Pharma Bio World - June 2014 by Pharma Bio World

June 2014 z

Vol.12

Issue 11

Mumbai

Price ` 150

www.pharmabioworld.com

ULTRA FAST AUTOMATION 1Îźs RESPONSE TIME www.br-automation.com/reACTION

Phone: +91-20-41478999

Email: sales.in@br-automation.com

< Replaces dedicated hardware < Freely programmable < IEC 61131, Function Block Diagram < Reduces CPU load < Reduces machine cycle time

reACTION TECHNOLOGY

Find out more.

PHARMA BIO WORLD R.N.I. No.: MAHENG/2002/8502 Chairman

Jasu Shah

Publisher & Printer

Maulik Jasubhai Shah

&KLHI ([HFXWLYH 2IÂżFHU

+HPDQW 6KHWW\

EDITORIAL Editor

Mittravinda Ranjan (mittra_ranjan@jasubhai.com)

Editorial Advisory Board

Ajit Singh, Jai Shankar, Dr Narges Mahaluxmivala, Dr Prabuddha Ganguly, Dr Satish Ravetkar, Utkarsh Palnitkar

Feature Writer

Mahesh Kallayil (mahesh_kallayil@jasubhai.com)

Design Team

Arun Parab, Umesh Chougule, Amol Patkar

Events Management Team

Abhijeet Mirashi

Marketing Co-ordinator

Brenda Fernandes

Subscription Team

Dilip Parab

3URGXFWLRQ 7HDP

9 5DM 0LVTXLWWD +HDG $UXQ 0DG\H

Vol. 12 | No. 11 | JUNE 2014 | MUMBAI | ` 150

PLACE OF PUBLICATION

Jasubhai Media Pvt Ltd 210, Taj Building, 3 rd Floor, Dr. D. N. Road, Fort, Mumbai 400 001, Tel: +91-22-4037 3636, Fax: +91-22-4037 3635

SALES General Manager, Sales : Amit Bhalerao (amit_bhalerao@jasubhai.com) Prashant Koshti (prashant_koshti@jasubhai.com) MARKETING TEAM & REGIONAL OFFICES Mumbai

Godfrey Lobo / V Ramdas 210, Taj Building, 3rd Floor, Dr. D. N. Road, Fort, Mumbai 400 001 Tel: +91-22-4037 3636 Fax: +91-22-4037 3635 E-mail: godfrey_lobo@jasubhai.com, v_ramdas@jasubhai.com

Ahmedabad

Vikas Kumar 64/A, Phase 1, GIDC Indl Estate, Vatva, Ahmedabad 382 445 Tel: +91-79-4900 3636 / Ext:627, Fax: +91-79-25831825 Mobile: +919712148258 E-mail: vikas_kumar@jasubhai.com

Vadodara

Pervindersingh Rawat 202 Concorde Bldg, Above Times of India Office, R C Dutt Road, Alkapuri, Baroda 390 007 Telefax: +91-265-2337189, Mobile: +919737114204 E-mail: pervinder_rawat@jasubhai.com

Bengaluru

Princebel M Mobile: +919444728035, +919481888718 E-mail: princebel_m@jasubhai.com

Chennai / Coimbatore

Princebel M / Yonack Pradeep 1-A, Jhaver Plaza, 1 st IORRU 1XQJDPEDNNDP +LJK 5RDG Chennai 600 034 Tel: +91-44-43123936 Mobile: +919444728035, +919176963737 E-mail: princebel_m@jasubhai.com, yonack_pradeep@jasubhai.com

Delhi

Priyaranjan Singh / Suman Kumar 803, Chiranjeev Tower, No 43, Nehru Place, New Delhi â&#x20AC;&#x201C; 110 019 Tel: +91-11-2629 3174, +91-11-4674 5513 Fax: +91-11-2642 7404 E-mail: pr_singh@jasubhai.com, suman_kumar@jasubhai.com

Hyderabad

Princebel M / Sunil Kulkarni Mobile: +919444728035, +919823410712 E-mail: princebel_m@jasubhai.com, sunil_kulkarni@jasubhai.com

Kolkata

E-mail: industrialmags@jasubhai.com

Pune

Sunil Kulkarni 6XLWH :KLWH +RXVH Sadashiv Peth, Tilak Road, Pune 411 030 Tel: +91-20-24494572, Telefax: +91-20-24482059 Mobile: +919823410712 E-mail: sunil_kulkarni@jasubhai.com

Single Copy Price: ` 150/-, Annual Subscription: ` 1530/-, Foreign: US$ 180

Jasubhai Media Pvt Ltd Registered Office: 26, Maker Chambers VI, 2 nd Floor, Nariman Point, Mumbai 400 021, INDIA. Tel.: +91-22-4037 3737 Fax: +91-22-2287 0502 E-mail: sales@jasubhai.com

Printed and published by Mr Maulik Jasubhai Shah on behalf of Jasubhai Media Private Limited, 26, Maker Chamber VI, Nariman Point, Mumbai 400 021 and printed at Varma Print, Pragati Industrial Estate, N M Joshi Marg, Lower Parel, Mumbai 400 011 and published from Mumbai. Editor: Ms Mittravinda Ranjan, 26, Maker Chamber VI, Nariman Point, Mumbai 400 021.

6 e June 2014

Pharma Bio World

EXPERT’S TAKE 10

Evolving Time in Indian IPR Regime - Prakash Kailasam, Aranca

IPR Regime in India: A Pharma Perspective - T C James, NIPO

FEATURES 22 16

Intellectual Property Rights and Access to Afordable Medicine - Dr Subir K Basak, Jubilant Life Sciences

Valuation of Intellectual Property in Pharmaceutical - DR B V Shivakumar, Enaltec Labs

Compulsory Licensing: Really a “Necessary Evil”? - Ramesh Vaidyanathan and Laxmi Joshi, Advaya Legal

Non-Patent Exclusivities - Dr Bhaswat S Chakraborty, Cadila Pharmaceuticals

Calculation of SPC and Patent Term Extension - Dr Manish A Rachchh, Gujarat Technological University

Role of IPR in Forming Legal Strategies for Pharma Industry - Ravi Bhola, Shivakumar and Pranav Mysore, K&S Partners

42 Rising Drug Prices

Challenges in Analytical Method Development for Drug Products - Dr Parag Gadkari, Inventia Healthcare Pvt Ltd

Data Breaches - Raj Samani, McAfee

NEWS UPDATE 28

Press Releases

53 55

Pharma News Biotech News

CORPORATE AFFAIRS 56

Product Trends

Events Diary

BACKYARD 42

61 62

Bookshelf AD Index Next Issue Focus: Pharma Innovation Next Issue Focus: Intellectual Property

8 e June 2014

Pharma Bio World

%& &'%

& % & %

*' *

* %

& (& %

& )

* %

& ( & %

(

* %

" # $

& '&)

(

@ ! %; @ % < *!

! "#$ %& ' ( ) & * + (( , &

- $.. ./$ 01 ! ,2 333!1 !

! 4 ( 5 6/# /$...7#$8$ 5 9 !: ( 01 ! , ; 1 !<! 5 6/# /=.7==./ . 5 3! 01 ! , ) ! &

( & + ) 5 6/# /.. #="### 5 (! &

( & + ) 01 ! , ,1 ! ; ; 3 5 6/# />7./8$#$# 5 &!& 3 01 ! , )& ! & ? & 5 6/# />#>88$= " 5 ! & 01 ! ,

expert's take

Evolving Time in in Indian IPR Regime In this article, Prakash Kailasam, AVP, Intellectual Research Practice, Aranca, elucidates the IPR development in India over the past years.

verall, there has been an increase in awareness of Intellectual Property across Indian pharmaceutical sectors, which is driven by recent changes in laws post 2005, litigations in some sectors such as Hi-tech, manufacturing, pharma etc. However, that is not translated into significant increase in patent filing as compared to other growing markets such as China and Korea. Table 1 shows the number of patents filed with the Indian Patent Office (IPO) for the last five years. Year

No of patents Filed

2008-09

36812

2009-10

34287

2010-11

39400

2011-12

43197

2012-13

43674

Table 1: No of patents filed in last five years. Source: Indian Patent Office

Off the 43,674 patents filed in the year 2012-1013, 9911 (~23 per cent) applications were filed by Indian nationals/ domestic corporations remaining 33,736 applications were filed by foreign nationals/companies. The number of patents filed in 2004 was 15,000. However, the majority of filing with the Indian patent office still comes from MNCs. Filing by local companies has been in the range of 20 to 23 per cent annually for the last five years. Both the overall, filing and the domestic contribution needs to improve significantly. 10 eJune 2014

Current Scenario In the recent times, lot of Indian companies operating in global markets have realised the importance of IP and have started filing patents aggressively in their markets. For example, Infosys and TCS started filing patents in 20022003 and have filed over 400 and 200 patent applications respectively in the last five years with the United States Patent and Trademark Office (USPTO). This indicates that few large Indian companies realise the importance of IP and gradually we might see other domestic companies filing patents globally in the key markets relevant for them. At a policy level, India has quite a strong IPR framework and is comparable to major developed markets in Europe. At the implementation level, there is still room for improvement. For eg, patent pendency period or the time taken to grant a patent is still very high and the patent office is facing significant backlog. However, the IPO has recently taken initiatives to increase the number of examiners and has developed training programmes to increase the efficiency of the examiners. We are certainly going to see improvement in this area. Table 2 (on next page) shows the number of patents reviewed by the Indian patent office in the last five years. There clearly is a major lag in terms of number of patents filed and number Pharma Bio World

expert's take Year

No of patents Filed

2008-09

17136

2009-10

11339

2010-11

Number of patents filed - 2012 Country

Number of applications Filed

No of patents Filed

12851

China

652777

2011-12

8488

2012-13

9027

542815

7.8

Japan

342796

0.1

Korea

188,915

5.6

EPO

148560

Germany

61340

3.2

Russia

44211

6.8

India

43955

3.9

Canada

35242

0.4

Brazil

30435

6.2

Table 2: No of patents reviewed in last five years. Source: Indian Patent Office

patents examined. Patent office has increased the number of examiners to 207 in 2013 from 79 in 2011. We certainly might see an increase in number of patents reviewed starting 2015 when the new examiners are well trained in reviewing of applications. There are lots of initiatives by the government departments such as CSIR, DST, DBT to promote innovation in India. There are also programmes run by various departments to identify and promote activities around developing IP generation activities in the small and medium enterprises. The government could benefit by creating more awareness around these programmes and running structured campaigns to attract enterprises towards these schemes. The number of patents filed has certainly reached post TRIPS compliance to 43674 in 2013 compared to ~15000 in 2004. However, this is far less than what was anticipated and also, the growth in filing has been very low as compared to other countries such as China, Korea where there has been a massive increase in filing in the last decade. For example, China has seen over 20 per cent growth in filing year on year in the last five years as compared to 1-2 per cent in India.

Table 3: No of applications & patents filed at major countries in the year 2012. Source: WIPO

Indian government should look at ways of incentivising inventors and companies to file more patents, which could include offering rewards, tax breaks and also look at alternate forms of IP such as utility models, which are less expensive to file and have limited statutory requirements as compared to patents. Contrary to the perception, Indian patent office has very clear and well defined rules when it comes to granting compulsory licenses. In the recent cases with IPAB, such as BDR Pharma vs BMS, there has been a thorough deliberation and fair hearing, before arriving at a decision. Having a provision for Compulsory Licensing is essential in the socioeconomic context of India and if a reasonable royalty is decided while taking

However, IPO has recently taken initiatives to increase the number of examiners and has developed training programmes to increase the efficiency of the examiners, but still to see improvement in this area. 12 eJune 2014

into consideration all the investment done by the company in research, it will not hamper the process of innovation in pharma sector. Global Trends Globally, USA, China, EU, Japan and Korea are top five patent filing countries. In 2012, these four countries filed maximum number of applications for patents, globally. There are lots of collaborative activities between the patent offices of these countries with respect to developing systems for faster review of patent application, coming up standardised classification systems for patents, work sharing framework. There are also ongoing discussions for harmonisation of IP laws across these countries. EPO and Indian patent Office has a collaborative platform for training of examiners, knowledge sharing, access to databases etc. Contact: srinivas.macha@aranca.com Pharma Bio World

expert's take

IP Regime in India: A Pharma Perspective T C James, President â&#x20AC;&#x201C; NIPO and Former Director (IPRs) â&#x20AC;&#x201C; DIPP, GOI weighs in on IPR scenario in India and its implication in Indian pharmaceutical sector.

ontrary to common belief, intellectual property protection is not a new concept to India. We had our first law on IPR enacted more than 160 years ago. The first Indian law on IPR was the copyright law enacted on 18 th December 1847. Ten years later, the first Indian law on patent was passed in 1857. In 1972, Patents Act 1970 came into force eliminating patent protection in India for pharmaceutical products and restricting patenting only to process. This was done with an objective to encourage the development of an indigenous Indian pharmaceutical industry and to guarantee that the Indian public had access to lowcost drugs. Pharmaceutical product patent were reintroduced in India with the Patent (amendment) Act 2005, which came into force from 1 st January 2005. Currently, India has a fairly good IPR environment which is quite consistent with its obligations under the TRIPS Agreement. We are member of most of the major international treaties like Paris convention, the Berne convention, Patent Cooperation Treaty (PCT) and so on. Our IP laws have been enacted keeping in mind the international obligation and commitment and bearing in mind the national interest as it should be. The IP regime in India complies very well with other international regimes particularly with developing countries and in certain areas like copyright, it is much more advanced than many developed countries. Notwithstanding, we have a lingering justice delivery system with regard to IPR. The delay in approval procedure

16 eJune 2014

along with bureaucratic red tape put Indian IP regime in a bad light and most of the positive things have gone unnoticed. A wrong perception created that Indian IP is not doing well. Indian patent office is an international searching authority and international preliminary examining authority under the patent cooperation treaty. There are only 15 such offices worldwide. TRIPs and Aftermath India is an original signatory of the TRIPs agreement and one of the few countries who brought in changes in the IP regime even as TRIPs negotiation was in its nascent stage. Post TRIPs agreement, India has made its IP laws TRIPs compliant through three amendments carried out during 1999 to 2005. In regard to product patents for pharmaceuticals, although applications were being received and also had provisions for exclusive marketing rights for pharmaceutical products for which application had been filed, under the Patents Act, it was from 1995 that granting exclusive marketing right effectively came into existance. Gleevec of Novartis, which is in news during the last few years, is one such drug which had received exclusive marketing rights. During the interregnum over 9000 mail box applications were filed. As of now, I do not envisage any further changes on account of TRIPs. The need is to have more incentives for creativity as well as inventions and innovations. Those incentives coupled with IP protection will lead the country to a better future, where we will see that more Pharma Bio World

expert's take We need to extend IPR protection to new areas like Utility Models in which India excels, particularly the rural sector. This will be a great boost to MSMEs as well as small innovators across the country. In the early stages of development, most developed countries like Germany and Japan had encouraged Utility Models. They continue to have such protection today. We also need to provide better protection to designs and trade secrets. As of now, there is no separate law for protection of trade secrets. Both these are complementary to patent protection.

Indian inventions and innovations get protection in India as well as outside. As of now India protects many more foreign patents than Indian one. In fact, after 2005, the percentage of domestic patents has been steadily going down. This is a worrying matter. In the pharmaceutical sector, we need to develop on the strength that we had developed during the period from 1972 to 1995 â&#x20AC;&#x201C; ie, the generic industry. To carry this forward we need to encourage more investment in R&D in this sector. The R&D is a two level approach; basic research will have to be done in universities and R&D institutions, which may result in inventions. Further innovation to bring them to the market will be done in the company R&D centres. This is the practice world over. Towards a Better IP Regime India has been following a fairly balanced IPR regime which takes care of the private rights of the IP owners and the public interest. What we need is more awareness among both stake holders and the general public about IPR matters. For this, we need to conduct IP awareness programmes and also introduction of IPRs in the education stream from school to university level. 18 eJune 2014

IP laws should not be viewed merely from the angle of a limited number of big corporations from the particular industrial field but from a perspective of how they can contribute to national development, which includes health and education as well as agricultural and industrial development keeping in view environmental protection, conservation of biological resources. We have not formally enunciated an IP policy and strategy. There is a need to bring out such a policy to provide more clarity and also to give a positive signal to the world about Indiaâ&#x20AC;&#x2122;s commitment to IP protection. Such a policy should include topics like promotion of commercial exploitation of IP besides general IP services. Development of IP management capabilities, etc. We have to develop a culture that respects IP. It should be closely linked with innovation and technology transfer. IP audit and valuation is an area, which is hardly paid any attention in the country. Owners of IP should be able to use it like other property such as collaterals, for taking loans, etc. Banking sector may have been geared for this. We need to develop incubation centres for young people who have IPs in their kit.

