2016, Indian Council of Medical Research (ICMR) released guidelines for conducting testing medicines from AYUSH to provide more clarity on testing ayurvedic formulations and other traditional medicines.

While there is unanimous accord on the good intent of the government, the industry is divided on its impact. Many believe that it would undoubtedly lead to better safety and efficacy of AYUSH drugs, but there are many dissenting voices who argue that such a step, if implemented with proper thought and planning, would not only curb the growth of the industry but also do it

unforetold harm.

Dr Ali Mehdi, Fellow & Project Leader, Health Policy Initiative from Indian Council for Research on International Economic Relations (ICRIER), a leading policy research institution supports the intent to mandate clinical trials for AYUSH drugs and states, “The AYUSH industry cannot sustainably thrive on faith! It has to be based on sound scientific and management principles.”

Opining that clinical trials are in the best interests of the AYUSH industry, he believes that it would empower the practitioners to feel more confident - and probably incentivised - to prescribe AYUSH medicines once they are convinced of their scientific value.

He says, “Right now, they are unable to take ownership and leave it to the patients to take them at their own risk.”

However, he believes that the move will meet with resistance from at least some segments of the AYUSH industry and recommends the government to engage with the industry and clearly explain the

Paying heed to the increasing clamour for evidence-based AYUSH, regulators and the government have been mulling over measures, systems, policies and processes to ensure better document and validate the drugs and practices of these alternative systems of medicine. Clinical trials for AYUSH drugs is one of them

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merits of the move.

VK Dhawan, CEO, Planet Herb Lifesciences also speaks in support of clinical trials. He says, “It will certainly help to build trust and authenticity amongst doctors and patients for herbal medicines. Today, many doctors, mainly practicing in Western medicines doubts and do not trust on herbal medicines due to lack of clinical studies done on these products. Once thorough studies are carried out it will help to support clinical claims about the brand/products. It will certainly encourage those organisations that are sincerely involved in research-based manufacturing activities and ready to spend good amount on R&D activities to develop quality product.”

He further states, “It will help in manufacturing quality medicines and to make clinical claims for these products. Only those manufacturers/brand owners will stay in the field who really have good research based formulations available.

Quality and efficacy of herbal medicines will go high and reliability of herbal medicines over allopathic medicines will improve a lot. Additionally, companies who really want to stay in the market shall be forced to set up their own R&D set up to deliver research based products. Copying of branded formulation will stop.”

However, he is also aware of the challenges that need to be tackled. He outlines, “Clinical trials are quite expensive, they require huge investment. Only those companies who are really sincere about conducting

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cover ) research based activities will survive once the clinical trials are made mandatory. Development of formulations will also be a big challenge to meet efficacy standards as per the clinical claim of products. All new formulation development will require thorough compliance to parameters tested to generate clinical data. Another challenge will be to develop more infrastructure and instrumentation to cater to huge volume of clinical studies of herbal products at a economic costs.”

Shaheen Majeed, Director, Sami-Sabinsa Group also feels that clinical trials can usher credibility in the sector but also foresees challenges. He points out, “The AYUSH market would be more valid for its strong claims if clinical trials are performed but there are a lot of grey areas such as standard protocols or trial designs to be followed w.r.t each clinical trial. The scope of it would be much more impressive but the costs of investing on clinical trials would slow down the product launch, which in turn can hit the manufacturers.

Ultimately, consumers lose out on a potentially beneficial product.”

He also points out that the move might also give rise to more employment opportunities in the sector but that too has its flipside. He predicts, “This can also spring up the employment opportunities to the upcoming AYUSH doctors both in government and private sectors. Different streams of learning for clinical research would erupt like short term diplomas, degrees and certificate exams to conduct the clinical trials. Again, the challenges would be standardisation in training and providing skillsets to match the level of research in other sectors. Initially, the investment in such areas would also be a challenge as to take risk-based chance.”

Jayesh Chaudhury, CEO, Vedic Lifesciences is however very sceptical of the effectiveness of mandating clinical trials for all AYUSH drugs. He

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is of the view that ensuring it for propritary medicines might be a good move, but enforcing it on Shastrokta drugs (medicines made as per the approved ancient texts) are not really necessary and would lead the players to incur heavy costs, which in turn will adversely effect the growth of the industry.

Thus, it might prove to be a counterproductive step.

Dr Surendra Chaudhary, District Ayurvedic and Unani officer, Government of Uttar Pradesh and President, Uttar Pradesh, Vishva Ayurveda Parishad is also opposed to the step as it may kill the small manufacturers since clinical trials are costly and lengthy processes. Though he agress that it will provide a certain amount of credibility to the drugs, especially in the case of international users, he also draws attention to the fact that the approval process of ASU drugs, already makes provisions to ensure safety and efficacy of drugs. After amending the rule 158 B of Drugs & Cosmetics Act vide G.S.R. 663(E) dated 10 August 2010, safety and efficacy proof are well defined.

Thus, though the industry lauds the intent behind making clincial trials compulsory, many doubt its effective implementation. This highlights the urgent need to devise better startegies to mainstream AYUSH and prove them as credible systems of medicines without any doubt. The need for effective steps to make AYUSH more evidence-based is more urgent than ever before.

Envisioning a starring role for AYUSH Fortunately, the government has realised this urgent need, and several measures have been initiated by the to drive access to affordable, reliable and easily accessible medical facilities to the masses through AYUSH. Programmes to increase research and MOUs to augment cooperation with other nations in the field of traditional systems of medicine

have also been undertaken.

The report of the Steering Committee on AYUSH for 12th Five Year Plan had envisioned a significant role for the sector.

In a foreword in the report, Dr Syeda Hameed, who chaired the Steering Committee of the Commission on Health which reviewed the National Health Policy of 2002, till its dissolution in 2015, outlines, “AYUSH and allopathic, both systems, often provide solutions to a common set of problems. Many times both systems complement each other also. Our endeavour during the 12th Five Plan period will be that both systems expand and progress together, based on their core competencies and inherent strengths. We must ensure that the healthcare delivery system in the country is designed and developed in such a way that, both, AYUSH and allopathic systems are available to every patient and the choice of system of treatment is the patient’s choice, based, of course, on set protocols.”

She further states, “AYUSH has presence in all parts of the country. In addition it has near universal acceptance, available practitioners and infrastructure. The strength of AYUSH system lies in preventive and promotive healthcare, diseases and health conditions relating to women and children, noncommunicable diseases, stress management, palliative care, rehabilitation etc. AYUSH has very little side effect, has a soft environmental footprint and is engrained in local temperament. It can play an important role in achieving the National Health Outcome Goals of reducing MMR, IMR, TFR, malnutrition, anaemia, population control and skewed child sex ratios. Its huge resource of hospitals beds and health workers need to be efficiently utilised to meet the National Health Outcome Goals.”

The current government, under the aegis of India’s PM Narendra Modi, has also offered strong support to the alternative medicines industry and introduced a number of

AYUSH ministry has been allocated `1,428.65 crores in the Union budget for the fiscal 201718. The total outlay for the ministry in last year’s budget was `1,326.20 crores noteworthy measures to fortify the sector. Forming a separate ministry of AYUSH and declaring a National AYUSH Mission have been some of them.

Mainstreaming of AYUSH has been a fundamental strategy under the National Rural Health Mission (NRHM) as well. Under NRHM, drug kits of ASHAs include AYUSH medications as well. Moreover, AYUSH formulation also form a part of the additional supply of generic drugs for common ailments at SC/PHC/CHC levels. The AYUSH ministry has been allocated Rs1,428.65 crores in the Union budget for the fiscal 2017-18. The total outlay for the ministry in last year’s budget was Rs 1,326.20 crores.

Thus, the government is engaged in several activities to improve our AYUSH systems and mainstream it. However, it is undeniable that a lot more needs to be done on different fronts to accelerate the pace of progress.

Recommendations from industry representatives:

Dr Ali Mehdi, Fellow & Project Leader, Health Policy Initiative from Indian Council for Research on International Economic Relations (ICRIER) I would say there are four main factors hindering the

growth of AYUSH - lack of scientific validation, innovation, public trust and marketing.

Both the government and the AYUSH industry need to take measures to address the above four concerns. And I think it’s important to also enable new players to come into this industry, players who can bring in scientific, technical and marketing expertise.

Another important measure could be the promotion of international cooperation - connecting Indian players in the AYUSH sector with their international counterparts and scientific associations so that they can benefit from best practices from around the world. I am sure India is not the only country trying to promote traditional medicines. From my perspective, alternative medicines enhance the choiceset of patients, which is neither a topic of discussion in India nor of serious consideration for policymakers.

A very important feature from a regulatory perspective would be transparency, something which even regulation of modern medicines needs badly in this country. There are a whole lot of trust issues, especially when it comes to critical illness, and without addressing them, the AYUSH industry stands little chance of emerging as a significant player in the pharma sector.

Then obviously, they need to have strong marketing muscle which modern pharma companies are well-known for.

cover )

Vasudha Wattal and Pallavi Joshi, Research Associates, Health Policy Intiative, ICRIER At present, Rule 158 B of the Drugs and Cosmetics Rules, 1945, lays down the regulatory requirements, including submission of proof of safety and effectiveness for licensing of AYUSH drugs.

Enforcement of these provisions is under purview of the state licensing authorities appointed by the state governments. For mainstreaming AYUSH – clear regulatory pathways would serve as a strong foundation. Hence, in promoting quality and credibility of AYUSH, carefully calibrated regulatory definitions, elaborative guidance documents for requirements to establish safety, efficacy and quality, and dedicated efforts are required for effective enforcement of legislation.

The need for further evidence based studies regarding the various complementary systems of medicines is a prerequisite for strengthening the AYUSH sector as a whole. Doing so would strengthen prescribers’

understanding of the implications of various drugs and therapies, as well as the interaction of treatments from across different systems.

However, it should be borne in mind that creating a pool of scientific literature based on rigorous studies will further require that certain guidelines and standards be put in place first (such as the Ayurvedic Pharmacopoeia of India which was released last year by the Ministry of AYUSH) in order to ensure that among other things, the trial design is appropriate and the data is reported in a standardised manner.

