tag:blogger.com,1999:blog-7015940731461719102024-02-08T23:50:17.232+05:30Biotechnology ManagementCommercial, Scientific, Legal, and Regulatory Business Models of Biotechnology CompaniesViren Kondehttp://www.blogger.com/profile/18090726614388750732noreply@blogger.comBlogger30125tag:blogger.com,1999:blog-701594073146171910.post-35160369546245943152012-07-04T11:29:00.000+05:302012-07-04T11:29:37.131+05:30Biotechnology Management will always have an edge...<div style="text-align: justify;">
Biotechnology is not just an innovative academic activity, but rather an intense industrial and commercial activity. Indian Biotechnology industry has crossed the 18,000 crores benchmark and its growing strong with almost 20 percent annual growth rate. India is already a World leader in vaccine production, biopharmaceuticals, industrial enzymes and biofuel production, bioremediation, hybrid seeds production, stem cell banking, and micropropogation commercialization, etc. The biotech market is further expected to accelerate in near future on the back of high demand for vaccines, CROs, biopesticides, biofertilizers, and biodiesel in India as well as at the global level. The Indian industry offers low cost, high quality FDA-approved products, diagnostics devices, contract manufacturing, and clinical trials services to the global markets.</div>
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Unfortunately, the supply of scientific knowledge coupled with managerial skills is not meeting the industry demand. The management talent is scarce and is often the weakest pillar in most biotechnology companies. The key to a successful career is to explore the many demanding untraditional career paths outside the routine R&D options, as many companies list the specific management positions. </div>
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This is slowly changing with the availability of biotech-oriented management programs, where the students learn how to develop and manage new ventures along with product commercialization, patenting, business development, and regulatory affairs that influences the biotechnology industry. With the growing interest in the business applications of biotechnology, this is a critical time to understand this multi-disciplinary nature of such post graduate degree program, where the students get a solid grounding in the core business disciplines in emerging bioscience industries.</div>
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The Biotechnology Management programme provides a strong and broad foundation to excel in wide range of career opportunities in the life sciences industry such as biotech business development, biotech marketing and sales, product management, intellectual property management, quality assurance and quality control management, regulatory affairs dossiers management, international business, and human resource management. Major biopharmaceutical companies hiring for such positions are Pfizer India, GlaxoSmithKline, Novartis, Abbott India, Panacea Biotec, Merck BioVentures, Sanofi-Aventis, Bayer Healthcare, Zydus Cadilla, Spinco Biotech, Emcure/Gennova biopharmaceuticals, and Lupin Biotech, etc.</div>Viren Kondehttp://www.blogger.com/profile/18090726614388750732noreply@blogger.com0tag:blogger.com,1999:blog-701594073146171910.post-56020736556238716482011-10-01T09:31:00.001+05:302011-10-01T09:32:22.472+05:30TB diagnostic innovations: Can India take the lead?<div style="text-align: justify;"></div><div class="MsoNormal" style="text-align: justify;"><b style="mso-bidi-font-weight: normal;">TB diagnostic innovations: Can India take the lead?</b></div><div class="MsoNormal" style="text-align: justify;"><br />
</div><div class="MsoNormal" style="text-align: justify;"><b>Guest article by <a href="http://www.medicine.mcgill.ca/epidemiology/pai">Madhukar Pai</a></b></div><div class="MsoNormal" style="text-align: justify;"><br />
</div><div class="MsoNormal" style="text-align: justify;"><span lang="EN-GB">No country has more cases of tuberculosis (TB) than India. </span><span lang="EN" style="color: black;">Research from India played a critical role in the development of the </span><span lang="DE"><a href="http://www.who.int/tb/strategy/en/"><span lang="EN">global strategy to stop TB</span></a></span><span lang="EN" style="color: black;">.</span><span lang="EN-GB">Yet, </span><span lang="EN" style="color: black;">Indian industry and academics have not developed any new tools (diagnostics, drugs or vaccines) for TB. Why has India has failed to innovate in TB R&D? To understand this better, we </span><span lang="DE"><a href="http://www.tbevidence.org/rescentre/presentations/bangalore.htm"><span lang="EN">recently organized a conference</span></a></span>at St. John´s Research Institute (<span lang="DE"><a href="http://www.sjri.res.in/"><span lang="EN-US">SJRI</span></a></span>)in Bangalore, India. For the first time, this meeting brought togetherover 200 representatives from industry, government, donors, academia, civil society and the media to discuss what it takes to innovate in TB diagnostics in India and to move from importation and imitation to innovation.<span lang="EN-GB">The goal was to </span><span lang="DE"><a href="http://www.nature.com/news/2011/110823/full/news.2011.489.html"><span lang="EN-GB">stimulate industry interest and investments in TB innovations</span></a></span><span lang="EN-GB">.</span></div><div class="MsoNormal" style="text-align: justify;"><br />
</div><div class="MsoNormal" style="text-align: justify;"><span lang="EN-GB">Why focus on India? India has already made a big contribution in the area of generic drugs and vaccines, and successes in areas such as information technology and mobile telephony have greatly inspired a burgeoning biotechnology industry. With a strong, growing economy, and a large talent pool, there is great potential for India to contribute to what is called as the “</span><span lang="DE"><a href="http://www.iveybusinessjournal.com/topics/innovation/silicon-valley-to-india-build-an-innovation-ecosystem-and-good-things-will-come"><span lang="EN-US">More (value) for less (cost) for more (people) or MLM innovation</span></a></span><span style="color: black;">,” especially in the area of </span><span lang="DE"><a href="http://www.businessresearch.eiu.com/sites/businessresearch.eiu.com/files/downloads/Healthcare.pdf"><span lang="EN-US">healthcare technologies and delivery innovations</span></a></span><span style="color: black;">.</span></div><div class="MsoNormal" style="text-align: justify;"><br />
</div><div class="MsoNormal" style="text-align: justify;">It is often said that industry interest in TB is low, in part because the disease mostly affects the poor in developing countries. While this is true, should<span lang="DE"><a href="http://www.who.int/tb/publications/global_report/2010/en/index.html"><span lang="EN-US">9.4 million TB cases/year</span></a></span> not translate into a large global market for companies? What exactly is the size and nature of the TB diagnostics market in India and elsewhere?<span lang="DE">A <a href="http://www.tbevidence.org/documents/rescentre/presentations/bangalore/Ajay%20Bakshi%20Business%20case%20-%20FINAL.pdf">preliminary analysis by McKinsey and Company</a> suggested that the TB diagnostics market in India might be in the ballpark of about $100 million, although there was uncertainty surrounding the estimates from the private sector which does not report TB. The Indian TB control program (<a href="http://www.tbcindia.org/">RNTCP</a>) screens over 7.5 million people with suspected active TB every year, and a similar number is likely to seek care in the private sector. Thus, 15 million persons with suspected TB should translate into a fairly sizeable Indian market.<span style="color: black;"> In addition, diagnostics will be needed to diagnose extrapulmonary TB, MDR-TB, childhood TB, and latent TB infection. If a good, </span><a href="http://www.treatmentactiongroup.org/publication.aspx?id=4634">point-of-care test</a><span style="color: black;">were to be developed, it might open the option of intensive and active case finding. Furthermore, if a new test were to be developed on a platform that can be used for other diseases, then this opens new markets beyond TB. Lastly, there is a large potential market outside of India. Clearly, we need a more detailed TB market size analysis to engage both industry and funders.</span></span></div><div class="MsoNormal" style="text-align: justify;"><br />
</div><div class="MsoNormal" style="text-align: justify;">The TB community has done a poor job of articulating its needs. ‘What products should we develop, and if we did develop products who purchase them?’ is a key question that industry representatives asked. A presentation by a <span lang="DE"><a href="http://www.tbevidence.org/documents/rescentre/presentations/bangalore/Sachdeva%20TB%20Diagnostics%20--%20Bangalore.pdf"><span lang="EN-US">senior RNTCP official</span></a></span> provided some clues: What the RNTCP needs most is a new point-of-care test for active TB that is simple, easy, cheap and can be performed with minimal training at primary healthcare level; in addition, the program needs an indigenous, economical, simple, automated (battery operated) or manual molecular test to detect drug resistance that can be done in a peripheral lab with minimal training. This wish list is a great place to start, but will need to be converted into <span lang="DE"><a href="http://healthresearchpolicy.org/blog/2011/sep/16/point-care-diagnostics-tb%E2%80%94-devil%E2%80%99s-details"><span lang="EN-US">clearly defined target product profiles (TPPs) that test developers and funders can aim for</span></a></span>.</div><div class="MsoNormal" style="text-align: justify;"><br />
</div><div class="MsoNormal" style="text-align: justify;">Other <span lang="DE"><a href="http://healthresearchpolicy.org/blog/2011/sep/13/challenges-innovation-tb-diagnostics"><span lang="EN-US">concerns raised by the industry</span></a></span> included: lack of access to Indian sample repositoriesfor test development and validation, and limited funding andR&D facilities for TB;poor regulatory mechanisms to evaluate new tests and assure quality; unclear prequalification processfor TB tests by the World Health Organization; lack of venture capital funding for R&D and lack of celebrity/philanthropic support from within India; lack of awareness about funding opportunities, weak or non-existent collaboration between RNTCP and industry, between industry and clinicians, industry and academia. In addition, there are <span lang="DE"><a href="http://www.iveybusinessjournal.com/topics/innovation/silicon-valley-to-india-build-an-innovation-ecosystem-and-good-things-will-come"><span lang="EN-US">the usual barriers to innovation in India</span></a></span>.</div><div class="MsoNormal" style="text-align: justify;"><br />