Coupled with this, we need to ensure proper ABS on the use of our biological resources, traditional knowledge and cultural expressions. With the new government sworn in, India expects changes in its IPR policies. The BJP agenda sets forth four points with regard to IPRs. They are: Â&#x2021; &UHDWH FRXUWV VSHFLDOO\ HTXLSSHG WR deal with IPR cases Â&#x2021; (YROYH D QDWLRQDO QHWZRUN RI specialised universities having expertise in complementary domains - like Forensics, Arbitration, IPR, International Law, etc Â&#x2021; (PEDUN RQ WKH SDWK RI ,35V DQG Patents in a big way Â&#x2021; &UHDWH DQ HFRV\VWHP IRU PXOWL FRXQWU\ and inter-disciplinary collaborative research and establish an Intellectual Property Rights Regime which maximises the incentive for generation and protection of intellectual property for all type of inventors. I hope the IP grant infrastructure will be greatly strengthened. Human resources DUH TXLWH LQVXIILFLHQW DV RI QRZ 6LPLODUO\ police and customs need to be provided DGHTXDWH WUDLQLQJ DQG IDFLOLWLHV WR WUDFH IP offences. Our judicial system also needs to be strengthened and facilitated in handling technical issues. Pharma Bio World

$ ! "# $ "% & # ! '

% & ' ( ) * ! '

( +$ , # ) * ! '

& & - * ) * ! '

. # ( ) * ! '

) # ( ) * ! '

( $ # # ) * ! '

# * ) * ! '

/ * ) * ! '

0 # "## ) * ! '

. - ) * ! '

## ! 1 # # ! '

% ( + -& -$

( ) * (02 $ # 1 $ ) * ! ' 3 & - $ # 1 $ ) * ! ' 3 , # $ # 1 $ ) * ! ' 3 * ) $ # 1 $ ) * ! ' 3 2 $ # 1 $ ) * ! ' 3 , * $ # 1 $ ) * ! ' 3 ) $ # 1 $ ) * ! ' 3 ) $ ) # $ # 1 $ ) * ! '

) $ . # $ # 1 $ ) * ! '

( $ $ # $ # , $ * ! '

+ , '* +4 1

# # ) * ! '

) # - # . 5 ) * ! '

) # - # ! # $ # ) * ! '

) * ! '

) & # ) * ! '

/ ) * ! '

1 "## 1 ) * ! '

, # ) * ! '

. # * ) * ! '

) $ # , # ) * ! '

## ! / # ! '

! " #!

expert's take Compulsory Licensing India has had a patent law since 1857 and during all these years, it had granted only one effective compulsory licence. Even after 2005, the Patent Office rejected two applications for compulsory licences. The one patent it had granted was for a product, which had not been produced in India or even imported in sufficient quantities. Further the price fixed by the patentee for that product was beyond the reach of as almost 99 per cent of the Indian population. When the office granted a CL for Bayerâ&#x20AC;&#x2122;s Nexavar (Sorafenib mesylate), to Natco which was to produce it at a monthly requirement price of ` 6800 as against Bayerâ&#x20AC;&#x2122;s price for the same quantity at ` 1,80,000, it also imposed a fair condition to pay a royalty of 6 per cent. The grant was transparent. Later the patentee approached the IPAB which approved the action by the Patent Office but raised the royalty to 7 per cent. I do not consider that the one single CL has had or will have any adverse impact on innovations in the pharmaceuticals. IPR and Generic Drugs India is one of the leading generic producers in the world, thanks to the 1970 Patents Act. The recent happenings regarding FDA ban on Indian generic drug created a bad image of the Indian pharmaceutical industry in international market. The US FDA has a strict quality and safety standard commencing from manufacturing stage. The pharma companies will definitely have to follow those standards. In fact, India should have very strict safety and quality standards in the area of medicines. Quality and safety cannot be compromised.

Generic companies have a large opportunity now. A large number of popular drugs are going off patent. Indian companies should utilise this opportunity well. IPR and Affordable Medicine As said above, India has a TRIPS compliant patent law which protects the exclusive rights of patent owners. At the same time, it has various provisions to ensure that such rights are not misused, particularly in a monopolistic way. These provisions include compulsory licences, use by government, etc. Besides, India follows strict standards in the grant of patents, particularly for pharmaceuticals to ensure that frivolous patents are not granted or very minor improvements are not granted a new patent when an earlier patent is about to expire. Patent cliff is a term being used generally to refer to the possible loss in revenue of a company whose revenue in a block buster drug falls at the end of the patent term. This is because during the patent period of 20 years it has been enjoying total monopoly and after the patent period there will be competition and the prices will be dictated by the market as in other cases. Expiry of a pharma patent gives an opportunity to generic producers to get into the market on those products and the competitive pricing is very good for patients on account of both availability and affordability. It is essentially a company specific issue. Secondary patenting is an unethical practice by many companies to obtain a patent on an existing product after making very minor or slight modifications. It must be remembered that world over the patent

India has a TRIPS compliant patent law which protects the exclusive rights of patent owners. At the same time, it has various provisions to ensure that such rights are not misused, particularly in a monopolistic way. 20 eJune 2014

period was for 14 years and it was the TRIPS which extended this period to 20 years taking into account the possible delay by the patent owners to get into the market. When you are taking a so called secondary patent you are actually preventing competitors and this is very bad for patients both in developed and developing countries. It must be remembered that the companies already enjoy considerable market lead and production facilities over their generic companies which they can effectively use to garner higher revenues than their generic competitors. Role of IPR in Forming Legal Strategies IPRs form an important element in the strategy of any pharmaceutical company whether generic or otherwise. Those who own patents will have to take special measures to protect them as well as using them. Negotiations for licensing involve legal strategies. They may have to watch out for possible infringements and obtain injunctive relief. As for other companies, they have to ensure that no infringement takes place. At the same time, they need to monitor the patent databases to see which patents are expiring and chalk out strategies accordingly. In regard to legal strategies, they need to be ready to face any possible threat of an infringement, even if they are not infringing and accordingly take pre-emptive action. Also companies have to be on the watch out for the patent trolls strategies adopted by many companies. Conclusion Discussions are going on in the international bodies, particularly WIPO to have more harmonisation in various processes among countries. So as far as PCT is concerned, this has been a long continuous process and many changes have been brought in that have positive effects on harmonisation. However, such harmonisation should be done through the international bodies like WIPO and not through bilateral treaties. Contact: prof.tcjames@gmail.com Pharma Bio World

PRESENCE:

MUMBAI

DELHI

BANGALORE

KOLKATA

CHENNAI

AHMEDABAD

PUNE

HYDERABAD

Intellectual Property Rights and Access to Affordable Medicines How will the enhanced IP protection affect access to low-priced medicines domestically and internationally? This article ponders over various avenues to make affordable medicines accessible to all and at the same time respecting IPR or patent of the stakeholders.

iseases that can be prevented, cured or treated cause the death of 18 million human lives across the world. Nearly 50,000 people die every day of diseases like tuberculosis, malaria etc that can be treated, cured or prevented. The loss of lives that can be prevented demolishes the hopes and livelihood of millions of families and spreads the prevalence of poverty. The economic strain resulting on the developing countries is catastrophic and affects their growth and productivity. Accessibility to affordable medicines will be a great relief to the suffering patients, families and to the economics of the developing nations. Increasing the access to affordable medicines without infringing the IPR of the pharmaceuticals is the major challenge faced by the world today. Intellectual Property Rights refers to ownership of an idea, design, methodology or structure of a molecule by the person or company who discovered or invented it. The person/company/institution owns the exclusive rights to the innovation and nobody is allowed to duplicate it for a defined period of time since the patent is filed. Strategic Partnerships in Drug Discovery and Development: Global Innovation

Dr Subir K Basak

President, Drug Discovery Jubilant Life Sciences 22 eJune 2014

Services

The cost of discovering a drug and advancing it into clinic is over 1 billion dollars, this huge cost largely owned by the pharmaceuticals are forced to put high price on their products. The time taken to advance a drug into the clinic takes about 10-15 years. Spiralling healthcare cost puts pressure on the pharmaceuticals to reduce the cost of discovery and development of drugs. The high price associated with the new medicines burdens the healthcare costs in mature markets like US, EU,

Japan, whereas it is largely unaffordable in emerging markets, developing countries and poor nations. The first step towards making global access to affordable medicines is by reducing the cost of Drug Discovery and Development. The global pharmaceutical companies have already taken this huge first step and have entered into strategic collaborative partnerships with small pharmaceutical companies, academics, medical institutions across the world especially in the emerging markets of India, China and Brazil. The collaborative drug discovery and development partnerships provides the global pharmaceutical companies access to large scientific pool of talent, different science, state of the art infrastructure at a low cost to advance innovative molecules into the clinic. In the discovery space, the strategic partners provide innovative-risk-shared business models to the global pharmaceutical companies thereby minimising the risk of failures and compensating the strategic partners with milestone payments on achieving specific targets. In the development space, where the investigational new drug is subjected to clinical trials, the global pharmaceutical companies through strategic collaborative partnerships gain access to large diverse pool of patients especially in India and China, educated medical investigators, conducive clinical environment possessing treatment na誰ve population ideal for recruitment as trial subjects, huge cost advantage as it is 30-45 per cent cheaper than the developed countries and state of the art IT infrastructure and professionals to document the clinical findings for the regulatory bodies. The investments to already existing good Pharma Bio World

ADVERTISE TO

EXPAND your reach through

For Details Contact

Jasubhai Media Pvt. Ltd. rd

Taj Building, 3 Floor, 210 Dr D N Road Fort, Mumbai - 400 001 Tel: 022-4037 3636, Fax: 022-4037 3635 Email: industrialmags@jasubhai.com

Public funding of drug discovery and development is a reform that can reduce the burden on pharmaceutical companies and has the potential to increase the affordability of the drugs. medical infrastructure are happening and the government bodies are streamlining the bottlenecks in regulatory reforms which will reduce the time taken for approval. The drug discovery and development collaborative partners mitigate the risk and in turn also gain royalties on drugs that enter the market. The strategic collaborative partnerships provides cost & time advantage and also provides access to fast growing emerging markets with low cost manufacturing capabilities. Collaborative partnerships aided reduction in cost coupled with reforms that does not affect the interest of the stakeholders will increase the access to affordable medicines to all. TRIPS Agreement and Selective Pricing of Drugs The TRIPS (Trade-Related Aspects of Intellectual Property Rights) agreement s i g n e d b y t h e W TO n a t i o n s p r o t e c t s the innovations in the form of patents typically for 20 years. This means that the patents are valid in all WTO nations and introduction of cheaper generic versions of patented medicines is unlawful. But the act allowed an option of compulsory license, in which the license can be awarded to a third party without the consent of the patent holder and a small percentage of royalty will be awarded to the patent holder. Many developing countries like Thailand, India awarded compulsory license for patented drugs and developed countries too like the US and Canada used it for negotiating the price. Though these recent developments might be seen as the socio-political approach by the countries to make healthcare accessible to its poor, the investments made by the pharmaceutical 24 eJune 2014

companies will be at stake and will in turn reflect negatively in their future investments on innovation. Innovation is the driving force of the pharmaceutical industry as there are thousands of unmet clinical needs that are still existing and expected to emerge with the growing and ageing population, increase in incidence of non communicable diseases associated with lifestyle (use of tobacco, fatty diets etc). It is important to protect innovation and think of reforms and strategies to provide the global population access to affordable medicines. Several ideas have been thought over by experts to make medicines accessible to all, one such is selective pricing of the patented products where in based on economy of the region, market size can be

Public Funding of R&D and Rewards for Innovators Public funding of drug discovery and development is a reform that can reduce the burden on pharmaceutical companies and has the potential to increase the affordability of the drugs. The US President had already called for an expansion of funding for the R&D in HIV prevention essentially for a vaccine and microbicides. This type of funding can be extended to other therapeutic areas as well but will hurt the tax payerâ&#x20AC;&#x2122;s money when the research programs fail as drug discovery business are risky business with the success rate of less than 1 per cent. In 2011, Senator Bernie Sanders introduced Medical Innovation Prize Fund Act in the US Congress, the bill proposes that every year several billion dollars equal to 0.55 per cent of US GDP roughly amounting to 80 billion dollars will be co-funded by federal government and health insurance companies and a committee will reward the drugs proportionally that has clinical efficiency and therapeutic gains. Innovators are rewarded and can go back to innovate again, and the drugs are open for generic market and made affordable. This bill might not be perfect as the global intellectual property center argues that prizes are one time settlements and does not create rewards to propel continuous improvements and advancements. Conclusion

introduced. This might cause resentment among the patients paying higher cost in developed regions. This idea has its own drawbacks, patient from affluent countries might opt to get treatment from countries where the drug is cheaper or it might promote smuggling of the low cost product into developed countries. The differential pricing might still be a huge burden financially to the pharma companies inflicting loss to them and might result in market failure.

The best strategies to manage affordable access to medicines without infringing the IPR of the innovator are still emerging. Global collaborative drug discovery efforts for cost effective innovation aided with streamlined regulatory reforms to reduce the time for approval and policies on pricing without affecting the innovation process can help in providing affordable access to medicines. Contact: kmittal@perfectrelations.com Pharma Bio World

! ! " ! # $ % %& % ' ()

! "# " !$ " " % ! $ # !

* +$ ,-$

. )' ' '

Valuation of Intellectual Property in Pharmaceutical Intellectual capital is recognised as the most important asset of pharmaceutical industry. It is the foundation for the market dominance and continuing profitability of leading corporations. This article talks about the implication of intellectual property valuation in pharmaceuticals

ntellectual property rights are the legally recognised exclusive rights to creations of the mind. Under intellectual property law, owners are granted certain exclusive rights to a variety of intangible assets, such as musical, literary, and artistic works; discoveries and inventions; and words, phrases, symbols, and designs. Common types of intellectual property rig h t s in c lude c opy right, trademark s , patents, industrial design rights, trade dress, and in some jurisdictions trade secrets. This article focuses on valuation of patent in pharmaceutical industry.

There is no such thing as a “provisional patent”. As most of the countries follow first to file system rather than first to invent system.

The pharmaceutical industry is a wonderful example of the importance of intellectual p r o p e r t y. P h a r m a c e u t i c a l r e s e a r c h companies operate under a challenging business model, ie, companies invest years of research and development, clinical trials and a lengthy regulatory approval process which cost an average of USD 1 billion before their products ever reach the market. In fact, only two out of every 10 medicines will recoup the money spent on their development.

In First to invent (FTI) system, the inventor who first conceived of the invention and then diligently reduc ed it to p r a c tic e by filing a patent application (or actual reduction to practice) is considered the first inventor and is entitled to patent protection.

IP laws are intended to give the investors an opportunity to recoup their costs, without intellectual property rights, competitors could simply copy pharmaceutical innovations as soon as they were proven safe and effective, offering their own versions without investing the time and money to develop the medicines. Innovators in the pharmaceutical industry could lose the ability to recoup their substantial investment in new drug development, making it more challenging to find funding.

Dr B V Shivakumar Chief Scientific Officer Enaltec Labs 26 eJune 2014

A patent is an exclusive right granted against the disclosure to a person who has invented a new and useful product or process or has improved an existing product. It is a monopoly right to prevent others from exploiting the invention, the rationale being that rewarding the inventor for the effort, skill and resources expended will encourage innovation.

First to file (FTF) and first to invent (FTI) are legal concepts that define who has the right to the grant of a patent for an invention. In a first-to-file system, the patent is granted to the inventor who is the first to file a patent application, regardless of the date of invention.

In pharmaceutical, the new creations are considered to be risky and they don’t get financial support to be implemented. The role of intellectual property (IP) management is essential for small and medium enterprises (SMEs) and it is necessary to develop IP strategies in order to manage effectively SME’s assets. In pharmaceutical industry most of small and medium enterprises (SMEs) conceive excellent innovative ideas (Inventions) and before implementation of innovative ideas they are filing patent application under provisional application. A provisional application is a legal document filed in the patent office that establishes an early filing date, but does not mature into an issued patent unless the applicant files a regular non-provisional patent application or complete specification within one year. As patent is a territorial right, SMEs seeks to protect their inventions in more than one country, either they have to file patent application separately in countries of interest within one year from the date of filing provisional patent application, which is very costly way and also SMEs Pharma Bio World

get short time of 12 months to decide in which country they desire to protect their invention; or they have to file PCT application designating countries of interest which is cost effective way and SMEs get extended timeline up to 31 months from the priority date ie, date of filing of provisional patent application for national phase entry in to countries of interest. Actually, SMEs gets period of one year for work out their invention with the limited resources they had. Sometimes this one year period is not sufficient to work out the invention. If a non-provisional patent application or complete specification is not expected to be filed within one year, and the patent is not otherwise barred by law, another provisional application may also be filed at any time and start another one year period (but this does not work in all cases due to restriction of patent on incremental inventions in some countries). However, the original priority date of any expired provisional applications will be forfeited. After that complete patent application or the PCT application derived from provisional patent application published within 18 months time period from the filing date of provisional patent application. Once patent application (complete specification or PCT application) published then request for examination need to be filed within 48 months from the priority date of application in India and National phase application derived from PCT application can be filed up to 30 or 31 months period (vary country to country) from the priority date of provisional patent application in different countries designating in PCT applications. The timeline for filing National phase application varies country wise. After filing of National phase application, the National phase application gets published and undergoes examination phase upon filing of request for examination. The examination of National patent application from National patent office usually takes approximate two to three years and once invention fulfilled the requirement Pharma Bio World

of patentability like “Novelty”, “Inventive Step”, “Industrial Application” and other legal requirement, then it converts into a granted patent, which can be enforced on others. The shortest time period for getting “Granted Patent” inspite of availability of important provisions like request for early publication and fast track examination of national phase application in India after paying an additional fee is also not less than four years due to the huge backlog of patent applications for which request for examination has been filed. In order to increase valuation of intellectual property, which will tend to help pharmaceutical companies to grow and invest in research and development of new life saving drugs which will directly benefit the human kind, there is a need to widen or explore the limits of intellectual property rights. Below are some of the facts which need to be highlighted; Firstly, there is need to rethink about timeline for filing non-provisional patent application or complete specification after considering the fact that most of the time patent application does not get chance for examination till three years from the priority date due to practices of Patent Office and huge backlog of unexamined patent applications of which request for examination has been filed. In case, timelines for filing non-provisional patent application or complete specification from period of one year is increased, the inventor gets sufficient time to work out their invention and generate adequate data for the invention so that common person skill in the art can understand the invention and use it in the form of readily available data after the expiry of the patent. Also SMEs needs financial support for implementation of their invention. So there is need of an agency who encourages the SMEs for creating good inventions or who monitors the SMEs patent applications

covering really good invention and providing them financial support for implementation of their invention, which will help in building well developed nation. S e c o n d l y, t h e r e h a s b e e n a g r o w i n g demand for lesser forms of protection for innovations in the field of technology in the face of high thresholds of inventiveness demanded in many jurisdictions for the grant of patent. Like patents, utility model is an exclusive right granted to an invention. This allows the grantee, the right to prevent others from commercially using the protected invention, without the grantee’s authorisation, for a limited period of time. It is very similar to patents and are often referred to as, “petty patents” or “innovation patents” but usually has a shorter term (often 6 to 15 years). At present patent law in India and many more countries do not provide for registration of Utility Model which if enforced will add valuation to intellectual property. Further, countries like India, China and many more do not have patent term extension like in USA; Canada (expected to be in 2015) and Supplementary Protection Certificate (SPC) in European Union member countries which is a unique intellectual property (IP) right that extends the duration of the exclusive right. It enters into force after expiry of a patent upon which it is based. This type of right is available for various regulated, biologically active agents, namely human or v eterinary medic aments a n d p la n t protection products and if globally accepted shall add a comparatively high in valuation of intellectual property rights. Further, there is a need to establish an organisation or a government body, which should assist inventor for protective their inventions in better manner and for reviewing the potential of published patent application, after that they should approach patent applicant for licensing and funding to afford expenses of patent prosecutions in different countries simultaneously. Contact: paradigmshiftpr@gmail.com June 2014f 27

Compulsory Licensing: Really a “Necessary Evil”? This article seeks to examine the first compulsory license granted in India, various drawbacks of compulsory licensing especially for the third world and developing nations as also the safeguards against these pitfalls provided in the agreement on Trade Related Aspects of Intellectual Property Rights.