Dharminder Nagar, MD, Paras Healthcare To make AYUSH more evidence-based, there is a need to work aggressively on devising new research strategies to corroborate facts in a scientific way. This includes instituting regular clinical trials to assess impact and efficacy of drugs, and finding out the right dosage and duration of treatment. In recent years, some research have been conducted to gauge the effect of AYUSH medicines which are essentially based on herbs on diseases such as diabetes and blood pressure etc. This needs to be implemented on a large scale to bridge the division between Western and AYUSH systems. Journals must be maintained to collate all data and figures. A more practical approach is of mutual co-

existence of all these systems.

For this to happen, we need studies and clinical trials to find out how well can supplementing patients with Ayurvedic or Unani medicines along with western medicine can aid their recovery.

Dr Surendra Chaudhary, Ex District Ayurvedic and Unani Officer, Government of UP & President, Uttar Pradesh, Vishva Ayurveda Parishad ◗All AYUSH physicians working with NHM must treat patients only with their respective expertise - be it Ayurveda, Unani or Homeopathy. ◗Specialty clinics for Panchkarma, anorectal surgeries be setup at primary healthcare centres (PHC) level and full time specialists be recruited to man these centres ◗Set up of good quality educational institutes ◗Making stringent check points to curb substandard educational and treatment centres through monitoring of GMP certification process. If a manufacturer doesn't have the required analytical facilities, we must have MoUs for drug testing facilities with AYUSH-certified laboratories. ◗Control over raw material quality should be strengthened ◗There must be clear guidelines about use of excipients- colouring agents, flavouring agents, sweeteners etc.

The global ayurvedic market accounted for $3,428.0 million in 2015 and is expected to reach $9,791.0 million by 2022

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◗The D&C is a central act and its rules should be followed uniformly across the country with a few changes as per state requirements. Granting of ASU manufacturing license and drugs approval process is so different with state to state.

Shaheen Majeed, Director, Sami-Sabinsa Group Quality of education, lack of research, non-transparency, lack of standardisation of product manufacturing, finished products and the treatment protocols, and lack of documentation, are some of the hindrances facing the promotion of AYUSH. Collaborations between educational institutes, research centres and industries can bring a lot of changes to uplift AYUSH. National programmes held by the states and central government to promote AYUSH systems can also bring awareness about these systems and their potential.

Let it have information exchange programmes conducted even by small sectors. Though a lot of exercise has been done on these lines, what we need is to one consolidate medicinal system under AYUSH which can be integrated with mainstream medicine to benefit the population of the country.

Jayesh Chaudhary, CEO, Vedic Life Sciences ◗ We should ensure quality by enhancing our quality montiroing systems and ensuring that cGMP is ensured at all the drug manufcturing centres ◗ We should fortify our data

collection systems and processes. Hospitals are a great place to collect data. We can do retrospective research by looking at case files and the progress during the treatment of patients to collect evidence.

It will give great information about the effectiveness and efficacy of the drugs and help build credible data to support the AYUSH systems. ◗ If the government is looking at clinical trials as a way to make AYUSH evidence-based then the government should help the SME players in this segment by setting up clinical trial centres and subsidising the compnay to carry out these trials. ◗ Pooling of resources by SME players with the same Shastrokt products to create and collect data could also be a way forward to promote evidence-based AYUSH.

The way forward AYUSH is garnering considerable attention and recognition globally. Reports reveal that the country’s export of AYUSH and valueadded products of medicinal plants in 2015-2016 stood at $358.60 million. A research report, ‘Ayurvedic-Global Market Outlook (2016-2022),’ published by OrbisResearch.com, the global ayurvedic market accounted for $3,428.0 million in 2015 and is expected to reach $9,791.0 million by 2022 growing at a CAGR of 16.2 per cent from 2015 to 2022.

Thus, it is time that we created a strategy which will use a multifarious approach to ensure natural and safe medicines, which are timetested, accessible and affordable to leverage the true potential of AYUSH. lakshmipriya.nair@expressindia.com

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MANAGEMENT INSIGHT

Let’s move this story forward Bharathi Ghanashyam, Founder &Editor, Journalists against TB, talks about the story of (multidrug-resistant tuberculosis) MDR – TB control in India, which seems to be stuck at the foreword and asks when does it move forward

F

or the first time in over 125 years we have new diagnostics, we have two new drugs — bedaquiline, manufactured by Janssen Pharmaceutica NV, and delaminid, manufactured by Otsuka Pharmaceuticals, after a wait of 50 years (this article will talk only about bedaquiline). We finally have strong tools with which to fight a disease that has been defeating us down the centuries. And it seems like we are frittering away the opportunities, stuck as we are in red-tape and seemingly needless delays in effectively using these tools.

MDR – TB is a lethal form of TB. As defined by World Health Organisation (WHO), it does not respond to at least isoniazid and rifampicin, the two most powerful anti-TB drugs. It currently requires the patient to be on treatment for 24 months or more, with six other drugs, including injectibles for an intensive phase of six months and a continuation phase with four drugs for 18 months or more. These drugs are toxic and induce severe side-effects.

The numbers are growing Dr Jennifer Furin, an infectious diseases specialist in Harvard Medical School has observed in one of her papers that “…unless the management of MDR TB changes radically, it will be one of the main drivers of antimicrobial resistance, which could kill more persons than cancer by 2050…”

According to WHO, about 480 000 people worldwide developed MDR-TB in 2015;

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nearly half of whom were in China, India, and the Russian Federation. Worldwide, only 52 per cent of MDR-TB patients and 28 per cent of XDR-TB are currently successfully treated.

More alarming was the fact that about 9.5 per cent of MDR-TB cases had extremely drug-resistant TB (XDR-TB).

As per the TB India 2017 report of the Central TB Division, India is home to the highest burden of MDR - TB. An estimated 1.3 lakh MDR - TB patients emerge annually in India. Despite the grim situation, instead of waging a full-scale war, we are still making our first weak battle cries. Let’s look at the history of what has been done.

The history of inaction January 2015: The Government of India approved the use of bedaquiline (BDQ) for about 500 patients under the national TB control programme.

However, no plans were announced to make the drug available to the private sector, when in India, traditionally, more than half of those afflicted with TB, including MDR – TB seek treatment from the private sector. No data is available for how many patients actually received BDQ that year.

March 2016: On the eve of World Tuberculosis Day, Health Minister JP Nadda launched BDQ as part of the national programme for MDR

– TB and XDR – TB patients.

The drug was to be introduced at six tertiary care centres across India, which had advanced facilities for laboratory testing and intensive care for patients. It was to also be introduced in 104 districts across five states. There is no data available on how many patients received BDQ during the year. A year had passed with little or no progress.

March 2017: The Government of India announced that it would expand access to BDQ and make it available in 140 government-run centres by November. The Annual Status Report of RNTCP reported that till December 2016, more than 207 drug resistant TB patients had been initiated on BDQ containing treatment (BDQ is given in combination with other drugs).

Dr Sunil D Kharpade, Deputy Director General, Head, Central TB Division,Project Director RNTCP, responding to questions by e-mail responded, “The yearly estimated number of BDQ eligible patients in the public sector as per existing criteria is around 7000 – 8000.” He also revealed that 443 patients have been enrolled into the programme across the sites.

Juxtaposed against the number of people requiring the drug, what has been achieved does not even do justice to a pilot-programme. These numbers also do not take into account patients in the private sector who are eligible for the drug. A press note uploaded on the website of the Central TB

Division of the Government of India on 25 May 2017 cautiously mentions, “For patients being treated outside the government system, the manufacturers are providing this drug under Compassionate Use Programme free of cost to the doctors, provided they follow the recommended guidelines for starting the drug and its close monitoring.”

A lot of time has gone by Implementation of the plans outlined by the Central TB Division for the use of BDQ has been something of a nonstarter. There has been no resolution to concerns on whether the drug stands the danger of being misused; whether it would end up being available over the counter without prescriptions and most of all whether patients would become resistant to the only really powerful weapon available for TB. These fears might be unfounded. Prof Furin says, “While it is certainly true that many antibiotics can be purchased without prescriptions, it is highly unlikely that newer agents like BDQ and delamanid would be purchased on the open market. They have no indications for use other than in the treatment of serious mycobacterial disease, such as TB. So the risk of them being sought after for broad use is very low.”

That patients in need of the new drug are running out of patience is evident from the case that was recently filed by the father of an 18-year old patient of XDR –TB in the Delhi High Court. He demanded that

his daughter be given BDQ as that was the only drug that could save her life. In counter argument, The National Institute of Tuberculosis & Respiratory Diseases (NITRD) argued that administering BDQ without testing the drug resistance of the bacteria in the patient and formulate the right bedaquiline containing regimen(emphasis by the author), might result in the bacteria becoming resistant to BDQ and spread in the community (as appeared in a leading daily).

Some experts have also remarked that the drug needs to be protected for future patients and hence rational use is advised. It is debatable

whether protecting the future at the cost of the present will be good strategy, because it is the present which will infect the future. Ignoring this might result in the perpetuation of a cycle which might be difficult to retrieve from.

There appear to be more barriers than enabling factors in the bid to use promising new drugs that can save lives. The irony is that this situation exists despite Janssen Pharmaceutica having come forward to donate 600 courses of BDQ to India under their compassionate use programme. India was unable to absorb these courses for reasons known and unknown.

As per the TB India 2017 report of the Central TB Division, India is home to the highest burden of MDR - TB

There seems to be movement at last. It is learnt that the Global Drug Facility (GDF) of the Stop TB partnership will be facilitating the USAID donation of 10,000 courses of BDQ to India before the end of 2018. 3,500 courses of these will be dispatched during 2017 and the balance 6,500 in 2018.

RNTCP has requested 1000 courses as first tranche, 660 of which are being dispatched immediately.

While this is good news, the numbers don’t add up. If as mentioned earlier in the article, only 443 have been enrolled, who will use the rest?

There are questions that the Central TB Division of the

Government of India needs to answer and answer fast.

It is pertinent to end this piece by quoting excerpts from the first press briefing by Dr Tedros Adhanom Ghebreyesus, WHO Director-General elect, on 24 May 2017. “I think something that was coming very, very clearly was people identifying health as a rights issue.

Health is a rights issue. All roads should lead to universal health coverage. And it should be the centre of gravity of our movement. And when you say universal health coverage, it’s addressing the financial barrier.

It’s addressing the challenge we are facing with regard to access to drugs.” I rest my case.

REPORTS

Global dermatology market set to benefit extensively from pipeline biologics According to GBI Research, the use of biologics in dermatology has gained prominence over the years, primarily in psoriatic disease THE GLOBAL dermatology market, which covers over 3,000 distinct dermatological conditions ranging from rare autoimmune disorders such as scleroderma to very common conditions such as acne, is set to see an increased presence of biologics over the next few years, particularly monoclonal antibodies (mAbs) and biosimilars, according to business intelligence provider GBI Research.

