Pharma Focus Asia - Issue 13 by Ochre Media Pvt. Ltd.

Published by Verticaltalk

The B2B Division of Ochre Media

A member of CII

Issue 13 2010

Patent Disputes Settlement by Arbitration

Clinical Trials: What Patients and Volunteers Need to Know

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M&A in Pharma Expert views

Foreword IT Clouds in Pharma All about the data IT clouds can help to make sense out of the piling data in the pharma industry Cloud computing is seen as the next big thing in networking, and it is not surprising that the pharma industry too is looking to benefit from it. An IT cloud is a system whereby shared resources, software and information are provided to computers on demand. It is a paradigm shift that follows the shift from mainframe to client-server in the early 1980s. The pharma industry itself has been undergoing a transformation over the past few years. Blockbusters are difficult to come by and pipelines are drying up. Given this, any cost savings are welcome, and reduction in IT infrastructure costs sure look attractive. Globalisation has brought with it networks that span globe. So, while research happens in a western country, the clinical trial would take place in an emerging Asian market. This has also led a proliferation of data of various types. This includes data related to research but also related to M&A, which is a preferred strategy for growth for the companies. For the pharma industry, data is a core asset, and cloud computing presents opportunities and challenges with regards to sharing it. Vendors today provide external and internal clouds. Of these, the latter is likely to be the preferred model given the sensitivity of data at hand. In this issue's cover story, Alan Louie, Research Director at IDC Health Insights, looks at the factors affecting the adoption of clouds in the pharma industry, areas of application and the likely direction this trend will take. Discovery research, clinical development, drug safety and M&A are likely to be the areas that see the widest application of IT clouds. The need to consolidate data on an organisation-wide basis will be the key driver for companies. However, challenges abound. The most important of these is the security of data. This is one factor that has delayed the wide-spread adoption of clouds. Some say that internal clouds are the best for managing customer data, while other argue that cloud providers have a strong incentive to maintain trust and as such employ a higher level of security. Meanwhile, the data continues to grow, and so does the need for a cloud-based solution despite all the risks. Managing data in silos across the globe hinders the prospects of partnering effectively across borders, making sense of the piling data becomes increasingly difficult. IT clouds, therefore, can be leveraged in short-term as well as long-term planning of the pharma companies. Moreover, no other option seems as attractive or efficient. The key for industry leaders will be incorporate clouds in a company's plan while taking into account the risks that come along.

Akhil Tandulwadihar Editor

Contents

CoverStory

Strategy 06 Patent Dispute Settlement by Arbitration Rustom Mody, Head, R & D and Quality Divisions Jayanthi Murthy, Senior Executive, Intellectual Property Management Department Intas Biopharmaceuticals Ltd., India.

10 Safety Reports Preparation, interpretation & relevance Rashmi Hegde, Director Pharmacovigilance Asia-Middle East-Australia-Canada, Global Abbott Products GmbH

Clinical Trials 20 BOOKS Fundamentals of Clinical Trials Lawrence M Friedman, Curt D Furberg and David L DeMets

Clinical Trials: What Patients and Volunteers Need to Know Author: Lorna Speid, Ph.D

Alan S Louie Research Director IDC Health Insights USA

Randomized Clinical Trials: Design, Practice and Reporting Authors: David Machin and Peter Fayers

Research & Development

22 The Promise of Stem Cells Exploiting the potential

Satish Totey, Chief Scientific Officer, Stempeutics Research Pvt. Ltd, India

EXPERT TALK 34 M&A in Pharma Expert views Sujay J Shetty, Associate Director, Pharma Life Sciences , Advisory Corporate Finance, PriceWaterhousecoopers, India Ganesh Nayak, Executive Director, Zydus Cadila, India Joseph Manoj Victor, Senior Research Analyst, Healthcare Practice, Frost & Sullivan,India R B Smarta, Founder and Managing Director, Interlink Marketing Consultancy Pvt. Ltd.

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Advisory Board

Alan S Louie Research Director, Health Industry Insights an IDC Company, USA

Christopher-Paul Milne Associate Director, Tufts Center for the Study of Drug Development, Tufts University, USA

Douglas Meyer Senior Director, Aptuit Informatics Inc., USA

Frank A Jaeger Director, New Business Development Solvay Pharmaceuticals, Inc., USA

Georg C Terstappen Chief Scientific Officer, Siena Biotech S.p.A., Italy

Editors Akhil Tandulwadikar Prasanthi Potluri Art Director M A Hannan Copy Editor Sri Lakshmi Kolla Jenny Jones Sales Team Khaja Ameeruddin Aravind Maroju Jeff Kenny Ben Johnson Compliance Team P Bhavani Prasad K Lavanya Sam Smith Megan John CRM Yahiya Sultan Subscriptions incharge Vijay Kumar Gaddam

Kenneth I Kaitin Director and Professor of Medicine, Tufts Center for the Study of Drug Development, Tufts University, USA

Laurence Flint Associate Director, Clinical Research Schering-Plough Research Institute, USA

IT Team Ifthakhar Mohammed Azeemuddin Mohammed Krishna Deepak Head - Operations S V Nageswara Rao

Neil J Campbell CEO, Mosaigen Inc. and Partner Endeavour Capital Asia Ltd., USA Pharma Focus Asia is published by

Phil Kaminsky Founder, Center for Biopharmaceutical Operations University of California, Berkeley, USA

Rustom Mody Director, Quality and Strategic Research Intas Biopharmaceuticals Limited, India

A member of

Confederation of Indian Industry

Ochre Media Private Limited, Media Resource Centre 6-3-1219/1/6, Street No. 1, Uma Nagar, Begumpet, Hyderabad - 500016, Andhra Pradesh, India Tel: +91 (0) 40 30455000, Fax: +91 (0) 40 30455140 / 41 Email: pharmafocusasia@ochre-media.com www.pharmafocusasia.com|www.verticaltalk.com|www.ochre-media.com

Sanjoy Ray Director, Technology Innovation Merck Research Laboratories, USA

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Sasikant Mishra Business, Policy and Network Strategist Pharmaceutical Industry, India

Copies of Pharma Focus Asia can be purchased at the indicated cover prices. For bulk order reprints minimum order required is 500 copies, POA.

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Strategy

Patent Disputes Settlement by Arbitration Disputes interfere with the successful use and commercialisation of patent rights. Providing way for resolving them as fairly and competently as possible, without disturbing underlying business relationships, is therefore an important challenge for international IP policy. Arbitration has a number of unique characteristics that can serve this purpose, and as such offers an important option for resolving patent disputes. Rustom Mody, Head, R & D and Quality Divisions Jayanthi Murthy, Senior Executive, Intellectual Property Management Department Intas Biopharmaceuticals Ltd., India

ntellectual Property Rights is one of most important property of almost all the domain globally. New technologies, in the field of life sciences, have resulted in the increase of number of patent applications filed worldwide. Exploitation, protection and enforcement of patent rights at the international level are very crucial for all the innovators. Additionally, patent litigation requires court proceedings in every jurisdiction where the patent is allegedly infringed. If the particular product is having a worldwide market, then the patent litigation has substantial legal and financial impact. Therefore, the use of Alternative Dispute Resolution (ADR), together with arbitration, to resolve patent litigations is getting increased. Before two years there was a sudden decrease in US patent litigation observed for the first time in the last 15 years. At the same time, around 400 IP cases were filed with American Arbitration Association (AAA). The purpose of this article is to enlighten the emerging popularity of arbitration for a wide range of IP litigations and to identify certain special advantages of IP arbitration. Article 2(viii) of the Convention Establishing the World Intellectual

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Property Organization (WIPO) provides that "intellectual property shall include rights relating to: • literary, artistic and scientific works, • performances of performing artists, phonograms and broadcasts, • inventions in all fields of human endeavor, • scientific discoveries, • industrial designs, • trademarks, service marks and commercial names and designations, • protection against unfair competition, and all other rights resulting from intellectual activity in the industrial, scientific, literary or artistic fields" Generally, intellectual property is divided into two types: industrial property and copyright. Industrial property includes patents, trademarks, industrial designs and geographic indications while copyright include creative works like novel, poems, plays, films, musical works, computer software and artistic works. The wide range of disputes commencing under joint research and development initiatives, disputes over agreements are

equally broad and can involve licenses like in-licensing, out-licensing and crosslicensing arrangements prior to litigation in several jurisdictions. The legal issues probably involved in such disputes include violation of contract, infringement, claim construction and enforcement through licenses and other agreements. Remedies for such disputes include damages, injunctions, declaratory relief, includes declaration of infringement and invalidation. Such disputes can only be resolved by either court litigation or by arbitration proceedings in which arbitration can be preferable for solving patent disputes. WIPO Arbitration and Mediation Center

To provide services for the resolution of commercial disputes through arbitration and mediation between the parties involving intellectual property, WIPO Arbitration and Mediation Center was established in 1994 situated in Geneva, Switzerland. The arbitration procedures offered by this Center are widely recognized as particularly appropriate for tech-

Strategy

Comparison between court litigation and arbitration Common Features of Many IP Disputes International

Court Litigation

Arbitration

Multiple proceedings under different laws, with risk of conflicting results.