Ramesh Vaidyanathan Managing Partner Advaya Legal

Laxmi Joshi Associate Advaya Legal

28 eJune 2014

recent World Health Organisation report made a prescient warning that antibiotic resistance is among the foremost threats to global medical security. While this may be primarily attributable to a rampant abuse of antibiotics by doctors and patients, another underrated reason for the same is lack of pharmaceutical research. Developing nations around the world have made it clear that they are not willing to accept “patent premium” charged by multinational drug companies for their products. Instead countries like India are manufacturing cheap generic replicas of patented drugs with little or no compensation being provided to multinationals for their research efforts. The recent grant of a compulsory license to Natco Pharma to produce Bayer’s anticancer drug “Nexavar” has set off alarm bells in some circles. As a result drug research around the world has largely coalesced towards lifestyle diseases that usually strike the wealthy. Antibiotics and other drugs that are essential to cure infectious diseases in poorer nations have been relatively ignored as they are not remunerative enough for these drug companies. Tr a d i t i o n a l l y, m o s t d e v e l o p i n g nations prohibited grant of patent on pharmaceuticals. At best they allowed patents only on the manufacturing process. This was to ensure ready availability of low cost generic drugs. This lack of protection was misused by drug manufacturers to reverse engineer the patented drugs and manufacture their replica without having to spend on paying royalties or c o n d u c t i n g r e s e a r c h . F u r t h e r, t h e s e manufacturers used substandard products and manufacturing practices. This practice created one of the world’s biggest and robust generic pharmaceutical industries in India, but at the cost of independent research and drug discovery.

The domestic pharmaceutical companies in India spent a huge chunk of money towards research and development (R&D) of reverse engineering. This compared to the developed nations that dedicated substantial portion of their revenue for innovation and discovery of new drugs. Thus, there was little or no incentive for the global pharmaceutical giants to conduct research or discover new drugs for disease/ailment atypical to developing nations such as infectious diseases which require antibiotics. Drugs essential to cure diseases in poorer nations were relatively ignored for not being remunerative enough for the drug companies. A perfect example is Tuberculosis, which has a fatality rate in India of about 1,000 people per day, but no new drugs have been discovered for treating it since the 1960s. In this scenario, the need of the hour for developing nations was to encourage its domestic healthcare research and innovation, by putting in place a regime that would recognise and protect the intellectual property rights (IPR) rights of the innovator. Italy, for example witnessed an increase of more than 60 per cent in its healthcare R&D in a decade’s time after enacting drug patent law in 1978. All this was hoped to be accomplished w i t h t h e e n a c t m e n t o f W o r l d Tr a d e Organization’s (WTO) agreement on traderelated aspects of Intellectual Property Rights (TRIPs) in 1995. TRIPs requires all the member nations to adhere to minimum IPR protection standard prescribed. This included grant of patent protection for pharmaceuticals. Developing nations were given additional time to align their IPR legislative regime with the standards set by TRIPs. TRIPs also addressed one of the biggest concerns ie, inaccessibility (financial and geographical) to the basic and life-saving patent protected drugs by majority of the developing and third world Pharma Bio World

The domestic pharmaceutical companies in India spent a huge chunk of money towards R&D of reverse engineering. This compared to the developed nations that dedicated substantial portion of their revenue for innovation and discovery of new drugs. nations. It incorporated a provision for grant of compulsory license ie, right of the state to grant license to manufacture and sell a patent protected drug to a third party without the consent of the patent holder only in certain situations and subject to certain conditions. These conditions are the check and balances incorporated b y T R I P s t o p r e v e nt u n d u e a b u se o f compulsory licensing. Article 31 of the TRIPs agreement inter alia lays down the following conditions for grant compulsory licensing; • Each case for grant of compulsory licensing must be considered on its merits. • F a i l u r e o f i n i t i a l a tte mp t to o b ta in authorisation from the patent holder through commercial terms within reasonable amount of time. This condition may be waived in case of national emergency or extreme urgency. • Payment of adequate remuneration to the patent-holder based on the economic value of the compulsory licensing scheme. • Only a non-exclusive and non-assignable license must be issued. • The license issued must be used only for the purpose it is granted and product manufactured using such license must be supplied only in the domestic market. India became TRIPs compliant in 2005, with the enactment of Patents (Amendment) Act of 2005 (Act). The Act introduced patent protection for pharmaceuticals. This was the end of road for local drug manufacturers, who used the protection afforded by the erstwhile patent law to manufacture cheap replicas. The Act Pharma Bio World

prohibited infringement of pharmaceutical patents and manufacture of generic version was restricted only to drugs patented before 1995 or drugs without a subsisting patent. Since the tightening of patent law, there has been an exponential increase in the R&D investment of Indian pharmaceutical industry for discovery of new drug manufacturing processes, formulations, molecular combinations and derivatives. There is a slow but steady shift in the focus of the Indian pharmaceutical companies, from advancement of generic formulation capabilities to increasing their new product R&D competencies. There are also a growing number of Indian pharmaceutical companies entering into regulated markets of US and various European countries. Despite the above, in what was seen as violation of TRIPs, India granted its first compulsory license for a pharmaceutical product in 2013. This license was granted by the Controller General of Patents (Controller) to Natco Pharma, an Indian generic company to manufacture and sell a generic version of American pharmaceutical giant Bayer Corporation’s patent protected drug ‘Sorafenib Tosyalte’ marketed as ‘Nexavar’. This drug is used for treating advanced kidney and liver cancer and permission to market the same in India was granted to Bayer in 2008. There is also an allegedly infringed low cost generic version of this drug being sold in India by Cipla. Bayer has filed a suit against Cipla in respect of such alleged infringement. In this case, Controller held that Bayer failed to ensure adequate availability of

the drug through local manufacture and granted compulsory license in respect of the drug to do so. However, grant of license to Natco was subject to payment quarterly royalty of 6 per cent net sales of the drug to Bayer. This order was challenged by Bayer before the Intellectual Property Appellate Board, which upheld the decision of the Controller but increased the royalty payable to 7 per cent. Following are the key highlights of this decision: 1) Onus of proving adequate availability of a product to the public at affordable price was held to vest on the patentee and in the instant case the Controller found that Bayer had failed to do so. The Controller dismissed Bayer’s arguments in this regard that sale of Cipla’s generic version of the drug must also be taken into account for deciding whether there was adequate availability of the drug at affordable price in India. Controller observed that having filed a case against Cipla for infringement, Bayer cannot rely on Cipla’s sale of the allegedly infringed drug to support its contention especially when the same runs the risk of being stopped on account of Bayer’s legal action. The Controller also rejected Bayer’s argument that it is not feasible for it manufacture the drugs locally on the ground that a patentee must prove non-feasibility and not merely state it. 2) As regards equal patent protection for all products regardless of location of its manufacturing as required under TRIPs, Controller held that protection for an imported patented product means protection from revocation of patent, but not compulsory license. It held that only local production by a patentee could be an effective bar to the grant of compulsory license unless the patentee can prove non-feasibility of local manufacture. This is seen by many as violation of Article 27 of the TRIPs, which provides that “patent shall be available and patent rights enjoyable without discrimination as to the place of invention, the field of technology and June 2014f 29

monopolistic practices, the same is unfortunately necessary because it permits an innovator to recover cost of R&D and finance further innovation. The grant of compulsory license creates the fear of increased and unbridled usage of compulsory licenses and inability of the state to protect the right of the innovators. This is an especially precarious situation for developing countries such as India, who are still dependent on the foreign companies for discovery of new drugs. F u r t h e r, f e a r i n g g r a n t o f c o m p u l s o r y license, pharmaceutical companies may decide to shift their manufacturing and clinical trial base to a “safer” venue resulting in a loss of foreign investment for the country. This turn may result in a loss of opportunities for talented scientists a n d r e s e a r c h e r s . M o r e o v e r, g r a n t o f compulsory license is also detrimental to bilateral trade relations of a developed nation with the developing nations having extremely stringent IPR regime.

Rising Drug Prices

There is a slow but steady shift in the focus of the Indian pharmaceutical companies, from advancement of generic formulation capabilities to increasing their new product R&D competencies. whether products are imported or locally produced”. It is apparent from this article, that equal patent protection must be given to imported products and that TRIPs does not envisage varying degrees of patent protection depending on where the product is manufactured. 3) With respect to the pricing, the Controller found the drug pricing of Bayer to be unaffordable for the Indian market. The Controller also refused to consider the cost incurred by Bayer as one of the key factors in determining the term “reasonably affordable price”, which in reality is indeed 30 eJune 2014

the key determinant of cost of a product. The onus of subsidising the drug price was placed solely on the patentee, without exploring avenues of state subsidies on the drug to ensure affordable availability atleast to the weaker section of the society. Although this decision is in keeping with the “TRIPs compliant” Act, it has once again highlighted India’s likelihood to lean towards the public interest argument in matter of pharmaceutical compulsory licensing.

There is no denying that the right of a patentee cannot be protected at the cost of human life and grant of compulsory license is inevitable in scenario where the public health is at stake. This has also been recognised by TRIPs which has sought to balance rights of a patent holder and public health requirement especially in developing nations. However, compulsory licensing is not always the “necessary” evil. Thus in every case for compulsory license, authorities must tread with extreme caution, ensure that the criteria of TRIPs is satisfactorily met and avoid taking extreme position entirely at the cost of the patentee. Contact: paradigmshiftpr@gmail.com

Compulsory licensing is a double edged sword. While patent encourages Pharma Bio World

Non-Patent Exclusivities This article discusses non-patent drug exclusivities available in the USA, Europe and India.

Dr Bhaswat S Chakraborty Sr Vice President, R&D Cadila Pharmaceuticals, Gujarat Pharma Bio World

iscovery and development of new drugs entail enormous intellectual and financial resources. Therefore, enough incentives and protections are required in order to motivate the innovators who obviously want to get a fair return on their investment. To this end, internationally, a twenty-year patent term from the date of discovery of the new molecular entity (NCE) is granted to innovative pharmaceutical products. This often results in eight to twelve years of exclusive sales rights. At the same time, this exclusivity is balanced with a legitimate competition from the low cost generic drugs. Although the development of generic drugs is of utmost importance to every society, especially, the mid- and low income countries, this article would focus on the â&#x20AC;&#x153;non-patentâ&#x20AC;? exclusivities awarded to the innovators and new data. Both the Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) provide several legal opportunities to extend the period during which innovators can market their drugs free of generic competition. These are called non-patent exclusivity provisions. Both patents and exclusivity are similar concepts and both work in a similar fashion. There are, however, some clear differences between them. Patents are granted by the patent and trademark office anywhere along the development lifeline of a drug and can encompass a wide range of claims. Exclusivity is exclusive marketing rights granted by the FDA upon approval of a drug and can run concurrently with a patent or not. Exclusivity is a statutory provision and is granted to an NDA applicant if statutory requirements are met. Exclusivity was designed to promote a balance between new drug innovation and generic drug competition. The readers should note that patents can expire before drug approval, they can be

issued after drug approval, or anywhere in between. Exclusivity, however, is granted only upon approval of a drug product, if the statutory requirements are met. Some drugs have both patent and exclusivity protections while others have just one or none. Patents and exclusivity may or may not run concurrently and may or may not encompass the same claims. Exclusivity is not added to the patent life. The United States Exclusivity Provisions In the US, five types of non-patent exclusivities exist which are listed in Table 1 on the next page. The total period of exclusivities over and above the patent term could be substantial and incentivising the innovators and new data generators. The following paragraphs describe the essential characteristics of these provisions of benefit in the US.1 Orphan Drug Entity (ODE) R a r e o r u n u s u a l d i s e a s e s ( a ff e c t i n g 200,000 or fewer patients) are often treated as orphan drugs as far as the pharmaceutical investment goes since drug companies are very reluctant to use resources for such small, often obscure markets. The orphan drug act of 1983 in the US was passed to address this genuine but often neglected area of drug treatment. This act provides the pharmaceutical manufacturers with seven years of market exclusivity period after its regulatory approval. If an ODE is approved by FDA, the latter may not entertain applications for generic or another innovator product that contains the same active ingredient and are labeled for the same orphan indications. However, a clinically superior or safer same orphan drug for the same indications may be granted by the FDA. 1 New Chemical Entity (NCE) An NCE is a drug containing an active moiety for which no new drug application June 2014f 31

S. No. Exclusivity

Term

Orphan Drug Entity (ODE)

7 years

New Chemical Entity (NCE)

5 years

“Other” Exclusivity (Mainly new clinical study exclusivity)

3 years

Pediatric Exclusivity (PED) – added to existing Patents/Exclusivity 6 months

Patent Challenge (PC ) – this exclusivity is for ANDAs only

180 days

Table 1: Non-patent exclusivities in the United States of America

(NDA) has been previously filed to the a g e n c y. T h e e m p h a s i s o f e x c l u s i v i t y here is on the new active moiety that is directly or indirectly responsible for the drug’s pharmacological action. The NCE exclusivity granted by the FDA is valid for a period of five years. During this period the FDA cannot approve a competitor’s generic [505(J)] or follow on [505(b)(2)] application which is based on the same NCE. Like the case stated above for ODE, the FDA can, however, accept or approve another NDA with evidence of adequate efficacy, safety, and quality based on the same NCE. 1 New Clinical Study Exclusivity New clinical study exclusivity is granted for submissions of reports of new clinical investigations (other than bioavailability studies) essential to the approval of the application or the supplemental application and conducted or sponsored by the applicant. Examples of clinical study exclusivity include formulations; salts; indications; dosing regimens; patient populations; OTC switches; or other label changes. The official requirements for new clinical study exclusivity include: a) Studies may not be bioequivalence or bioavailability in nature; b) Studies must be conducted or sponsored by applicant; c) T h e n e w r e s u l t s n o t r e l y o n F D A reference files of previously submitted data by another applicant or innovator; and d) Studies must be essential to approval in that no other available data would support the decision of approval.. 32 eJune 2014

This type of exclusivity is granted for 3 years and during this period a competitor’s ANDA will not be approved by the FDA. However, unlike NCE exclusivity, the FDA can review an ANDA with the same drug during this exclusivity period. 1,2 Pediatric Exclusivity (PED) The FDA modernisation act of 1997 empowers the applicants to receive an exclusivity of 6 months who complete FDA requested clinical trials of a drug in a pediatric population. Children as patients may not metabolize and respond to a drug like their adult counterparts do, thus warranting appropriate and adequate clinical trials of the same drug on pediatric population to develop useful information of safety and efficacy. It should be noted that the generated pediatric efficacy and safety data need not be successful in statistical and conventional sense but the data itself is of prime importance. When pediatric exclusivity is granted to a drug product, a period of 6 months exclusivity is added to all existing patents and exclusivity on all applications held by the sponsor for that active moiety. Pediatric exclusivity does not stand alone. PED is annotated in the exclusivity column and is linked to exclusivity formerly granted. In the patent column, the patent

is shown twice – once with the original patent expiration date and a second time reflecting the six month period of exclusivity that links to that particular patent. 1,2 Patent Challenge (PC) Patent challenge or generic drug exclusivity came into existence by virtue of Hatch-Waxman Act of 1984. This act provides for an exclusivity to the first ANDA applicant who submits its substantial ANDA containing a paragraph IV certification. A paragraph IV certification means that the applicant shall provide the patent number and certify, in its opinion and to the best of its knowledge, that the patent is invalid, unenforceable, or will not be infringed by the manufacture, use, or sale of the drug product for which the abbreviated application is submitted [CFR 314.94(a) (12)(i)(A)(4)]. A substantially complete ANDA contains data that is sufficient to permit a full review. The length of patent challenge exclusivity is 180 days from the day of beginning of commercial marketing of the product. For the FDA to begin the approval process of paragraph IV, the generic applicant must: a) Certify in its ANDA that the patent in question is invalid or is not infringed by the generic product (paragraph IV certification as mentioned above); and b) N o t i f y t h e p a t e n t h o l d e r o f t h e submission of the NDA. If the patent holder files an infringement suit against the generic applicant within 45 days of the ANDA notification, FDA approval to market the generic drug is