The company’s latest report states that for the past decade the majority of the therapeutic dermatology market has been saturated and highly genericised. There is a significant unmet need for more efficacious and safer treatment options, as the long-term use of many available treatments is associated with poor efficacy, low patient compliance, and problematic

safety profiles.

Jennifer Goossens, Associate Analyst, GBI Research, explains, “In contrast with the market, the dermatology pipeline is highly diverse in terms of molecule type. Small molecules continue to dominate over half of the pipeline, while biologics represent over

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a third, and around 10 per cent are made up of a range of rarer molecule types including cell therapies, gene therapies, and synthetic peptides.

“While mAbs have started to establish their market presence, gene therapies, vaccines, and cell therapies are not yet well established in the derma-

tology market. A particularly high degree of diversity is seen at the discovery and preclinical stages, at which mAbs, proteins, oligonucleotides, and synthetic peptides account for a considerable proportion of the pipeline.”

A greater understanding of the inflammatory and systemic nature of many skin diseases has led to the development of biologics with the ability to target specific pro-inflammatory cytokines, or other relevant inflammatory mediators involved in dermatological disorders. The use of biologics in dermatology has gained prominence over the years, primarily in psoriatic disease, a condition in which clinical success has created enthusiasm for their use in other dermatological conditions.

Goossens continues, “This is reflected in the various

biologics currently in the pipeline for major skin disorders, for which there is a significant unmet need in patients with moderate to severe conditions. Biologics represent over a third of pipeline molecules, despite only accounting for a small fraction of the marketed products landscape, where they are vastly outnumbered by small molecules. This strong presence could have a considerable impact on treatment algorithms in the dermatology therapy area, according to GBI Research. For example, the first biologic for the major dermatological disease atopic dermatitis, Dupixent (dupilumab), was approved by the FDA on 28 March 2017 and is expected to signal the start of a new trend for biologics in the dermatology space.”

EP News Bureau

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MANAGEMENT

Long-acting therapies could transform HIVtreatment by boosting compliance Adherence challenges or incarcerated patients might find this kind of antiretroviral regimen desirable ONE OF the most pressing unmet needs in the human immunodeficiency virus (HIV) market, which is set to reach $22.5 billion by 2025, lies in the current lack of long-acting and safer treatments, according to research and consulting firm GlobalData.

The company’s report states that adherence to antiretroviral therapy (ART) is a significant concern in the treatment of HIV, and current treatment options all require a minimum of once-daily dosing. While long-acting therapies would likely involve clinician-administered injections and would not appeal to all patients, those with adherence challenges or incarcerated patients, for example, might find

this kind of antiretroviral regimen desirable.

David Fratoni, PharmD, Healthcare Analyst, Global-

Data, explains: “Currently, ART is dependent on combination of several antiretroviral drugs, and this will likely also be the case for long-acting anti-HIV treatments.

Therefore, long-acting drugs would ideally be co-formulated as a single, long-acting treatment that could, for example, be administered as an intravenous injection once a month.”

In terms of recent efforts to address this unmet need, ViiV and Janssen are working to develop a long-acting formulation composed of the INI, cabotegravir, in combination with the non-nucleoside reverse transcriptase inhibitor (NNRTI), rilpivirine, which is already marketed under the

brand name of Edurant.

Fratoni continues, “The development of novel, longacting treatments for HIV-1 is ongoing, and according to GlobalData’s insight, there is a high possibility that these will replace the current treatment for many HIV patients in the forecast period.

“While long-acting formulations are likely to appeal mostly to specific patient populations, such as incarcerated and homeless patients, there is still a sizeable commercial opportunity for those people who find it difficult to take one or more pills every day to comply with the treatment regimen.”

EP News Bureau

NASH market will increase more than 40 fold by 2026 Rising rate of obesity and diabetes globally and launches of multiple late-stage pipeline products will transform the market THE NON-ALCOHOLIC steatohepatitis (NASH) space across the seven major markets of the US, France, Germany, Italy, Spain, the UK, and Japan, is set to rise from $618 million in 2016 to around $25.3 billion by 2026, representing a very rapid compound annual growth rate of 45 per cent, according to research and consulting firm GlobalData.

The company’s latest report states that major drivers of this impressive growth include the rising rate of obesity and diabetes globally and the launches of multiple late-stage pipeline products, which will transform the market from one dominated by the use of off-label generics to a burgeoning, competitive space.

Lakshmi Dharmarajan, Managing Healthcare Analyst,

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GlobalData, explains: “Currently, the NASH market has no approved therapies and is dependent on off-label agents that only offer sub-optimal safety and efficacy outcomes to patients.

However, despite NASH drug developments being historically slow, several companies developing late-stage pipeline drugs for the disease have been actively employing strategies to identify biomarkers in recent years.”

GlobalData believes that most of the pipeline drugs in late-stage development for NASH are superior to the standard of care, vitamin E, and other off-label therapies in terms of the clinical and commercial profiles. The initial uptake of the drugs will be slow, due to their high cost and reimbursement issues. However, towards the end

of the forecast period, it is expected that these drugs will displace current treatments, driven by the launch of biomarkers.

These biomarkers will work in multiple ways, by identifying the

target patient pool and by predicting treatment outcomes, both essential in demonstrating the pharmaco-economic value of the new agents to payers.

Dharmarajan continues,

“Due to their different mechanisms of action, it is also expected that each of the pipeline drugs will have a place in treating a specific segment of the heterogeneous patient population, so the NASH market is likely to be highly fragmented, with each drug garnering a small share of the total market.”

By 2026, the vast majority of global sales for NASH treatments will come from drugs that are currently in the pipeline.

Among these drugs, Gilead’s selonsertib, Intercept’s Ocaliva, and Genfit’s elafibranor will be the highest revenue earners, accounting for around 29 per cent, 22 per cent, and 21 per cent of 2026 global sales for the pipeline drugs, respectively.

EP News Bureau

MANAGEMENT

Asia-Pacific asthma market will hit $6 billion by 2023 According to GBI Research, the strong growth will be driven by an expanding aging population, increase in air pollution, a promising product pipeline and the launch of first-in-class molecules THE ASIA-PACIFIC (APAC) asthma therapeutics market, which covers India, China, Australia, South Korea and Japan, is expected to grow significantly from $4.1 billion in 2016 to around $6 billion by 2023, representing a compound annual growth rate of 5.4 per cent, according to business intelligence provider GBI Research.

The company’s latest report states that this strong growth will be driven by an expanding aging population, increases in air pollution, a promising product pipeline and the launch of first-in-class molecules.

Gautam Arora, Analyst, GBI Research, explains, “There are a number of therapies currently in development for asthma designed to address unmet needs in the market that will, depending on clinician uptake, drive the annual cost of therapy associated with the disease. The most prominent examples are interleukin-targeting monoclonal antibodies (mAbs), including reslizumab, dupilumab, tralokinumab, and benralizumab.

“Mepolizumab and omalizumab represent a clear shift towards personalised medicine for the treatment of asthma.

The high price of these biologics, which is due to the costliness of manufacturing a biologic agent, as well as the potential first-to-market status for severe asthma, will contribute to the high sales figures.”

A rise in biologic development in the asthma market is possibly attributable to the success of Xolair (omalizumab), one of the currently marketed mAbs, which reached blockbuster status in 2014. The drug was approved in 2003 in India, Australia, Japan, and South Korea, as an add-on therapy for those aged 12 and over with moderate-to-severe allergic asthmas and symptoms not adequately controlled with inhaled corticosteroids. It was the first biologic to reach the APAC asthma market, and its launch

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addressed a significant unmet need for personalized therapy in asthma.

Arora continues: “Drug de-

velopers are now looking to follow the example of Xolair, which is widely prescribed in Japan, Australia, and South Korea, by

developing highly targeted biologics and mAbs aimed at specific patient sub-types, with the hope of benefiting previously

underserved patients and generating strong revenues.

EP News Bureau

RESEARCH I N T E R V I E W

SPORE is focussed on a specific organ site, such as breast or lung cancer Dr George R Simon, Professor of Medicine and Section Chief, Translational Research, Department of Thoracic/Head and Neck Medical Oncology, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas talks about the SPORE programme for controlling lung cancer incidence and explains the role and impact of DNA repair pathways in therapeutic efficacy, in an interview with Viveka Roychowdhury India has a high burden of lung cancer. What are the causes specific to the country for this growing incidence?

About 1.8-2 million new lung cancer cases are estimated to occur globally, 6.9 per cent of which are from India.

Globally, the disease is one of the commonest cancers and cause of cancer related deaths, and in India, lung cancer is the commonest cancer and cause of cancer related mortality in men.

Factors that are known to contribute to the growing incidence of lung cancer in India include smoking, bidi smoking, exposure to biomass fuel and environmental pollution. The incidence and pattern of lung cancer tend to differ with geographic region and ethnicity and largely reflect the prevalence and pattern of smoking in the country.

As the Section Chief, Translational Research, Department of Thoracic/Head and Neck Medical Oncology, what are the most promising areas of research to treat lung

26 EXPRESS PHARMA June 16-30, 2017

cancer?

Today, most research on lung cancer is focussed on areas of prevention, early detection and treatment. Promising lung cancer treatment options that have emerged include videoassisted thoracic surgery (VATS) to treat small lung tumours, image guided radiation therapy (IGRT), newer combinations of chemotherapy drugs, immunotherapy and targeted therapy. Several new and exciting targeted therapies and immunotherapies have been approved in the last two years.

These drugs have dramatically improved the lung cancer landscape. Newer treatment strategies evolve as resistance develops to existing treatments. Understanding these resistance treatments leads to the development of newer drugs to mitigate emerging mechanisms of resistance.

Could you give us more details of SPORE, the Specialized Program of Research Excellence programme and what hope does it offer lung cancer

patients?

Specialized Programs of Research Excellence (SPORE) is a cornerstone of National

Cancer Institute (NCI’s) efforts to promote collaborative, interdisciplinary translational cancer research. SPORE

grants involve both basic and clinical/applied scientists working together and support projects that will result in new and diverse approaches to the prevention, early detection, diagnosis and treatment of human cancers. Each SPORE is focussed on a specific organ site, such as breast or lung cancer, on a group of highly related cancers, such as gastrointestinal cancers and sarcomas, or on a common pathway or theme that ties together the cancers under study.