A single proceeding under the law determined by parties.

Possibility of actual or perceived home court advantage of party that litigates in its own country

Arbitral procedure and nationality of arbitrator can be neutral to law, language and institutional culture of parties

Technical

Decision maker might not have relevant expertise

Parties can select arbitrator(s) with relevant expertise

Urgent

Procedures often drawn-out Injunctive relief available in certain jurisdictions

Arbitrator(s) and parties can shorten the procedure WIPO Arbitration may include provisional measures and does not preclude seeking court-ordered injunction

Require finality

Possibility of appeal

Limited appeal option

Confidential/ trade secrets and risk to reputation

Public proceedings

Proceedings and award are confidential Source: WIPO Arbitration & Mediation Center

nology, entertainment and other disputes involving intellectual property. Advantages of arbitration in Patent disputes

Patent rights are territorial rights by nature, associated with the specific jurisdiction in which the protection is sorted. Therefore, patent litigation procedures of various jurisdictions cannot be merged and are subjected to the countryâ&#x20AC;&#x2122;s law where the invention is protected. The legal system of different jurisdictions differs in the procedure, method of handling the similar issues, time-lines and decision makers with varying degrees of experience and technical expertise. Among the available patent dispute resolution alternatives to the courts, arbitration is the one most extremely used internationally because of its distinct advantages which are mentioned below.

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Strategy

Principal steps in WIPO Arbitration Principal steps in WIPO Arbitration

Answer to Request for Arbitration

Establishment of the Tribunal

Statement of Claim

Statement of Defense

Further written statements and witness statements

Within 30 days of receipt of the request for arbitration, the respondent must file an answer to the request. The parties may choose the number of arbitrators that will sit on the tribunal, in the absence of an agreement by the parties, the WIPO Center will appoint a sole arbitrator, except where the WIPO Center determines that three arbitrators are appropriate. The statement of claim must be filed within 30 days of the constitution of the tribunal.

The statement of defense must be filed within 30 days of the receipt of the statement of claim

The tribunal may schedule further submissions

Hearing

By party request, or by tribunal discretion, a hearing may be held for the presentation of evidence by witnesses and experts, and for oral argument.

Closure of Proceedings

When the tribunal is satisfied that the parties have had adequate opportunity to present submission and evidence, it will declare the proceedings closed.

Final Award

Single Procedure – Patent disputes are often involved parties from different countries. So, usually court litigation results inconsistency due to the differences in the legal procedures in different countries. Arbitration helps the parties to solve the patent disputes in a single procedure and less expensive. It helps to avoid complication and inconsistency in the litigation proceedings in several jurisdictions. Resolution with Neutrality – In the case of Arbitration, parties will be able to opt for the law, language, procedures, 10

WIPO arbitration begins with a claimant submitting a request for arbitration to the WIPO Arbitration and Mediation Center. The request for arbitration should contain summary details concerning the dispute.

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The final award by the tribunal should be delivered within three months of the closure of the proceedings.

rules and customs which are neutral and negotiable. Arbitration could happen anywhere, in any language and with the arbitrators belongs to any nationality. Confidentiality – The resolution of the disputes through arbitration hearings can be kept confidential. Faster and Economical – Arbitration procedure is speedy and less expensive than litigation proceedings in the courts. Final, enforceability of decision

Unlike court’s judgment which can usually

be appealed or contested in higher court, arbitration results is final and resolution comes into force immediately. Freedom to choose a competent decision maker One of the most important features of arbitration is that the parties will be able to select their arbitral committee, and thereby to make sure that their dispute is heard by a committee that they trust, considered to be independent, neutral and experienced in the relevant subjectmatter. Where a higher level of technical competence is required, the arbitral committee allows the parties to select an arbitrator of their choice, preferably the one who has inherent understanding of the case in disputes. Disadvantages of Arbitration over Patent disputes

Even though arbitration is the better way of resolving the patent dispute, it does also have its limitations. For example, certain disputes can only be resolved through court litigation. Especially, it is impossible to resolve the dispute that would set a public legal criterion through arbitration. The results of an arbitration procedure, an arbitral award or a settlement agreement, are mainly binding on only the parties involved. If a party wants to obtain a generally binding decision that the claims of a particular patent were valid or invalid, the only means of obtaining such decision will be through a court judgment. Additionally, the harmonious nature of arbitration makes it less appropriate if one of the two parties is not cooperating. Since both parties must agree to use arbitration, no party can force another to participate. Unable to settle the subject matter Sometimes through arbitration, issues of the patent dispute may not be able to settle under the law of the particular state. For example, in a patent dispute over an infringement, an arbitral committee will not able to determine whether a patent is being infringed or not. In addition, an arbitrator/ committee may not

Strategy

have power to grant injunctions where a court has the rights to grant. Lack of access to Precedents

Since arbitration resolutions are private hence the precedents on earlier arbitration resolutions may not be accessible and may not provide a deterrent to other infringers.

become more complex. The advantages of arbitration are more visible in cases where technical skills in a certain area are required. Parties who would like to maintain a good relationship and who want to have their dispute out of the public knowledge would also prefer the arbitration route.

References

1. Smith, M.A., et al “Arbitration of Patent Infringement and validity issues worldwide” Harvard Journal of Law & Technology 19; 2, (2006); 299 – 356 2. Theurich, Sarah., “Efficient Alternative Dispute Resolution in Intellectual Property” WIPO Magazine, June 2009; 20 - 22

Selecting the arbitration route to pursue the course of action will vary from one case to another. Basically, arbitration offers a self help route to resolve the disputes outside the court where the parties are having greater control over the proceedings. Generally arbitration is a better way of resolving the patent disputes because it is more efficient, less procedural and less expensive way of resolving disputes. But sometimes this may not essentially be the case as arbitral proceedings

Author BIO

Conclusion Rustom Mody completed his Ph.D., from Department of Microbiology, M.S. University, Baroda, India. He was a Research Associate for six years at the University of Nebraska Medical Center at Omaha, U.S.A, where he worked in diverse research areas such as immunochemistry, molecular immunology and cancer biology. Currently, he is heading R & D and Quality Divisions of Intas Biopharmaceuticals Ltd., with a focus on developing products and Intellectual Property that could give the company a strategic advantage and global reach. Jayanthi Murthy is working as a Senior Executive in Intellectual Property Management Department of Intas Biopharmaceuticals Ltd., She completed her Post Graduate Diploma in Patents Law, from Nalsar University, Hyderabad and having 5 years of professional experience in biotech industry. She joined IBPL in 2004 and is associated with handling patent related issues of biotech products.