Patents can expire before drug approval, they can be issued after drug approval, or anywhere in between. Exclusivity, however, is granted only upon approval of a drug product, if the statutory requirements are met. Pharma Bio World

automatically postponed for 30 months, unless, before that time, the patent expires or is judged to be invalid or not infringed. This 30-month postponement allows the patent holder time to assert its patent rights in court before a generic competitor is permitted to enter. 1,2 Supplementary Protection Certificates (SPCs) in Europe Pursuing patents in the United States and abroad can be a very expensive, but necessary, proposition. In most countries throughout the world, including the U.S. and European countries, a patent expires 20 years after its earliest filing date. However, the process of obtaining a patent may take many years, effectively reducing the length that the patentee is allowed to exclude others from practicing the patent. T he E u r o p e a n p a t e n t la w o ffe rs to a manufacturer to apply for a Supplementary Patent Protection Certificate (SPC) in order to compensate patent holders for the regulatory delays caused by marketing authorisation procedures for medicinal and plant protection products. By way of an SPC, the statutory 20-year maximum patent term can be extended by up to five years. The readers should note that SPCs can be obtained only for products that have been authorised for the first time as medicinal products in the EU. 2 In Lithuania, however, an SPC may be obtained for any approved patented product, provided the basic patent was filed after February 1 st , 1994. 2 Other Exclusivities in Europe As described above, data exclusivity applies for a period of time during which a co m p a n y c a n n o t c ro ss-re fe r to th e data in support of another marketing authorisation. Under the data exclusivity directive, pharmaceutical companies may receive up to 11 years to market their product without risk of competition. These 11 years of exclusivity are comprised of Pharma Bio World

The Indian Patents Amendment Act of 2005 excludes patentability for derivatives of known substances; unless it is proved that the efficacy is significantly greater than the original substance. what the European parliament has termed an “8+2+1” regime. A drug company introducing its product to market in the EU can enjoy eight years of data exclusivity, two years of marketing exclusivity and a one year extension. During the eight-year period of data exclusivity competitors cannot submit generic applications for marketing authorisation. During this time, the innovator’s data is treated as a trade secret and new entrants cannot reference the data until the expiration of the eightyear data exclusivity period. A company that wishes to apply for marketing approval within the data exclusivity period must perform its own safety and toxicology studies, and its own clinical trials, without dependence on the innovator’s data. EU also has exclusivity for orphan drugs and pediatric medicines. The basis for orphan drugs is that the patients affected by rare diseases have the same rights as fellow citizens. The orphan designation criteria include rarity of condition (<5 in 10,000) or insufficient return on investment; seriousness of condition (life threatening/ chronically debilitating) and existence of satisfactory methods of diagnosis, prevention, or treatment in the EU. If a method does not exist, the medicinal product should be of significant benefit to those affected by the condition. Once a marketing authorisation for an orphan drug is granted in EU’s centralised procedure or by all member states, the community and the member states will not, for 10 years, accept another application for a marketing authorisation for the same drug and indication. 3 In Europe, pediatric drug development exclusivity rewards include:

a) Six months of patent extension for pediatric studies that have been performed as described in the pediatric investigation plan (PIP); b) One year patent extension for products that have demonstrated a significant clinical pediatric benefit for an approved indication; c) Two years of additional marketing exclusivity are granted for orphan products for which pediatric studies are conducted as described in the PIP; and d) The pediatric use marketing authorisation (PUMA) may provide eight years of data exclusivity and 10 years marketing exclusivity for those products developed exclusively for use in the pediatric population. 4 The Indian Scenario Until 1994, India had relatively weak patent laws so that all life-saving drugs could be provided to Indian citizens at low cost. However, under the auspices of World Trade Organization (WTO) regime, India signed the Trade Related Aspects of Intellectual Property Rights agreement (TRIPs) of the General Agreement on Tariffs and Trade (GATT) on April 15, 1994. Following this agreement and its actual implementation in the Patent Amendment Act of 2005, saw that the Indian industry is in full compliance with TRIPs in all aspects. As a result, both products and processes of all APIs and finished dosage forms are supposed to be non-infringing of existing relevant patents. 5 In practice, however, there are significant concerns. There is no guaranteed data exclusivity in India.6 Such non-exclusivity allows generic companies sometimes to introduce competing products without June 2014f 33

doing their own safety and efficacy tests. In the same context, The Indian Patents Amendment Act of 2005 excludes patentability for derivatives of known substances; unless it is proved that the e ff i c a c y i s s i g n i f i c a n t l y g r e a t e r t h a n the original substance. Additionally, the drug price control order (DPCO) of 2013 has ~350 essential drugs under price control thus not encouraging non-patent exclusivity to the extent described above for US or EU. Concluding Remarks

exclusivities along with the remaining patent term after approval provide for an optimal benefit to these stakeholders. When properly informed about these exclusivities, an innovator, NDDS sponsor or a generic manufacturer can develop their strategies for an appropriate short or long term, whatever is applicable in its case.

O r p h a n d e s i g n a t i o n . h t t p : / / w w w. e m a . europa.eu/ema/index.jsp?curl=pages/ regulation/general/general_content_000029. jsp&mid=WC0b01ac05800240ce 4 ) E u r o p e a n M e d i c i n e s A g e n c y. ( 2 0 1 3 ) . Medicines for children. http://www.ema.europa. eu/ema/index.jsp?curl=pages/special_topics/ general/general_content_000302.jsp 5) Chakraborty B.S. (2011). Towards New

References

Horizons in Pharma Research. Ingredients

1) US Food and Drug Administration. (2011). How can I better understand Patents and Exclusivity? http://www.fda.gov/ForIndustry/

It is fitting that pharmaceutical innovators would like to enjoy a favorable return on their R&D investments since the investments often exceed the billion dollar mark these days. The non-patent market

3 ) E u r o p e a n M e d i c i n e s A g e n c y. ( 2 0 1 3 ) .

FDABasicsforIndustry/ucm238582.htm 2) Hathaway C., Manthei J., Scherer C. (2009) Exclusivity Strategies in the United States and European Union. FDLI Update, May/June issue, 34-39.

South Asia, October 16-31 issue, 34-36. 6) Janodia M.D., Chauhan A., Hakak S.M., Sreedhar D., Ligade V.S., Udupa N. (2008) Data Exclusivity Provisions in India: Impact on Public Health. Journal of Intellectual Property Rights, 13, 442-446.

Contact: drb.chakraborty@cadilapharma.co.in

ADVERTISE TO EXPAND your reach through INSIGHT INTO THE PHARMACEUTICAL AND BIOTECH INDUSTRIES

For Details Contact

Jasubhai Media Pvt. Ltd. Taj Building, 3rd Floor, 210 Dr D N Road, Fort, Mumbai - 400 001 Tel: 022-4037 3636, Fax: 022-4037 3635 Email: industrialmags@jasubhai.com 34 eJune 2014

Pharma Bio World

Calculation of SPC and Patent Term Extension This article provides a general description of laws and regulations for patent extension in US, EU and Australia.

he US, the EU and Australia all provide patent extensions of up to five years for certain patents. These laws and regulations are directed towards pharmaceuticals. The marketing approval process for new prescription drugs is lengthy and erodes the effective patent life for pharmaceutical products. Patent extensions are thus designed to reward innovation and compensate for the time taken in clinical trials and regulatory review. The provision of patent extension available in European Union is known as “Supplementary Protection Certificate (SPC)”, while in US it is known as “Patent Term Extension (PTE)”. In European Union member countries, a Supplementary Protection Certificate (SPC) is a unique (sui generics) intellectual property (IP) right that extends the duration of the exclusive right. It enters into force after expiry of a patent upon which it is based. This type of right is available for various regulated, biologically active agents, namely human or veterinary medicaments and plant protection products (eg, insecticides, and herbicides). Supplementary protection certificates were introduced to encourage innovation by compensating for the long time needed to obtain regulatory approval of these products (ie, authorisation to put these products on the market). 1 Laws and Regulation in European Union for SPC

Dr Manish A Rachchh

Associate Professor, Center of Pharmaceutical Studies & Drug Delivery Technologies, Gujarat Technological University, Ahmedabad Pharma Bio World

The European Parliament enacted Supplementary Protection Certificate legislation in relation to ‘medicinal products’ on 2 nd July 1992. This legislation was adopted in Council Regulation (EEC) 1768/92 (the SPC Regulation) and became effective on 2 nd January 1993. 2 The SPC Regulation applies in Austria, Belgium, Denmark, Finland, France,

G e r m a n y, G r e e c e , I r e l a n d , I t a l y, Luxembourg, Netherlands, Portugal, Spain, Sweden and the United Kingdom. The purpose of the SPC Regulation can be discerned from its recitals. The recitals expressly recognise that the period of effective patent life is ‘insufficient’ to compensate patentees for the research costs associated with the development of medicinal products. Accordingly, the (maximum) 15-year period of market exclusivity afforded by a Supplementary Protection Certificate (SPC) is intended to provide adequate compensation in respect of such costs. a) Scope of Extension Provisions SPCs do not provide for a formal extension of the term of the relevant patent, namely, the patent which protects the medicinal p r o d u c t i n q u e s t i o n . R a t h e r, a S P C achieves its objective of conferring an additional period of market exclusivity by conferring the same rights as a patent for a limited period commencing at the expiration of the original patent term. However, the practical effect of a SPC is not dissimilar to the effect of an extension of patent term. In particular, the rights conferred by a SPC correspond with (and are subject to the same limitations and obligations as) the rights conferred by the relevant patent in relation to a claim for an authorised m e d i c i n a l p r o d u c t . 3 A c c o r d i n g l y, t h e extension of protection provided by a SPC is hereafter referred to as an extension of term. Article 4 of the SPC Regulation effectively restricts the nature of patent claims in respect of which a SPC may be granted. The protection conferred by a SPC is restricted to: • The active ingredient of a medicinal product which has been subject to market authorisation, ie. claims to the authorised compound itself; and June 2014f 35

in which the application for a certificate is made; 7 • Market authorisation for the product has been granted in the aforementioned EU member state and this is the first such authorisation granted; and • The product has not previously received a SPC.

• Any use of the active ingredient as a medicinal product that has been subject to authorisation, ie. claims to authorised uses of the compound. 4 In summary, the protection conferred by a SPC will be restricted to the particular active ingredient or use of active ingredient in respect of which market authorisation has been granted. 5 Therefore, active ingredients and uses of active ingredients (described or claimed in a patent) will not receive the protection conferred by a SPC unless those ingredients or uses have been granted authorisation.

SPCs take effect from the date of patent expiration (Article 13(1)) and subsist for a period equal to the period between the application date of the ‘basic patent’ and the first market authorisation date for the product, minus 5 years. However, the duration of a SPC cannot exceed five years. (SPC Regulation, Article 13(1) and 13(2)). Therefore, SPCs provide for a maximum effective patent life of 15 years.

In summary, ‘Medicinal product’ is defined as any substance used for: • The treatment or prevention of disease in human being or animals; • Medical diagnosis in humans or in animals; or • Modifying physiological functions in humans or in animals. 6

A SPC will only be granted if (as at the date of the application) the following conditions are fulfilled: • The product is protected by a ‘basic patent’ in force in the EU member state

The Hatch-Waxman Act sought to balance the interests of innovator drug companies and generic manufacturers. First, the Act restored part of the patent term ‘lost’ during the process of obtaining regulatory approval, thereby creating new incentives for investing in research and development in relation to products which are subject to regulatory regimes. 9 In return, generic manufactures were granted expedited approval procedures (ANDA):

(a) Scope of Extension Provisions U/s 35 U.S.C. §156

Employing the symbols above, the length of EU patent extensions (F) can be expressed in the following terms: F = A + B + C + D – 5 (Where: F 5)

First Permitted Clinical Trial

Amendments introduced by the Drug Price Competition and Patent Term Restoration Act of 1984 (the Hatch-Waxman Act) provided for extensions to the term of certain patents (US extension provisions). The US extension provisions are codified in 35 U.S.C. §156.

The emboldened black line in Figure 1 represents the period of time which can be taken into consideration for the purposes of calculating the length of a SPC. In particular, the length of a SPC is equal to the period represented by the emboldened black line, minus 5 years (provided that the length of the SPC does not exceed 5 years).

b) Requirements for an Extension of Term

Grant Date

The standard term of a US patent is 20 years from the date of application. 8 The 1994 Uruguay Round Agreements Act (URAA) changed the term of US patents from 17 years from the date of grant to 20 years from the date of application, thus ensuring US compliance with the TRIPS Agreement.

c) Length of Extension Period

A SPC can only be granted in respect of the active ingredient (or combination of active ingredients) of a ‘medicinal product’.

Filing of Basic Patent

Laws and Regulations in United States for PTE

Termination of Clinical Trials

The US extension provisions apply to patents which claim methods of manufacturing or

Marketing Authorisation Date

Standard Term Expires

Extension Period Ends

Employing the symbols above, the length of EU patent extensions (F) can be expressed in the following terms: F = A + B + C + D – 5 (Where: F 5) Figure 1: Period of time for calculating the length of SPC

36 eJune 2014

Pharma Bio World

First Permitted Submission Clinical of Application Issue Date Trial to FDA

Application Date

Marketing Approval Date

Standard Term Expires

Extension Period Ends

Employing the symbols above, the length of US patent extensions (F) can be expressed in the following terms: F = C/2+D – period where patentee did not act with due diligence. Where; F 5 E + F 14 A + B + C + D + E = 20 years Figure 2: Method for calculating the length of US patent extensions

using a ‘product’, in addition to claims to the ‘product’ itself. 10 The US extension provisions only apply to patents which claim a ‘product’ or a method of using or manufacturing a ‘product’. Therefore, the scope of the US extension provisions corresponds with the scope of the following definition of ‘product’: • The active ingredient of a new drug, antibiotic drug, or human biological product (as those terms are used in the Federal Food, Drug, and Cosmetic Act and the Public Health Service Act); • The active ingredient of a new animal drug or veterinary biological product (as those terms are used in the Federal Food, Drug, and Cosmetic Act and the VirusSerum-Toxin Act) which is not primarily manufactured using recombinant DNA, recombinant RNA, hybridoma technology, or other processes involving site specific genetic manipulation techniques; or • Any medical device, food or colour additive subject to regulation under the Federal Food, Drug and Cosmetic Act. b) Requirements for an Extension of Term 10 The following conditions must be satisfied before an extension of term will be granted Pharma Bio World

under the US extension provisions: • An application for extension must be submitted by the owner of record of the patent or its agent prior to the expiration of the original term of the patent; • The term of the patent must not have been extended previously; • The product must have been subject to a regulatory review period before its commercial marketing or use; and • Permission for the commercial marketing or use of the product (after such regulatory review) must be the first such permission granted. In circu ms tances where a product is protected by more than one patent, only one of those patents may be the subject of an extension of term.

the Federal Food, Drug and Cosmetic Act. 12 Significantly, the formula for calculating the length of US patent extensions is subject to the following limitations 13: • Extensions of term under the HatchWaxman Act cannot exceed 5 years; • Maximum effective patent life is expressly limited to 14 years; • Periods during which the applicant for extension ‘did not act with due diligence’ are subtracted from the total term of extension; and • The length of extension cannot exceed 2 years in respect of patents for ‘pipeline drugs’.

c) Length of Extension Period

In summary, ‘pipeline drugs’ r ef er t o patented drugs which, as at the date of the enactment of the Hatch-Waxman Act, had commenced a process of clinical tests but were awaiting FDA approval.

The formula for calculating the length of an extension to the term of US patents is based on the length of the ‘regulatory review period’. 11 In summary, the US extension provisions allow for an extension of term equal to 50 per cent of the time devoted to the clinical testing phase plus 100 per cent of the time spent obtaining approval under

Figure 2 illustrates the method for calculating the length of US patent extensions. In particular, the emboldened black line represents the total length of the extension period, provided that such period does not exceed five years or result in an effective patent life of greater than 14 years. June 2014f 37

Jurisdiction

Nature of Claims Covered

Nature of Substances Covered

Maximum Length of Extension

Maximum Effective Life

Product, process and use claims

Extends to drugs for humans and animals

5 years

14 years

Canada

N/A

0 years

N/A

Product, process and use claims

Extends to drugs for humans and animals and to ‘plant protection products’

5 years

15 years

Australia

Product claims only (unless recombinant DNA process used)

Extends to drugs for humans only

5 years

15 years

Table 1: Comparison of principles of US and European Union system for Patent extension

d) Patent Extensions Pursuant to 35 USC § 154 14,15

Comparision of US and EU System for Patent Extension

Section 154(b) of USC 35 provides an independent basis for extending patent terms, whether in relation to pharmaceutical patents or otherwise. In particular, section 154(b) of USC 35 allows for extensions of term in circumstances where the issue of an original patent is delayed due to interference proceedings, secrecy orders or appellate review by the Board of Patent Appeals and Interferences or by a Federal Court.

The difference between US and European Union system in terms of principles as well as calculation for Patent extension can be summarised as per Table no. 1 and Table no. 2 respectively.