</div><div class="MsoNormal" style="text-align: justify;">Companies, especially those not working in TB, want “mentorship” or technical advice on TB, and it is not clear who they can approach for issues specific to TB. When and how should companies engage with agencies such as WHO (globally) and RNTCP (within India) for advice, possible endorsement or evaluation? What is the procedure for companies to access the government market for TB tests? How will the RNTCP decide on which tests to scale-up, and how much is the RNTCP willing to spend?</div><div class="MsoNormal" style="text-align: justify;"><br />
</div><div class="MsoNormal" style="text-align: justify;">As more TB products get developed, it is not clear which agency or organization can conduct head-to-head validation studies to identify the best products for scale-up. More importantly, which agency or organization should take on a “honest broker” role to bring together key stakeholders that make up the complete value chain for TB innovations in India?</div><div class="MsoNormal" style="text-align: justify;"><br />
</div><div class="MsoNormal" style="text-align: justify;">Increased industry involvement and investment in TB R&D is an important goal. While the Bangalore conference was clearly a first step to <span lang="DE"><a href="http://sciencespeaksblog.org/2011/09/26/engaging-indian-industry-in-tb-diagnostic-innovations/"><span lang="EN-US">begin a dialogue among the various stakeholders</span></a></span>,it became clear that a lot more work is needed to address the needs articulated by the industry.Innovations in TB will also require the support of civil society, media, and patient groups which can bring attention to the need for new TB tools, advocating for scale-up of new products that are already available, and advocacy for increased investment in TB R&D. Lastly, if new tools have to be adopted and scaled-up to achieve impact, <span lang="DE"><a href="http://ictph.org.in/blog/nachikets-note/essential-health-system-design-innovation-a-speech-by-dr-nachiket-mor-at-the-tb-diagnostics-conference-in-bangalore-india/"><span lang="EN-US">health system design and delivery innovations</span></a></span> are equally important.</div><div class="MsoNormal" style="text-align: justify;"><br />
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" /><span style="font-size: small;"><span style="color: black; line-height: 115%;"> </span></span></div><div style="text-align: justify;"><span style="font-size: small;"><span style="color: black; line-height: 115%;">Dr Madhukar Pai is a professor</span><span style="color: black; line-height: 115%;"> and TB researcher based at </span><span lang="DE"><a href="http://www.medicine.mcgill.ca/epidemiology/pai"><span lang="EN-US" style="line-height: 115%;">McGill University</span></a></span><span style="color: black; line-height: 115%;">, Montreal, Canada.</span><span style="line-height: 115%;"> He serves as co-chair of the Stop TB Partnership's </span><span lang="DE"><a href="http://www.stoptb.org/wg/new_diagnostics"><span lang="EN-US" style="line-height: 115%;">New Diagnostics Working Group</span></a></span><span style="line-height: 115%;"> (NDWG), and as a consultant to the </span><span lang="DE"><a href="http://www.gatesfoundation.org/Pages/home.aspx"><span lang="EN-US" style="line-height: 115%;">Bill & Melinda Gates Foundation</span></a></span><span style="line-height: 115%;"> (BMGF).</span><span lang="EN-CA" style="color: black; line-height: 115%;"> The views expressed in this article are the <i>author's own</i>and<i>do not</i>necessarily<i>reflect those of NDWG or BMGF. </i>Initially posted on </span><span lang="DE"><a href="http://blogs.plos.org/speakingofmedicine/2011/09/28/diagnosing-tuberculosis-can-india-take-the-lead/"><span lang="EN-CA" style="line-height: 115%;">Speaking of Medicine</span></a></span></span><span lang="EN-CA" style="color: black; font-size: 10pt; line-height: 115%;"></span></div>Viren Kondehttp://www.blogger.com/profile/18090726614388750732noreply@blogger.com0tag:blogger.com,1999:blog-701594073146171910.post-35131857647220904642011-06-11T11:58:00.001+05:302011-06-11T11:58:54.429+05:30TB diagnostics in India: From importation and imitation to innovation (August 25 - 26, 2011, Bangalore, India)<p align="justify"><strong>TB diagnostics in India: From importation and imitation to innovation</strong></p> <ul> <li> <div align="left">August 25 - 26, 2011, Bangalore, India </div> </li> <li> <div align="left">Host : St. John’s Research Institute, Bangalore, India </div> </li> <li> <div align="left">Sponsors : McGill University & Global Health Strategies </div> </li> <li> <div align="left">Technical partners : Bill & Melinda Gates Foundation, Foundation for Innovative New Diagnostics, International Centre for </div> </li> <li> <div align="left">Genetic Engineering and Biotechnology (ICGEB), India & Stop TB Partnership </div> </li> <li> <div align="left">Industry partners : Association of Biotechnology Led Enterprises (ABLE) & Confederation of Indian Industry (CII)</div> </li> <li> <div align="left">Media partners: BioSpectrum Asia, Express Pharma & Express Healthcare</div> </li> </ul> <p align="justify"><strong>Context and rationale </strong></p> <p align="justify">The scale up of DOTS in India is a great public health accomplishment, and yet undiagnosed and poorly managed TB continues to fuel the epidemic. Recognizing these challenges, the Government of India has set an ambitious goal of providing universal access to quality diagnosis and treatment for all TB patients. Innovative tools and delivery systems in both the public and private sectors are critical for reaching this goal. The current in-vitro diagnostics market in India is dominated by imported and generic products, with virtually no innovations. But India has the potential to solve its TB problem with “home-grown” solutions. Just as Indian pharma and biotech companies revolutionized access to high-quality, affordable AIDS drugs and hepatitis vaccines through generic production, Indian diagnostic companies could also become the world’s hub for high-quality generic diagnostics. India also has the potential to lead the world in developing innovative TB diagnostics. For this to happen, Indian industry must move from the import and imitation approach to genuine innovation in both product development as well as delivery. This will require permissive policies, enhanced funding, and greater collaboration between government, donors, researchers and the private industry.</p> <p align="justify"><strong>Content and themes </strong></p> <p align="justify">This conference will convene industry leaders, innovative thinkers, researchers, funders, and policy makers, to stimulate increased industry/biotech engagement in diagnostic innovations that can help TB control in India and elsewhere. Sessions will focus on topics such as market size for TB diagnostics, IVD market analysis and value chain, target product profiles and market needs, frugal innovation and affordable diagnostics, intellectual property issues, regulation of diagnostics, sources of funding, prize models, business models for engaging private sector, scientific obstacles for R&D, barriers to innovation in India, academia-industry relations, and role of emerging economies and BRICS in the next wave of TB innovations. </p> <p align="justify"><strong>Confirmed speakers & panelists </strong></p> <ul> <li> <div align="justify">Anu Acharya, Ocimum Biosolutions, Hyderabad, India </div> </li> <li> <div align="justify">Ramnik Ahuja, Confederation of Indian Industry, India </div> </li> <li> <div align="justify">Tanjore Balganesh, AstraZeneca, Bangalore, India </div> </li> <li> <div align="justify">Steven Buchsbaum, Bill & Melinda Gates Foundation, USA </div> </li> <li> <div align="justify">Sanjeev Chaudhry, SRL, India </div> </li> <li> <div align="justify">Vir S. Chauhan, ICGEB, New Delhi, India </div> </li> <li> <div align="justify">Anand Daniel, Accel Partners, Bangalore, India </div> </li> <li> <div align="justify">Satya Dash, Association of Biotechnology Led Enterprises, India </div> </li> <li> <div align="justify">Dhananjaya Dendukuri, Achira Labs, Bangalore, India</div> </li> <li> <div align="justify">Pradip Desai, Span Diagnostics, Surat, India </div> </li> <li> <div align="justify">Bindu Dey, Department of Biotechnology, New Delhi, India </div> </li> <li> <div align="justify">Puneet Dewan, WHO, SEARO, New Delhi, India </div> </li> <li> <div align="justify">Gopi Gopalakrishnan, World Health Partners, New Delhi, India </div> </li> <li> <div align="justify">Sami Guzder, Avesthagen, Bangalore, India </div> </li> <li> <div align="justify">Rekha Hemrajani, Exelixis Inc. & Omidyar Network, USA </div> </li> <li> <div align="justify">Szymon Jaroslawski, IBAB, Bangalore, India </div> </li> <li> <div align="justify">Nalini Krishnan, REACH, Chennai, India </div> </li> <li> <div align="justify">Rishikesha Krishnan, IIM, Bangalore, India </div> </li> <li> <div align="justify">Ashok Kumar, Central TB Division, DGHS, New Delhi, India </div> </li> <li> <div align="justify">Blessi Kumar, TB/HIV activist and consultant, Delhi, India </div> </li> <li> <div align="justify">BV Ravi Kumar, XCyton Diagnostics, Bangalore, India </div> </li> <li> <div align="justify">Bala S Manian, ReaMetrix, Bangalore, India </div> </li> <li> <div align="justify">Jaykumar Menon, X Prize Foundation, USA </div> </li> <li> <div align="justify">Shirshendu Mukherjee, Wellcome Trust, India </div> </li> <li> <div align="justify">Chandrasekhar Nair, BigTec Labs, Bangalore, India </div> </li> <li> <div align="justify">Anjali Nayyar, Global Health Strategies, India </div> </li> <li> <div align="justify">V Raja, GE Healthcare, Bangalore, India </div> </li> <li> <div align="justify">Viveka Roychowdhury, Express Pharma & Express Healthcare, India </div> </li> <li> <div align="justify">Camilla Rodrigues, Hinduja Hospital, Mumbai, India </div> </li> <li> <div align="justify">Gayatri Saberwal, IBAB, Bangalore, India </div> </li> <li> <div align="justify">Sandeep Sen, Sen Labs, Patna, India </div> </li> <li> <div align="justify">Anand Sivaraman, Remidio, Bangalore, India </div> </li> <li> <div align="justify">Narayanan Suresh, BioSpectrum Asia & Technology Review, India </div> </li> <li> <div align="justify">Peter Small, Bill & Melinda Gates Foundation, USA </div> </li> <li> <div align="justify">Natarajan Sriram, Tulip Group, Goa, India </div> </li> <li> <div align="justify">Soumya Swaminathan, TRC, Chennai </div> </li> <li> <div align="justify">Javid Syed, Treatment Action Group, New York, USA </div> </li> <li> <div align="justify">Jaya Tyagi, AIIMS, New Delhi, India </div> </li> <li> <div align="justify">Brad Tytel, Global Health Strategies, India & New York </div> </li> <li> <div align="justify">Suresh Vazirani, Transasia Biomedicals, Mumbai, India </div> </li> <li> <div align="justify">Suri Venkatachalam, Connexios, Bangalore, India </div> </li> <li> <div align="justify">Gene Walther, Bill & Melinda Gates Foundation, USA </div> </li> </ul> <p align="center"><strong>Space is limited. Industry participants from India will get preference.Registration form available at: <a href="http://www.sjri.res.in">www.sjri.res.in</a></strong></p> <p align="center"><strong>Meeting coordinators</strong></p> <ul> <li> <div align="center">Dr John Kenneth, MD, SJRI, Bangalore [johnkennet@gmail.com]</div> </li> <li> <div align="center">Dr Madhukar Pai, MD, PhD, McGill University, Montreal [madhukar.pai@mcgill.ca]</div> </li> </ul> Viren Kondehttp://www.blogger.com/profile/18090726614388750732noreply@blogger.com0tag:blogger.com,1999:blog-701594073146171910.post-52345243602037556312011-05-20T11:42:00.000+05:302011-05-20T11:42:49.950+05:30Trade Secrets, Biotechnology and India<h2 class="asset-name entry-title"><span style="font-size: small;">Trade Secrets, Biotechnology and India</span></h2><h2 class="asset-name entry-title"><span style="font-size: small;"><span style="font-weight: normal;">These are some of the blog posts on Biotechnology and India that appeared on the Nature Biotechnology's Bioentrepreneur blog, Trade secrets. </span></span></h2><ul><li><h2 class="asset-name entry-title"><span style="font-size: small;"><a href="http://blogs.nature.com/trade_secrets/2011/05/13/the-business-model-of-biotechnology-incubators" rel="bookmark">The Business Model of Biotechnology Incubators</a> </span></h2><h2 class="asset-name entry-title"><span style="font-size: small;">-<a href="http://www.linkedin.com/in/virenkonde" style="font-weight: normal;">Viren Konde</a></span></h2></li>