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Strategy

y t e f Sa orts Repp , n o i t a ar Pre n o i t a t e interpr ce n a v e l e &r

in the ey role e k a y pla hil fety. W reports Safety ent of drug sa rts is a po m hese re iate approval assess t f o n pr atio prepar h task, appro ution and t o rib mamm orisation, dist pliance m th and au g of timely co epared r . in r rocess ing of p p monito iv e h h c t r a e in as inclusiv as well is s n io s submis nce acovigila tor Pharm a, Global Abbott c e ir D , e egd nad Rashmi H East-Australia-Ca dle Asia-Mid GmbH Products

afety Reports are essential documents, which are crucial to the global process of assessment of Drug Safety. Safety Reports are designated as Periodic Safety Update Reports (PSUR), Addendum Reports (AR) and Summary Bridging Reports (SBR), depending on the periodicity of the submissions as well as the contents of the document. The regulatory requirements, in most countries make it obligatory to submit the PSUR for all Registered Products and not merely for Marketed Products. Annual Safety Reports and Development Safety Update Reports (DSURs) cover the Safety Summary from Medicinal Products which are in Development or in Clinical Trials. 12

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A Periodic Safety Update Report (PSUR) is a Safety Report, encompassing complete, global Product Safety Information for a registered product, which is periodically submitted to the regulatory ruthorities, at a defined point in time, Post-Authorisation of the Product. The periodicity of the submission is determined by the stage of the Product Lifecycle and may change whenever there is any novel safety information or extended Product indication or extended population use for the product. The Addendum Report (AR) provides the most recent update to the PSUR. It is usually a safety update outside the usual schedule (upto 6 months since the

last PSUR). This document is usually brief, and does not provide any in-depth analysis. The Summary Bridging Report (SBR) covers a specified period and is prepared on the request of the Competent Authority. This document integrates information presented in two or more PSURs. Both the AR and the SBR are brief documents which are attached to the PSUR, and hence this discussion will relate primarily to PSURs. The guidelines that are currently considered for the preparation of this document include the Regulation 726/2004/EC (March 2004) and Directive 2001/83/EC (November 2001)

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Strategy

and the Volume 9A (September 2008) which correlates most closely with the ICH E2C guidelines. Expectations of the authorities

The Competent Authority requires that the Safety Report received from the Marketing Authorisation Holder (MAH), provides a complete validated summary of Product Safety in the Development Phase and the Market Lifecycle of the Product. It is expected that this document will be the source of comprehensive Pharmacovigilance data which is available within the company and made available to the Authority for a review of the product. In the Safety Report, the MAH is expected to review the safety profile, assess the Risk-Benefit Balance of the Product, and update the Summary of Product Characteristics (SmPC) and the Package Leaflet based on currently available safety Information. Goals of safety reports

For most EU authorities, the acceptable format is as defined in Chapter 1.6 of the Volume 9A document. The focus of the document for the MAH should be the presentation, analysis and evaluation of new or changing safety data received in the period covered by the document. The Safety Summary is expected to provide a critical evaluation of Product “RiskBenefit” in the light of dynamic safety knowledge. Submission cycle

Safety Report submission is mandatory for all products following registration. While submission cycles vary slightly from region to region, the usual cycle which is followed in the countries of the European Union is 6 monthly for the first two years after registration annually for the next 2 years and at 3 yearly intervals thereafter. The international birth date – that is, the date of first marketing authorisation granted to any MAH anywhere in the world – is the date that is conformed for the Data Lock Point (DLP). Submission of the report 14

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to the competent authority is required within 60 days of the DLP; rarely the submission date is extendible by 30 more days on prior request. Some national authorities do require that the PSUR submission cycle follows the national birth date, that is, the date of first marketing authorisation in the country. In these cases, providing an addendum report to the most recent PSUR is usually satisfactory. For renewal of marketing authorisation after 5 years of marketing, reports are prepared covering a period of at least 4 years and 4 months. These reports are submitted within 60 days after DLP. As a rule, the renewal of marketing authorisation does not change the original reporting schedule of the product. The periodicity of the safety report, may change with line extensions. It also changes with the authorisation of generic products and may be shorter for products with a risk management plan in place that require special monitoring. Process engineering

The decision on preparation of the PSUR is determined by the periodicity of the Product as well as the marketing life cycle of the product. The planning and preparation is resolved in keeping with the Submission timelines and based on the international birth date or the national birth date as per the requirements of the competent authority in question and commenced before the data lock point. In cases where the marketing of the product is authorised to more than one MAH, it is expedient to qualify the data source in order to avoid data duplication, which may sometimes be a concern. While the preparation of the document is in itself a mammoth task, appropriate approval and authorisation of the prepared PSURs, distribution and monitoring of timely distribution compliance as well as archiving of prepared submissions is inclusive in the process. An easy aid to this process is a timetable of expected submissions based on the data lock point of the product.

The PSUR must cover the following

• All Indications • All Dosage forms • All Regimens of Treatment • Separate PSURs required for Fixed Combination Products • Address comments of the Competent Authority on previous PSURs • Use English language (in most countries)

Sections of the PSUR

Topic

Executive Summary

Introduction

3 4 5

Worldwide Marketing Authorisation Status Update to Regulatory of MAH actions for Safety Reasons Changes to Reference Safety Information

Patient Exposure

Individual Case Data Line listings Tabulations Analysis of Case Histories

Clinical Studies

Safety Related Information Risk Management Plans Risk Benefit Analysis

Safety Evaluation

Conclusion

The Future of Pharma is Asia Reshaping the pharmaceutical industry's quality

there is scepticism over trial involvement by western

standards is currently the top priority for the Chinese

consumers and difficulties in finding the right kind of

government. Earlier announcements by its Ministry

patients.â&#x20AC;?

of Health to issue new tougher Good Manufacturing Processes (GMP) standards for medical products comes

The committee will be made of representatives from

at the right time as current regulations do not meet

A-Bio - Steven Lee, CEO, Novartis - Kalai Kalaiarasan,

international standards which result in poor performance

Head Supply Chain Mgmt APAC, Africa, ME & Greater

by Chinese companies in the international market. In

China, AstraZeneca - Uma Nandan Misra, VP Operations,

order to respond to these GMP changes, Chinese

Celltrion - Daniel Slone, VP Manufacturing and Eisai

manufacturers however are in urgent need to upgrade

Inc. - Sanjit Singh Lamba, President.

their facilities and technologies, as failure to comply will result in closure. The NGP Asia committee has

With the US seeing $110 billion in global sales

called an emergency meeting to combat the current

exposed to generic competition for the top 50

situation.

pharmaceutical companies through to 2014, branded pharma must look to emerging markets, biologics

Asia has become a more attractive place to conduct clinical trials (CT) but as it grows so do the

and continued cost-saving initiatives to drive growth according to Analysts.

challenges. For pharmaceutical companies, Contract Research Organizations (CROs) or Central laboratories

The top 50 pharma companies are forecast to

(CL) the biggest challenge is keeping trials on track,

experience a US sales decline of 1.3 percent year-

on time and on budget; all three are key to global

on-year, with sales falling from US$228 billion to

competitiveness. In the last 10 years Asia has been

US$214 billion. However, major markets outside the

targeted by pharmaceutical companies from across the

US are forecast to grow by 2.4 percent year-on-year,

globe who wish to take advantage of the regionâ&#x20AC;&#x2122;s ethnic

offsetting the US decline. Emerging markets are forecast

diversity and huge population to test their medicines at

to experience double-digit growth rates over the next

an affordable price. Asia has now moved to a position

few years, with an average year-on-year growth rate

where they can challenge to become the number one

of 12 percent. It is this growth rate that will see Asia

contender for CT, the US.

fill the gap.

The NGP Asia Committee, who will be meeting at the

If you require any further information about this

NGP Asia summit believes the revitalized competitiveness

topic or enquire about interview opportunities please

of Asia is down to two main factors: â&#x20AC;&#x153;Firstly, conducting

contact Emma Naylor on 0117 921 2764 or email at

trials in the west is increasingly expensive. Secondly,

emma@ngonlinenews.com Advertorial www.pharmafocusasia.com

Strategy

Executive summary

Patient exposure data

This section is a composite of the different sections that are presented in the later sections. It provides an overall impression of the safety profile of the product. This review would include the worldwide MAH status of the product and other relevant regulatory information. It would summate the information from spontaneous cases, studies, and literature. The summary would provide data on exposure of the product and discuss new signals and safety concerns, if any. Usually, the executive summary would be written at the conclusion of all sections of the PSUR, to enable the author to provide a synopsis of past, current and future safety related information of the product.

The world wide sales data is used to estimate Patient exposure. An average daily dose assumption is made, and patient exposure is provided in terms of persontime-exposure (days, months, years). It is expected that details on method of estimation of patient exposure is provided. In case it is relevant to the safety assessment, broken down patient exposure data can also be provided in terms of market versus clinical exposure, adult vs paediatric or geriatric exposure.

Regulatory safety information

Sections 3 & 4 of the PSUR, which provide regulatory related safety information, include notification on global regulatory status of the product, including any qualifications, limits to indication, product withdrawal and restrictions to treatment populations. Any updates from the regulatory authority or any company actions related to safety, including differences in previous and current information, target use populations, urgent safety restrictions, Dear Dr letters, for the product, would be presented in this section. Reference safety information (RSI)

In practice, the company core safety information (CCSI) is used for RSI purposes. The concerned document should be numbered, dated and appended to the PSUR. The RSI/ CCSI should be used to assess listedness, and the local / EU Summary of Product Characteristics (SPC) to define expectedness. For 6sixmonthly and yearly PSURs, the RSI coming into effect at the beginning of the reference period is used. For PSURs covering a period greater than one year, the latest effective RSI is used. Details and evidence for changes to CCSI during the reference period are provided, within the PSUR document. 16

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allows proper assessment of the safety information. Meaningful interpretations can also be drawn from the background information, reporter frequency as well as quality of reports. Additionally, for the specified period, the published scientific literature is reviewed for all the safety related information. In instances where relevant cases are found within literature, these are provided in the case listing.