Extensions of term granted pursuant to section 154(b) cannot exceed 5 years and are subject to further qualifications if the extension arises out of a period of appellate review. Section 154(b) is not limited in application to patents of a particular kind, in contrast to the extension provisions codified in section 156 and discussed above. Therefore, section 154(b) appears to provide a basis for extending patent terms which is independent of (and additional to) the pharmaceutical extension provisions codified in section 156 and discussed above. Section 154(b) was inserted into 35 USC by the Patent Term Guarantee Act of 1999 and applies to patent applications filed on or after 29 May 2000. 38 eJune 2014

Due to difference in principle as well as calculation of patent term extension, the extended period of Patent in US is normally shorter as compared to patent extension provision available in Australia. Examples of certain API’s patent extension in these 3 major countries are tabulated as in Table 3.

and consumers by and large. So there is an inmate need of multilateral treaty for harmonization purpose. References 1) Council Regulation (EEC) No 1768/92 of 18 June 1992 2) Thomas Vinje, ‘Symposium on U.S.-E.C. Legal Relations: Recent Developments In European Intellectual Property Law: How will they affect you and when?’ (1994) The Journal of Law and Commerce 301, at 312. 3) SPC Regulation, Article 5. 4) SPC Regulation, Article 4. 5) Edward H Mazer, ‘Supplementary Protection

Conclusion

Certificates in the European Economic

Referring to variation in regulation about patent extension in different countries, we can say that there is need to harmonize regulations among the countries to make either SPC or PTE as a tool to provide benefit to the innovators, while also safe guarding the interest of stack holders Extension Formula Jurisdiction ‘F’ refers to the length of the extension period

Community’, (1993) 48 Food & Drug Law Journal 571, 574. 6) SPC Regulation, Article 1 7) SPC Regulation, Article 3(a). 8) 35 U.S.C. §154(a)(2). 9) Shilpa Patel, ‘Patent Fairness Act of 1999: The Implications of Extending Patents

Maximum Length of Extension

Maximum Effective Life

F = C/2+D – period where patentee did not act with due diligence

5 years

14 years

F=A+B+C+D-5

5 years

15 years

Australia

F=A+B+C+D-5

5 years

15 years

Table 2: Comparison of Extension Formula of US and European Union system

Pharma Bio World

Jurisdiction

Generic Drug Name

Brand Name

Australian Patent Extension Length

US Patent Extension Length

Differences between Australia and US

Differences between Australia and UK

simvastatin

Zocor

1,638 days

1,704 days

822 days

-66 days(US)

+816 (AU)

Atorvastatin (DITR list: atovasatin x 2)

Lipitor

1,827 days

1,213 days

1,622 days

+614 days (AU)

+205 (AU)

Amlodipine

Norvasc

1,814 days

1,252 days

365 days

+562 days (AU)

+1449 (AU)

Lansoprazole

Prevacid/Zoton

1,505 days

1,381 days

132 days

+124 days(AU)

+1373 (AU)

loratadine

Claritin/ Claratyne

1,826 days

730 days

537 days

+1096 days (AU)

+1289 (AU)

Sertraline

Zoloft

1,826 days

1,228 days

1,825 days

+598 days (AU)

+1(AU)

Pravastatin

Pravachol

1,826 days

1,598 days

1, 158 days

+228 days(AU)

+668 days (AU)

Amoxicillin + potassium clavulanate (not found in DITR list)

Augmentin

Ciprofloxacin

Ciproxin

478 days

3 years (1096 days)

161 days

-618 days (US)

+317 (AU)

Cetirizine (DITR list: cetirizine

Zyrtec

1,826 days

Lisinopril (not found in DITR list)

Prinivil

Famotidine

Pepcid

1,219 days

293 days

202 days

+926 days (AU)

+1,017 days (AU)

Quinapril

Accupril

225 days

2 years (730 days)

924 days

-505 days (US)

-699 days (UK)

Lovastatin (not found in DITR list)

Mevacor

Fosinopril

Monopril

1,826 days

2 years (730 days)

1,825 days

+1096 days (AU)

+1 day (AU)

Nefazodone

Serzone

1,826

3 years (1096 days)

161 days

-618 days (US)

+317 (AU)

1,465 days

1,079 days

1,055 days

+386 days (AU)

+493 (AU)

Average

No patent number available in DITR list – Patent extension length unconfirmed

Table 3: Comparison of actual patent term extension for APIs in US, EU and AU

for Pipeline Drugs’ Journal of Intellectual Property Law vol .8, pp145-148, 2000.

Pharmaceutical Market Entry’, Food Drug

Companies to Pull the Plug on Innovation’,

Law Journal vol. 55, pp. 373-388, 2000.

Kentucky Law Journal vol 90, pp.495- 512,

10)35 USC §156(a).

13) 35 USC §156(g)(6)(A).

11) 35 USC §156(c)(4)

14)Mandy Wilson, ‘Pharmaceutical Patent

12)Edward Hore. ‘A Comparison of United States

Protection: More Generic Favoured

and Canadian Laws as They Affect Generic

Legislation May Cause Pioneer Drug

Pharma Bio World

2001. 15) 35 USC § 154(b)(1).

Contact: manish.rachchh@gtu.edu.in June 2014f 39

Role of IPR in Forming Legal Strategies for Pharma Industry Pharmaceutical industry currently has an evolving IPR strategy requiring a better focus and approach in the coming era. This article chalks out the evolving role of IPR in framing legal strategies for pharmaceutical industry.

Ravi Bhola

Partner K&S Partners, Bengaluru

Shivakumar

Sr Associate K&S Partners, Bengaluru

Pranav Mysore

Sr Associate K&S Partners, Bengaluru 40 eJune 2014

n the era of globalisation, there is a constant technological race especially in the field of pharmaceuticals to develop new/improvised drugs. Due to this, pharmaceutical companies are making huge investments on R&D and hence, it is imperative to protect the Intellectual Property (IP) associated therein and obtain returns by its commercialisation. Accordingly, it is no surprise that IP, particularly patents have become important in framing legal strategies for pharmaceutical companies, right from the commencement of research till the expiry of patents. Frequently, pharmaceutical companies strategise on procuring and enforcing their patents, however, such strategies are not focused on how to maintain their patents when challenged for validity. On the other hand, economic liberalisation has seeded a competitive market pressurising the competitors to come out with generic or biosimilar versions for which suitable strategies have to be formulated 1 .

The exclusive monopolistic rights over an invention granted to pharmaceutical companies under the existing Indian Patent Regime are affected by issues such as restrictions during procurement of patents, lack of presumption of validity, use of patents under “Bolar Provision” and so on. Restrictions for procurement of patents come by way of issues relating to patentable inventions, lack of enablement and pre-grant opposition by third parties. It is pertinent to mention here that the recently proposed guidelines by Indian Patent Office for examining pharmaceutical applications recommend enablement for all the groups claimed under “Markush Structure”. The guideline with respect to enablement for all the groups under “Markush Structure” is unique in the sense that other jurisdictions accept enablement for some of the groups while Indian Patent

Office suggests enablement for all the groups. Though these guidelines have not come into force and there may be a debate on this aspect, it is still better to consider these guidelines while drafting the application. In addition to lack of enablement, it is seen that presently most patent applications in the field of pharmaceuticals do not comply with requirements of “enhanced therapeutic efficacy” under section 3(d) of Indian Patents Act, 1970. Often, while filing application for patent on an invention, enhanced efficacy data is misconstrued as the activity data of the compound so claimed. Per contra, enhanced efficacy data would mean a comparative data demonstrating enhanced efficacy of the compound so claimed over closest known compounds. Such misinterpretation has resulted in rejection of several patent applications in India. Although other countries do not have such an express provision, they do conduct examination and raise objections under inventiveness as it is sometimes raised under section 3(d). Lack of enhanced efficacy data not only affects the patents from being granted by the patent offices, but also allows third party to file pre-grant opposition. Such rigorous process during prosecution and a right given to third party to oppose grant puts evergreening of patents under scrutiny. Even if a third party loses out on filing a pre-grant opposition, options to invalidate a granted patent are available by way of post-grant opposition or revocation of patent. Yet again, these provisions act as a check on evergreening of patents amongst other legislative framework. On the other hand, patentee can institute infringement action against the infringer to protect and safeguard the interest in the patent, thus preventing anyone from practicing patentee’s invention for commercial gains. Pharma Bio World

During proceedings such as opposition, revocation or infringement, the strategy lies in providing appropriate information that would support and strengthen the stand taken by concerned parties. For example: A patent is said to be infringed on the grounds that the patentee has monopoly over a particular compound A. The patentee identified that a third party is infringing the patent by selling salt Y of the compound A. It was found during proceedings that the patentee had filed another application for salt Y of the compound A which was abandoned later. The defendant argued that it is imperative from these facts that the plaintiff (patentee) themselves considered compound A and salt Y of compound A to be different from one another. Such being the case, the patent covering compound A cannot be said to be infringed by the defendants product - salt Y of compound A, even though the patent claims relate to pharmaceutically acceptable salts of compound A. The Hon’ble Delhi High Court held that the plaintiff ought to have shown the defendant’s product remained equivalent to compound A to establish prima facie case of infringement 2 . The decision was appealed and the order is yet to be passed in this case. It appears that the case would have been in favour of the patentee if the activity of the compound A and its salt form Y was shown as equivalent. Even though such proof could be furnished at the appeal stage, the issue could have been resolved in the preliminary stage itself if it was proved. Another important factor to be considered based on this case is to decide on the need for filing independent patent applications for related subject-matter as such filings have a bearing on the parent application at a later date. One probable option that pharmaceutical companies can consider in such situation is to file a divisional application/patent of addition depending on case to case basis rather than filing an independent application for related subject-matter. Pharma Bio World

Having said the above, there are certain provisions in the law which allow third party to use patent granted to the patentee. One such provision relates to compulsory licensing, wherein any person interested may request for issuance of an involuntary licence to practice a granted patent, subject to certain conditions - meeting reasonable requirement of public such as accessibility and affordability, in addition to working of the patented invention in India. IPAB has held that the term “Worked” has a flexible meaning based on the specific facts 3 . If the working of the invention is not feasible, the onus lies with the patentee to prove as to how the working was not feasible without merely making a statement to this extent. Another provision under which a patent can be used by third party is “Bolar Provision”

patented drug solely for the purpose of research and development and for the purpose of procuring regulatory approvals. Any misuse of this provision would be construed as infringement and necessary action can be instituted by the patentee. Generally, the regulations in obtaining approval under Bolar Provision or after the expiry of the patent is simpler for generic drugs compared to biosimilars owing to the differences in the process by which the patented drug and biosimilars are produced. Thus, it is necessary to furnish clinical trial data for biosimilar versions while seeking approval from a regulatory authority. Though the regulatory aspect is not binding on Indian Patent Provisions for approving a patented drug, pharmaceutical companies are bound by such provisions for not selling the approved drug for

Bolar Provision is a specific enablement towards using the patent without authorisation of the patentee for the purpose of research, development and to obtain approval from regulatory authority. which is present in legislative framework of many countries. Bolar Provision is a specific enablement towards using the patent without authorisation of the patentee for the purpose of research, development and to obtain approval from regulatory authority. India has added one extra element to this Bolar Provision which enables a person to even sell the patented product. The legislative intent incorporating this element to the existing known Bolar Provision should not be misinterpreted to state that any person can sell/manufacture the drug on a commercial scale. It has to be interpreted in a manner which is necessary for procuring approvals from various quarters of the Government.

commercial purposes until the expiry of the patent owing to the issues of infringement. In conclusion, framing right legal strategies based on the provisions available within the Indian legal framework would help pharmaceutical companies in addressing issues relating to procurement, enforcement and commercialisation of patents. Such strategies would lessen the challenges even if one cannot avoid the issues completely. References: 1) www.ircc.iitv.ac.in/ipcourse/patent.html 2) Merck v/s Glenmark – CS (OS) 586/2013 –Delhi High Court – order dated 05-04-2013. 3) Bayer vs. NATCO – OA/35/2012/PT/MUM –

Hence, Indian Bolar Provision has to be interpreted to state that any person can use/manufacture/sell /import the

IPAB – order dated 04/03/20138)

Contact: avishek@knspartners.com June 2014f 41

Challenges in Analytical Method Development for Drug Products This article gives a perspective on growing importance of analytical method development in the discovery, development and manufacture of pharmaceuticals.

nalytical method development has gained lot of importance these days. This forms an integral part of regulatory filing in Europe & US. Tr e m e n d o u s Te c h n o l o g i c a l a d v a n c e s in Analytical Instrumentation with focus towards reducing time of analysis without compromise in Precision & accuracy of analytical results. Globally there are various strategic alliances of pioneers of Analytical Instrument Manufacturers eg, Agilent & Varian. All pharmaceutical organisations are investing a lot in such advance analytical equipment. Dedicated specialised Functional Department is formed in many of Pharma companies named â&#x20AC;&#x201C; Analytical R&D. Due to which Stability Indicating Analytical Method Development is getting day by day more & more challenging. Regulatory Guidance To ensure compliance with quality and safety standards, the United States, Europe, Japan, and other countries have published compendia, or pharmacopeias, that describe official test methods for many marketed drug products. For example, compendia analytical methods found in United States Pharmacopeia 25 (USP 25) are legally recognised analytical procedures under section 501 (b) of the Federal Food, Drug, and Cosmetic Act. For these compendia methods, USP provides regulatory guidance for method validation (1). In addition, validation of analytical methods is covered by the United States Code of Federal Regulations (CFR). Specific references are 21 CFR 211.165 (e) and 21 CFR 211.194 (a).

Dr Parag Gadkari

Vice President â&#x20AC;&#x201C; Analytical Research & Development, Inventia Healthcare Pvt Ltd 42 eJune 2014

As part of this initiative, the International Conference on Harmonisation (ICH) has issued guidelines for analytical method validation. The recent FDA methods validation draft guidance document guidelines. Analytical guidance documents recently published by the ICH are the following;

1) Stability Testing (Q1) 2) Validation of Analytical Procedures (Q2) 3) Impurities in Drug Substances & Drug Products (Q3) 4) Specifications for New Drug Substances & Products (Q6) Method Development Process The steps involved in method development and method validation depend upon the type of method being developed. However, the following steps are similar to most types of projects; 1) Method Development Plan 2) Gathering background information 3) Laboratory method development 4) Generation of test procedure 5) Validation protocol 6) Laboratory method validation 7) Validated test method generation 8) Validation report Specific Tests Tests designed for special quality parameters such as Micron size, Polymorphism, Spatial structure, chirality of drug substance (API) 1) X-Ray Diffraction 2) Particle size determination 3) Residual solvent determination by GC/ GC-HS 4) Specific optical rotation 5) TLC for any specific chemical entity Stability Indicating Method A stability indicating method (SIM) is a quantitative test method that can detect possible degradants and impurities of drug substance (API) and drug products, normally using High Performance Liquid Chromatography. Stability information is needed for regulatory submissions such as IND (Investigational New Drug Application) and NDA (New Drug Applications) and to set expiration dates for the API or drug product. Pharma Bio World

Pharmacopoeial Analytical Methods

Identification Tests

Potency / Assays

Impurity Tests

Figure 1: Main Categories of Pharmaceutical Analytical Methods

Before performing stability studies, a stability indicating method is necessary so that any possible degradants generated during storage conditions (such as 5°C, 25°C / 60% RH and 40°C/ 75% RH) can be separated, detected, and quantitated. SIM is useful for check the quality of the drug substance or product changes over time in response to environmental factors such as temperature, humidity and light. It establishes the storage and packaging conditions for the drug product. The method should be sensitive to the reportable impurity level. LOQ (Limit of quantitation), which is typically 0.05 per cent of Label Claim, should be established in the method, and the method should be linear from LOQ to typically up to 150 per cent of the nominal standard (std) concentration. When are stability indicating methods needed? 1) Stability studies 2) API release 3) Drug product release 4) Toxicology dosing solutions 5) E x c i p i e n t c o m p a t i b i l i t y a n d p r e formulation 6) Packaging studies 7) Line extension Cases where stability indicating methods are not needed; 1) In process controls 2) Titration 3) Inorganics 4) Limit tests 5) Cleaning validation Pharma Bio World

Main process flow of Analytical method development includes; 1) Generating the sample 2) Developing the method 3) Validate the method The essential validation parameters are included as follows; 1) Specificity - Ability to measured desired analyte in complex mixture. 2) Accuracy - Agreement between measured & real value. 3) Linearity - Proportionality of measured value to concentration. 4) Precision - Agreement between series of measurements. 5) Range - Concentration interval in which method is precise, linear, accurate. 6) Detection Limit - Lowest amount of analyte that can be detected. 7) Quantitaiton Limit - Lowest amount of analyte that can be measured. 8) Robustness - Reproducibility under normal but variable laboratory conditions. Challenges in Method Development Analytical method development, validation and transfer are key elements of any pharmaceutical developmental programme. Often considered routine too little attention is paid to them with regards for their potential to contribute to overall developmental time and cost efficiency. Effective method development ensures that laboratory resources are optimised, while methods meet the objectives required at each stage of development. Method validation required by regulatory agencies

at certain stages of drug approval process is defined as the process of demonstrating that analytical procedures are suitable for their intended use. Method transfer is the formal process of assessing the suitability of methods in another laboratory. Each of this process contributes to continual improvement of the methods and results in more efficient drug development. According to International Conference on Harmonisation (ICH), the most common types of analytical procedures are; 1) identification test 2) quantitative test of the active moiety in samples of API or drug product or other selected components in the drug product 3) quantitative tests for impurities content 4) limit tests for the control of impurities Specificity / Selectivity / Sensitivity 1) Chemical Degradation of Drug Substance / Drug Product 2) Hydrolysis 3) Dehydration 4) Oxidation 5) Isomerization / Racemization 6) Photo degradation Degradation Phenomenon in Drug Product a) Drug - Excipient/s Interaction b) Drug - Drug Interaction Factors Enhancing Degradation of Dosage Forms Changes in functional groups in dosage forms occurring due to with time as follows; 1) Changes in mechanical strength changes due to coating polymers in coated dosage terms 2) Changes in capsule shells with time & storage conditions 3) Changes indicating release rate from polymeric matrix dosage forms including microspheres 4) Drug leakage from Liposome’s 5) C h a n g e s i n M e l t i n g P a t t e r n s of Suppositories June 2014f 43

1) For most qualitative and quantitative PDA detector 2) F o r N o n - a b s o r b i n g i m p u r i t i e s – ELSD/CAD 3)For some specific molecules – Fluorescence/RI 4) Hyphenated techniques – LCMS/GC – MS/LC-NMR 5) After specificity is established – UV Detector is choice Forced Degradation (Chemical Stress) Studies 6) 7) 8) 9)

Aggregation in Emulsions Moisture adsorption Discoloration Transfer of container components onto/ into Drug by Adsorption &/or Absorption

Sample Preparation Important information concerning sample composition and properties Most sample preparations involve the use of organic-aqueous and acid-base extraction techniques. Therefore it is very helpful to understand the chemical, physical properties of the analytes, structurally related compounds, solubility and pKa of the analytes. Solubility in different organic or aqueous solvents determines the best composition of the sample solvent. pKa determines the pH in which the analyte will exist as a neutral or ionic species. This information will facilitate an efficient sample extraction scheme and determine the optimum pH in mobile phase to achieve good separations. Sample Pretreatment Samples come in various forms; 1) Solutions ready for injection 2) Solutions that require dilution, buffering, addition of an internal standard, or other volumetric manipulation 3) Solids that must first be dissolved or extracted 4) Samples that require sample pretreatment to remove interferences and / or protect the column or equipment from damage 44 eJune 2014

Sample Preparation Critical for solids, semi-solids, suspension preparations of solution are as follows; 1) Selection of sample size 2) Sample pretreatment for reduction of particle size 3) Selection of extracting solvent for bringing Active Ingredient into solution 4) Solubility of any molecule 5) Nature of dosage form 6) Chemical structure Uses of instruments are as follows; 1) Mechanical Shaker 2) Ultra-sonication 3) Homogenisation Filtration Technique 1) A d s o r p t i o n : E x c i p i e n t s a n d d r u g adsorption can hinder filtration of solution 2) A b s o r p t i o n : R e f e r e n c e – U S P monograph of Nifidepine formulations (similar molecule Isradipine also exhibit same effect) For Handling Sample Preparation of Liquids 1)Liquid-liquid extraction 2)Solid phase extraction 3)Precipitation with organic solvents Selection of Analytical Technique As far as separation technique is concerned fast LC/HPLC will be first choice.