<li><h2 class="asset-name entry-title"><span style="font-size: small;"><a href="http://blogs.nature.com/trade_secrets/2011/04/25/growing-by-merger" rel="bookmark">Growing By Merger</a> </span></h2><h2 class="asset-name entry-title"><span style="font-size: small; font-weight: normal;">-Anu Acharya (<a href="http://www.linkedin.com/profile/view?id=39880701&locale=en_US&trk=tab_pro">Brady Huggett</a></span><span style="font-size: small;"><span style="font-weight: normal;">)</span></span></h2></li>
<li><h2 class="asset-name entry-title"><span style="font-size: small;"><a href="http://blogs.nature.com/trade_secrets/2011/05/11/reverse-brain-drain-and-the-indian-biotech-niche" rel="bookmark">Reverse brain drain and the Indian biotech "niche"</a></span></h2><h2 class="asset-name entry-title"> <span style="font-size: small; font-weight: normal;">-<a href="http://network.nature.com/profile/UDD2D0BB0">Samuel JK Abraham</a></span></h2></li>
<li><h2 class="asset-name entry-title"><span style="font-size: small;"><a href="http://blogs.nature.com/trade_secrets/2011/04/20/funding-and-biotech-parks" rel="bookmark">Funding and biotech parks</a></span></h2><h2 class="asset-name entry-title"><span style="font-size: small; font-weight: normal;">-<a href="http://www.linkedin.com/in/virenkonde">Viren Konde</a></span><span style="font-size: small;"> </span></h2></li>
<li><h2 class="asset-name entry-title"><span style="font-size: small;"><a href="http://blogs.nature.com/trade_secrets/2011/04/11/registering-a-company-in-india" rel="bookmark">Registering a company in India</a></span></h2><h2 class="asset-name entry-title"><span style="font-size: small; font-weight: normal;">-<a href="http://www.linkedin.com/in/bagali">Prashanth Bagali</a></span><span style="font-size: small;"> </span></h2></li>
<li><h2 class="asset-name entry-title"><span style="font-size: small;"><a href="http://blogs.nature.com/trade_secrets/2011/04/04/financing-know-hows-for-biotech-start-ups-in-india" rel="bookmark">Financing Know-Hows for Biotech Start-ups in India</a></span> </h2><h2 class="asset-name entry-title" style="font-weight: normal;"><span style="font-size: small;"><a href="http://www.linkedin.com/in/virenkonde">-Viren Konde</a></span></h2></li>
<li><h2 class="asset-name entry-title"><span style="font-size: small;"><a href="http://blogs.nature.com/trade_secrets/2011/03/30/tomorrow-is-still-one-day-late" rel="bookmark">Tomorrow is still one day late!</a> </span></h2><h2 class="asset-name entry-title"><span style="font-size: small; font-weight: normal;">-<a href="http://network.nature.com/profile/UDD2D0BB0">Samuel JK Abraham</a></span><span style="font-size: small;"> </span></h2></li>
<li><h2 class="asset-name entry-title"><span style="font-size: small;"><a href="http://blogs.nature.com/trade_secrets/2011/03/08/technology-transfer-in-india" rel="bookmark">Technology Transfer in India</a></span></h2><h2 class="asset-name entry-title" style="font-weight: normal;"><span style="font-size: small;"><a href="http://www.jnu.ac.in/main.asp?sendval=LifeFaculty">- Pramod Yadava</a></span><span style="font-size: small;"> </span></h2><h2 class="asset-name entry-title" style="font-weight: normal;"></h2></li>
</ul><h2 class="asset-name entry-title"><span style="font-weight: normal;"> </span><span style="font-size: small; font-weight: normal;">Please feel free to comment on it!</span></h2><h2 class="asset-name entry-title"><span style="font-size: small;"> </span></h2>Viren Kondehttp://www.blogger.com/profile/18090726614388750732noreply@blogger.com0tag:blogger.com,1999:blog-701594073146171910.post-52805563584421334232011-03-24T17:01:00.003+05:302011-04-12T16:03:29.123+05:30‘Trade Secrets’ a Nature Biotechnology's blog about life science entrepreneurship<div class="separator" style="clear: both; text-align: left;"><a href="http://fastart.nature.com/23034-04/header.gif" imageanchor="1" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img border="0" height="80" src="http://fastart.nature.com/23034-04/header.gif" width="400" /></a></div><div align="justify">To those of you who are interested in discussion on Nature Biotechnology's Bioentrepreneur blog about life science entrepreneurship, get ready for sharing ‘<a href="http://blogs.nature.com/trade_secrets/">Trade Secrets</a>’ in an interactive blogging experience.<br />
<br />
</div><div align="justify">Thanks to the joint efforts of <a href="http://www.nature.com/nbt/about/about_eds/index.html">Brady Huggett</a>, Business Editor of Nature Biotechnology and <a href="http://www.mrcglobal.org/justin_chakma">Justin Chakma</a>, Commercialization and Innovation Consultant at McLaughlin-Rotman Centre for Global Health, University of Toronto for the recent initiative tailored specifically for the core readership of its Bioentrepreneur section.<br />
<br />
</div><div align="justify">The blog is an extension of <em>Nature Biotechnology</em>'s <a href="http://www.nature.com/bioent/index.html">Bioentrepreneur portal</a> and provides a forum for biotechnology's international voices. Contributors hail from India, China, Latin American, North America, Europe and beyond, and their backgrounds span the biotech spectrum. This forum will provide regular insight and commentary from those actually building biotechnology sectors around the globe. We anticipate a lively, global conversation, and we invite aspiring entrepreneurs, investors, students and educators, life science researchers and anyone else with an interest in commercial translation of discoveries to join the dialogue. You'll need to sign up with Nature Network to post comments - it is free to do so.<br />
<br />
</div><div align="justify">Since 1998, <em>Nature Biotechnology</em>'s Bioentrepreneur has been capturing key insights and advice for those directly involved in shaping the innovative biotech sector. In turn, we've passed down this guidance from industry insiders and past entrepreneurs to the new generation of innovators. The result is more than 300 accumulated articles in the <a href="http://www.nature.com/bioent/archive/index.html">Bioentrepreneur archives</a> and the creation of a rich resource - often from notable, primary sources - for those just beginning to make their way in the biotech industry.</div>Viren Kondehttp://www.blogger.com/profile/18090726614388750732noreply@blogger.com0tag:blogger.com,1999:blog-701594073146171910.post-22265878743650536612010-10-01T14:44:00.004+05:302010-10-04T15:01:20.193+05:30Healthcare Biotechnology: A Practical Guide<div style="text-align: justify;"><span style="font-weight: bold;">Healthcare Biotechnology: A Practical Guide</span><br />
<span style="font-style: italic;">By Dimitris Dogramatzis, R.Ph., Ph.D.</span><br />
<br />
<a href="http://cid-d9e4c2e0f6d348ca.office.live.com/self.aspx/.Documents/Healthcare%20Biotechnology%20by%20Dogramatzis%20-%20Use%20as%20Textbook.pdf">In Classroom: Use as a Textbook Tool </a><br />
<br />
<span style="font-weight: bold;">Author Biography</span><br />
<br />
<span id="authorBiographyId">Dr. Dimitris Dogramatzis was born in Greece in 1962. After earning a Bachelor's diploma in Pharmacy from the University of Patras in Greece, he spent the next seven years in Texas studying and working for the University of Texas system. During this period, he completed his Ph.D. in Pharmacology and Toxicology at the University of Texas Medical Branch at Galveston. Later he went on to complete two successive postdoctoral trainings at the University of Texas Medical Branch at Galveston, as well as at the M.D. Anderson Cancer Center at Houston, Texas. He is currently the owner of a retail pharmacy in Athens, a business consultant, and a writer.</span><br />
<br />
<span style="font-weight: bold;">Specifications</span><br />
<br />
Price: $99.95, Binding/Format: eBook, ISBN: 978-1-4398474-7-3, Publish Date: December 6th 2010, Imprint: CRC Press, Pages: 768 pages<br />
<br />
<span style="font-weight: bold;">Features</span><br />
<br />
<div style="text-align: left;">* Provides end-of-chapter problems and appropriate essays for each subject covered<br />
* Offers a practical step-by-step guide for both graduate students and industry professionals<br />
* Offers many illustrations, including over 350 tables and figures<br />
* Contains extensive references at the end of each chapter as well as three appendices to enhance further study</div><br />
<span style="font-weight: bold;">Summary</span><br />
<br />
A first of its kind to focus on the management of health-care related biotechnology, this text is a resourceful practical guide that assists all healthcare related biotech professionals in their day-to-day activities. The book contains chapters on bioeconomy, biolicensing, biofinance, biopartnering, biodrug research, biomarketing planning, biopromotion, product life cycle management, and biobusiness models, among others. Written by a well-established professional and registered pharmacist, this reference is appropriate for graduate students and industry professionals. It contains over 350 tables and figures and end-of-section problems accompany each chapter. There are also extensive references following each chapter to enhance further study.<br />
<br />
<span style="font-weight: bold;">Websites</span><br />
<br />
http://www.crcpress.com/product/isbn/9781439847466<br />
http://www.routledge.com/books/details/9781439847473/<br />
http://www.taylorandfrancis.com/books/details/9781574911183/<br />
http://www.amazon.com/Dimitris-Dogramatzis/e/B001K8K4V6/ref=ntt_athr_dp_pel_pop_1<br />