Cases to be included in PSURs Sources of Individual Case Safety Reports ( ICSRs) Market Clinical Studies Post Marketing Studies Post Authorization Safety Study Compassionate Use Programs Literature Regulatory Authorities Others – Partners, Registries, Epidemiological Databases

A satisfactory case description is one in which patient and reporter demographic information and description of ADR, progress and outcomes; company causality, dechallenge and rechallenge information is made available. All unsolicited cases regardless of causality are included in the assessment. In addition, serious solicited cases that are assessed as ‘Suspect’ are also included. The cases which are selected for analysis are those with relevant safety findings rather than the rare cases. In cases with serious, unanticipated findings, comments are provided. The Line listings provide a short summary of all the cases discussed in the PSUR. The Tabulations provide specific details on certain groups of patients. The purpose of Case Analysis, Line listings and Tabulations is to create ‘Medically Meaningful Clusters’ – which

• All serious adverse reactions and non-serious unlisted adverse reactions • from spontaneous reporting from healthcare professionals • All serious adverse reactions available from post-authorization safety • studies and other studies or namedpatient/compassionate use • All serious adverse reactions, and non-serious unlisted adverse reactions • from the literature • All serious adverse reactions transmitted to the MAH by worldwide • regulatory authorities • All non-serious listed adverse reactions from spontaneous reporting from • healthcare professionals • All serious and non-serious adverse reactions reported by • patients/consumers and other non-healthcare professionals.

Studies

Product studies included within the PSUR are non-clinical, clinical, and epidemiological studies. A description of the studies is provided, along with a discussion on the safety sample and the safety relevance of studies. The basis for any new, planned safety studies is as well discussed. Meanwhile, published studies are discussed in the light of their safety relevance.

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Strategy

Other information in the form of efficacy related information, late breaking information and follow-up of cases of special interest from previous PSURs is also made available in this section. Safety-related information

In this section, follow-up of risk management plans and a risk-benefit analysis of the product is provided. Safety evaluation

Statistical ratios such as the proportional reporting rate are used to assess new, serious or increased ADR rates. The identified Safety signals are discussed and measures proposed – heightened surveillance, change to the reference safety information, routine monitoring, or no action. The overall safety evaluation also includes a discussion on any new or increased drug interactions, overdose, misuse / abuse, and use in pregnancy / lactation, or in special patient groups – such as paediatric or geriatric population. Conclusion

Any variation of data in comparison to the previous experience or disparities from the reference safety information document is discussed in this section. All safety actions taken are listed and justified. In case there are amendments to Summary of Product Characteristics (SPC), these are discussed. The conclusion section should clearly delineate the risk-benefit balance for the product.

Consonance in pre- and postmarketed pPhase

The Annual Safety Report or the DSUR for products in development phase will transition to the PSUR document in the phase of product registration and thereafter. Pharmacovigilance risk management plans from the clinical phase can be switched to the post-marketing phase as per product safety requirements and regulations.

The regulatory requirements in most countries make it obligatory to submit the PSUR for all Registered Products and not merely for Marketed Products.

What is deemed as non-compliance with safety report regulations?

The safety reports require to be peer reviewed by medical affairs, product department, clinical and regulatory affairs for correctness and validation of different parts of the document. For the European authorities, the PSUR is prepared by the product safety expert and authorised by the qualified person.

Complete non-submission or submission outside the stipulated timeframes is the most common form of non-compliance. Besides, submission in the incorrect format, poor quality of reports, and omission of key information, are other forms of non-compliance. Failure to address the comments or requests from the Competent Authority to the previous PSUR is also considered as noncompliance.

Archiving

Amendment to periodicity of PSURs

The signed paper copies and peer reviewed copies are archived at the central office,

The following situations could change the periodic cycle of PSUR submission

Peer review

where the documents originate. In the different affiliates, the submission documents as well as the covering letter will require to be archived. The distribution list also forms part of the archives. All correspondence with the competent authorities, is archived for future reference as well as for audit / inspection purposes.

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– line extensions, pediatric indications, new indications or use in new populations, dosages, routes of administration. One possible reason for the change in the periodic cycle of the PSUR could be specific safety concerns which necessitate the provision of risk management plans. List of appendices

• Worldwide MAH Status • CCSI • Serious and non-serious unlisted ICSRs/ADRs from Health Care Professional • Non-serious listed ICSRs/ADRs from Health Care Professional • ICSRs/ADRs from consumers • Serious ADRs, all-time • Listing of studies • Identified or updated safety signals • Risk benefit analysis report • Bibliography Safety Report Requirements by Various Authorities US FDA

The US FDA Safety Report has four sections fulfilling usually the same objectives as the EU PSUR. It is acceptable to these authorities to submit on basis of international birth date rather than on national birth date. The submission cycle is quarterly for the first three years of registration and annually thereafter. The document has four sections which capture the same data as per the Volume 9A requirements for PSURs. Health Canada

PSURs are not routinely submitted to the Canadian authorities, Health Canada. They are habitually required to be submitted within 30 days and on request only. Sometimes PSURs may be requested annually or biannually depending on the product safety characteristics. The CCSI and Local labeling comparison document is provided along with the PSUR. PSURs are also submitted along with Regulatory submissions which involve local labeling safety updates.

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Strategy

TGA, Australia

PSURs (and ARs and SBRs if relevant) are submitted annually to cover a period of three years from the date of local registration. The first PSUR must be submitted no later than 15 months after approval and subsequent reports are submitted annually. The format of the documents as described in the ICH guidelines or the Vol 9A are acceptable to the TGA authorities. TGA does not specify precise requirements and IBD is acceptable provided it meets the submission timelines as noted above. Wrap up

The PSUR and related Safety Reports are the presentation of comprehensive safety evaluation available from all sources for the period under discussion.

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This document aims to address relevant, current safety issues and provide resolution for those safety concerns that continue to exist. The current move to define the Development Safety Update Reports and the Annual Safety Reports will ensure alignment of product safety during the pre-marketed and post-marketed phases of the product life-cycle, and may likely prevent or at the very least reduce the occasions of Product withdrawal due to safety related concerns.

Author BIO

The PSUR format prepared for submission per Vol 9A is usually acceptable to the Health Canada authorities.

The key imperative seems to be the analysis and inferences to be drawn from the data, rather than a mere presentation of data in the standard format. A good document serves as a guide to comprehend the product safety profile and provide recommendations, if any, on further required safety actions. The intent of the actions should be to ensure complete knowledge on product safety and thus to proactively guarantee patient safety.

Rashmi Hegde is a Paediatrician by training and has vast experience with the Medical departments of Pharmaceuticals companies. She has now been associated with the Pharmaceutical Industry for over 17 years in several global companies such as Novartis. Dr Hegde has previously led Medical Affairs including Medical Training, Medico-Marketing, Medical Information, Strategic Planning, Clinical Trials, Biotechnology and Pharmacovigilance in these companies. Her mostrecent position prior to the current one has been Medical Director â&#x20AC;&#x201C; India/ SE Asia at Solvay Pharmaceuticals.

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Clinical Trials

Books

Fundamentals of Clinical Trials Authors: Lawrence M Friedman, Curt D Furberg and David L DeMets No of Pages: 390 Year of Publishing: 2010 Description: This is the fourth edition of a very successful textbook on clinical trials methodology, written by three recognized experts who have long and extensive experience in all areas of clinical trials. Most chapters have been revised considerably from the third edition. A chapter on ethics has been added and topics such as noninferiority and adaptive designs now receive considerable discussion. There is much new material on adverse events, adherence, data monitoring, and issues in analysis. This book is intended for the clinical researcher who is interested in designing a clinical trial and developing a protocol. It is also of value to researchers and practitioners who must critically evaluate the literature of published clinical trials and assess the merits of each trial and the implications for the care and treatment of patients. The authors use numerous examples of published clinical trials from a variety of medical disciplines to illustrate the fundamentals. The text is organized sequentially from defining the question to trial closeout.