Forced degradation studies typically involve the exposure of representative samples of the drug substance or drug product to the relevant stress conditions of light, heat, humidity, acid/base hydrolysis, and oxidation. These experiments play an important role in the drug development process to facilitate: stability indicating method development, drug formulation design, selection of storage conditions and packaging, better understanding of the potential liabilities of the drug molecule chemistry and the resolution of stability related problems. An appropriate sample solvent and mobile phase must be found that affords suitable stability and compatibility with the components of interest as well as the potential impurities and degradants. The method should be carefully examined for its ability to distinguish primary degradants from secondary degradants (degradation products of the primary degradants). An optimal wavelength must be selected that suitably detects all of the critical impurities and degradants. Finally, the method should provide adequate mass balance recovery of the major degradants. Example : Conditions for Forced Degradation The goal is to degrade the active moiety to 5-10 per cent in sample for which the conditions can be used as follows: Pharma Bio World

Study

Conditions

Acidic pH

0.1N HCl

Neutral pH

pH 7.0 phosphate buffer

Basic pH

0.1N NaOH

Oxidation

O2 Atmosphere, H2O2

Photolysis (UV)

1000 Watts Hrs/M2

Photolysis (Fluorescence)

6 x 106 Lux Hrs

Reporting Threshold & Dosage Relation Maximum Daily Dose

< 1 mg >1g

Threshold b Thresholds for Reporting 0.1% 0.05% a-The amount of drug substance administered per day b-Threshold is based on % of Drug Substance

Reporting Threshold & Dosage Relation Maximum Daily Dose

Thresholds for Identification TDI-Total Daily Intake < 1 mg 1.0% or 5 g TDI, whichever is lower 1 10 mg 0.5 % or 20 g TDI, whichever is lower > 10 mg 2g 0.2 % or 2 mg TDI, whichever is lower >2g 0.1% Reporting Threshold & Dosage Relation Maximum Daily Dose < 10 mg

Pharma Bio World

Threshold for Qualification 1.0% or 50 g TDI, whichever is lower

100 mg

lower > 100 mg lower > 2g

0.5 % or 200 g TDI, whichever is 0.2 % or 2 mg TDI, whichever is 0.1%

Stability Indicating Method development Exercise A stability indicating method (SIM) is a quantitative procedure used to detect a decrease in the amount of the active pharmaceutical ingredient (API) present due to degradation. According to FDA guidelines, a SIM is defined as a validated analytical procedure that accurately and precisely measures active ingredients (drug substance or drug product) free from potential interferences like degradation products, process impurities, excipients, or other stability impurities, and the FDA recommends that all assay procedures for stability studies be stability indicating. The steps involved in stability indicating method developmental exercise as follows ; 1) I n f o r m a t i o n o n s a m p l e , d e f i n e separation goals 2) Need for special HPLC procedure, sample pretreatment, etc 3) Choose detector and detector settings 4) Chose LC method, preliminary run, estimate best separation conditions 5) Optimise separation conditions 6) Check for problem or requirement for special procedure 7) Quantitative calibration 8) Va l i d a t e m e t h o d t o r e l e a s e f o r routine laboratory Case study – Sample preparation 1) USP monograph for Extended release tablets mentions use of solvent as Acetonitrile : water (2:98) with use of homogeniser Final estimation on HPLC Findings : All the brands cannot be analysed by using above solvent and apparatus

Solutions found : Use of organic solvent like ethanol or methanol is essential for dispersion of polymeric matrix in SR formulation. 2) U S P m o n o g r a p h o f C P H a n d P P H combination Extended release capsules mentioned in old monograph as use of solvent as water and dilute phosphoric acid and shaking by mechanical means Final estimation on HPLC Findings: All the brands cannot be analysed by using above solvent and apparatus Solution found: Recent monograph has been updated as use of water and dilute phosphoric acid as solvent; however solution is heated till completely dispersion of matrix. 3) Extraction of drug from fixed dose combinations 2 or 3 activities in Tablet Labeled amount of active ranging from 5mg to 500mg with variable polarities. Findings: All standard solvents like ethanol, methanol, methanolic HCl/NaOH, Not effective to bring into solution. Solution found: Use of Dimethyl formamide in combination with organic solvents and or mobile phase. 4) Challenge Run time For Related Substance (RS) run time exceeds more than 50mins. Findings: Longer run time are costlier. Solutions found: Analytical equipment change like Fast LC (Rapid Resolution Liquid Chromatography) shorten run time resulting in reduction in man p o w e r, a n a l y s i s c o s t d u e t o l o w e r solvent composition. Reference BP/EP method for Azithromycin RS.

Contact: parag.gadkari@inventiahealthcare.com June 2014f 45

Data Breaches For pharmaceutical and biotech companies that have critical information assets such as customer data, intellectual property and trade secrets the risk of a data breach is now higher than ever before. This article put forward some solutions to significantly reduce the risk of data breach.

irtual theft in pharmaceutical and biotech organisations has increased in recent years. Migrating to electronic records, as well as providing broader access to user information increases the risk of data breaches w i t h i n t h e o r g a n i s a t i o n s . To p r e v e n t such data breaches without negatively impacting patient care requires careful consideration. This is demonstrated by various studies, for example according to the Privacy Rights Clearinghouse, more than 260 million “records” have been breached since January 2005. According PGP-sponsored 2008 Ponemon Institute survey that witnessed participation from 43 organisations said the average cost of a data breach has increased to more than USD 200 per record and the average total cost per reporting company was more than USD 6.7 million per breach. It’s just not deployment of security technology but ensuring that processes and employees fully understand the value of sensitive/personal data. Solutions like Data Loss Prevention can help organisations realign IT security policies and fine tune them to protect data by providing in depth and transparent visibility into current status and posture of data protection. Possible Causes Apart from the reasons above, 90 per cent of the records and revenues are lost due to insider negligence. This is one of the most sensitive and difficult part to control.

Raj Samani

VP, EMEA Chief Technology Officer McAfee, Part of Intel Security 46 eJune 2014

Moreover, for pharmaceutical organisations the challenge will be to provide security whilst balancing the needs of clinical staff. Therefore traditional approaches of information security such as access control (locking down access to records) will have to balance with the needs of the staff.

Possible Complications It’s just not lack of proper tool s l i k e Data Loss Prevention which would lead to such incidences. A tool can just help you enforce/measure/monitor such policies. It’s the organisation’s culture that IT security policy is implemented and enforced among its employees. Security tools alone cannot achieve the data protection objectives. Data protection has to be imbibed as working style of an organisation or employee. Ensuring that employees understand the value of data is critical, and one of the biggest challenges for pharmaceutical organisations. Preventive Methods A s e x p l a i n e d e a r l i e r, i t ’ s a d e l i c a t e combination of people, processes and technology whilst balancing the needs of the organisation. Organisations should ensure that they consider the clinical requirements to develop a policy that is appropriately enforced. Some of the best practices that many organisations follow to keep their data secure are listed below; • Use encryption – both for data in transit, and at rest. • A very secure host level protection on the end points at pharmaceutical companies and branches • A matured and advanced DLP solution both on host level and network level • A good identity management and access control mechanism • A good data management mechanism. Advanced security tools to give them good visibility and control of the entire infrastructure so that they have good “situational awareness” and proactive control. • Strong security awareness activities, and testing Pharma Bio World

Threats from Cloud Computing, Mobiles Phone and Social Websites Risks in such new technologies like cloud computing or BYOD or social websites can pose a massive risk to IP. However it is important to note that there will likely be regulations that will govern the use of technology such as cloud, in particular data residency requirements. However such technologies should not be excluded for consideration because they can bring huge efficiencies to pharmaceutical and biotechnology organisations. As with any such technologies there should be a formal risk assessment that will govern how they are managed, and the risk is mitigated to an acceptable level. Laws Related to Data Security in India We have no dedicated data protection laws in India. Data of individuals and companies require both constitutional as well as statutory protection. The constitutional analysis of data protection in India has still not attracted the attention of either individuals/companies nor of Indian government. The statutory aspects of data protection in India are scattered under various enactments. The Information Technology Act 2000 (IT Act 2000) and the (Indian) Contract Act, 1872, which is the cyber law of India, also incorporate few provisions regarding data protection in India. However, till now we have no dedicated statutory and constitutional data privacy laws in India. Having said this, many of our pharmaceutical and biotechnology organisations who are serving Indian clients are mandated to follow their client specific regulations as well as various data protection regulations. Contact: bhuvana.k@text100.co.in Pharma Bio World

June 2014f 47

press release Cancer Genetics to Buy BioServe Cancer Genetics, Inc, a DNA-based diagnostics company focused on developing genomic-based oncology tests and services, has announced the agreement to acquire BioServe Biotechnologies (India) Pvt Ltd for approximately USD 1.9 million, primarily in CGIX stock and other deferred consideration. The transaction is expected to close during the third quarter of 2014 and is subject to customary closing conditions and government approvals in India. Under the terms of the agreement, BioServe Biotechnologies (India) Pvt Ltd, headquartered in Hyderabad, India, will become a subsidiary of CGI, and will be renamed Cancer Genetics India Pvt Ltd. CGI plans on retaining all 33 current employees of BioServe India, and further expanding and strengthening the sales and clinical teams in India. BioServe India currently operates out of a state-of-the-art 14,000-square-foot genomics facility in Hyderabad. BioServe India is backed by Ventureast, a pioneering venture capital institution based in India, which has enabled over 80 seed, early and growth stage businesses in a broad array of sectors including technology, life sciences and clean environment. BioServe India is a state-of-the-art genomics services provider and molecular kit manufacturer serving both the research and clinical markets. By utilising BioServe India’s molecular services, researchers can identify genetic markers, validate drug targets and correlate clinical and molecular data to accelerate the development of new and effective drugs. Additionally, BioServe India’s growing clinical diagnostics capabilities in oncology and next-generation sequencing are well-positioned to serve the needs of improving oncology diagnostics care and management throughout India.

Kiran Mazumdar-Shaw is the third woman to receive the Othmer Gold Medal and the first Indian to make it to this prestigious group. Nineteen people have been conferred with this honor till date, including Arnold O Beckman, Carl Djerassi, Mary Lowe Good, Harry B Gray, Jon M Huntsman, Kazuo Inamori, Robert S Langer, P Roy Vagelos, James D Watson, George Whitesides and Ahmed Zewail.

Bristol-Myers Squibb, Syngene Extent Collaboration Bristol-Myers Squibb and Syngene International, India’s largest contract research organisation, have announced a five-year extension of their drug discovery and development collaboration in India. Financial terms were not disclosed. Since 2007, Bristol-Myers Squibb has been working with Syngene and its corporate parent, Biocon Ltd, to develop integrated capabilities in medicinal and process chemistry, biology, biotechnology, biomarkers, drug metabolism and pharmacokinetics, analytical research, and pharmaceutical development at the Biocon Bristol-Myers Squibb Research Center (BBRC) in Bengaluru. The US-India collaboration has produced six drug candidates for further study and also helped Bristol-Myers Squibb reduce the time and costs associated with advancing new compounds to first-inhuman studies. One drug candidate currently in clinical trials was discovered at BBRC and early nonclinical development work done at BBRC has enabled most of Bristol-Myers Squibb’s small molecule assets to advance to later stages of development over the last five years.

Biocon CMD Receives Othmer Gold Medal 2014 Lucrative Biosimilars Space to Erode Biocon Ltd, Asia’s premier biotechnology Biologics Market from 2019 company, has announced that its Chairperson and Managing Director, Kiran Mazumdar-Shaw, received the ‘Othmer Gold Medal 2014’ on Thursday, May 15, in Philadelphia, Pennsylvania, USA.

Established by the Chemical Heritage Foundation (CHF) in 1997, the annual award honors outstanding individuals who have made multifaceted contributions to chemical and scientific heritage through outstanding activity in such areas as innovation, entrepreneurship, research, education, public understanding, legislation or philanthropy.

Kiran Mazumdar-Shaw CMD, Biocon

48 eJune 2014

The increasing prevalence of biosimilars will have a noticeably negative impact on the biologics market beyond 2019, despite an initial projected Compound Annual Growth Rate (CAGR) of 8.3 per cent, taking the overall biologics market value from USD 162 billion in 2013 to more than USD 262 billion by 2019, says research and consulting firm GlobalData. The company’s latest report states that patent expirations of branded biologics and the introduction of clearer regulatory frameworks for biosimilars after 2019 will see the latter capturing the market share from biologics. Joshua Owide, GlobalData’s Director of Healthcare Industry Dynamics, says: “There are a number of factors driving the initiative towards the global adoption of biosimilars, from austerity measures and slow economic growth in the US, to an aging population and increasing demand for healthcare in countries such as Japan. Pharma Bio World

press release A Rise in IPOs Revive Investments for the Global Pharma and Biotech Industry The heightened private equity and venture capital (PEVC) deal activity in the global healthcare industry during the recession years, 2008-2010, witnessed a decline post-2010. However, the fall in deals was not uniform among the constituent sectors, with the pharmaceutical, biotechnology and healthcare equipment sectors experiencing a much sharper decline in investor interest than the healthcare technology and provider segments. Investors started to bet on providers based with the conviction they can provide quicker and safer returns than the pharmaceutical and biotechnology space, which is ridden with regulatory challenges and patent expires. New analysis from Frost & Sullivan’s Private Equity and Venture Capital Investment in the Global Pharmaceutical and Biotechnology Industry reveals the total number of PEVC deals in the pharmaceutical and biotechnology industry decreased from 1063 in 2010 to 480 in 2013. Though the returns from the pharmaceutical and biotechnology industry have been dwindling, they are better compared to the performance of other industries.

NuLEAP, Venostic Sign Partnership Deal NuLEAP Technologies and Venostic Solutions announced a new strategic partnership to support Indian pharmaceutical companies’ needs for Computer Systems Validation and IT Compliance as per international global requirements. Under the terms of the collaboration, NuLEAP and Venostic will provide a comprehensive set of services that will enable Indian pharmaceutical companies to develop regulatory processes for their computer systems validation and IT policies to ensure data integrity as per international norms. Several regulatory actions in recent months are driving the requirement for an in-depth review and solutions to meet international standards for data integrity and IT policies. NuLEAP’s local presence combined with Venostic’s international team will provide Indian organisations with the tools and services to effectively streamline their infrastructure, work practices and validation policies to meet international IT regulatory requirements that have been the subject of much attention in recent times.

(FDA) for food contact applications. Extensively researched and supported with comprehensive toxicology testing, Weston 705 antioxidant provides superior safety as well as enhanced polymer performance and higher processing productivity vs. conventional solid phosphites. The product delivers major benefits across the entire value chain, from resin producers and converters to retailers and consumers. Further, Addivant’s Weston 705 antioxidant is produced in multiple facilities worldwide ensuring security of supply for customers around the globe.

TGA Okeys Venus to Market Meropenem in Australia Venus Remedies Limited, a leading research-driven global pharmaceutical company, has received marketing authorisation for meropenem from Australia’s Therapeutic Goods Administration (TGA). The company has tied up Pawan Chaudhary with Lupin to sell this drug in CMD Venus Remedies Australia. Eyeing a sizeable share in Australia’s USD 15 million meropenem market in the first year of launch, it plans to market the drug by the third quarter of this year. With marketing approvals from more than 35 countries, Venus Remedies is poised to capture a significant share in the USD 1.3-billion global meropenem market. Hailing the achievement, Venus Remedies Chairman and Managing Director Pawan Chaudhary said, “The marketing authorisation from TGA has once again proved the company’s capabilities in developing world-class products that meet the most stringent regulatory requirements.

US FDA Approves Addivant Weston 705 Liquid Antioxidant

This is yet another milestone for Venus Remedies in its journey of obtaining a significant share in the meropenem market globally. Having established strategic tie-ups to market the drug in countries where Venus Remedies has a presence, we enjoy an edge over other competitors.”