Lung cancer became an early focus of the SPORE Programme due to the huge burden in terms of morbidity and mortality. The lung cancer SPORE was originally given jointly to MD Anderson and The University of Texas Southwestern Medical Center in Dallas in 1996. Both institutions have received $6.5 million in SPORE renewed funding. The collaboration has produced several key findings including the identification of three lung cancer tumour suppressor genes on chromosome 3 that dramatically reduced human

The deregulation of DNA repair proteins within cells may provide an attractive therapeutic window. Such an approach is exemplified by the PARP inhibitors, which show potential use in the treatment of cancers deficient of functional BRCA1 or BRCA2 lung cancer growth in mice. Apart from this, lung cancer SPORE has also been granted to University of Colorado Cancer Center, University of Pittsburgh & Yale University. Other lung cancer SPORE’s have been granted to other institutions over time.

What have been the drawbacks associated with traditional chemotherapeutics and treatment pathways to treat lung cancer?

Traditional chemotherapeutics cannot distinguish between normal healthy body cells and cancerous cells, which means that they damage while they cure. They work by attacking cells that divide quickly, which is a characteristic of cancer cells. However, other cells in the body, such as those in the bone marrow (where new blood cells are made), the lining of the mouth and intestines, and the hair follicles, also divide quickly. In addition to the cancer cells, these healthy body cells are also affected. Traditional chemotherapeutics are a non-direct, aggressive treatment option, which lead to side effects such as hair loss, mouth sores, nausea, vomiting, diarrhoea, fatigue, and an increased risk of easy bruising or bleeding. Today, we are moving towards targeted, personalised medicine which takes advantage of the inherent differences that exist between normal cells and cancer cells, and only targets to eliminate the latter. Lung cancer is a typical cancer type to be treated by driver mutation status (EGFR, ALK, ROS). EGFR mutation which is more common in Asians (25 – 65 per cent) is a targetable mutation and can be treated with generations of tyrosine kinase inhibitors. More recently there are immunotherapies which seems to work better in patients whose tumour’s express higher levels of a biomarker called PD-L1.

What is the role and impact of DNA repair pathways in therapeutic efficacy?

Tumour cells possess certain DNA

repair pathways that enable these cells to survive DNA damage induced by chemotherapeutic treatments, which reduce cancer treatment efficacy. We are now exploring the use of DNA repair inhibitors, particularly small-molecule inhibitors, which prevent these repair mechanisms within tumour cells. These inhibitors hold promise for damaging tumour cells, with their specificity taking us several steps closer to truly personalised medicine.

What is the approach used in DNA repair targeted therapy? What have been the results so far?

We have sufficient evidence that suggests that all cancers display defects in DNA repair. It has also been demonstrated that the ability of cancer cells to repair therapeutically-induced DNA damage impacts treatment efficacy. This has led to researchers targeting DNA repair pathways and proteins to develop anti-cancer agents that increase sensitivity of the cancer cell to traditional chemotherapeutics.

Platinum-based DNA damaging agents such as cisplatin and carboplatin form the foundation of many lung cancer treatment regimes today. These drugs are selectively lethal to rapidly dividing cells, where they cause irreparable DNA damage, subsequently directing cancer cells towards apoptotic cell death. However, although this approach shows initial efficacy, our main challenge with these agents remains the eventual development of drug resistance, the precise mechanisms of which remain poorly understood.

The deregulation of DNA repair proteins within cells may provide an attractive therapeutic window. Such an approach is exemplified by the PARP inhibitors, which show potential use in the treatment of cancers deficient of functional BRCA1 or BRCA2. In addition, these drugs may show increased efficacy in combination with DNA-damaging agents. viveka.r@expressindia.com

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RESEARCH UPDATES

Sheffield scientist investigates how to stop breast cancer spreading to the bone Research identified molecule which plays a critical role in helping secondary breast tumours form in the bone A LEADING scientist from the University of Sheffield is investigating a possible key to preventing breast cancer spreading to the bone. The cutting-edge research is funded by a grant worth almost £200,000 by research charity Breast Cancer Now. If breast cancer spreads around the body – known as secondary breast cancer – it becomes incurable. Over 1,000 women in South Yorkshire are diagnosed with breast cancer every year, and more than 220 women in the region die from the disease each year.

The majority of the 11,500 women who die as a result of breast cancer each year in the UK will have seen their cancer spread. The bone is one of the most common places for breast cancer to spread to, with around 70 per cent of secondary breast cancer patients having tumours in the bone.

With previous funding from Breast Cancer Now, Professor

Alison Gartland from the University of Sheffield’s Department of Oncology and Metabolism made a significant discovery – published in the journal Nature - that a molecule called lysyl oxidase (LOX), which is released by primary breast tumours, is responsible for making holes in bones. These holes help prepare or ‘prime’ bone for the arrival of breast cancer cells, increasing the tendency of cancer cells to spread there.

Professor Gartland’s team will now investigate how a second molecule – P2X7R – interacts with LOX to help breast cancer spread, and whether it could be targeted with drugs to stop breast cancer spreading.

“We have since found that P2X7R can work with LOX to prepare the bone environment for the arrival of secondary cancer cells, so this Breast Cancer Now grant will enable us to investigate this further.

“We hope to find out whether drugs that block P2X7R, which

have already been shown to be safe in clinical trials for arthritis, could prevent cancer spreading to the bone. This would be of great benefit in the fight against this horrendous disease that has such devastating effects."

Firstly, the team will study how P2X7R interacts with LOX in individual bone cells, before examining how drugs that block P2X7R modify the effect of LOX on bone tissue. By doing this, the team hopes to establish whether LOX is only able to prime the bones in the presence of P2X7R, and will investigate whether any other molecules are also involved in helping cancer to spread. Next, the research team will test the effects of drugs that block P2X7R and LOX using mouse models of primary and secondary breast cancer.

They will use micro-CT scans to assess the number and size of the holes in bone following this treatment, as well as taking blood samples to measure

levels of LOX and other molecules that indicate possible spread to the bone. They will also analyse tumour growth across a variety of metastatic sites, to assess the effects of blocking P2X7R on the formation of secondary tumours.

Dr Richard Berks, Senior Research Communications Officer, Breast Cancer Now, said, “If we are to stop people dying from breast cancer, we must find a way to prevent the disease spreading. Professor Gartland’s

research could help uncover which molecules are vital in helping breast cancer spread to the bones, and identify drugs that might stop this happening.”

Breast Cancer Now is the largest breast cancer charity in the UK, dedicated to funding pioneering research into this devastating disease. The charity’s ambition is that, by 2050, everyone who develops breast cancer will live.

EP News Bureau

Childhood cancer survivors have less long-term side effects There were improvements with regards to endocrine conditions such as diabetes, thyroid disease BETTER TREATMENT strategies for paediatric cancers are helping survivors live longer, with fewer serious health problems related to their treatment, US researchers said recently.

The finding, presented at the American Society of Clinical Oncology meeting in Chicago, is based on analysis of data from 23,600 participants in the Childhood Cancer Survivor Study funded by the National Institutes of Health.

Overall, severe health conditions arising within 15 years of

28 EXPRESS PHARMA June 16-30, 2017

childhood cancer diagnosis fell to 8.8 per cent of survivors in the 1990s, from 12.7 per cent in the 1970s, the study found.

The findings show that childhood cancer survivors who were given more modern treatment approaches, such as reduced exposure to radiation and lower doses of chemotherapy, were faring better, said Todd Gibson of St. Jude Children's Research Hospital in Memphis, who led the study.

The researchers focussed on severe, disabling, life-threaten-

ing or fatal health problems that occurred within 15 years of being diagnosed with a paediatric cancer between 1970 and 1999.

The biggest declines in health problems related to treatment occurred in survivors of Wilms' tumour, a rare kidney cancer. In this group, serious complications fell to five per cent of survivors in the 1990s, from a high of 13 per cent in the 1970s.

In survivors of childhood Hodgkin lymphoma, latent complication rates fell to 11 per cent,

from 18 per cent in the 1970s.

Improvements were also seen for astrocytoma, the second most common childhood cancer, and acute lymphoblastic leukemia, the most common childhood cancer.

There were no reductions in long-term side effects among survivors of neuroblastoma, acute myeloid leukemia, soft-tissue sarcoma and osteoscarcoma. The biggest improvements were seen with regards to endocrine conditions such as diabetes, thyroid disease or

growth hormone deficiency. The researchers saw endocrine problems fall to 1.6 per cent for childhood cancer survivors surveyed in the 1990s, compared with four per cent in the 1970s.

Gastrointestinal and neurological conditions also improved.

But there was no improvement in rates of heart or lung conditions, which the researchers said served as a reminder of the need for close follow-up in childhood cancer survivors.

Reuters

RESEARCH

Grail passes early test in quest to find cancer in blood Grail's test scans blood samples for mutations in 508 genes, reading each region of the genome some 60,000 times AN EARLY stage trial of an ultra-sensitive 'liquid biopsy' that scans blood samples for traces of cancer DNA showed it was able to pick up at least one cancer mutation in most of the patients with advanced cancers that were studied.

The findings, presented at the American Society of Clinical Oncology meeting in Chicago, show the new test by Grail, a spin-off of gene sequencing company Illumina, can identify bits of cancer DNA in the blood of patients already known to have cancer.

The study is the first of many the company must perform as it aims to develop a blood test to find early stage cancers in people with no symptoms of the disease.

“It's an important first step. We show that what we call a high-intensity approach works,” said Dr Pedram Razavi of Memorial Sloan Kettering in New York, who led the study.

Most liquid biopsies use next-generation sequencing to scan blood samples for fragments of tumour DNA in people previously diagnosed with cancer.

Such tests, from a host of companies including Guardant Health, Foundation Medicine, Qiagen NV, Genomic Health and Myriad Genetics, offer a non-invasive alternative to standard tissue biopsies and are expected to be a multibillion-dollar market. They are used to identify which genes are driving a person's cancer or measure the effectiveness of treatment.

Cancer experts say it is difficult enough to find cancer DNA in the bloodstream of patients with advanced tumours, but it will be far more challenging to find rare cancer genes in blood from healthy people.

To achieve this, Grail's test scans blood samples for mutations in 508 genes, reading each region of the genome some 60,000 times. The company says the process yields 100 times more data than other liquid biopsy approaches.