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Clinical Trials: What Patients and Volunteers Need to Know

Randomized Clinical Trials: Design, Practice and Reporting

Author: Lorna Speid Ph.D No. of Pages: 208 Year of Publishing: 2010 Description: Every year, hundreds of thousands of healthy volunteers and patients worldwide undertake the journey through the maze that can be clinical trials. Research participants take part in clinical trials for a variety of reasons. The healthy volunteers may be seeking extra money to pay off college tuition, or they may know someone who is suffering and would potentially benefit from the results of the trial. The patient who is terminally ill might participate in a clinical trial simply as a last hope for a cure. Whatever the goals, though, most participants will experience the same sense of bewilderment as they encounter the jargon and medical terminology that they will hear and have to read about and understand during the course of the clinical trial.

Authors: David Machin and Peter Fayers No. of pages: 374 Year of publishing: 2010 Description: Randomized clinical trials are the principal method for determining the relative efficacy and safety of alternative treatments, interventions or medical devices.? They are conducted by groups comprising one or more of pharmaceutical and allied health-care organisations, academic institutions, and charity supported research groups.? In many cases such trials provide the key evidence necessary for the regulatory approval of a new product for future patient use.? Randomized Clinical Trials provides comprehensive coverage of such trials, ranging from elementary to advanced level.

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Research & Development

The Promise of Stem Cells Exploiting the potential

Stem Cells have been repeatedly talked in public and scientific community and all the stem cell biologists and scientists agree that stem cell have the potential for treating human diseases and disorders. For the business purpose the possibilities of a transfer of these biological concepts to clinical practice continue to attract extremely high interests. Therefore, stem cells are a resource providing unprecedented potential for biological discovery, drug development & future cellular medicines. Satish Totey, Chief Scientific Officer, Stempeutics Research Pvt. Ltd., India

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t is widely believed that stem cells hold great promises and potential for both basic sciences and medicine. Stem cells are expected to improve our understanding of fundamental biological processes, help in developing model for human diseases such as birth defect or cancer, help in establishing a platform for drug screening and toxicity studies in order to shorten the process of drug development and most importantly stem cell promise created lots of hope to find way of using these cells to repair damaged tissues and curing serious diseases for which currently no treatments are available.

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Research & Development

What is Stem Cell?

In a laymanâ&#x20AC;&#x2122;s term stem cells are capable of self renewal and are capable of differentiating into multiple cell types of ectoderm, endoderm and mesoderm. For example stem cells can be differentiated into liver cells, brain cells or skin cells. This process is called as differentiation. These differentiated cells that have certain function and properties therefore can be used for cell replacement therapies. Thus, stem cell has a capacity to develop into any kind of cells in the human body. Stem cells are broadly classified as embryonic stem cells (ESC) since they are derived from pre-implantation stage embryos such as blastocyst (day 5 embryo) and adult stem cells, those found in various adult tissues. Stem cells from different sources vary in their abilities to differentiate or to produce mature cell types. Embryonic stem cells (ESC) can give rise to any cell type in the adult body, whereas adult and cord blood-derived stem cells are more restricted in their ability to differentiate into various cell lineages. Understanding the versatility of a given stem cell type is crucial to unlocking its therapeutic potential.

administration of MSC can home to the site of injury, can circumvent problem of immune incompatibility and they are non-tumorigenic and hence can develop affordable off the self therapeutic product for multiple patients. Market opportunity

To a certain degree, tissue regeneration takes place in the human body throughout life. For example, blood and skin are continuously restored, and bone, muscle, liver, and blood vessels have a limited capacity for self-renewal. However, disease or trauma can cause a significant loss of functional cells that the regenerative power of the body cannot repair. Although the general public is keenly aware of the stem cell promise for curing many diseases, many people do not realize that stem cell therapy is already a reality in clinics today. In fact, hematopoietic

Adult Stem Cells

Adult stem cells are most widely used stem cells for human therapy and clinical trial. Global stem cell market is currently dominated by the adult stem cells. More than 58% of the companies are currently using adult stem cells for research and therapies. Among the adult stem cells, bone marrow derived stem cells are most preferred stem cells that are currently being used for therapy. Other adult stems cells are adipose tissue derived stem cells, keratinocytes, cord blood and neural stem cells. Recently bone marrow derived Mesenchymal stem cells (MSCs) showed promising tools in newly emerging avenues of regenerative medicine. MSCs have multipotential properties and currently being used for several clinical applications. Several scientific reports demonstrated that the

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Stem cell based therapies offer a promise for curing serious debilitating diseases for which currently no treatments are available.

stem cell (HSC) transplantation for the treatment blood diseases, such as leukemia, lymphomas, and anemia, has been around for more than 40 years. Originally such transplants were performed using bone marrow, but more recently, they are performed using mobilized stem cells from peripheral blood, as well as cord blood stem cells. From a business perspective, current HSC transplants are not considered to be a commercial product. The procedures are carried out by medical transplant centers; therefore, the financial benefits are relegated to the health care providers and affiliated institutions. Clearly not every single patient suffering from a degenerative condition will require a cell-based treatment. Nevertheless, experts believe that if indeed stem cell treatments are truly disease modifying and produce a significant clinical benefit to a patient, some of them could achieve a blockbuster status. By some predictions, cell-based therapies could be a US$ 20 billion market by 2010. Market assessment indicates that India and other Asia â&#x20AC;&#x201C;Pacific countries like Singapore, Taiwan, Malaysia and Thailand are the immediate market for entry. As per the estimation India as a region with maximum market annual potential approximate US$ 540 million followed by Taiwan US$ 320 million, Thailand US$ 230 million, Malaysia US$ 157 million and Singapore US$ 100 million. In the APAC region, Singapore has the highest penetration rate with CAGR of almost 66 per cent for market penetration over the next 5 years. Malaysia leads second with CAGR of 33 per cent whereas Taiwan and Thailand leads on the basis of shear numbers but would have comparatively lower demand trajectory due to restrictive healthcare policies. Adult stem cell therapy currently dominates the global stem cells market with share of almost 58 per cent and bone marrow derived stem cell is predominantly in use for therapies. Therapies for

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Research & Development

osteochondral disorders are the forefront of development with two successfully launched products already in the market. Cardiovascular therapies for advanced cardiac failure and neo-vascularization in acute myocardial infarction are the second most developed therapeutic areas. Spinal Cord injuries & Parkinsonâ&#x20AC;&#x2122;s rank third in development and followed by development in the renal and hepatic disorders. Clinical applications

Today, stem cell therapy is a reality. Results showed that stem cell therapy for myocardial infarction can improve ejection fraction significantly and reduce the infarct size. Similarly, stem cell therapy for leg ischemia, spinal cord injury, stroke, multiple sclerosis and several other diseases has shown significant improvement during phase-I and II clinical trials. Diabetes cardiovascular disorder and spinal cord injury are the therapeutic area that will benefit from stem cell treatment because in these categories there is large patients pool and offer no permanent cures, and that will allow patient rapid product acceptance by the medical community. It has already shown that stem cells can be used successfully in 132 diseases and there are more than 1500 clinical trials currently in progress around the globe. Challenges

Despite the blockbuster promises of stem cells, investors are still shy away from investing money in this initiative. Reasons are multiple and may take years to understand. First and foremost, stem cell science is still in infancy. Despite significant progress and breakthrough discoveries, fundamental knowledge of stem cell differentiation is seriously lacking. We have yet to solve the mystery of several questions. For example we do not know what causes stem cell to maintain them in an undifferentiated state? What signals do the stem cells take from the organs where they were injected so as to differentiate into appropriate lineage?

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Several scientific reports demonstrated that the administration of MSC can home to the site of injury, can circumvent problem of immune incompatibility and they are non-tumorigenic and hence can develop affordable off the self therapeutic product for multiple patients What genetic or environmental signals affect differentiation? Technique for safe and efficient delivery system of stem cells to the tissues has to be identified. Second major challenge is funding for stem cell research. There is growing consensus that countries like India, China, Singapore, Malaysia, Taiwan and Thailand are likely to play a key role in the scientific, clinical and commercial development of stem cells research. Unfortunately, research funding for stem cells in these countries are meager. India has spent US$ 2 million annually on stem cell research in comparison to that of US$ 550 million in US. Third challenge is politically charged area. Stem cell science is one of the most controversial sciences because of its ethical reason especially in human embryonic stem cell. Unfortunately, due to such high profile political interference, scientific facts have been lost in the media and religious debate and every other country drag themselves into this controversy. However, more than 200 genetically diverse stem cell lines were developed and established after the discovery and ban on human embryonic stem cell derivation in US and most of them were derived in US and Asia. It was thought that the US ban had opened up a â&#x20AC;&#x153;new pot of goldâ&#x20AC;? for Asian science and business and opportunity to march ahead in this field. Several Asian countries have taken this opportunity and made significant progress in stem cell research for example, China, Korea, Taiwan and Singapore. Unfortunately progress of stem cell research in India and Malaysia is very slow and insignificant in comparison with other Asian countries.