Addivant, a global leader in polymer additive technologies, announced that Weston 705 liquid antioxidant, the next generation of nonylphenol-free phosphite technology, has received approval from the US Food and Drug Administration

Meropenem is an off-patented antibacterial agent of the carbapenem class of antibiotics that caters to diseases with a broad range of serious infections caused by single or multiple susceptible bacteria in both adults and children.

Pharma Bio World

June 2014f 51

press release Global Anti-Hypertensive Market Value to Decline

Jubilant Life Sciences increase focus on the pharmaceutical sector and strengthen its generic drug manufacturing facilities in India.

Multiple major drug patent expiries will cause the global antihypertensive market value to decline from USD 40 billion in 2013 to USD 37.6 billion by 2020, at a negative Compound Annual Growth Rate (CAGR) of 0.9 per cent, says business intelligence provider GBI Research.

“We consider IFC a long-term partner with significant healthcare expertise across emerging markets. IFC’s contribution goes beyond financing. IFC will also help us strengthen our quality assurance and risk mitigation mechanisms and make the company systems more robust,” said Shyam S Bhartia, Chairman and Managing Director, Jubilant Life Sciences. “IFC’s long-term financing package will consolidate our entire pharmaceuticals business under Jubilant Pharma and build global competitiveness.”

The company’s latest report states that while the antihypertensive market value is first expected to increase to USD 44.5 billion by 2017, representing a CAGR of 2.6 per cent, it will then fall at a negative CAGR of 5.4 per cent through to 2020. Arti Singh, Analyst for GBI Research, says: “The initial expansion of this market will result from the increased penetration of fixed-dose combination drugs, such as Amturnide, Exforge, Tribenzor, Azor, Tekamlo and Valturna. A rise in the prevalence of hypertension, from a population of 181 million to 190 million, combined with the anticipated launches of azilsartan + amlodipine and AHU377 + valsartan, will also contribute.” However, the hypertension market growth will be countered by significant drug patent expirations both prior to and during the forecast period, including those of Cozaar in 2010, Diovan, Avapro and Atacand in 2012, Exforge in 2014, Benicar in 2016 and Tekturna and Tekturna HCT in 2018. A low diagnosis rate, teamed with a rise in generic penetration, will also drive the decline.

Bosch Expands PreVAS Portfolio At Interpack 2014, Bosch Packaging Technology, a leading supplier of process and packaging technology, presented the expanded portfolio of the single-use filling system PreVAS. “The existing system has been successfully introduced to the market. Now the time has come to offer our customers additional solutions for their existing line concepts and to consequently extend our portfolio,” Klaus Ullherr, product manager at Bosch Packaging Technology said. The name PreVAS stands for prevalidated, pre-assembled and pre-sterilized single-use filling systems, which Bosch Packaging Technology has developed in cooperation with Sartorius Stedim Biotech (SSB).

Jubilant Bags USD 147.5 Mln from US FDA Licenses Novartis’ Holly IFC Springs Facility

Shyam S Bhartia CMD Jubilant Life Sciences

IFC, a member of the World Bank Group, is lending USD 147.5 million to Jubilant Pharma Limited to enable better access to quality and affordable pharmaceuticals in underserved markets in India and across the world. Jubilant Pharma, a wholly owned subsidiary of Jubilant Life Sciences Limited, is incorporated in Singapore, with manufacturing operations in India, USA, and Canada.

Of the total financing package, USD 110 million is from IFC’s own account. The remaining USD 37.5 million is from IFC’s Managed Co-Lending Portfolio Program, which provides additional longterm financing through co-financing partners. The loan will help 52 eJune 2014

Novartis has announced that the US Food and Drug Administration (FDA) licensed its manufacturing facility in Holly Springs, NC for the production of cell-culture influenza vaccines. This is the first US facility of its kind and is now approved for commercial production. The site will produce seasonal and pre-pandemic influenza vaccines, and has the capacity to significantly ramp up production in the event of a pandemic. Novartis utilises cell-culture technology to produce Flucelvax (Influenza Virus Vaccine), which was the first FDA-approved seasonal influenza vaccine not manufactured with chicken eggs. Flucelvax, approved for individuals 18 years of age and older, does not contain any antibiotics or preservatives. With the licensure of the Holly Springs facility, Flucelvax will be produced in the US for the first time. Pharma Bio World

pharma news Granules India Paracetamol Facility Passes US FDA Inspection Granules India Ltd, a fast growing pharmaceutical manufacturing company, announced its paracetamol facility successfully passed a US FDA inspection without any 483 observations. The facility has the world’s largest single API production line by volume. Granules’ four API facilities have successfully passed US FDA inspections in the past 12 months. All of Granules’ facilities including its finished dosage and PFI facility are approved by leading regulatory agencies including the US FDA, EDQM, Health Canada and Korean FDA.

Endo Ends Early Stage Drug Discovery Portfolio Sale Endo International plc has announced that its Endo Pharmaceuticals subsidiary has completed the sale of its branded pharmaceutical drug discovery platform to AsanaBioSciences, LLC, an independent member of the Amneal Alliance of Companies. The deal includes an upfront payment as well Rajiv De Silva President & CEO as milestones on the achievement of certain Endo development objectives. Endo initiated the exploration of strategic alternatives for the portfolio of early stage drug discovery assets in 2013 as part of the company’s portfolio optimisation process. The sale includes multiple early-stage drug discovery and development candidates in a variety of therapeutic areas, including oncology, pain and inflammation, among others. “The sale of the early stage discovery platform is another step in the transformation of Endo,” said Rajiv De Silva, president and CEO of Endo. “We continue to make progress against the strategic objectives we set forth in 2013 and remain enthusiastic about what lies ahead for Endo. We are committed to supporting the organic growth of our existing business segments as we search for attractive acquisition targets to enhance our portfolio of pharmaceutical products.”

Cellectis, Thermo Fisher Sign Deal on Talen Cellectis, a leader of engineered CART cell therapies, and Thermo Fisher Scientific have entered into a series of agreements covering the uses of TAL nucleases under the brand name TALEN. Pharma Bio World

Pursuant to these agreements, Thermo Fisher is granted a worldwide license under Cellectis’ rights to the TAL nucleases outside the therapeutic field, with exclusive rights to grant sublicenses in research and development, bioproduction and certain applied markets. Thermo Fisher currently markets TALEN for these applications under its Life Technologies brand. Cellectis is granted a worldwide license under Thermo Fisher’s rights to TAL nucleases in the research and development field for internal and collaborative research, for commercialisation of TAL gene editing for Cellectis bioresearch’s products and services, and in the plant biotechnology field for Cellectis plant sciences’ in-house and collaborative research and development. Finally, Cellectis is granted a worldwide license for therapeutic research and development, including rights to grant sublicenses for therapeutic uses in the fields of T cells and Natural Killer cells. Commercial terms of the agreements were not disclosed.

Strides Arcolab Gets US FDA Nod for Methoxsalen Capsules Strides Arcolab has received approval from the United States Food & Drug Administration (USFDA) for Methoxsalen Capsules USP, 10 mg (Soft Gelatin Capsules). According to IMS data, the US market for generic Methoxsalen Capsule is approximately USD 13.6 Million, with no generic player. The product will be manufactured at the Company’s USFDA approved Oral dosage facility at Bangalore and marketed directly by Strides in the US Market.

inVentiv to Market Aprecia’s Unique Technology Platform inVentiv Health, a life science knowledge and services company, and Aprecia Pharmaceuticals, a specialty pharmaceutical company, have announced an exclusive sales and marketing alliance. This partnership will launch the Aprecia brand, as well as provide comprehensive commercialisation of Aprecia’s pioneering technology platform and initial pharmaceutical products. Aprecia is the first and only pharmaceutical company offering the proprietary ZipDose product platform using three-dimensional printing (3DP) technology to create fast-melt products. These products promise to change how patients experience taking their medicine by making drugs easier to administer and swallow. Aprecia has completed clinical work and expects to file its first New Drug Application with the Food and Drug Administration (FDA) in the second half of 2014. June 2014f 53

pharma news USPTO Grants Patent Term Extension to Amag’s Ferumoxytol Amag Pharmaceuticals, Inc announced that the United States Patent and Trademark Office (USPTO) has issued a US patent term extension certificate extending the term of US Patent No. 6,599,498 by 1,209 days. With this extension the ‘498 patent will now expire June 30, 2023. This patent William Heiden CEO, Amag is directed to reduced polysaccharide iron oxide complexes, including ferumoxytol. The ‘498 patent is listed in Approved Drug Products with Therapeutic Equivalence Evaluations (commonly known as the Orange Book), published by the United States Food and Drug Administration. The patent term extension certificate was granted under the patent restoration provisions of the Drug Price Competition and Patent Term Restoration Act of 1984. The patent term certificate extends the term of the ‘498 patent from its original expiration date of 2020. “This patent extension for ferumoxytol further lengthens our intellectual property protection and enhances the long-term value of a product that generated 28 percent revenue growth in the US in 2013 for our company,” said William Heiden, chief executive officer of Amag. Amag has five Orange Book-listed patents relating to ferumoxytol, including the ‘498 patent.

GPSA Opens New Facility in Switzerland Glenmark Pharmaceuticals SA (GPSA), a wholly owned subsidiary of Glenmark Pharmaceuticals Limited, India (GPL), announced the opening of its new cGMP compliant monoclonal antibody manufacturing facility in La Chaux-deFonds, Switzerland. This manufacturing facility supplements Glenmark’s existing in-house discovery and development capabilities and will supply material for clinical development. Glenmark Pharmaceuticals’ Swiss research center is an integrated antibody discovery and development unit. The research center has fully developed in-house capabilities and infrastructure for conducting antibody discovery, cell line development, in vitro testing and characterisation of antibodies, process development and analytical research. The new manufacturing facility supplements the research and development capabilities and will facilitate production of clinical grade material. 54 eJune 2014

The manufacturing facility has been designed for use of single use bioreactor systems and also houses a suite for manufacturing cell banks. The facility is fully compliant with quality, environmental and safety standards for manufacturing clinical trial material.

EMA Accepts MAA for Venda’s Hetlioz

Mihael H Polymeropoulos MD, Vanda Pharmaceuticals

Vanda Pharmaceuticals Inc’s Marketing Authorisation Application (MAA) for oral hetlioz (tasimelteon) capsules has been accepted for evaluation by the European Medicines Agency (EMA) for the treatment of Non-24-Hour Sleep-Wake Disorder (Non-24).

“The EMA submission is an important milestone towards providing a treatment option for people living with Non-24 in the European Union,” said Mihael H Polymeropoulos, MD, Vanda’s President and CEO. “This continues our efforts to expand the availability of hetlioz to markets outside the US” Hetlioz has been granted orphan drug designation for the treatment of Non-24 in blind people with no light perception from the European Commission. Hetlioz was approved by the FDA in January 2014 and is available through specialty pharmacies in the US.

Mylan, Pfizer Settle Celebrex Patent Litigation Mylan Inc has entered into a settlement and license agreement with Pfizer Inc relating to Mylan’s Abbreviated New Drug Application (ANDA) filed with the US Food and Drug Administration (FDA) for Celecoxib Capsules, 50 mg, 100 mg, 200 mg and 400 mg. This product is the generic version of Celebrex, which is indicated for the relief of the signs and symptoms of osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis, and for the management of acute pain in adults. Under the terms of the agreement, Mylan will begin selling product at the earliest market formation, however in any case not later than December 2014. All other terms and conditions of the settlement and license agreement are confidential, and the agreement itself is subject to review by the US Department of Justice and the Federal Trade Commission. Additionally, Mylan has appealed the decision by the United States District Court for the Northern District of West Virginia denying Mylan’s request for an injunction in its suit against the FDA. Mylan continues to believe that FDA seriously erred in its decision awarding one party eligibility for 180 days of exclusivity on Celecoxib, and will continue with this suit independent of the aforementioned settlement. Pharma Bio World

biotech news Ganeden Biotech Widens Global Footprint Aduro Receives USD 55 Million Series Financing Ganeden Biotech is pleased to announce that GanedenBC30 has received numerous international regulatory approvals and is now being shipped to six of the seven continents. This means that GanedenBC30’s remarkable digestive and immune benefits are now available globally for food and beverage fortification. The global market of probiotic ingredients, supplements, and foods is expected to reach nearly USD 27.1 billion in 2013 and climb at a compound annual growth rate of 6.2 per cent over the next five years to reach USD 36.7 billion in 2018, according to Wellesley, MA- based technology markets research firm BCC Research. “The international probiotic market is growing at a breakneck pace, and the interest in GanedenBC30 is astounding,” said Mike Bush, Senior VP at Ganeden Biotech. “Achieving a Global footprint for GanedenBC30 has been an ongoing goal for Ganeden Biotech that could only be achieved by a significant investment in international regulatory compliance and patent prosecution, working with international distributors and continuing to publish studies in peer reviewed journals that support claims for safety and efficacy.”

ANSM Grants GMP Compliance Certificate to TxCell’s Besançon Facility TxCell SA, a biotechnology company developing innovative, personalised cell-based immunotherapies using antigen specific regulatory T-cells (Ag-Tregs) for severe chronic inflammatory and autoimmune diseases, has been granted Certificate of Good Manufacturing Practice (GMP) compliance for its cell therapy manufacturing facility in Besançon, France. The certificate was granted by French National Agency for Drug Safety (ANSM), the French authority for the quality, safety and efficacy of medicines and health products. This certificate follows the Manufacturing Accreditation, also delivered by ANSM on December 3, 2013. “The certificate of GMP compliance for our manufacturing facility is a key step in TxCell’s development for our lead candidate Ovasave. We believe this is a product that may offer a breakthrough innovation for the treatment of refractory Crohn’s disease. There are currently 160,000 such patients per year in Europe and in the US for Crohn’s Disease alone,” said Damian Marron, chief executive officer, TxCell. “This in turn allows us to accelerate the development of all our innovative, personalised cellular immunotherapies. These therapies target niche and orphan indications for which there are few or no treatment options and high unmet medical needs.” Pharma Bio World

Aduro BioTech, Inc, a clinical-stage biotechnology company, has announced the closing of a USD 55 million Series C financing. New investor Johnson & Johnson Development Corporation (JJDC) joined the Morningside group and other new and existing investors in the transaction. Aduro plans to use the new capital to advance its lead program in metastatic pancreatic cancer through its ongoing Phase 2b ECLIPSE clinical trial, to continue clinical development in mesothelioma and high-grade glioma, to expand into additional indications and to advance its small molecule program targeting the immunomodulatory STING receptor. The equity financing follows the company’s recent agreement facilitated by the Johnson & Johnson Innovation center in California, which granted Janssen Biotech, Inc. an exclusive, worldwide license to certain product candidates specifically engineered for the treatment of prostate cancer based on Aduro’s novel LADD immunotherapy platform. Since inception, Aduro has raised a total of USD 84 million from equity financings. “The financing will allow us to build on the momentum from the recent positive clinical data presented at ASCO in metastatic pancreatic cancer and mesothelioma and to expand our clinical development efforts into additional cancer types and combination therapies,” said Stephen T Isaacs, chairman, president and chief executive officer of Aduro. “Ultimately, our goal is to provide cancer patients with more effective, less toxic therapeutic alternatives through novel immunotherapies.”

Paragon’s Phenylephrine Hydrochloride Ophthalmic Solution Gets FDA Nod Paragon BioTeck, Inc, a privately held biopharmaceutical company specialising in the development of ophthalmic pharmaceuticals and therapies, received FDA approval of Phenylephrine Hydrochloride Ophthalmic Solution, USP 2.5 per cent and 10 per cent, to dilate the pupil on March 21, 2013. There is no longer a need to continue using unapproved versions of Phenylephrine Hydrochloride Ophthalmic Solution, as Paragon BioTeck’s FDA approved Phenylephrine Hydrochloride Ophthalmic Solution, USP 2.5 per cent and 10 per cent is readily available through Bausch + Lomb or your primary wholesaler. June 2014f 55

Microbioreactors micro-Matrix offers an integrated, easy-to-use, and cost-effective technology platform for the rapid handling and growth of large number of microbial strains, clone libraries, mutant banks and cells. The system offers 24 independent bioreactors in a cost-effective microtiter plate footprint. pH and dissolved oxygen can be controlled in each individual bioreactor via gas and liquid addition. Temperature is controlled individually in each bioreactor by the integrated cooling and heating system. The micro-Matrix offers a true scale down of small-scale bioreactors. The bioreactorâ&#x20AC;&#x2122;s square well cassette design is based upon the popular SBSformat microtiter plates, which seamlessly integrates into lab automation robots. The PC-based human interface offers simple, intuitive interaction for advanced process control in each of the 24 bioreactors.

Multi Mill TAP multi mill is used for high speed granulating, pulverising, mixing, shredding and chopping, etc, of a wide range of wet and dry materials without special attachments. As compared to the four common principles of size reduction, ie, grinding, compression, impact and shearing, which often do not produce controlled size reduction, this machine utilises the principles of variable force swing hammer blades having both knife and impact edges rotating with a carefully selected screen to control size reduction. Flow path of material in vertical rotor machine is streamlined. During comminuting, material entering the chamber travels to the periphery and passes through the screen tangentially and radially avoiding chocking and temperature rise. It finds application in chemicals, pharma, dyestuff, colours, ceramics, food products, cosmetics, pesticides, plastics, spices, resins, insecticides, etc.