The company was formed in 2016 with $100 million in investments from Illumina and others including Amazon.com founder Jeff Bezos and Microsoft Corp co-founder and philanthropist Bill Gates. In March, the company said it had raised more than $900

The study is the first of many the company must perform as it aims to develop a blood test to find early stage cancers in people with no symptoms of the disease million in financing.

For the feasibility study, researchers from Sloan Kettering and Grail analysed tissue and blood samples from 124 patients with metastatic breast, lung, and prostate cancers, to see if the blood test detected mutations that were identified in separate tests from tissue biopsies.

In 89 per cent of patients, at least one genetic change detected in the tumour was also found in the blood.

“Basically, what they're showing is that they can detect in blood the majority of the same mutations that they can detect in tissue of patients with advanced cancer,” said Dr Richard Schilsky, Chief Medical Officer, ASCO, who was not involved in the study.

Schilsky said the study is a first step in validating the test, adding diagnosing early stage cancers from a blood test "is a very high hurdle."

Even if Grail proves it can find early stage cancers, such a test could create a challenge for doctors, who would need to find the tumour so it could be removed. Razavi said scientists are already considering that problem, too.

Mark Lee, head of clinical development and medical affairs at Grail, said the company plans to use its test on hundreds of thousands of people with and without cancer to map out the characteristics that distinguish early stage cancers from normal DNA.

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Reuters

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RESEARCH

Teva’s migraine drug clears late-stage study Patients treated with fremanezumab experienced a statistically significant reduction in the number of monthly headache days for both monthly TEVA PHARMACEUTICAL Industries said that its experimental drug to prevent migraine cleared a late-stage study, paving the way for a US regulatory submission later this year.

Patients treated with Teva’s drug, fremanezumab, experienced a statistically significant reduction in the number of monthly headache days for both monthly and quarterly dosing regimens, the Israel-based company said.

About 40 million Americans suffer from migraine - intense headache characterised by throbbing pain and sensitivity to light and nausea. The condition, which can last for days, is incurable.

Teva joins companies such as Amgen, Eli Lilly Co and Alder BioPharmaceuticals that are developing similar drugs to target calcitonin gene-related peptide, or CGRP, a protein involved in pain-signalling during migraine.

The most important data point is that the

quarterly dosing regimen worked for Teva, Evercore ISI's Umer Raffat said, noting that Lilly and Amgen's compounds are being developed for use only on a monthly basis.

In the 1,130-patient trial, fremanezumab was evaluated against a placebo in patients suffering from chronic migraine - those who experience 15 or more headache days per month.

Data from a separate study in patients

with episodic migraine — those who experience up to 14 headache days per month — is expected in the coming weeks.

Currently, patients are treated with triptans, a class of drugs that hit the market in the 1990s. These medicines work by constricting blood vessels in the brain and cannot be used in up to 35 per cent of patients due to high cardiovascular risk.

A host of other drugs, including anti-depressants, medicines for hypertension and even botox, are also used to treat migraine but with little success.

Overall, migraine cost the US roughly $36 billion a year in terms of healthcare and lost productivity, according to the Migraine Research Foundation.

The lack of effective medicines and the sheer number of patients guarantee that each company's drug, if approved, will eventually generate at least $1 billion in sales, analysts have forecast.

Reuters

Pfizer drug delays lung cancer growth longer than Astra’s Iressa: Study Liver enzyme abnormalities were the most common serious side effect observed in the Iressa patients A TARGETED drug being developed by Pfizer held advanced lung cancer in check longer than AstraZeneca's Iressa in newly diagnosed patients, but with a higher rate of side effects, according to data presented.

The late-stage study of 452 patients with EGFR-positive non-small cell lung cancer (NSCLC) compared Pfizer's next generation oral drug, dacomitinib, with the older standard treatment that also targets abnormal epidermal growth factor receptor genes in advanced lung cancer.

Dacomitinib delayed the cancer from worsening for 14.7 months compared with 9.2 months for Iressa, a measure known as progression-free sur-

30 EXPRESS PHARMA June 16-30, 2017

vival, researchers reported.

That translates into a 41 per cent lower risk of cancer progression with the experimental medicine.

The data was presented at the American Society of Clinical Oncology meeting in Chicago.

With the increased potency, however, came stronger suppression of normal EGFR genes in healthy tissue in the skin and gastrointestinal tract, causing a higher rate of acne and diarrhoea, researchers reported.

About 60 per cent of patients receiving the Pfizer drug in the study had the dose lowered due to side effects. Liver enzyme abnormalities were the most common serious side effect observed in the Iressa patients.

Despite the higher rate of side effects, "the activity seen in this study should allow for consideration of this effective therapy in this patient population," Dr Tony Mok from Chinese University of Hong Kong,

who led the study, said in a statement.

Pfizer said it expects to discuss the data with regulatory authorities as it plans to seek approvals for the drug.

Boehringer Ingelheim already markets a next generation EGFR inhibitor for advanced NSCLC called Gilotrif (afatinib) that the Pfizer drug would compete with if approved.

Iressa, known chemically as gefitinib, was among the first targeted drugs that replaced chemotherapy as a treatment of choice for these patients.

About 140,000 patients worldwide and 15,000 in the US are diagnosed each year with EGFR-positive NSCLC. Reuters

Chinese cell therapy effective in small multiple myeloma trial A SMALL trial conducted in China found that an experimental therapy using altered cells to recruit the body's immune system to attack cancer can induce remission in most patients with advanced multiple myeloma, a blood plasma cancer.

The study of 35 patients tested a chimeric antigen receptor T-cell (CAR-T) therapy developed by China's Nanjing Legend Biotech Co. The drug candidate, known as LCAR-B38M, targets a protein called BCMA found on cancerous blood plasma cells the same target being pursued

by Bluebird Bio and Celgene Corp with their CAR-T called bb2121.

CAR-T therapies require a complicated process of extracting immune system T cells from an individual patient, altering their DNA to sharpen their ability to spot and kill cancer cells, and infusing them back into the same patient.

The American Society of Clinical Oncology, which featured the data here at its annual meeting, said that out of 19 trial patients followed for more than four months, 14 reached complete remission. One patient had a partial response and four patients reached ‘very good partial remission,’ but the cancer did get worse in one of those patients.

Multiple myeloma “is a disease you can treat pretty well with other drugs, but this could be long-term remission,” said Dr Bruce Johnson, Chief Clinical Research Officer, Boston's Dana-Farber Cancer Institute and ASCO's incoming president.

Reuters

RESEARCH

Older adults might be able to stave off arthritis knee pain with fibre Fibre can act as a pre-biotic meaning that it can help fuel the growth of beneficial microbes in the gut, which in turn also reduces inflammation OLDER PEOPLE who eat the most fibre are at lower risk of developing knee pain and stiffness due to osteoarthritis (OA), new research shows.

Diets rich in fibre from plant-based foods have clear health benefits, such as lower cholesterol, better-controlled blood sugar, and a healthier weight, but most people in the US don’t eat enough fibre, lead author Dr Zhaoli Dai of Boston University School of Medicine said.

The current average fibre intake among US adults is about 15 grams, she noted. “This is far below the recommended level, which is 22.4 grams for women and 28 grams per day for men 51 years and above,” Dai said.

OA, which occurs when wear and tear on the joints degrades cartilage and leads to bone abnormalities, is extremely common in people 60 and older. It can be painful, and is also a leading cause of disability. There is no treatment for OA, aside from joint replacement, and therapies to address symptoms, such as anti-inflammatories for pain and swelling.

Given that dietary fibre is known to help prevent obesity and reduce inflammation, both of which are associated with arthritis, Dai’s team looked at diet and arthritis risk over time in two study groups. In the Osteoarthritis Initiative, which included 4,796 men and women with OA or at risk for OA, people who consumed the most dietary fibre at the start of the study were 30 per cent less likely than those who ate the least fibre to develop knee pain, stiffness or swelling due to OA, or to worsening of OA, during four years of follow-up.

In the Framingham Offspring Study, which included 1,268 adults in their early 50s, on average, the top quarter of fiber consumers had a 61 per cent lower risk of knee OA symptoms nine years later than the bottom quarter.

There are many mechanisms through which increased fibre intake could help ease knee arthritis symptoms, Dai said, for example by reducing

inflammation and helping people to maintain a healthy weight. Fibre can also act as a pre-biotic, she added, meaning that it can help fuel the growth of beneficial microbes in the gut, which in turn also reduces inflammation.

“This is the first study to show that consuming more dietary fibre is related to lower risk of painful knee osteoarthritis,” Dai said. “Changing diets by increasing intake of dietary fibre seems to be one of the most economic ways to reduce the risk of knee osteoarthritis.”

Older adults, especially those who are overweight or obese, should consider increasing their fibre intake, she added.

Reuters

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RESEARCH

AstraZeneca’s Lynparza slows advanced breast cancer progression Women in the study had metastatic breast cancer classified as hormone receptor-positive or triple negative and had undergone prior chemotherapy

WOMEN WITH advanced breast cancer who carry specific genetic mutations experienced double the response rate and delayed disease progression when treated with AstraZeneca's Lynparza compared with standard chemotherapy, according to data from a late-stage trial.

In the study of 302 patients with inherited mutations of the BRCA1 or BRCA2 genes, about 60 per cent who received the oral treatment Lynparza experienced significant tumour shrinkage compared with 29 per cent who got chemotherapy. Nine per cent of Lynparza patients had a complete response versus two per cent on chemotherapy.

Median time to disease worsening was seven months with Lynparza versus 4.2 months for chemotherapy, a statistically significant 42 per cent reduction in progression risk.

In addition, “There was a delay in the time until their quality of life began to deteriorate,” said Dr Mark Robson

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of Memorial Sloan Kettering Cancer Center in New York, who led the study.

Women in the study had metastatic breast cancer classified as hormone receptorpositive or triple negative and had undergone prior chemotherapy.

"Triple negative breast cancer in particular is difficult to treat after it's failed a couple of chemotherapy regimens. To have a relatively well-tolerated oral agent as an alternative for these women is certainly exciting," said Robson, who presented the data at the American Society of Clinical Oncology (ASCO) meeting in Chicago.

Lynparza, known chemically as olaparib, belongs to a class of drugs called PARP inhibitors already approved for ovarian cancer.

Michelle Werner, head of US oncology for AstraZeneca, said the data represents "the first time that a PARP has demonstrated benefits outside of the ovarian cancer space."

The company expects to

seek approval for use of the drug in breast cancer toward the end of this year, she said.