Urgency of laying down rules for this new branch of medical research is supported by the governments of all nations encouraging stem cell research as there are chances of misuse of this technology. Already exaggerated claims of curing certain diseases using stem cells are being made by some institutions and private clinics around the world. It would be appropriate to develop clear cut guideline for stem cell research and therapy so that such misuse can be avoided. Fourth challenge is autologous or allogenic therapy. We all know that bone marrow transplantation could not translate into commercial product. Turning cell based therapies into commercial product require development of scalable manufacturing processes where cells are produced under current good manufacturing practices. Autologous Vs Allogenic could greatly influence the manufacturing cost and thus profit margin. Moreover, having universal allogenic stem cell therapy will make much more compelling product from business perspective. Critical cases such as acute myocardial infarction or cerebral stroke or in any genetic diseases alllogenic stem cell therapy should be a choice. Summary Stem cell holds enormous potential for both science and medicine. Stem cell based therapies offer a promise for curing serious debilitating diseases for which currently no treatment s are available. In our opinion, within next two years stem cell field is poised to reach an inflection point which would position it for a substantial expansion. However, power of this knowledge need to be used carefully without putting a patient to a risk.

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information technology

atent expirations and their associated loss of blockbuster revenues across the life science industry have forced companies to take a hard look at ways to improve operational efficiency. As part of a deep introspection that has never before been considered, companies are critically assessing which activities are truly core to the business and which activities can be performed more efficiently by a partner. IT infrastructure is clearly an area under review and it is becoming clear that some, if not all of this activity can be performed more effectively and efficiently outside of the organisation. With data and information as core assets to the industry, companies are finding that not all information is equal and that the willingness to relinquish control of information varies, depending on where in the organisation the information resides. Ongoing innovation in the commercial IT cloud solution space has recognised these concerns and is developing (and evolving) product offerings for each need.

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Cloud solutions offer immediate returns in improving operational performance and reducing costs. Multiple approaches to cloud solutions will be needed to satisfy life science industry needs, complicating the development of a coherent cloud strategy.

Alan S Louie Research Director IDC Health Insights USA

Key factors surrounding it cloud adoption in the life science industry

Fundamentally, the opportunity for IT cloud solutions is driven by the need to reduce costs while maintaining the same, or better, organisation-wide operational

performance. While near term ROI is driving investment today, the shift to IT cloud solutions is also supported by the significant potential for long term benefits for the organisation. While external, public IT cloud solutions (e.g. Amazon Web Services Elastic

CoverStory

The life science industry is becoming increasingly global, in part due to outsourcing to lower cost regions, but also due to growing opportunities in emerging markets.

Cloud 2) have the potential to reduce IT infrastructure costs by as much as 90 per cent and enable access to increased computational resources on-demand, this approach requires that company data reside outside of the organisation, which potentially exposes the organisation to the risk of accidental, or malicious data access by external parties. For efforts critical to the organisation (e.g. clinical trials or M&A), the risk of uncontrolled access, no matter how small, is typically too great to accept, and in these situations, the status quo, or better controlled options (e.g. internal IT clouds) are likely to remain the norm for the foreseeable future. It is also clear that the industry is undergoing transformational change in a number of areas that are relevant to the discussion. The life science industry is becoming increasingly global, in part due to outsourcing to lower cost regions, but also due to growing opportunities in emerging markets. At the same time, M&A is increasingly

becoming the near term path to backfilling anticipated revenue losses from blockbuster patent expirations, requiring organisations to regularly integrate and manage new assets and capabilities as they seek to build for the long term. This constant change would challenge the IT strategy and infrastructure of any organisation, but comes at an especially difficult time as the industry seeks rapid change while needing to maintain tight regulatory control to avoid compliance issues and potential penalties. Additional pressures on IT are arising from the geometric growth in the amounts of data that are being generated by life science research. While most of the data is being generated during discovery research, data in clinical development is also growing (particularly from imaging and genomics), as is the data supporting M&A activities. Effective management of these growing data and information requirements will be key to organisational success over the long term.

Who, When and Where

A critical mistake for cloud vendors focused on the life science industry would be to assume a (one size fits all) approach to the adoption of IT cloud solutions. Information within the industry can be heavily siloed, often by design, and management of different data often carries regulatory compliance requirements that also bear financial risks. In looking at the way that data and information are managed in the industry, one needs to focus on the key industry segments as key differentiators as to how much control organisations are willing to relinquish in pursuit of direct cost savings and improved operational effectiveness. Key areas and their segmentspecific requirements include: Discovery research: This early part of the life science value chain is largely unregulated, highly diverse, and multi-faceted in its generation of and use of data and information. New innovations and technology advances are increasingly automating the generation of large quantities of www.pharmafocusasia.com

information technology

data and it is not uncommon to need to create and manage terabytes of data on a routine basis. The very large datasets are often unstructured and the underlying purpose and design of the research that generated the data is typically not associated with the data directly. As a result, the risk to the organisation form accidental access or release of discovery research data is relatively low. In discussions with major life science companies, it is clear that this area is a prime opportunity for external IT cloud services. Key to the value delivered to discovery research efforts includes paying for only what you need from both storage and computing perspectives, the ability to

With the regulated nature of the data also comes a financial penalty for non-compliance as well as the potentially more devastating risk of damage to the industry's high standards for ethics and value to humanity.

access increased capacity on-demand, not paying for excess capabilities and significant reduction in IT infrastructure capital and operating expenses over time. Clinical Development: Data generated and used in the management of clinical trials is tightly regulated and core to the ability of an organisation to successfully advance a new drug to market. Clinical development efforts routinely involve human patients, introducing additional issues and concerns over drug safety in addition to the fundamental issues over whether a drug works or not. While the diversity of data types used in the course of a clinical trial is much more limited than data generated during discovery research, additional complexity is introduced by the global nature of the clini32

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cal development effort, often requiring hundreds of trial principal investigators located in as many locations around the world. Timely access to information is critical even as companies work to tightly control the collection, transmission, and analysis of the data. With the regulated nature of the data also comes a financial penalty for non-compliance as well as the potentially more devastating risk of damage to the industry's high standards for ethics and value to humanity. As a result, external IT cloud services are not perceived as appropriate for this segment and alternatives, both private IT clouds and vendor-based private cloud approaches (i.e. hosted applications and software-as-a-service [SaaS] are likely to remain the key approaches to data and information management in this space over the long term. Drug safety: Although primarily an effort under the umbrella of clinical development, drug safety is a key area that merits separate consideration. Individual drug safety issues are defined as â&#x20AC;&#x2DC;adverse eventsâ&#x20AC;&#x2122; in the industry and severe adverse events (SAEs, including death or other major life threatening impacts) have specific regulatory requirements that companies must meet to maintain regulatory compliance. In particular, SAEs must typically be reported to regulatory agencies within 10 days or severe penalties may result. This issue becomes more complicated as clinical trials are conducted globally, since multiple jurisdictions become involved. The critical nature of safety data, combined with the regulated nature of the clinical trials suggest that cost savings and general operational efficiency improvements are likely to be secondary to meeting regulatory requirements. That said, drug safety is increasingly being looked at as a non-core competency within life science companies and is increasingly being outsourced to qualified application vendors (i.e. general contract research organisations [CROs] or specialty drug safety service providers) along with their private IT infrastructures [i.e. private IT clouds].