For more information, please contact:

Applikon Biotechnology BV Heertjeslaan 2 2326JG Delft, The Netherlands Tel: +/+ 31102083555 E-mail: info@applikon-biotechnology.com

Tapasya Engg Works Pvt Ltd A-212, Road No: 30, Wagle Indl Estate Thane (W), Maharashtra 400 604 Tel: 022-25822287, 25823250 | Fax: 91-022-25825243 E-mail: sales@tapasyaindia.net

Laboratory Meter Hanna Instruments offers edge, a full featured, affordable laboratory meter with revolutionary design features. edge measures pH, conductivity and dissolved oxygen: it is incredibly thin and lightweight, measuring only half an inch thick and weighing just 9 ounces; blending elements of portable meters and bench top meters into a seamless design. This versatile design allows customers to use edge as a benchtop meter, a portable meter or even attached to a wall to free-up valuable bench space in a laboratory. edge features a large 5.5â&#x20AC;? LCD with a wide viewing angle, capacitive touch keypad, dual USB ports, cradle with swivel arm electrode holder and an included wall mount. edge works with digital smart electrodes. These electrodes are nearly as advanced as the meter itself: featuring a built-in microchip that stores sensor type, ID, and calibration information that is automatically retrieved by edge once the electrode is plugged in. The electrodes have a 3.5 mm connector so customers do not have to worry about alignment and pins bending or breaking. For more information, please contact: Hanna Equipments (India) Pvt Ltd Aum Sai Bldg, 3/4/5/6, 1 st Floor Plot No: 23-C, Sector 7, Kharghar, Navi Mumbai 410 210 Tel: 022 27746554, 27746555, 27746556 E-mail: sales@hanna-india.com

56 e June 2014

Pharma Bio World

Air Motor

Guided Wave Radar Transmitter

AMRO Airtech offers heavy duty vane air motor DAM-6AM-1. It has 4-HP and free speed of 3,000 RPM. It gives 10 nm torque. All steel construction makes it rugged for use. It is reversible. Noise is reduced by exhaust silencer. It gives trouble-free operation on a 24x7 service duty. It can be supplied as non-lubricated air motor for special applications in pharma industries. It can be coupled to gear boxes of various gear ratios. It can give very low speed at a very high torque. It is useful for stirring and mixing of highly viscous liquids. With suitable combination of stirrer rods and impellers, it can mix a variety of fluids in small, medium and big capacity tanks. AMRO Airtech also manufactures light and medium duty air motors and piston air motors. For more information, please contact: AMRO Airtech S No: 6/3, Opp: Z P School Nanded Village, Sinhagad Road Pune, Maharashtra 411 041 E-mail: amroairtech@gmail.com

Magnetrol offers Eclipse Model 706 transmitter with Foundation fieldbus digital output communications. This is the first guided wave radar (GWR) transmitter to pass the Fieldbus Foundation testing using the latest Foundation fieldbus interoperability test kit ITK 6.1.1. This device offers all of the advantages of the standard 4-20 mA (HART) ECLIPSE Model 706, such as: improved signal to noise ratio (SNR); improved diagnostics (meets NAMUR NE 107); full complement of overfill-capable probes; etc. This new ECLIPSE Model 706 transmitter will contain the following Function Blocks: resource block; transducer blocks; analog input blocks; PID blocks; arithmetic block; input selector; signal characterizer block; integrator block; etc. For more information, please contact: Magnetrol International NV Worldwide Level & Flow Solutions Heikensstraat 6 - 9240 Zele - Belgium Tel: +32 (0)52 45 11 11 | Fax: +32 (0)52 45 09 93 E-mail: kgeerinckx@magnetrol.be

Submersible Motor Pump for handling Waste water KSB offers Amarex N, a new cost-ef¿cient low-weight pump set, which is compact enough to be installed in narrow sumps and tanks. The pump is designed for handling all types of waste water in municipal, industrial and commercial applications. Amarex N is available in 7 models ranging from DN 50 to 100 size, with maximum Àow rate of 53 liters per second and a discharge head of up to 49 meters. Standard variant can withstand Àuid temperature up to 550C. The pump will primarily be used in pumped drainage systems where wastewater needs to be drained from below the Àood level or in systems with long discharge pipes and insuf¿cient natural slope for gravity drainage. The pump is equipped with free Àow impeller (Type F), which can handle solids up to size 100 mm max. An option of cutter impeller (Type S) is available in size 50 mm with the free passage of 6 mm to cut any ¿brous material in the Àuid. This bene¿ts in selection of lower size pump which in turn saves initial investments and running costs. The shaft is sealed-off towards the motor by a shaft seal ring and by a bi-rotational mechanical seal at the pump end, so the motor is protected against Àuid ingress. A reservoir between the two seals, which is ¿lled with environmentally compatible oil, ensures proper cooling and lubrication of the mechanical seal even SS shaft. For more information, please contact: KSB Pumps Ltd Mumbai-Pune Road, Pimpri Pune, Maharashtra 411 018 Tel: 020-2710 1234, 27101000 | Fax: 91-020-274260000 E-mail: Suhas.shiras@ksb.com

Pharma Bio World

June 2014 f 57

Dew Point Sensor CS Instruments GmbH Germany offers dew point sensor FA400 required for niche market for aluminium smelter, steel plant, pharma industry and health care products for continuous monitoring with local digital display. Dew point sensor FA400 has 3 different ranges: refrigeration, adsorption and membrane dryer. Dew point sensor FA400 has digital integrated display has extremely precise long term stability with quick response time, output 4-20 mA analogue output and has also PC connection with SDI interface with standard measuring chamber up to 16 bar with special optional features up to 350 bar. Output signal via software or DS400 dew point set possible to show engineering unit %RH, Ctd, g/m3, mg/m3, ppm V/V. In addition to above excellent features of FA400 dew point sensor the user can define alarm to optimize and achieve better air quality and threshold value adjustable via keypad for alarm relay maximum 60 V DC and 0.5 A.

Quaternary Diaphragm Pumps Quattroflow offers 1200SU-M Series Single-Use Quaternary Diaphragm Pumps with plastic pump chambers engineered with injected moulded polyethylene. Manufactured to be a more cost-effective alternative to standard solid plastic pump chambers, these injected moulded PE pump chambers are assembled under controlled and clean conditions to accommodate a wide variety of pharmaceutical and biotech systems. Equipped with a product wetted plastic pump chamber that can be replaced as a complete unit, Quattroflow 1200SU-M Series single-use pumps have been specifically designed to meet the needs within demanding biotech and pharma applications. The simple disposal of the pump chamber saves time and money, removing the need for extensive cleaning, sterilization and complex cleaning validation. In addition, 1200SU Series pumps reduce downtime between batches and are quick and easy to change.

For more information, please contact:

AV Measurement & Control (India) Plot No: P46/1, 102 Sonata Comml Complex MIDC, Dombivli (E), Dist: Thane, Maharashtra 421203 Tel: 0251-2424418, 6458885 E-mail: vadnerkar@avmacindia.com | sheeja@avmacindia.com

Dover India Pvt Ltd â&#x20AC;&#x201C; PSG 40 Poonamallee By-pass Senneerkuppam, Chennai 500 056 Tel: 044-26271020, 25271023 E-mail: sales.psgindia@psgdover.com

Organizing and Managing Unstructured Plant Data Intergraph has released SmartPlant Fusion 2014, the latest version of its breakthrough solution for EPC companies and plant operators to rapidly find, capture, organize, link and visualize large volumes of information through a simple web portal. SmartPlant Fusion 2014 delivers several significant functionality enhancements for addressing problems, including exponentially faster document loading; improved user experience and navigation; a reporting and charting engine with a number of out-ofthe-box reports for document lists, tag lists, document status, tag-document relationships and more; improved integration with Leica TruView laser scans for more intuitive navigation; and multi-site capability. SmartPlant Fusion also provides interoperability with Intergraphâ&#x20AC;&#x2122;s template solutions for EPCs and owner operators. SmartPlant Fusion users can incrementally promote documents with their related tags into a fully managed environment within SmartPlant Enterprise or SmartPlant Enterprise for Owner Operators (SPO) with integrated tools, automated work processes, check-in/check-out, electronic sign-off, transmittals, management of change, and much more. For more information, please contact: Intergraph Consulting Pvt Ltd PPM Div (Subsidiary Intergraph Corpn) 2C, 2 nd Floor, 1-8-382, Queens Plaza, S P Road, Secunderabad, Andhra Pradesh 500 003 Tel: 040-33184000, Fax: 91-040-33184001 E-mail: Mahesh.Nerurkar@intergraph.com

58 e June 2014

Pharma Bio World

Tablet Dissolution Testing The PTWS D610 is fully USP 711/724 and EP 2.9.3/4 compliant. It offers the possibility of performing two sets of six tests each with either the same or variable stirrer speed setting or even with different tool sets. A 2-in-1 dissolution tester for the same footprint. Identical speed setting is possible as well. This bath design offers the same physical conditions for all 12 samples inside the dissolution vessels: the same tool speed, same temperature and the same immunity to both internal and external potential vibration sources. The testing positions are arranged in two rows (6+6) and offer staggered start capability. The vessels are covered by individual lids. Each lid features openings for sample withdrawal, temperature or pH measurements. For manual sampling Pharma Test Instruments India Pvt Ltd offer the PT-MDS manual sampling device. For more information, please contact: Pharma Test Instruments India Pvt Ltd No: 2, Sree Datri Niwas, 2 nd Floor Nagwara Circle, Outer Ring Road Opp: Manyata Softech Park, Bengaluru, Karnataka 560 045 E-mail: c.neelam@pharma-test.de

Barcode Reader Cognex DataMan 8050 Series handheld barcode readers, which are designed speciÂżcally for the pharma industry, with a rugged polycarbonate housing to handle harsh factory Ă&#x20AC;oor conditions and feature Cognex 1DMax+ with Hotbars barcode reading algorithms. The 210 mm x 115 mm x 85 mm readers feature a 752 x 480 global shutter sensor, integrated LEDs with near/far optics, and DataMan Setup Tool software, which enables imaging viewing, Java scripting, and data formatting options. DataMan 8050 reads all type of codes â&#x20AC;&#x201C; 1D, 2D and pharma code; helps in reading codes on the shipping cartons; and reads code on labels, packets, boxes and shipping cartons. The DataMan 8050 barcode readers are optimized for reading 1-D and 2-D label-based barcodes with the fastest performance. For more information, please contact: Cognex Sensors India Pvt Ltd Regus Level 6 Pentagon Towers P2, Magarphatta City Hadapsar, Pune, Maharashtra 411 028 Tel: 020-40147840 | Fax: 91-020-66280011 E-mail: info.in@cognex.com.

Zetasizer NanoSampler The new Zetasizer NanoSampler from Malvern Instruments is a versatile, compact, fully automated sample delivery system for the Zetasizer Nano, the most widely used system for nanoparticle and colloid characterization. Delivering precise and reproducible automated sample loading, and accommodating up to 96 sample vials, the NanoSampler enables unattended operation of the Zetasizer Nano, to maximize analytical productivity. It is especially suitable for laboratories where reproducibility is critical and where multivariate studies are routine. The new NanoSampler will work with all of the sizing systems in the Zetasizer Nano instrument range. This range includes both exceptionally high performance and entry level systems that measure particle and molecular size using dynamic light scattering, covering a size range from less than one nanometer up to several microns. Samples can be selected for analysis via the Zetasizer software through a simple-to-use Standard Operating Procedure. Each sample is delivered through solvent-resistant tubing and into the quartz analysis cell within the Zetasizer Nano. Automatic size measurements are then made, without the need for user intervention. After analysis, the results from all selected samples are clearly displayed in the Records View in the normal way. For more information, please contact: Malvern Aimil Instruments Pvt Ltd Naimex House, BSEL Tech Park B Wing, 906 Sector 30A, Opp: Vashi Railway Station, Vashi, Navi Mumbai 400 705 Tel: 022-39183596, Fax: 91-022-39183562 E-mail: Stuart.Wakefield@malvern.com

Pharma Bio World

June 2014 f 59

events diary

Contract Manufacturing 2014

Pharmabiotika 2014 - Bonsai Meet

Dates: 11th July 2014

Date: 26 th August 2014

Venue: Hotel Hilton, Sahar, Mumbai

Venue: Hitex Exhibition Centre, Hyderabad

IDMA has successfully organised many Industry specific events. This conference theme is”360 degrees of Contract Manufacturing” in order to update and exceed the current contract manufacturing requirements & Science based systems approach in Pharmaceutical Industry.

Pharmabiotika is a significant event that contributes significantly in the development of the pharma industry. This is a leading event that helps the professionals and experts to connect and interact with each other and to significantly contribute in the growth and expansion of the sector. It presents an ideal opportunity and platform for the professionals to discuss about the latest developments of the industry and also presents them with a great scope to share and exchange their valuable experiences and to develop their knowledge.

The Contract Manufacturing Industry in India has evidently grown exponentially over the last decade. More pricing pressures in the global markets are driving CMO growth in India. However, with recent Quality & Compliance requirements coming to the fore for all global markets, it is most important for CMOs working with thin margins to manage their organisation with a 360 degree approach. Contact: Indian Drug Manufacturers’ Association 102 - B, ‘A’ Wing, Poonam Chambers Dr Annie Besant Road, Worli, Mumbai – 400018 Tel: +91-22-24944624/24974308, Fax: +91-22-24950723 Email: ppr@idmaindia.com

Pharmac South 2014 Dates: 18 th -19 th July 2014 Venue: Chennai Trade Centre, Chennai An International Exhibition for Contract Manufacturers in Pharmaceutical, Nutraceutical, Ayurvedic products along with Pharma Machinery, Packaging, Equipment, Material, Bulk Drug, API, Clean Room & Water Technology. Pharmac South 2014 is jointly organised by Orbit Exhibitions Pvt Ltd & One of the Premier Associations of Pharma Industry – Indian Drug Manufacturers’ Association (TNPSB) Contact: Ramesh Vartak, COO 103, Navyug Industrial Estate, T J Road Sewri (W), Mumbai - 400 015 Tel: +91-22-24102801/2/3, +91-22-67282400 Email: ramesh.v@orbitzexhibitions.com 60 eJune 2014

Contact: Human Crayon Management Ser vices Pvt Ltd C-28, Sector - 4, Noida - 201301, India Tel: +91-120- 6528801, +91-11- 65378800 Email: info@crayon4.com Web : www.pharmabiotika.com

Frost & Sullivan’s 6 th Annual India Healthcare Excellence Awards 2014 Date: 19 th September 2014 Venue: Taj Lands End, Mumbai Frost & Sullivan’s Annual India Healthcare Excellence Awards programme recognises companies for their superior planning, leadership, strategy, growth, innovation, integration, marketing, and financial performance. The award categories span across various healthcare segments such as Pharmaceuticals and Biotechnology, Medical Technologies, Healthcare Delivery Services and Special Awards. Contact: Akshata Mahtre, Ranjani Shanker Tel: +91-22-66072029 Mobile: +91-9884872658 Email: akshatam@frost.com; ranjanis@frost.com Pharma Bio World

bookshelf Intellectual Property, Pharmaceuticals, and Public Health: Access to Drugs in Developing Countries [Hardcover] Authors: Kenneth C Shadlen, Samira Guennif , Alenka Guzman, N Lalitha Price: USD 137.75 No of Pages: 352 pages About the Book:This up-to-date book examines pharmaceutical development, access to medicines, and the protection of public health in the context of two fundamental changes that the global political economy has undergone since the 1970s, the globalisation of trade and production and the increased harmonisation of national regulations on intellectual property rights. With authors from eleven different countries presenting case studies of national experiences in Africa, Asia and the Americas, the book analyses national strategies to promote pharmaceutical innovation, while at the same time assuring widespread access to medicines through generic pharmaceutical production and generic pharmaceutical importation.

The Generic Challenge: Understanding Patents, FDA and Pharmaceutical Life-Cycle Management [Paperback] Author: Martin A Voet Price: USD 36.00 No of Pages: 198 pages About the Book: The Generic Challenge is a must-read for pharmaceutical executives and managers, and regulatory, legal, business development, R&D and strategic marketing professionals and anyone who has an interest in the future of the leading American pharmaceutical and biotechnology industries and the high value jobs they provide. It explains clearly and understandably the role of patents, FDA regulation of generic drugs and the Hatch Waxman Act on drug development today and how improvements in innovative drug products provide enhanced benefits to patients while extending the commercial lives of the drugs. There is simply no other book of its kind available on this important subject.

Pharmaceutical Patent Law, 2nd Edition [Hardcover] Author: John R Thomas Price: USD 422.75 No of Pages: 1000 pages About the Book: A comprehensive review of the critical issues at the intersection of patent law and food and drug law, with a new chapter on Follow-on Biologics. In recent years, pharmaceutical patent laws have been subjected to significant legislative reforms, controversial amendments to FDA regulations, numerous investigations by antitrust enforcement authorities, judicial precedent from the Supreme Court, and far-reaching pronouncements from the World Trade Organisation. Pharmaceutical Patent Law, Second Edition takes on the complicated tasks of tracking legal developments within the PTO, FDA, Congress, the courts, the FTC, the Department of Justice, and the WTO; examining how these agencies and organisations interact with each other; and determining how they impact strategies within a practitioners core area of expertise.

Pharma Bio World

June 2014 f 61

ad index Sr. No

Clientâ&#x20AC;&#x2122;s Name

Page No

B & R Automation

Front Cover

Bhavya Polymers

Boge Compressors (India) Pvt Ltd

Busch Vacuum India Pvt Ltd

Chemtech World Expo 2015

Inside Cover I

Citizen Industries

Enviro Technologies

Frost & Sullivan

Gardner Denver Engineered Products India Pvt Ltd

Kimberly-Clark Hygiene Products Pvt Ltd

Pharma World Expo 2015

Inside Cover

Praj HiPurity Systems Ltd

Back Cover

Smart I Electronics Systems Pvt Ltd

Warade Automation Solution Pvt Ltd

WaterEX World Expo 2015

62 eJune 2014

17 21 & 23

Inside Cover II

Pharma Bio World

R.N.I. No.: MAHENG/2002/08502. Date of Publication: 1â&#x20AC;&#x2122;st of every month. Postal Registration No: MH/MR/SOUTH-284/2014-16 Posted at Patrika Channel Sorting Office, Mumbai 400001, on 26th & 27th of every month. Total Pages:- 64