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</div>Viren Kondehttp://www.blogger.com/profile/18090726614388750732noreply@blogger.com0tag:blogger.com,1999:blog-701594073146171910.post-88941728134959960522009-11-18T11:34:00.003+05:302009-11-25T15:05:03.624+05:30Book Review: Biopreneurs - The Molecular Millionaires<div style="text-align: justify;"><span style="font-weight: bold; font-style: italic;">Book Review</span><br /><br /><span style="font-weight: bold;">Biopreneurs: The Molecular Millionaires</span><br /><br />Ryan Baidya, PhD, MBA & Miyuki Shiratani, MBA California Takshila University Press, Santa Clara, CA, USA<br /><br />Soft Cover, 280 Pages, 70 color images, tables and illustrations, US $35.50 First Edition, 2008, ISBN-10: 0-9822001-0-2, ISBN-13: 978-0-9822001-1-7<br /><br />Bhaidya and Shiratani have attempted to interpret the diverse nature biotechnology industry and its relation with entrepreneurship by co-authoring a biotechnology guide mostly intended for venture capitalists, other investors, biotech executives and scientists with the special emphasis on how and why to invest in start-up and early-stage ventures. This book is based on the Bio-MBA lectures, invited seminar series organized by Japan’s External Trade Organization (JETRO) and hands-on experience by the authors in developing biotech businesses from academic to industry. The book is written keeping in mind the novice readers with or without the background in biotechnology or life sciences, thus keeping aside the dry hard facts of life science subjects and financial figures of the stock market.<br /><br />The book contains 15 chapters divided into three broad areas which cover biotech entrepreneurship development, biotech drug development, and biotech business development (marketing, funding and valuation) along with four supplements of drug development section, attempting to address a quick-fix for the potential investors. The approach taken by the authors is not to describe specific companies (case studies) or specific industry sectors (value chain) but rather to discuss broader areas of entrepreneurship paths in biotechnology.<br /><br />The book begins by explaining the basics of entrepreneurship in biotechnology by taking the readers through the traits of researchers and biopreneurs, to lessons to learn, and Dos and Don’ts (paths to success) as well. The chapters on biotech drug development provide in-depth analysis of pre-clinical and clinical development citing numerous figures and tables from the authors’ personal research and experience. The business of biotechnology section includes chapters on business plan, role of marketing, funding, fund raising and valuation for bio-ventures. The chapter on beginning a bioventure is a summarized version whereas; a larger section has been devoted to chapters on financing, investment and valuation which are explained in great detail (from idea to IPO and beyond). The role of marketing have been mostly concentrated on the differential strategy rather than on segmentation, targeting and positioning of biotech products.<br /><br />In summary, this book reveals a lot of imagination that has gone into developing biotech companies, which is regarded as important. For those contemplating to set up a bioventure, there are lots of ideas that would be helpful for the first-time investors of bio-enterprises. Although, the authors have touched some of the important aspects of the science and business development, they did not really explain the implications of it. The book would have been still better, firstly, by including some relevant case studies in bio-entrepreneurship development, thus providing historical adventures by the early entrepreneurs and their bio-ventures. Secondly, the role of intellectual property, technology transfer and regulation of biotech products (drugs and diagnostics) in starting and managing biotech ventures would have been a great starter information for the students as well as potential investors of this industry. The audience for such a book is most definitely investors new to the biotech sector, to understand the underlying drivers and students enrolled for enterprise education, and unfamiliar to this sector.<br /><br /><span style="font-style: italic;">"If you would like to get a copy, use the code </span><span style="font-weight: bold; font-style: italic;">84710</span><span style="font-style: italic;"> on the website www.ctuniv.org/affiliate.htm for your 10% discount. You will be termed an Affiliate and you can enter the code after you enter your credit card information to get your discount."</span><br /><br /></div>Viren Kondehttp://www.blogger.com/profile/18090726614388750732noreply@blogger.com0tag:blogger.com,1999:blog-701594073146171910.post-72323514424980285632009-03-04T11:19:00.004+05:302009-04-18T18:04:10.725+05:30Licensing in the Business of Biotechnology<div style="TEXT-ALIGN: justify">Business-wise, the biotechnology industry is divided into companies that create tools and technologies and companies that develop and commercialize products using these tools and technologies. The success of biotechnology companies largely depends on their licensing ability to transfer intellectual property rights of the tools or technologies for an appropriate value in either the consolidation agreements or partnering relationships. A license in biotechnology often arises in joint ventures and collaboration arrangements, while its value is determined by the rights granted by it. Considering the estimated costs of $1.2 billion to bring a drug to market, the licensing agreement remains the bridge between the companies to succeed with mutual benefit. Biotechnology companies at all stages of growth need capital and a robust product pipeline. As part of the survival strategy, the smaller biotechnology companies often provide a technology platform necessary for larger pharmaceutical companies to supplement their late-stage product pipeline. The innovations in the genomics-based drug discovery, target validation, diagnostics/ screening technologies have introduced numerous such licensing agreements between the larger-but-poor-pipeline and smaller-fund-deficient-but-innovative-technology companies in the biotechnology sector. To assess the potential value of the licensed technology or products, due diligence analysis becomes the most critical step of all licensing transactions while managing the IP portfolio of the companies. In biotechnology licensing agreements, the licensor and the licensee needs to include issues like the rights to make or sell, co-develop, manufacture, supply, transfer know-how, manufacturing know-how, sublicense to third-parties, IP rights, rights to second-generation products retained by the licensor and/or acquired by the licensee, and the access to the licensee's drug applications, etc.<br /><br />Patent license agreements can be divided into in-licenses and out-licenses. In-licensing refers to agreements by which a party acquires the rights to use a patent, whereas out-licensing refers to agreements in which a patent holder grants a third party the right to use a patent. In biotechnology, in-licensing is important for large pharmaceutical companies to develop new or improved products. Because in-licensing is a way to avoid expensive and time-consuming research and development, such companies are committed to in-licensing development compounds. Companies often find it necessary to develop biotechnology products for which patented enabling technology exists (e.g., patented genetic engineering techniques). And, out-licensing is useful when a company is unable to commercially export technology. It allows a licensee to perform basic research and development during the risky development stage. Patented starting materials and processes can be out-licensed to maximize the value of technology, even by licensing basic enabling technology to multiple users. Applications of the same patented core technology are also divisible by out-licensing; e.g., by diagnostic and therapeutic market (field-of-use restrictions). This provides multiple royalty incomes from single-core technology. It is also possible to extract multiple royalties by out-licensing a single biotechnology product. Patent rights to a gene can be licensed to a number of companies. Those rights may include, for example, manufacturing a specific protein from the gene, developing diagnostics and/or therapeutics using the gene, and developing a gene-specific delivery system.<br /><br />IP transfer agreements can be further categorized into confidentiality agreements, material transfer agreements, de¬velopment (the licensee assumes all responsibility for further development), co-development agreements (two parties collaborate on continued development), and distribution agreements. In confidentiality or nondisclosure agreements, the development of a drug candidate involves the use of confidential informa¬tion such as source, research findings, methods of production, technology used, and business in¬formation and thus all informa¬tion need to be protected. The materials transfer agreements are made when a licensor provides the drug samples or information pertaining to it to a potential licensee who wants to evaluate a new product or process. Even after acquiring new IP from a public institution, it is not always possible or feasible for a single private company to carry out all stages of production and marketing. The company may need to collaborate with others in order to complete prod¬uct evaluation (preclinical toxicity tests, clinical trials, and so on). Besides, high-quality, good manu¬facturing practice (GMP) production facilities are needed to develop products for the mar¬ket. The licensee can either pay other agencies to perform some of the tasks or collaborate on mutual beneficial licensing terms with them. In return, the partnering company may request a share of the IP rights or a portion of the revenue generated by product sales. Technology licensing agreements allow one company to use the proprietary materials or know-how of others. Such an agreement clearly defines the validity of the license, the kind of license (ex¬clusive or nonexclusive), the territory in which the license is valid, the market in which the product will be released (public sector or open market), whether or not the product can be sublicensed, the amount of money to be paid up front, and the royalties that the licensor will receive. The territory is the geo¬graphic region in which the licensee is permitted to sell the product. Sometimes, nonexclusive licenses are awarded to licensees in order to promote competition between them. Or an exclusive license may be granted to market an expensive product within a limited market—un¬less such market exclusivity is guaranteed, no one may be willing to manufacture it. The guiding principle for deciding whether to grant exclusive licenses of nonexclusive licenses should be that while it is most important to bring new products to market at affordable prices. Health-related products can lead to liabilities; especially susceptible products, such as vaccines, are tested on healthy volunteers. Often, compa¬nies are unwilling to market a product because of potential liabilities. The licensing agreement for a health-related technology must define the cases in which the investigators will, and will not, be held responsible (for example, such cases might involve bad or inferior product, improper storage and use, administration of the wrong dosage) and the licensee must take out an appropriate amount of insurance before starting trials. The clinical tri¬al agreement should also describe how, and how much, an individual who is harmed by a health product should be compensated.