“I'm convinced PARP inhibitors are here to stay in breast cancer,” said Dr Daniel Hayes, President, ASCO, who was not involved in the study.

About three per cent of breast cancers occur in people with inherited BRCA1 or BRCA2 mutations that lower a cell's ability to repair damaged DNA. Up to 65 per cent of women who inherit the mutations will develop breast cancer, often much younger than is typical for the disease.

Serious side effects were reported in 37 per cent of Lynparza patients compared with 50 per cent for chemotherapy, but just five per cent discontinued Lynparza due to side effects.

Robson said the AstraZeneca drug should be tested in combination with a variety of other therapies to assess if they "can improve the responses and extend the benefit."

Reuters

Early use of J&J’s Zytiga extends prostate cancer survival Zytiga, or abiraterone acetate, is a pill that decreases production of testosterone, the hormone that stimulates growth of prostate tumours ADDING JOHNSON & Johnson's Zytiga to standard hormone therapy reduced by nearly 40 per cent the chance of death for men newly diagnosed with high-risk prostate cancer that had spread to other parts of the body, according to new trial results.

The data, which supports expanding the drug's use to earlier stages of prostate cancer, is “likely to change clinical practice overnight,” said Dr Richard Shilsky, Chief Medical Officer, American Society of Clinical Oncology, which featured the studies on Saturday at its annual meeting in Chicago.

J&J is already seeking European Union approval in the earlier treatment setting, but is still considering whether to pursue US approval.

Zytiga, or abiraterone acetate, is a pill that decreases production of testosterone, the hormone that stimulates growth of prostate tumours. It is approved for men whose cancer has worsened after treatment with docetaxel chemotherapy and for use before chemo for disease resistant to traditional hormone drugs.

At a US list price of $9,400 a month, Zytiga is expensive.

J&J's domestic Zytiga sales totalled just over $1 billion last year, and global sales were $2.26 billion.

“The difference here is ... patients who have not been on hormonal therapy,” said Craig Tendler, Head of Global Medical Affairs, J&J’s Janssen division.

"This is much less common in the US where we have very aggressive screening guidelines."

Those guidelines, however, are changing and more men are declining to undergo testing.

In late 2011, the US Preventive Services Task Force, a government-backed panel of independent physicians, recommended against routine prostate cancer testing, citing concerns that it often caught tumours that did not need treatment and led to unnecessary procedures with side effects such as impotence and incontinence.

The latest studies, following 2015 trials showing an advantage with chemotherapy, offer the first new options for metastatic prostate cancer patients in nearly 70 years, said Dr Karim Fizazi, head of the department of cancer medicine at France's Gustave Roussy Cancer Center, who led one study.

He estimated that just three to five per cent of men in developed countries have metastatic cancer by the time the disease is diagnosed, but the number rises to 60 per cent in countries like China and India where screening is less common.

The Gustave Roussy trial showed that at a median of 30 months after beginning treatment, men taking Zytiga and the steroid prednisone plus standard hormone therapy had a 38 per cent lower risk of death compared with men given hormone therapy and a placebo.

Zytiga was also associated with a 53 per cent lower risk of the cancer worsening.

Severe side effects from the drug included high blood pressure in 20 per cent of patients.

Fizazi said a trial to see if Zytiga has a benefit when added to hormone therapy and chemotherapy is still under way.

Reuters

PHARMA ALLY VENDOR NEWS

Coloron opens new technical services lab in Noida The laboratory, which is Colorcon’s 20th across the world, is strategically located to provide convenient access for customers across the region COLORCON HAS opened a new technical service laboratory and conference facility in Noida, to support continuing industry growth and extend local assistance to customers in the northern part of India. The new laboratory, which is Colorcon’s 20 th across the world, is strategically located to provide convenient access for customers across the region.

Rajesh Parab, GM, Colorcon South Asia said, “The northern part of India is significant for Colorcon as it’s a pharmaceutical development and manufacturing hub, this strategic investment demonstrates Colorcon’s commitment and focus to the fastgrowing Indian pharma market in this region.”

Sailesh Verma, Regional Sales Manager, Colorcon adds, “The new laboratory in Noida, brings a fast response to our customers and helps them to respond to market dynamics, bringing product to market faster. The facility extends Colorcon’s direct support to customers and supplements

the existing laboratory facilities established in Goa to provide a faster turnaround time for their projects and easy access to technical services.”

Shantanu Damle, Technical Manager – Coloron South Asia, explains, “Being located closer to our customers (in the north), this technical centre will provide the opportunity for customers to directly visit and conduct laboratory scale coating trials using conventional and automated coating equipment that aligns with the equipment in their facilities, saving them valuable development and scale-up time.”

The facility also provides the opportunity to extend the educational events offered through the Colorcon Academy, with resources to conduct Colorcon coating schools and formulation training programmes which will facilitate knowledge sharing and benefit individuals as well as their companies.

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EP News Bureau

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June 16-30, 2017

PHARMA ALLY

LANXESS appoints Dr Jens-Christian Blad as new head of corporate development Dr Blad will assume the role by September 1, 2017

Lanxess global sales increases by 25 per cent to EUR 2.4 billion L

S

pecialty chemicals company LANXESS has appointed a new head of Corporate Development. Dr Jens-Christian Blad will assume responsibility for the group function by September 1, 2017.

Blad studied chemistry in Kiel, obtained his doctorate in Muenster and is regarded by many in the industry as a specialty chemicals expert. He has been with the global management consulting firm McKinsey & Company since 2006, where he is in charge of the ‘Megatrends-supported growth in chemicals’ initiative

ANXESS started 2017 with a very good first quarter. Global sales of the specialty chemicals company increased by a substantial 25 per cent to EUR 2.4 billion, up from EUR 1.9 billion a year earlier. EBITDA pre exceptionals also improved by 25 per cent to EUR 328 million, compared with EUR 262 million in the first quarter of 2016. Net income rose by a substantial 47 per cent to EUR 78 million, against EUR 53 million in the year-earlier quarter. In view of the positive operational development and the successfully completed acquisition of Chemtura, the company expects to post EBITDA pre-exceptionals of between EUR 1,225 million and EUR 1,300 million for the full year 2017. This forecast takes account of the earnings contribution from the newly acquired Chemtura businesses. 2017 could therefore be the most successful fiscal year in the company’s history.

“LANXESS today is a realigned enterprise

and a member of the Chemicals Practice.

Following the closing of the acquisition of US-based chemical company Chemtura, the current head of corporate development, Dr Markus Eckert, has assumed responsibil-

that is profitable, stable and fast-growing,” stressed Matthias Zachert, Chairman of the Board of Management, LANXESS, said in his presentation before the stockholders at the LANXESS arena in Cologne.

In view of the encouraging business results, the Board of Management and the Supervisory Board proposed to the annual stockholders’ meeting that a dividend of EUR 0.70 be paid out – an increase of 17 per cent against the previous year. This would result in a total dividend payout of around EUR 64 million.“We are thus achieving our goal of paying an increasing but at least stable dividend,” said Zachert. EBITDA pre exceptionals of LANXESS rose by 12.4 per cent to EUR 995 million in 2016, compared with EUR 885 million a year earlier. The main drivers of this positive development were higher volumes in all segments, the associated increase in capacity utilisation and cost savings resulting from the

ity for the new Urethane Systems business unit. Until his successor begins his new role, Eckert will remain responsible for the group function, in addition to his new role.

“I am delighted we have secured the appointment of

improved competitiveness of the company’s plants and processes.

The Group’s EBITDA margin pre exceptionals improved from 11.2 per cent to 12.9 per cent. Net income rose by a substantial 16.4 per cent to EUR 192 million from EUR 165 million. Sales declined slightly, from EUR 7.9 billion in 2015 to EUR 7.7 billion, primarily due to the adjustment in selling prices to reflect lower raw material costs.

At the end of the past fiscal year, net financial liabilities fell very substantially from EUR 1.2 billion to EUR 269 million. This was mainly due to the proceeds from the joint venture for synthetic rubber with Saudi Aramco. In 2016, capital expenditures amounted to EUR 439 million, which was more or less level with the prior-year figure of EUR 434 million.

EP News Bureau

Jens-Christian Blad, a recognised industry expert and an experienced consultant, to lead the group function and help us press ahead with our realignment,” said Matthias Zachert, Board of Management Chairman, LANXESS.

“On behalf of the Board of Management, I would like to thank Eckert for his outstanding work and wish him continued success in his new area of responsibility,” he added.

EP News Bureau

Mukund Turakhia, Founder and MD receives UAA-ICT Distinguished Alumnus Award The award was in recognition of Mukund’s contribution to the Indian dyestuff industry NEELIKON'S, FOUNDER and MD, Mukund Turakhia, was presented the 'UAA-ICT Distinguished Alumnus Award’ (Entrepreneur Category) for the year 2017-2018. The award was presented at the Foundation Day Celebrations of the UDCT Alumni Association (UAA), at the Institute of Chemical Technology (ICT) in Mumbai.

The award was in recognition of Mukund‘s more than 50 years contri-

34 EXPRESS PHARMA June 16-30, 2017

bution to the Indian dyestuff industry and specifically to his pioneering role in developing food, drug and cosmetic dyes and fluorescent dyes manufacturing in India with indigenous technology.

Mukund is an alumni (1962-1966) of ICT which was founded in 1933 as a University Department of Chemical Technology (UDCT) of the University of Mumbai.

EP News Bureau

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PHARMA ALLY

Aptar Pharma’s electronic lockout device approved by EMA Takeda will launch Instanyl DoseGuard in Europe in several multidose strengths APTAR PHARMA, a world leader in innovative drug delivery systems, has announced the approval by the European Medicines Agency (EMA) of the first integrated electronic nasal lockout device (e-Lockout) following a multi-year development with Takeda Pharmaceuticals International. Aptar Pharma agreed to supply Takeda with its e-Lockout device for a multi-dose nasal spray version of Instanyl. The EMA has granted marketing authorisation for this multidose nasal spray treatment under the name Instanyl DoseGuard.

This represents a major milestone for Aptar Pharma, with the e-Lockout device being the first and only fully integrated electronic nasal drug delivery device to be approved by a US or European regulatory authority.

Already available in unidose and multidose nasal spray versions, Takeda will launch Instanyl DoseGuard in Europe in several multidose strengths, all using Aptar Pharma’s patented electronic lockout system, which marks another product innovation in the management of breakthrough pain.