M&A: Mergers and acquisitions, along with other collaborative efforts, is a growing effort within the life science industry. Partnerships of all kinds are changing the way that organisations manage and share data, requiring new thinking regarding how data is held and used. For traditional M&A, data security and control are paramount, since any lapses can result in lost opportunity. In these cases, the high risk necessitates the tightest control over data and information and, in some cases; companies are only now shifting away from paper, human couriers, and face-to-face signoffs. Access across corporate firewalls is tightly managed and IT clouds are unlikely to deliver sufficient value to drive change in this space over the foreseeable future. Broader partnership and collaborative efforts, on the other hand, are also growing (e.g. academic collaborations, pre-competitive consortia, and translational research efforts) and to a large extent are being driven by data and information sharing. In these cases, it becomes possible to exploit both external and internal IT cloud solutions as separate, isolated IT ecosystems where key information is available and accessible only to collaborators, separate from other corporate data. Companies today are actively seeking to consolidate data on an organisation-wide basis as part of ongoing efforts to apply business intelligence to both scientific and business management. Almost by default, these efforts are running into concurrent efforts to apply IT cloud solutions to improve operational efficiency at the operational level. The diversity and scope of implemented IT cloud solutions is likely to complicate these data consolidation efforts. Regardless of the specific approaches selected, it will be critical for organisations to incorporate IT clouds into an overall, organisationwide data management strategy, based on the additional complexity that is likely to be introduced from increased dependence on external partners for IT infrastructure.

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information technology

Access across corporate firewalls is tightly managed and IT clouds are unlikely to deliver sufficient value to drive change in this space over the foreseeable future.

Where we are going

The life science industry is clearly in the midst of transformational change and it is reasonable to expect that IT will be a core element in the change process. The industry overall is finally reali sing that it is not significantly different from other major industries in many ways and, as a result, realising that it could benefit from best practices proven in other industries. As an example, the financial industry regularly addresses data security and privacy concerns and M&A issues are regularly addressed by industry in general. It can be expected that IT infrastructure in the life science industry is likely to become increasingly commoditised over the near term, with particular industry segments seeing early adoption as companies look to gain near term cost savings and improved

operational effectiveness. Risk and perceived risk can be expected to slow the adoption of IT cloud innovations in other industry segments, with limited or no progress in specific areas where cost concerns are secondary. Globalisation, geometric data growth, and increasingly complex partnering relationships are major challenges that will require changes in the life science industry IT landscape. As companies expand to emerging regions, they are increasingly finding that existing IT infrastructure is inadequate to do science and conduct business effectively. This shortcoming, while transient, can slow progress at a time when the industry can least afford it. Continuing rapid growth in the generation of data of all kinds is increasingly limited by our ability to digest and extract meaningful insights and is continually complicated by islands of diverse data silos. And finally, the promises of partnering to more efficiently advance pre-competitive research, reduce the overall risk in advancing new drugs to market, and improve patient outcomes over the near term will all require new ways

of sharing data and insights that were historically discouraged, requiring new mindsets and social change as organisations seek to work smarter, faster and more efficiently. While only a single component in broader efforts to advance information management, IT cloud solutions have arrived at a time when they can be effectively leveraged into both short term solutions and long term strategic planning. While taking the jump into IT clouds can be easy, fast, and cheap, it will be important for both senior management and IT administrators to take a step back and reflect on the larger picture to ensure that their efforts are consistent with long term goals and expectations. The life science industry is large, complex, and ripe for opportunity for those companies willing to properly think through their near and long term goals for information management. It is clear that information is, and always has been, key to success and a broader information management strategy that includes IT cloud solutions is likely to be important as both an enabler in the near term and a requirement over the long term.

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M&A in Pharma Expert views they have specific skills that they can tap into which can be better addressed in partnership, for example drug discovery, if they want to do drug discovery then may be partnership is better. But if they want to gain scale and gain size in India, then may be acquisition is better. So it is directed towards the objective.

2. With smaller firms being targeted, where does this leave the big pharma acquisitions that were so rampant not so long ago?

Sujay J Shetty, Associate Director, Pharma Life Sciences , Advisory Corporate Finance, PriceWaterhousecoopers, India

1. From and Indian biotech / pharma companyâ&#x20AC;&#x2122;s point-of-view, what is better, a partnership or an acquisition? It is difficult to answer because it is different for each company. It depends on the strategies and the objectives of the acquirer. If they feel

Both small and large firms are being targeted. If you see in recent days there was lot of talk about Wockhardt, Nicholas Piramal in the press. Talking from an Indian perspective, those are large firms. And in the global level, you have seen some billion dollar mega mergers between Pfizer and Wyeth, Merck and Schering Plough. On the contrary, big firms are equally in demand.

3. With more multinational companies showing interest, the M&A activity in India is expected to go up in the near a product pipeline is being considered seriously and will be an essential factor for the growth of the Indian pharma market. Strategic alliances in terms of co-marketing and co-promotion will be an important issue for those who would like to promote their products in Indian markets. Similarly, partnerships with Indian companies as well as multinationals which are happening at different levels-at equity level, market level, manufacturing level and R&D level-will be very useful for the growth of the pharma market in India.

Joseph Manoj Victor, Senior Research Analyst, Healthcare Practice, Frost & Sullivan, India

1. How important will be strategic alliances and partnerships for the growth of Indian pharmaceutical market? Alliances and partnerships will be very important because of two reasons. 1) The Indian market has already entered into the patent era and 2) Indian companies still have very lean product pipeline as of now. Developing

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2. How do you see the Indian pharma industry in the next five years in terms of innovation as well as partnering with the big pharma? In terms of partnerships, there are very good chances-a number of companies are likely to come to India. India has created that hype-now we can use the word hype. Today every country is looking at India and everybody sees India as a very big opportunity. So partnering with India will definitely happen. In terms of innovation, it will be at

future. What does this mean for the Indian pharma sector? Do you think it was long overdue? I donâ&#x20AC;&#x2122;t think it is long overdue. It is just that now after Daiichi Sankyo bought Ranbaxy a lot of Indian promoters began to think about should we sell or should we hold on. Because if we hold on, it would require a lot of investment and in far away future generics may become increasingly difficult to make money from. It is a big business, but may be if the big pharma enter, the returns may go down. So it is better to sell now when the value is high than later. So one thinking like that has come. In terms of foreign multi-national companies, they also have started thinking last two to three years that India and China are the most attractive markets. And they need to do more to increase the size of their companies here which is actually small. So both from MNCs who want to increase the size in India, and from Indian promoters who may want to cash in, that means that there is a likelihood that the deal may be done.

the co-development level where lot of innovations will take place in collaborations like co-development, co-assistance, co-marketing, co-selling, co-promotion, etc. There is a lot to be done because, still people are worried about taking the responsibility of hiring and training manpower. Everyone would like to get into more innovation partnerships in India and that will happen.

3. Should the Indian pharma companies look at partnering with other Indian companies? Yes. But there is a mindset issue. It is the not issue of economics but the identity which Indian companies try to keep intact. For example, in Indore, we have nearly six or seven companies which are operating in formulations. Each one of them has around 300 to 400 people and is worth not more than Rs. 25 crores. Merged together they will perhaps become a Rs.150 crore company and may not require the 1800 (300 x 6) people. Given the economies of scale that will follow will they be able to come together? The answer is perhaps NO.

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Ganesh Nayak, Executive Director, Zydus Cadila, India

1. With more multinational companies showing interest, the M&A activity in India is expected to go up in the near future. What does this mean for the Indian pharma sector? Do you think it was long overdue?

R B Smarta, Founder and Managing Director, Interlink Marketing Consultancy Pvt. Ltd.

1. Why do you think PPPs are necessary in the current scenario? The global pharmaceutical industry is in the middle of a pipeline crisis. The number of incidences of approved drugs being withdrawn from the market and the molecules from development is increasing. Added to this, the looming loss of revenue from a number of blockbuster drugs going off patent in the next few years has put a lot of pressure on global pharma companies to come up with novel drugs which are safe

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Historically, Indian pharma companies have been founded and managed by owner-entrepeneurs. Consequently, Indian pharma companies are cost-conscious and responsive organisations. The growth trajectory of the Indian pharma companies began with establishment of Indian Patents Act 1970. However, most companies remained essentially domestic players till 1990. Thereafter, the Indian Economy started opening up, and the industry made efforts to integrate with its global counterpart. Increased M&A activity is the consequence. Indian pharma companies have acquired companies abroad and Multinationals have made acquisitions in India. To the Indian pharma companies, this brings an opportunity to play on a much bigger turf, and learn to acquire skills to play on a much wider turf. The acquired organisations will expect to see quantum jump in the volume of activities, since most acquirers would like to leverage the cost advantage to supply to global markets. The

acquirers would have to learn to ‘quickly digest the acquisitions’ and operate in different, challenging and rapidly changing environments.

and can meet regulatory requirements. Indian companies which till recently were not under pressure to innovate too have been forced to go down the challenging path of drug discovery and development thanks to the TRIPS agreement. One way of overcoming these issues is through collaborations and partnerships. Partnerships with both private companies and public funded institutions i.e. PPPs is being seen as an effective strategy to reduce pipeline stress and also keep the spiralling cost of drug discovery and development under control.

knowledge are increasingly being used in today’s drug and diagnostic development. But the expertise for this type of high-end basic research lies with academic research institutes. Scientists in private companies have the ability to apply this basic research into developing novel products and services.