<br /><br />Generally, the licensing payments are determined by the type of the technology, patent portfolio, drug regulations, stage of development, market size, and exclusivity (exclusive, sole, or nonexclusive and/or restricted by field of use, territory or time), etc. The licensing fee includes signing-up fees or up-front payments, milestone payments and royalties. The signing fees allow a licensor to compensate money spent on developing technology or drug delivery platform. These fees are usually modest for basic or undeveloped technology and nonexclusive licensing. Many biotechnology inventions require substantial development or must be combined with other technologies to create a product (e.g. delivery devices). Therefore, a common strategy is to keep the signing fee modest but allow other fees to increase as the technology becomes more promising. Milestone or benchmark payments are used to compensate the licensor when an invention demonstrates value that was not yet proven at the time of licensing. Milestone payments are tied to such contingencies as filing an investigational new drug application (IND) and beginning phase I, II, and III clinical trials as well as to stages that indicate a potential for success —such as when filing a new drug or product license application (NDA or PLA) or receiving approval to market. They can offset non-reimbursed costs that remain with the license and are usually back-end loaded. Milestone payments are critical revenue generators and are likely to be high for early-stage molecules and more for later-stage molecules. It is extremely difficult to estimate royalty rates for biotechnology inventions because the final product is often unknown at the time of licensing. In general, a therapeutic compound carries a higher royalty than a research tool such as a screening assay. Royalty payments are only made as a percentage of net sales of the therapeutic or technology to develop the molecules.<br /><br />For example, a company can acquire a product for a modest up-front fee, conduct preliminary tests till phase 2 trials for the target indication, and reach an attractive financial position rapidly and relatively inexpensively. Reaching this stage costs more, and takes longer, for a startup. Nevertheless, building organizations is something that venture capitalists are good at, making it a fairly low-risk activity. Although the cost of any component can be debated, it is clear that in-licensing is a cheaper, faster way to start a biopharmaceutical company than building one around a new technology and venture capitalists too favor certain business model over others when evaluating new plans. Thus, licensing becomes an inherent part in the business model of biotechnology companies to achieve near-term or long-term strategic goals. This issue is more relevant from the perspectives of developing countries that either do not have expertise to deal with such complex IP licensing issues or the government officials are ignorant and/or lack expertise which discourages private companies that might be interested in collaborations. To make any comments or suggestions, please write to virenkonde at gmail dot com. Thanks!<br />----------------------------------------------------------<pr>---------------------<br />Healthcare <a href="http://www.unifirst.com/">Uniforms</a> - To enhance your business image!<br /><br /></pr></div>Viren Kondehttp://www.blogger.com/profile/18090726614388750732noreply@blogger.com0tag:blogger.com,1999:blog-701594073146171910.post-85186600448941038462009-02-20T10:42:00.002+05:302009-02-20T10:45:39.240+05:30The Art & Science of Valuation in the Biotechnology Marketplace<div style="text-align: justify;">A company’s value lies in its potential to generate a stream of profits in the future and it is the criteria that matters most to the investors. Almost all valuation exercises are thus based on assumptions or educated guesses as to what a company’s future would be down the line meaning what important milestones to be achieved and what timely strategic decisions to be taken. These assumptions are grounded by three fundamental factors: first, the state of the market targeted by the company; second, the principle elements of a company’s science and technology; and third, the ability of management to deliver on the business plan.<br /><br />Valuation is essential for the most crucial steps of a biotechnology company. The value of biotechnology companies is driven by anticipated future product and revenue streams, or by the impact that a technology platform is expected to have on the value of assets. The amount of money at stake justifies and requires a careful and thorough valuation. Biotechnology companies face the need for valuation at various stages: fund raising, license contracts, initial public offerings, and mergers and acquisitions. Quantitative financial evaluation of biotechnology investments is not an easy task. Biotechnology companies are typically dealing with innovative yet uncertain technologies and drug development candidates. The applications and the impact of a technology are often not clearly defined, and new drug development targets are not validated. However, financial evaluation and risk analysis are essential for investors as financial indicators and definite value propositions to fund biotechnology operations, and to the senior management of biotechnology companies needs to understand the risk and expected financial impact of their projects for prioritization and maximization of company value and while establishing technology partnerships and licensing agreements, the involved parties need to understand the financial value generated by a deal, and to ensure market-conformity and fair deal terms. The determinants of value in the biotechnology industry are expected cash inflows from marketed assets, R&D and market uncertainty, cost and speed of development, and strategic opportunities arising from technologies and projects.<br /><br />Although, a company can have as many values as the number of different people evaluating it, every valuation starts with a systematic and rigorous testing of a company’s artistic hypotheses such as economic, technological and managerial abilities in combination with the following three scientific approaches:<br /><br /><span style="font-weight: bold;">Discounted Cash Flow or Net Present Value</span><br /><br />The most common approach to primary valuation is the discounted cash flow (DCF) method, whereby a company is valued at the present value of the future cash flows it will be able to generate. The same approach is also called as net present value (NPV), or risk-adjusted net present value (rNPV) or expected net present value (eNPV). The idea underlying this method is to compare revenues and costs. If income exceeds expenses, then the project is profitable and the company should start or continue the project. But if, different cash flows do not occur at the same time or have the same likelihood, then adjust the cash flows for their time difference by discounting them and for their likelihood by multiplying with their probability to occur.<br /><br />These methods are conceptually robust but can prove difficult to implement in high uncertainty environments, such as those of early-stage biotechnology firms. Typical problems include highly uncertain and distant positive cash flows, a business model based on many assumptions and a difficult risk profile of the company. Therefore, in principle, what is needed is to estimate the expected future cash flows of the business and to discount back to the present all these future cash flows, using a discount rate consistent with the level of risk in the project. In practical terms, there are some difficulties in implementing this approach as to projecting performance for several years into the future is a process considered as too speculative to be useful, then selecting a forecast for the future cash flows is purely arbitrary and questions the residual value of the business at the end of it, and obtaining an appropriate discount rate for an early-stage, privately held company presents difficulties too.<br /><br /><span style="font-weight: bold;">Comparable market data valuation</span><br /><br />The comparable method is also known as a ‘secondary’ valuation method because it uses the market value of comparable companies or transactions as reference points. The method relies on available key figures, such as earnings, sales, number of employees, and R&D expenditures, etc to estimate value. In a sense, secondary valuation makes the assumption that these comparable companies have been properly valued, and can serve as benchmarks when assessing a company.<br /><br />A comparable valuation for a biotechnology company of interest is based upon a financial investment into a comparable company. Based on the information, the ratios such as price/revenue, price/employee and price/R&D can be calculated and used to estimate the value of the company of interest. These ratios are used because they have a direct or indirect impact on the valuation. It makes more sense to use earnings or cash flows as the ultimate basis of comparisons across firms. Unfortunately, most early-stage companies, as development entities, tend to burn more cash than they generate, and usually have negative earnings as well. Comparing losses or cash burns would obviously lead to speculative valuations. The amount spent on R&D, the number of employees for a company and the level of revenues that can be generated are seen as better indicators of future performance.<br /><br /><span style="font-weight: bold;">Real Options Pricing Model</span><br /><br />Real options valuation is primarily based on the investments and financial options. An option is the right but not the obligation to buy or sell an asset at a prefixed price until a certain expiry date. Some investments can be modeled as options. For example, a company with Phase III trial compounds, where the results are expected in 30 months. If the results are positive, the company has the option to file a new drug application (NDA) and then launch the product. However, the company will do so only if the expected sales exceed the costs necessary to bring the drug to market. The costs of clinical Phase III correspond to the purchase of this option. Equally, with the costs of clinical Phase II the company buys the option to acquire the above-mentioned option after a successful trial. The investment for clinical Phase I is then the price for an option on an option on an option. In finance, these options on options are called iterated compound options, nested options or multi-stage options. The companies exercise the options only if the necessary investments (the costs of the subsequent phase or the launch costs) are less than the value the company gets in return. The launch costs are the option fee to launch the drug. In return, the company gets the sales revenues of the drug.