Instanyl is a fast-acting nasal opioid approved for relieving breakthrough pain in adult cancer patients already treated with opioids for their usual pain. Breakthrough pain is an additional sudden pain that occurs despite having taken one’s usual pain relieving medicines.

Aptar Pharma’s e-Lockout device uses advanced electronic technology to help patient compliance in the treatment of chronic disease. Aptar Pharma’s e-Lockout device is intended to ensure safe patient compliance by limiting the number of doses available during a 24-hour period.

The system’s built-in lock-out mechanism prevents the device from being used for a period of time after a pre-defined number of spray actuations. The electronic display shows the number of priming strokes, the number of doses left in the device and whether the nasal spray is locked or

ready for use. The e-Lockout also features a child-resistant cap.

The multi-year supply agreement reinforces a long-standing partnership between Takeda and Aptar Pharma, who currently supplies Takeda with unidose and multidose nasal spray devices for Instanyl in Europe.

Committed to accompanying pharmaceutical companies throughout their product lifecycle management, Aptar Pharma continues to partner to provide customers with innovative and smart solutions to enable safe, convenient and compliant medication delivery.

“This approval and subsequent product launch underscores Aptar Pharma’s ability to partner with the pharma industry to bring innovative, compliant and safer devices through the regulatory authorisation process,” explained Salim Haffar, President, Aptar Pharma. “This is yet another example of Aptar Pharma’s expertise and technology at the heart of a new market launch. This is a significant step in strengthening Aptar Pharma’s credentials in the electronics and connected health markets. We are pleased to be building on our trusted, longterm partnership with Takeda,” he added.

EP News Bureau

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PHARMA ALLY PRODUCTS

Gandhi Automations launches high speed doors GANDHI AUTOMATIONS is India’s number one entrance automation and loading bay equipment company, which offers high speed doors. High speed doors designed and manufactured by Gandhi Automations are sturdy, dependable and are the ideal solution for medium and large entrances.

The doors are manufactured with European collaboration and technology with innovative and creative engineering.

Fast moving functional and reliable doors are needed in industrial and commercial contexts. Gandhi designed and manufactured high speed doors are versatile and solid ensuring long-lasting reliability.

The modular structure of the curtains, assembled and joined by anodised aluminium extrusions, provides for a wide range

of polyester sections available in a variety of colours. Wide, full-width window panels ensure a safer traffic and allow more light in. Their fast and easy replacement, in case of accidental tearing, saves money and time. The alternating metal tubular structure there inserted ensures high wind-re-

sistance.

Prime high speed doors are the ideal solution for internal and external entrances and effectively operate in any situation, even when strong winds are blowing and in rooms with high volume traffic. Sturdy and dependable, Prime is the intelligent door for medium and large

entrances.

High speed doors for external entrance are equipped with spring steel wind lock in curtain pocket that ensures silent door travel, higher wind loads and curtain stability.

Contact details Gandhi Automations

Chawda Commercial Centre Link Road, Malad (W) Mumbai – 400064 Off: +91 22 66720200 / 66720300(200 Lines) Fax: +91 22 66720201 Email: sales@geapl.co.inWebsite: www.geapl.co.in http://geapl.co.in/high-speeddoors.html

Alfa Laval’s introduces mixproof valves PROCESSES IN hygienic industries such as beverage, food, dairy, pharma and personal care - are becoming increasingly complex. Some of the challenges include higher volumes, increased efficiency, reduction in water and energy use. That is why it is essential to optimise flow management without compromising flexibility, plant safety, product quality or hygiene.

A valve matrix - also known as valve cluster - is a great option for maximising process efficiency through optimised flow management. Each stage of the design and installation process is an important component to fully realising potential in your process by saving time and avoiding lost revenue associated with production downtime.

Compared to traditional flow plates, a valve matrix is designed to allow simultaneous circulation of liquids - including CIP - on several levels with the exact number of lines and rows to match the specific requirements of your process.

The matrix ensures the flexibility for you to run multiple products to multiple destinations, while other lines are being

36 EXPRESS PHARMA June 16-30, 2017

cleaned.

Installing a valve matrix with Alfa Laval Unique Mixproof Valves brings you outstanding product safety with good cleaning conditions and no risk of cross-

contamination. It rules out the opportunity of human errors, which can occur using manual connection of lines and handling of swing bends.

Alfa Laval are specialists in providing

pre-built valve matrices customised to meet specific, individual requirements.

Its expertise helps ensure that there is most efficient flow management, using as few components as possible and dealing effectively with key issues that include thermal cycling, cleanability, drainability and flow control.

Alfa Laval valve matrices can be supplied pre-assembled and pre-tested as well as fully wired and with all the necessary pneumatic tubing, junction boxes and control panels pre-connected. This means one can bring even complex installations online as quickly as possible, saving time and avoiding lost revenue associated with on-site assembly, troubleshooting and downtime.

Advice on optimal solution address product type, process flexibility, utility consumption, plant constraints, thermal expansion and many more considerations.

Contact details Suzie Moore Communication suzie.moore@alfalaval.com http://www.alfalaval.com

PHARMA ALLY VALUE ADD

Falsified medicines directive: Don’t lose track of compliance Arthur Smith, Global Marketing Manager, Videojet Technologies, looks at the falsified medicines directive and the delegated act that makes coding and marking technology vital to compliance THE FALSIFIED Medicines Directive (FMD), otherwise known as Directive 2011/62/EU, was implemented in July 2011 due to a marked increase in falsified medicines making their way into European supply chains.

Member states of the EU were required to comply by January 2013, which added to the already heavily regulated sector, and licensing, manufacturing and distribution of medicines remains tightly controlled.

Increases in the number of falsified medicines globally have been dramatic. In 2013, the World Health Organization (WHO) launched a global surveillance and monitoring system designed to encourage member states to report incidents of substandard, spurious, falsely labelled, falsified and counterfeit (SSFFC) medical products in a structured and systematic way. Up until January 2016, 920 medical products had been reported across all main therapeutic categories and included both innovator and generic medicines1 - from inexpensive pain medication to very expensive products for the treatment of cancer.

Benoit Goyens of the World Customs Organization (WCO), speaking at the Medicines for Europe Conference in Croatia last year, predicted that criminal organisations could generate up to £1bn in 2017 from the sale of illicit medicines2 – many of which will be purchased through seemingly bona fide websites via the Internet. The figures are staggering, therefore improvements to the regulations were necessary to help in the fight against this highly dangerous, often fatal3, practice.

What are falsified medicines?

Falsified medicines are products that have been made illegally to ‘mimic’ real medicines.

Essentially they are fakes that pass themselves off as the real thing. The ingredients used in these products can be of a significantly lower quality than the approved genuine version and often have lower levels of the active ingredient require for effectiveness. Dosage levels can also be wrong, or the wrong ingredients altogether could be used in their preparation, and fake packaging is generally used to conceal the source of the product and the identity of its manufacturer.

Medicines that are falsified are often confused with counterfeit products and it is very important to make the distinction between the two. While counterfeit products are illegal, they are generally produced using patented technologies that are not the rightful property of the manufacturer. This technology can be used accurately to produce medicines that do not comply with intellectual property rights or trademark laws – thus making them counterfeit.

To subscribe: bpd.subscription@expressindia.com

3640-2d-carton

Falsified medicines, by contrast, represent a higher risk to the public as they are made to resemble genuine products.

Unfortunately, this distinction between falsified products and counterfeit products made in the EU is not necessarily used around the world, and in the language people use they will sometimes refer to counterfeit when they actually mean falsified.

How has the FMD changed where coding and marking is concerned?

The introduction of the FMD

has presented challenges to the pharmaceutical industry, in that it requires a far higher level of data management than ever before. Section 11 of the FMD states that: ‘Safety features for medicinal products should be harmonised within the [European] Union in order to take account of new risk profiles, while ensuring the functioning of the internal market for medicinal products. Those safety features should allow verification of the authenticity and identification of individual packs, and provide evidence of tampering’4. These requirements were set out re-

cently in a Deregulated Regulation (EU2016/161), published in February 2016. It states that two new safety features must be present on the packaging of most medicines that are intended for human use – a unique identifier and an antitampering device.Serialisation will be required at secondary pack level, information for which must be provided via a 2D barcode and in human readable form. The information present must include a unique serial number, expiry date, batch number and product code. At present, there are dif-

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PHARMA ALLY ferences that exist in terms of classification of medicines.

Some member states may consider a product a prescription item, for example, while another deems it an over the counter product. The directive only applies to prescribed medicinal products so, depending on the destination country, a national reimbursement number may also be required. This will be added by manufacturers and repackagers accordingly.

Products will need to be guaranteed authentic via an end to end verification system, in addition to risk-based verification by wholesalers. A final level of security is provided by further verification of the product at pharmacy level – ensuring authenticity at point of sale.

For products sold via the Internet, a new online logo has also been designed to indicate companies that are operating legally. This can be clicked to check the authenticity of the company in question against a verified database. These new measures will apply as of February 9, 2019.

Videojet 3640 Laser

Coding and marking – a vital piece of the FMD puzzle The two most common technologies for serialised marking are laser and thermal inkjet (TIJ), as both are able to produce high resolution codes that meet the detail requirements for 2D DataMatrix codes. TIJ printers fire tiny ink drops onto packaging as it passes by the cartridge, or print head. These ink drops are propelled out of a row (or rows) of fine-gauge nozzles by the rapid cycling of a small resistor underneath each nozzle. These resistors boil a small amount of ink which creates a small steam bubble that propels the ink drop. In contrast, laser coders use a focused beam of light to inscribe or physically alter the top layer of a substrate. The beam of light is steered by two mirror galvanometers which direct the laser beam in two planes.

In the first instance, manufacturers should look at the packaging substrate they intend to code or mark. Pharma cartons and paper labels are commonly used and often feature an aqueous overcoat to

38 EXPRESS PHARMA June 16-30, 2017

videojet-tij-pharma-carton

protect the packaging material.

Historically this would be an issue for TIJ, as water-based inks would not adhere to the surface of the packaging. Advances in ink technology, however, have seen the introduction of methyl ethyl ketone (MEK) or other light-solvents - broadening the spectrum of applications TIJ can address. Substrates such as foils, films, plastics and coated paper stocks are all now addressable with a TIJ technology that utilises MEK-based inks.