2. What promise does the Public Private Partnership model hold for the industry today? PPP is one of the ways in which industry can tap into the vast knowledge base that has been generated by these institutions in basic sciences. Today it is acknowledged that in order to make effective and safe drugs we need to apply basic biology knowledge to the process of drug development. This knowledge is mainly found in academia and the scientists and researchers from these institutions are well placed to apply this knowledge to the drug discovery and development process. Genomics, Proteomics and Systems Biology

2. With smaller firms being targeted, where does this leave the big pharma acquisitions that were so rampant not so long ago? Large or small, companies are valued for their strategic worth. There has been a healthy debate on ‘sense’ of Big Bang Acquisitions in Pharma Industry for a while. Big Bang acquisitions are difficult to digest. Going forward, wisdom shall prevail. However, as of now, many large pharma companies have made their intent public by announcing that they would stay away from Big acquisitions.

3. From and Indian biotech / pharma company’s point-of-view, what is better, a partnership or an acquisition? Partnering is always a better option from Indian perspective.

3. What are the prerequisites for a successful adoption and use of the Public Private Partnership model? One of the most important prerequisites for a successful PPP is a proper due diligence process in order to confirm the mutual benefits of the cooperation. The objectives of the cooperation have to be clearly communicated between the partners. Both parties should be committed to dedicate time and resources for the project. The project for which the PPP model is being utilised has to be commercially feasible. An effective mechanism has to be agreed upon by the two parties on the commercialisation of IP generated from the partnership. Steps should be taken to maintain confidentiality of the data generated. These steps should be worked out in consultation with both parties and has to be agreed upon before the partnership can take off.

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Lotus Pharmaceuticals Issues New Patent For ControlledRelease Diabetes Drug Lotus Pharmaceuticals, Inc., has announced that its wholly owned subsidiary, En Ze Jia Shi Pharmaceuticals, has been issued a patent for controlled-release of oral gliclazide, which is commonly used to control mild to moderate adult-onset Type 2 diabetes. The patent that covers the composition and preparation methods for the drug through 2030 has been issued by the State Intellectual Property Office of the People's Republic of China. Gliclazide falls under the second generation of sulfonylureas, a class of anti-diabetic drugs that stimulate the pancreas to release more insulin. Chairman and Chief Executive Officer Mr. Zhongyi Liu said that they expect to start clinical trials in 2012 after receiving authorization from the State Food and Drug Administration, with regulatory approval expected in 2014.

Thomas Jefferson to Conduct First Clinical Trial Test on Robot for Prostate Cancer Patients A robot designed by Thomas Jefferson University scientists will be used to place therapeutic radioactive seeds in prostate cancer patients in a first-of-a-kind clinical trial. The study supported by National Cancer Institute, which will enroll 14 patients, was approved by federal Food and Drug Administration to test the device at Thomas Jefferson University Hospital. The robot will provide the steadiest and most precise method possible to implant scores of the seeds

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Clinical Trials

NEWS

in the Shepherd Center - a spinal cord and brain injury rehabilitation hospital in Atlanta, Georgia. It is one of seven potential sites in the US that may enroll patients in the Geron clinical trial. The results of those trials will be presented at as many as seven centers around the country.

World's largest study on use of fast neutron therapy for prostate cancer directly at the site of a cancerous tumor in the prostate gland, eliminating the possibility of human error. The robot, which is controlled by a physician via a hand-held controller and a computer interface, can systemically and accurately place the seeds with its motorised controls and imaging feedback. The robot is capable of reverting to manual needle and seed insertion any time the physician desires.

Landmark Clinical Trial Begins for Stem Cell Therapy The world's first clinical trial for stem cell therapy has begun, which is still in its very early stages and is still a landmark event. The trial was announced by Geron Corporation of California recently. The primary objective of this Phase I study is to assess the safety and tolerability of GRNOPC1 in patients with complete American Spinal Injury Association (ASIA) Impairment Scale grade A thoracic spinal cord injuries. The test will enroll only 10 people who have suffered recent spinal cord injuries. This first patient has been enrolled

Scientists from the Barbara Ann Karmanos Cancer Institute and Wayne State University School of Medicine (WSU SOM) in Detroit will present the world's largest study that shows the long-term results of fast neutron radiotherapy (FNRT) in the treatment of localized prostate cancer. The findings will be formally announced Tuesday, November 2, at the American Society of Therapeutic Radiology and Oncology (ASTRO) Annual Meeting. For the study, researchers analysed the results of multiple clinical trials that were held at Karmanos and WSU SOM from 1992 to 2007. In the study, researchers looked at the effects of FNRT in the treatment of low, intermediate and high-risk prostate cancer cases. Overall survival and biochemical progression-free survival were analysed within risk groups, in groups where post-radiotherapy hormones were used, and by race. They found that treatment of prostate cancer patients with FNRT resulted in excellent long-term overall survival and biochemical progression free survival for all risk groups, with low rates of late GI and GU toxicities. The use of hormone therapy improved overall survival in low and intermediate risk groups, though not in high-risk groups.

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Strategy Aseptic Projectss............................................. 11 Biocult BV......................................................... 17 Bonfiglioli.......................................................... 07 Brevetti Angela................................................. 05 Halides Chemicals Pvt Ltd............................... 09 Health Protection Agency.............................. IBC Pall India Pvt Ltd............................................ IFC Parexel.......................................................... OBC PRTM................................................................ 21 UBM India Pvt Ltd............................................ 35

Company..........................................Page no. Aseptic Projectss.............................................. 11 www.asepticprojectss.com Biocult BV.......................................................... 17 www.sandtcourses.nl Bonfiglioli........................................................... 07 www.bonfigliolipharma.com www.bonfiglioliengineering.com Brevetti Angela.................................................. 05 www.brevettiangela.com Gleneagles........................................................ 27 www.gleneaglescrc.com

Research & Development Aseptic Projectss............................................. 11 Gleneagles....................................................... 27 Health Protection Agency.............................. IBC Morepen Laboratories Ltd............................... 18 PRTM................................................................ 21 Siemens........................................................... 03 Vertis Biotech................................................... 37

Halides Chemicals Pvt Ltd................................ 09 www.halides-pltd.com

Clinical trials Aseptic Projectss............................................. 11 Gleneagles....................................................... 27 Matrix Laboratories.......................................... 33 Parexel.......................................................... OBC

Pall India Pvt Ltd..............................................IFC www.pall.com

Manufacturing Biocult BV......................................................... 17 Bonfiglioli.......................................................... 07 Brevetti Angela................................................. 05 Halides Chemicals Pvt Ltd............................... 09 Health Protection Agency.............................. IBC Morepen Laboratories Ltd............................... 18 Parexel.......................................................... OBC PG Foils Limited............................................... 31 Siemens........................................................... 03 UPM.................................................................. 25 Information Technology Halides Chemicals Pvt Ltd............................... 09 Morepen Laboratories Ltd............................... 18 Trebing & Himstedt Prozessautomation GMBH & Co..................... 19

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Company........................................ Page no.

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ISSUE - 13 2010

Health Protection Agency............................... IBC www.hpa.org.uk Matrix Laboratories........................................... 33 www.matrixlabsindia.com Morepen Laboratories Ltd................................ 18 www.morepen.com

Parexel........................................................... OBC www.parexel.com PG Foils Limited................................................ 31 www.pgfoils.in PRTM................................................................. 21 www.prtm.com Royal Artist........................................................ 32 www.royalartist.com Siemens............................................................ 03 www.siemens.com/pharma Trebing & Himstedt Prozessautomation GMBH & Co...................... 19 www.t-h.de UBM India Pvt Ltd............................................. 35 www.ubm.com UPM................................................................... 25 www.upmraflatac.com Vertis Biotech.................................................... 37 www.vertis-biotech.com

IFC : Inside Front Cover IBC : Inside Back Cover OBC : Outside Back cover

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ISSUE - 13 2010

P h a rm a F o c u s A s i A

ISSUE - 13 2010