<br /><br />“Price is what you pay. Value is what you get.” -- Warren Buffett<br /><br /></div>Viren Kondehttp://www.blogger.com/profile/18090726614388750732noreply@blogger.com0tag:blogger.com,1999:blog-701594073146171910.post-64472587993865357522009-02-14T14:07:00.006+05:302009-03-02T10:23:52.515+05:30Consolidation Strategies of the Biotechnology Companies<div style="text-align: justify;">In the current market, the biotechnology industry is undergoing a period of dramatic change, a change that necessitates the creation of new business models. Consolidations are on the rise and it might be a solution to many of biotechnology’s problems. Therefore, the question, what drives mergers and acquisitions (M&A) in the biotechnology industry needs to be answered.<br /><br />Biotechnology mergers and acquisitions can help the industry’s fully integrated players to increase in size and market value, boost the emerging companies’ efforts to reach full integration or allow the start-ups to survive cyclical financial crises. M&A in the biotechnology sector (including inter-sector deals between the pharmaceutical and biotechnology companies or intra-sector deals within the biotechnology sectors) serves three main purposes, where one company acquires another in order to increase pipeline productivity and innovation or aid the transition to become full integrated biopharmaceutical company (FIBCO) or a company merges equally with another to support product development, market expansion or sustainable profitability.<br /><br />The dramatic situation has brought down valuations and dried up access to financing, for many biotechnology companies. However, for the leading pharmaceutical and biopharmaceutical companies that still have access to capital; the ongoing crisis is an opportunity to acquire valuable additions to their own product portfolios and technological base. Subsequently, as the industry under pressure needs to demonstrate sustained profitability and increased shareholder’s value; the acquiring process becomes eminent to boost its specialization. These deals are either within the same sector from which the acquirer increases its product pipeline or technological capabilities within a niche market or the deals in which the acquirer adds a new business unit to its supply chain, thus enhancing its internal capabilities, or in order to achieve diversification (which would be difficult during a crisis period), the acquirer gains a new business outside its current portfolio.<br /><br /><span style="font-weight: bold;">Pharma-Biotech Consolidations</span> <span style="font-style: italic;">(Transactions: mostly acquisitions)</span><br /><br />While the leading pharma or biotechnology sectors have managed to maintain stable growth performance, the consolidations have been unavoidable as a means to accelerate productivity and revenue growth, identify profitable areas and attend global focus. The deals mostly comprise of licensing agreements or joint ventures in the first place. Direct acquisition is usually considered at a later stage, as experts believe, that might affect the R&D productivity of the innovative company. Usually the drivers for the licensing agreements or mergers are in the first place. In many cases, successful acquisition of the target company occurs with the companies in alliances, in such a way that productivity is left intact. While the major pharma players acquire significant research knowledge or attractive product pipelines they also allow the biotechnology player to grow its talent and unique business independently to maintain the higher productivity of this sector. The fully integrated companies acquire emerging mid-size biotechnology companies that carry strong research and drug development capabilities but that are not able to market their own products.<br /><br />In short, the strategic rationale for the pharma-biotech consolidation is to i) Strengthen product pipeline through acquisition, ii) Strengthen technology platform, and iii) Target company’s’ features should include products with clinical proof of concept, strong intellectual property capabilities and good value for money.<br /><br /><span style="font-weight: bold;">Biotech-Biotech Consolidations</span> <span style="font-style: italic;">(Transactions: mostly mergers)</span><br /><br />Regardless of innovative companies’ characteristics, to maintain sustained profitability and to protect shareholder’s value in the highly competitive environments, the emerging biotechnology companies need to increase in size and reach, which includes both revenue and asset growth, and that fuels the merger activities among themselves. A consolidation within the emerging sector brings the firms closer to full integration and potentially to sustainable profitability. The goal is to expand the technological reach of a company’s product portfolio, thereby lowering the level of risk resulting from operating in a small number of markets. Despite coming closer to sustainable profitability in the long term, the emerging sector is likely to face significant challenges related to manufacturing or regulatory complexities. However, the demand for bio-services sector in the hard financial times and subsequent consolidations might become a cure for the declining market values.<br /><br />In short, the strategic rationale for the biotech-biotech consolidation is to i) Build critical mass and increase value, ii) Achieve reasonable degree of integration along value chain, iii) Resolve financing issues, iv) Resolve capability issues, and v) Create exit opportunities.<br /><br />In conclusion, the consolidation wave hits all the players that are unable to secure either enough funding to grow their technological platforms or expand their customer base. However, it would also be interesting to know if some types of alliances make more value than others, for example multiple target or product deals with a single biotechnology company vs. smaller alliance deals with several companies.<br /><br /><br /></div>Viren Kondehttp://www.blogger.com/profile/18090726614388750732noreply@blogger.com0tag:blogger.com,1999:blog-701594073146171910.post-15624759282728841952009-02-10T19:04:00.004+05:302009-02-14T14:12:56.122+05:30Strategic Financing Models of the Biotechnology Companies<div style="text-align: justify; color: rgb(0, 0, 0);"><span style="font-style: italic;">“Life science startups are the only companies that are forced to define their corporate strategy as a function of their financing rather than to gather financing in accordance to a previously well-defined corporate strategy.” -Steven G. Burrill, Annual Report on the Life Science Industry</span><br /><br />Besides having the essential elements like innovative science, solid management team, strong intellectual property and ingenious marketing strategies, the success of any biotechnology company largely depends on how the strategic financial models are structured into the business plan. After all, questions pop-up like, who are these financing sources; how much do they give; how much do they take; when and how to approach them; and the current trends in financing biotechnology firms. A thorough knowledge of all financing opportunities is critical to succeed in the biotechnology business.<br /><br /><span style="font-style: italic;">This write-up is also to encourage readers to add examples in each category of the financing partners for the biotechnology industry, without which it’s incomplete to conclude. Comments or suggestions to virenkonde at gmail dot com. Thanks!</span><br /><br />1. <span style="font-weight: bold;">Venture Philanthropists</span> are a network of wealthy individuals or not-for-profit foundations which provide non-dilutive initial capital along with mentorship, disease knowledge, patient access and an understanding of the end market that few traditional VCs can offer. <span style="font-weight: bold;">Government</span> provides small amount of non-dilutive grants, while research is still in the laboratory. <span style="font-weight: bold;">Technology Transfer Offices</span> are part of the academic institutes which provides small amount of non-dilutive seed capital along with help in the IP processes such as out-licensing deals of technology or a lead molecule. Although, these funding sources are available at an early stage of drug development, they are not always efficient.<br /><br /><span style="font-style: italic;">Do you know of any wealthy individuals, non-profit foundations, government grants or licensing deals out of the university spin-offs that have contributed to the growth of life sciences-based industries?</span><br /><br />2. <span style="font-weight: bold;">Angel Investors</span> are wealthy individuals or groups usually from industry itself interested in high returns on investments. They provide small to medium capital with mentorship, creditability, and network of contacts. However, they are assembled into a closed circle and sometimes hard to reach. A typical Angel Investor will demand a larger share of the company as they are interested in the company’s management activities. However, you might actually benefit from their experience and advice. Most angel investors are in for a single round of investments and they aren't repetitive investors.<br /><br /><span style="font-style: italic;">Do you know of any angel investors or their associations that have contributed to the growth of life sciences-based industries?</span><br /><br />3. <span style="font-weight: bold;">Venture Capitalists</span> are investors with mostly industry background which also demand a fair amount of control over your operations and decision-making. However, they also rally around the business, helping with management, promoting it and providing contacts, and to protect their investment. Most VCs usually commit for two or more rounds but may expect a greater return on investments as a result. They provide management expertise and creditability; however they only finance 1:100 opportunities and seek early exit. The success of both the angel and VC investor is their ability to gain liquidity via a timely exit either through an IPO or the company being sold.<br /><br /><span style="font-weight: bold;">Stages of Venture Capital Financing</span><br /><br /><span style="font-weight: bold;">Early Stage or Seed Funding</span> usually knocks on the door when the company holds innovative project combined with a compelling business plan (and maybe an angel on board). Clinical discovery stage with strong IP is certainly a good start.<br /><br /><span style="font-weight: bold;">Start-up or Round I Funding</span> comes with demonstrated efficiency by the business-driven strong management team which has contributed towards significant progress since the inception of the company. This stage is indicated by the path from discovery to lead optimization or rise of the first molecules from a technology platform.