Laser systems are able to mark on a wider range of materials, such as paper, plastics, metal and glass. Lasers are also able to code on curved surfaces

such as vials or bottles. There are two considerations when it comes to verifying suitability of the substrate with laser technology: absorption of laser light and creating a print window with sufficient contrast for high quality codes. Absorption is a function of the substrate and the selected wavelength of the laser and the correct combination should be recommended by an expert coding and marking supplier. For proper code contrast, it is commonly required to modify packaging with a print window of dark ink, referred to as a 'flood fill.' The laser burns off the top layer of dark ink to expose the lighter underlying substrate – making

a negative image.

Data management is critical Manufacturers will find it necessary to adopt track and trace technology to enable compliance with the FMD and its associated delegated regulations, and the ability of coding and marking systems to interact with these technologies cannot be overlooked. There are a number of ways in which these interactions can take place.

Asynchronous communications, for example, allows the coder to send unsolicited information to the line control system. This functionality provides the dual benefits of active notifi-

cation of a printer event and reduced network traffic, which translates to faster notifications and higher potential throughput. Remote communication protocols too enable sensitive information and commands to be passed between the coding system and the host data system. This is important to remember when choosing a coding and marking system, as using a printer that features a tested, validated and secure protocol and command set designed specifically for managing sophisticated communications is critical.

Finally, buffer management is key to consider. Can your chosen system code and mark unbuffered, where variable data is received and printed one record at a time, or buffered, where multiple records are sent at the same time but are only printed once each. These features are particularly important to consider in countries where serial numbers have to be purchased. Correct management will enable manufacturers to redeem those codes that have not been used, which represents a useful cost saving.

Whichever technology is best for your individual needs, what is clear from the legislation is that coding solutions for FMD need to feature robust data management, seamless integration into manufacturing equipment and high resolution print capability to convey information throughout the supply chain. Through working with an expert supplier, manufacturers can ensure that the products they produce can be 100 per cent authenticated at all points along the supply chain – helping to make the illegal falsification of medicines a far more difficult practice going forward.

References 1. http://www.who.int/mediacentre/factsheets/fs275/en/ 2. http://www.pmlive.com/ pharma_news/the_global_scourge _of_counterfeit_medicines_1145731 3. http://europa.eu/rapid/pressrelease_IP-14-378_en.htm 4. https://ec.europa.eu/health/ sites/health/files/files/eudralex/vol -1/dir_2011_62/ dir_2011_62_en.pdf

PHARMA ALLY VALUE ADD

Mechanistic absorption modelling for extending biowaivers to BCS Class IVCompounds John DiBella, Vice President, Marketing & Sales, Simulations Plus, Viera Lukacova, Team Leader – Simulation Technologies and Dr Neelam Sayed, Application Scientist, give an insight about one of the first biowaivers granted by the US FDA for Class IV drugs through the use of mechanistic modeling THE USE of in silico modelling to support drug discovery research has been around for over 25 years. Only recently, however, has mechanistic absorption modelling (MAM), coupled with physiologicallybased pharmacokinetic (PBPK) modelling, gained widespread attention in the preclinical and clinical development stages. In 2016, the European Medicines Agency (EMA) and US Food and Drug Administration (US FDA) issued the first draft guidance documents focussed on the use of mechanistic modelling methods, where clear directives were given to sponsors planning to include these approaches in submissions. The use of this technology has been encouraged by regulatory agencies by waiving certain clinical studies (e.g., drugdrug interactions) based on modelling results.

Studies have shown how GastroPlus, the top-ranked MAM/PBPK modelling platform, has been used to justify biowaivers for BCS Class I, II, and III compounds.1,2,3,4 Simulations Plus, a leading provider of modelling and simulation (M&S) solutions for the pharmaceutical, biotech, and chemicals industries, worked closely with the sponsor to build models using GastroPlus software and prepared biowaiver reports that were ultimately approved.

proval of the product by many months. However, the sponsor was able to present a M &S plan for a biowaiver extension, utilising GastroPlus modelling with in vitro physicochemical API characterisation studies, that the US FDA reviewed and approved.

The modelling objectives

John DiBella, Vice President, Marketing & Sales, Simulations Plus

Viera Lukacova, Team Leader, Simulation Technologies

Dr Neelam Sayed, Application Scientist

tical ingredient (API). In these cases, the US FDA requires proof that the API’s oral bioavailability (F per cent) and bioequivalence are not adversely impacted by these changes. In the case presented here, the granulation process was changed from high shear to fluid bed granulation, and an in-line milling step was added to the crystallisation process as part of the overall

process improvement. This was introduced to reduce the fines in the crystallisation step and narrow the particle size distribution (particle engineered, PE). The API from the original crystallisation process (non-particle engineered, NPE) was used to manufacture several Phase 1 and 2 clinical supply lots. Examination of these different API lots showed that two early

batches of the NPE API had a broader particle size distribution than those of the PE API lot. Evidence needed to be supplied to show that this change did not adversely impact either its F per cent or bio-equivalence.

Initially, the US FDA requested the sponsor to design an expensive relative bioavailability study for this BCS Class IV drug, delaying the ap-

TABLE 1

◗ Build the baseline mechanistic model for the API using clinical data from prior studies. ◗ Assess sensitivity of API particle size distribution on drug exposure. ◗ Compare predicted bioequivalence of the tablets from the NPE and PE API lots.

All simulations were carried out with GastroPlus v7.

The physicochemical and pharmacokinetic parameters values used as inputs into the model are defined in Table 1.

The drug’s sponsor provided complete and/or cumulative particle size distribution (PSD) data for all lots, along

TABLE 2

Introduction Changes in a compound’s manufacturing process can affect the particle size distribution of the active pharmaceu-

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PHARMA ALLY with pharmacokinetic data across three dose levels (50, 100, and 300 mg) in a patient population with four different NPE API lots.

The first step was to build the mechanistic model in GastroPlus and validate it against available clinical data. Figure 1 illustrates the validation of this model for 50, 100 and 300 mg doses of a particular NPE API lot. The graphs demonstrate that the same model does a reasonable job of predicting the observed plasma concentration-time data across three different doses of the NPE API lots.

RESULTS

FIGURE 1

API lots were compared, with sample results seen in Table 2.

These bioequivalence calculations, as defined by the FDA’s guidance on Bioequivalence Studies, were implemented to show the similarities between AUC and Cmax for the NPE API lots (up to 30 - 40 µm) versus the PE API lot.

Conclusion The BCS system currently allows for biowaivers for rapidly dissolving immediate-release (IR) products of Class I drugs. Here, we show one of the first cases where mechanistic modelling with GastroPlus was used to extend biowaivers to IR products of Class IV compounds, which is a breakthrough in formulation development. By eliminating bioequivalence studies, where appropriate, significant reductions in both costs and time to market reformulated drug products can be realised while ensuring good drug product performance. Moreover, while the case study described here focuses on post-approval changes, the principle can be applied to generics when filing for ANDAs.

Assessment of particle size changes The PSA mode was used to establish particle size specifications, which is the allowed variability in mean particle size and standard deviation before any significant changes in predicted outcomes are observed. Since the drug is a Class IV compound with known dissolution limitations, simulations were run changing both the particle size and dose together to determine if an increase in dose would result in a higher or lower sensitivity to the change in particle size. Figure 2 illustrates the results of these simulations on absorption, which indicated that there would be very small changes, if any, in the fraction absorbed until the largest mean particle sizes of the NPE API lots (> 30 - 40 µm) were reached and the dose exceeded 100 mg.

FIGURE 2

Virtual bioequivalence trials The Population Simulator in GastroPlus predicts likely population distributions of results across subjects. This feature is commonly used to simulate crossover studies and evaluate whether two formulations are likely to be bioequivalent. Here, the Population Simulator was used to carry out simulations for 10 different populations, each with 25 virtual subjects. A combination of default and observed variability from the analysis of individual subject data from the clinical studies was used to define inputs for the population

40 EXPRESS PHARMA June 16-30, 2017

Simulations Plus, a leading provider of modelling and simulation solutions for the pharmaceutical, biotech, and chemicals industries, worked closely with the sponsor to build models using GastroPlus software and prepared biowaiver reports that were ultimately approved runs. To account for intra-subject and inter-occasion variability, a random multiplica-

tive error term with CV=15 per cent was added to each of the simulated profiles.

Simulated AUC and Cmax values for the tablets manufactured from the NPE and PE

References 1. Application of gastrointestinal simulation for extensions for biowaivers of highly permeable compounds. Tubic-Grozdanis M, Bolger MB, and Langguth P. (2008) AAPS J. 10(1):213-26.

2. An investigation into the importance of "very rapid dissolution" criteria for drug bioequivalence demonstration using gastrointestinal simulation technology. Kovacevi I, Parojci J, Tubi-Grozdanis M, Langguth P. (2009) AAPS J. 11(2):381-4.

3. The biowaivers extension for BCS Class III drugs: the effect of dissolution rate on the bioequivalence of BCS Class III IR drugs predicted by computer simulation. Tsume Y, Amidon GL. (2010) Mol Pharm.

7(4):1235-43.

4. The role of predictive biopharmaceutical modeling and simulation in drug development and regulatory evaluation.

Jiang W, Kim S, Zhang X, Lionberger RA, Davit BM, Conner DP, Yu LX. (2011) Int J Pharm.

418(2):151-60.

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Clean Room Solutions

HVAC Designing & Execution Modular Cleanroom Building Management System (BMS) & Electrical System Clean Room Flooring Cleanroom Light Fixtures & Equipments

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Tel,: +91-22-2172 1115/16 Email: info@hvax.in Web: www.hvax.in

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Reduce your time-to-market Integrated engineering with Totally Integrated Automation Portal

Integrated engineering in the Totally Integrated Automation Portal (TIA Portal) substantially shortens development times. Time-tomarket is greatly reduced thanks to coordinated work in interdisciplinary teams and the automatic generation of automation solutions instead of manual programming. That makes the TIA Portal the perfect gateway to automation in the Digital Enterprise.

For more information, call us on 1800 209 1800 or visit us at www.siemens.com/tia-portal

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TIA Portal V14

REGD.WITH RNI NO. MAHENG/2005/21398, POSTAL REGD. NO. MCS/164/2016 – 18,PUBLISHED ON 5TH / 20TH EVERY FORTNIGHT, POSTED ON 5TH, 6TH, 7TH & 20TH, 21ST, 22ND OF EVERY FORTNIGHT POSTED AT MUMBAI PATRIKA CHANNEL SORTING OFFICE, MUMBAI – 400001