<br /><br /><span style="font-weight: bold;">Expansion or Round II Funding</span> is for the demonstrated significant milestone achievements that are close to generating revenues (out-licensing, partnering, etc.). For example where new drug IND is filed and ready to go to clinical trials or it is already in Phase I clinical trials.<br /><br /><span style="font-weight: bold;">Mezzanine or Round III</span> Funding is similarly for the demonstrated excellent milestone achievements with completed some strategic alliances with a clear exit strategy. For example a couple of pre-IND, IND and Phase I/II compounds and company is close to acquisition or IPO.<br /><br /><span style="font-weight: bold;">Bridge Loans</span> provide some cash before an IPO (in advance of about 6-12 months).<br /><br /><span style="font-style: italic;">Do you know of any VC investors or their associations that have contributed to the growth of life sciences-based industries?</span><br /><br />4. Although equity is the main source of sustenance for biotechnology companies, <span style="font-weight: bold;">Venture Debt Financing</span> is a layer of capital that is becoming increasingly important. Securing loans early on can ease financial worries down the road for biotechnology startups. For example, equipment financing is the practice of using a firm's equipment as collateral to receive cash. Biotechnology companies can benefit greatly by using their equipment to secure debt financing. It gives them an extended cash runway and more time to negotiate their next equity round. Cash is king at every stage of growth for a life science company, and it is the fuel that drives the development of products in the pipeline.<br /><br />Venture Leasing provides financing in return for equipment lease payments, whereas Venture Lending is an alternative to traditional lending from financing institutions. The main purpose is to enhance existing funding round with no equity dilution, it acts a bridge between financial rounds which contribute towards financial “buffer” and credibility. Thus, venture debt financing can extend cash runaway without eating-up equity.<br /><br />Venture debt is available at every stage of the company’s growth. Venture leasing is available for start-ups that are VC-backed and needs money to buy large assets. Lease payments are made on the fixed assets as collateral. Venture lending is a available for large companies that are close to raising capital, with strong management team and support of the investors with variable and fixed asset (IP, receivables, etc.) as collateral.<br /><br />5. Investors offering cash in exchange for the license royalty payments are categorized under <span style="font-weight: bold;">Royalty Financing</span>. These investors also fund future research, product development, product acquisitions, and product launch costs which minimizes dilution. The transactions can also be customized by delaying out-licensing deals and diversifying the risk.<br /><br />6. Funding a Public Company comprises of Initial Public Offering (IPO), Private Investments in Public Equities (PIPE) and Follow-On Public Offering (FOPO) entities.<br /><br />Initial Public Offering (<span style="font-weight: bold;">IPO</span>) is a regulated process by which a public company issues public shares for the first time in the market. This helps provide capital or an alternative to acquisition or reimbursement of venture debt for the company. Major shareholders control the company, however it is very sensitive to market conditions as stock prices are very milestone sensitive and affected by n number of factors. It is a combination of factors that makes a stronger and successful IPO in the biotechnology industry. The factors that indicate the strength of an IPO are Market timings, Company credentials, Management team and its track record, Prior investors and amount of investment prior to IPO, Quality of underwriters, Stage of product development (outstanding phase III data, good phase II results and persistent phase I compounds), and Deals with Major pharma companies (a licensing deal is good and a licensing deal with an equity investment is still better).<br /><br /><span style="font-style: italic;">Do you know of any company in the biotechnology industry that has gone public recently?</span><br /><br />Private Investments in Public Equities (<span style="font-weight: bold;">PIPE</span>) are a small group of investors buying common shares of a public company at a discounted price. This provides capital although it is not a lengthy process like IPO or FOPO as it can be done quickly by Investment Banks and it is not very market sensitive. However a large amount of securities are being offered to a limited number of investors that might want to play an active role in the company.<br /><br />Follow-On Public Offering (<span style="font-weight: bold;">FOPO</span>) is an offering of shares to the public after the company has already gone through an IPO. This provides capital, however it can be interpreted as a “red flag” indicating that the company is strapped for cash.<br /><br />7. <span style="font-weight: bold;">Strategic Alliances</span> such as Mergers & Acquisitions (M&A), Licensing Agreements, Partnerships or Collaborations etc. are the variation of different deals in order to in-license or out-license, co-develop or co-market products. This provides capital, products, access to expertise (contract research and manufacturing services, sales, and marketing, etc.) however it requires planning, vision and a detailed strategic approach.<br /><br /><span style="font-style: italic;">Do you know of any strategic alliances that have occurred in the life sciences sector recently?</span><br /><br /></div>Viren Kondehttp://www.blogger.com/profile/18090726614388750732noreply@blogger.com0tag:blogger.com,1999:blog-701594073146171910.post-13395731944687834492009-02-10T18:58:00.005+05:302009-02-11T10:50:30.878+05:30Indian Bio-Scenario in the Current Economic Meltdown (Q408-Q109) - Part III<div style="text-align: justify;">The analysis of Indian Bio-Scenario in the current economic downturn is based on the opinion of industry experts, analysts, and market news and it is divided into three parts. <a href="http://biotechmanage.blogspot.com/2009/02/indian-bio-scenario-in-current-economic.html">Part I discusses about the current investment trends in the Indian biotechnology sector</a>; <a href="http://biotechmanage.blogspot.com/2009/02/indian-bio-scenario-in-current-economic_10.html">Part II talks about the current business trends of the Indian biotechnology industry</a>; and <a href="http://biotechmanage.blogspot.com/2009/02/indian-bio-scenario-in-current-economic_6690.html">Part III provides strategies to improve the current Indian biotechnology scenario</a>.<br /><br /><span style="font-weight: bold;">Part III. Strategies to improve the current Indian biotechnology industry scenario</span><br /><br />1. Following the recent economic downturn in the private and public equity markets, many biotechnology start-ups are now under considerable pressure. In this environment, the struggling start-ups should secure financing as their valuations are being trimmed by investors. In order to survive, these firms should adjust their business models to satisfy the existing as well as future investors, enter alliances to decrease their cash burn and consolidate with external assets to build the critical mass internally.<br /><br />2. The Indian biotechnology companies will need to demonstrate capabilities to generate IPR and innovative ideas along with maturity to execute them. Biotechnology firms with promising pipelines could team up with publicly traded firms with plenty of cash reserves but weaker pipelines. In other words, companies having a richer pipeline but not the cash to get any of your products to the market, should pursue long-term partnership deals with more mature biotechnology or pharma companies that have significant cash reserves and complementary clinical assets.<br /><br />3. Companies need to not only generate revenues, but also monetize the assets. Companies with products reaching the clinic pursue the ‘specialty investors’ for financing against existing or future revenues associated with specific clinical development programs. Moreover, demand by the major pharma firms for the innovative technologies developed by biotechnology firms remains strong. Although not easy, reassessing the firm’s long-term objectives (business models) and planning to reposition for long-term success by refocusing both on the further development of their drug discovery platforms and on various downstream clinical development projects would be a good strategy.<br /><br />4. Companies needing short-term liquidity should first seek support from existing private investors—an option that, surprisingly, companies today often overlook. Existing investors already have a stake in a firm’s future. In addition, bringing in new investors during periods of financial crisis usually comes at a comparatively high price to existing investors in terms of the dilution of their equity. Therefore, existing investors have an interest in providing short-term cash infusion to give managers time to get their act together and reposition their firms.<br /><br />5. Companies should exploit the growing number of funding opportunities outside the commercial sector. Apart from enhancing your cash position and credibility in the marketplace, funding from the government or charities generally comes with the added benefit of not diluting equity. Companies should approach nonprofit foundations such as Wellcome Trust, Gates Foundation, particularly if the company’s portfolio is in a therapeutic niche area not served by the major pharmaceutical companies.<br /><br />6. Indian companies can ensure greater access to US/EU markets by locating some of their research operations. Finally, the wave of consolidation (M&A), partnerships, licensing agreements etc. is might be able to weather the current economic slowdown and would face less competition in the future. In fact, these trying times would force companies to be more disciplined, strategic, and resourceful. They should also look further for financing and potential partners. The United States may no longer be the market of choice. Therefore, Indian pharma companies should be ready to grab the opportunities available in the CIS (Commonwealth of Independent States, Kazakhstan, Kyrgyzstan, Tajikistan, Turkmenistan and Uzbekistan) markets.<br /><br />7. Finally, Indian government is taking certain countermeasures to eliminate or reduce the effect of recession (economic slowdown) for a turnaround. In November, the Indian government unveiled a national strategy for biotechnology (NBDS), supported by a $1.6-billion commitment over the next five years that includes the incentives to promote R&D investment from foreign equity investments and foreign direct investments (FDI). It calls for 1/3rd of the government’s research budget to be spent on biotech—a 450% increase over the previous five years—in partnership with private sector funding. Under NBDS, the government is establishing a National Biotechnology Regulatory Authority (NBRA) - multi-regulatory structure for GM crops and human health products. It is extremely advantageous for the biotech industry to have a meaningful regulatory pathway, before product development as it would remove uncertainty in terms of both timelines to market and possibility of obtaining final product approval.<br /><br />Building sustainable business models would be a key to the success of this industry.<br /><br />Please feel free to post your comments or write to virenkonde at gmail dot com for your suggestions!<br /><br /></div>Viren Kondehttp://www.blogger.com/profile/18090726614388750732noreply@blogger.com0tag:blogger.com,1999:blog-701594073146171910.post-74914781142652269592009-02-10T18:54:00.005+05:302009-02-11T10:52:45.717+05:30Indian Bio-Scenario in the Current Economic Meltdown (Q408-Q109) - Part II<div style="text-align: justify;">The analysis of Indian Bio-Scenario in the current economic downturn is based on the opinion of industry experts, analysts, and market news and it is divided into three parts. <a href="http://biotechmanage.blogspot.com/2009/02/indian-bio-scenario-in-current-economic.html">Part I discusses about the current investment trends in the Indian biotechnology sector</a>; <a href="http://biotechmanage.blogspot.com/2009/02/indian-bio-scenario-in-current-economic_10.html">Part II talks about the current business trends of the Indian biotechnology industry</a>; and <a href="http://biotechmanage.blogspot.com/2009/02/indian-bio-scenario-in-current-economic_6690.html">Part III provides strategies to improve the current Indian biotechnology scenario</a>.<br /><br /><span style="font-weight: bold;">Part II. Business trends of the Indian biotechnology firms today</span><br /><br /><span style="font-weight: bold;">1. Spinning-off R&D or bio-services sector into a separate entity</span><br /><br />Major biotechnology and pharma companies are spinning-off their R&D into new companies to drive contract research, which analysts say can help attract investors into the low cost drug development and delivery sector. The current financial crisis has not had much effect on major biotechnology companies like Biocon, which plans to increase its investment in R&D in the next fiscal year to keep pace with increased orders from multinational firms. Biocon is spinning off its R&D division into a separate company. Currently, Biocon is getting the formulation done on contract basis but looks forward to set up a dedicated greenfield facility to manufacture tablet formulations. Formulations are a growing business and thus investing in it. This segment accounts for about 10 per cent of Biocon’s revenues but could yield up to $20M. Ranbaxy recently announced plans to spin off its R&D unit. Pharma majors, including Sun Pharma, Wockhardt, Orchid Research, Glenmark Pharmaceuticals, and Nicholas Piramal have all announced similar plans. India is betting its lower costs and talent pool will give it a leg up in the global pharmaceutical market in the coming years. Merck turns to Ranbaxy for $100M R&D effort, five-year pact to develop new anti-infectives. This new deal signals an ongoing effort by big pharma companies to reduce their expenses by shifting development programs into China and India. Eli Lilly has also aggressively pursued an Asian strategy for its R&D work as well. Genzyme to set up R&D centres in India. The company currently markets two drugs in India while some others are being examined for regulatory approval. Although the company’s drugs are not patented in India, the company says it will not have competition in India since their products are highly complex biotech drugs which will not be easy for generic companies to develop.<br /><br /><span style="font-weight: bold;">2. Consolidations (Mergers, Acquisitions), Agreements, and Partnerships on the rise</span><br /><br />The industry is also grappling with global meltdown, where it has paved way for a lot of joint ventures and collaboration in the sector. The mergers & acquisitions, licensing agreements and partnerships by Indian companies are on some reasonably attractive terms: Indian companies are looking to acquire a few overseas companies with good marketing, manufacturing, distribution, and clinical trial capabilities or to enter into US market, companies merging with equals and keeping products that sell and getting rid of products that don't make sense, major companies buying big and small companies, and consolidation amongst small and medium sized firms. The collaborations are being looked upon as means to bring down the cost of developing products to make the entire process quite affordable. The scenario looks favorable for the Indian biotechnology firms as industry experts say, they should focus on acquiring biotechnology units in foreign countries like the US, where global meltdown has led to fall in their valuations. Moreover, competition is tightening, meaning consolidation is inevitable. There might be more acquisitions as the industry has begun consolidating. Many biotechnology companies started during or after the dotcom doldrums are now in merger and acquisition mode to either exit or build on existing expertise. The future looks bright for the industry and industry experts feel that Indian firms must focus on buying overseas biotechnology units in countries like the US, which are seeing plunging valuations due to the global meltdown. Major pharma companies have traditionally been cash-rich and therefore relatively debt-free over the years. Therefore, the smaller biotechnology firms with lower valuations are now good acquisition targets for these major pharma companies – even in the current recessionary period.<br /><br />Major pharma companies like Ranbaxy, Cadila Healthcare, Lupin, Wockhardt, Dr. Reddy’s and Intas etc., are diversifying into biotech, But because India’s track record is in generics, many firms lack the experience of taking a new biological entity all the way to regulatory approval. Now, to remain in high gear as well as move higher up the innovation food chain, companies are turning to strategic growth. The Indian life sciences industry gained technology largely through acquiring western companies and joint ventures with these companies. Acquisitions represent a long-term strategy for companies wanting to break in to new markets, add new technologies and skills, and gain size and scale. Besides hiving off their R&D arms into separate entities to de-risk research, Indian pharma companies are interested in acquiring good biotech products and business models to spruce up their pipeline.<br /><br />India seems to be taking the necessary steps to lay a fertile field for increased global biotech activity. Indian biotech companies are also growing by looking further a field through acquisitions, joint ventures and collaborations. Biocon establishes EU presence with acquisition of marketing & distribution co. AxiCorp GmbH (Ger). Dr. Reddy's will acquire a portion of Dowpharma Small Molecules UK business. Avesthagen has made four strategic acquisitions, largely to ramp up its manufacturing and marketing capabilities. Ocimum Biosolutions, a life sciences R&D enabling company, bought Maryland-based Gene Logic for $10 million. Serum Institute Ltd., picked up a 14% stake in Lipoxen PLC, a biopharmaceutical company specializing in the development of differentiated biologicals, vaccines and oncology drugs. Lipoxen has raised £2.6 million in new funds from the Serum Institute through a subscription agreement and associated warrant agreement. Intas Biopharma acquires Biologics Process Development (US) to facilitate entry to US market. RFCL Limited acquired Wipro Biomed, a division of the software major Wipro Technologies to propel it into the fast-growing in vivo diagnostics market, fully automated clinical chemistry, and hematology sectors. Ranbaxy Laboratories, aquired Hyderabad-based Zenotech Labs since Zenotech has a strong pipeline of biotech and specialty drugs, whereas Ranbaxy rules the market in generics.<br /><br />Ranbaxy signs licensing agreement with Debiopharm, a Swiss biopharma co., to market its New Chemical Entity (NCE). Wockhardt takes huge strides towards In-licensing and collaborative agreements with UK based Sinclair Pharma to market a range of dermatology and dental products. Foreign companies entering Indian market through acquisitions or licensing agreements. Advinus Therapeutics Partnership with Genzyme (US): Collaboration to develop oral compounds to treat malaria in at-risk populations. Panacea Biotech Ltd -Alliance -PharmAthene, Inc (US): Strategic alliance for vaccine development & commercialization; Panacea takes equity stake in PharAthene. Jubilant -Joint Venture -Eli Lilly & Co (US): JV pharma/CRO collaboration for drug discovery.<br /><br /><span style="font-weight: bold;">3. Strategic alliances to allow foreign companies to enter Indian biotechnology market</span><br /><br />From the perspective of western firms, the implementation of TRIPS in India (a shift from Process Patents regime to Product Patents regime; Patents [Amendment] Act, 2005) may encourage them to introduce new brand drugs because such products can establish monopoly under the patent protection - a situation not possible since 1970. This does not mean, however, that high-priced, western-manufactured products can be directly shoehorned into the Indian market. Though TRIPS gives exclusive rights to Western companies to market their brand products in India - eliminating competition from local companies that copy inventions - these multinationals are unlikely to benefit from selling their products at high prices because Indian consumers simply cannot afford the high costs of drugs developed and manufactured abroad. Therefore, it will be necessary for Western and Indian companies to enter into strategic alliances so that novel drugs can be manufactured under license for local consumption. Such alliances will lead to a win-win situation for all, both biotech companies and the public. Thus, the impact of TRIPS on either the commercial strategies of foreign companies or their strategic alliances with Indian companies will be used in making foreign investment decisions.<br /><br />In an ideal situation, this would motivate Indian firms to invest in the creation of innovations and become primary innovators and would be less inclined to invest in the re-engineering and marketing of drugs already protected by pre-existing foreign patents. The Indian government’s substantial investment in patent infrastructure, together with recent modifications to Indian patent laws, reflects the country’s commitment to adhering to the principles laid down by the World Trade Organization’s (WTO, Geneva) agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS). For India’s biotech sector, however, a stronger patent system is unlikely to be sufficient to spark a boom of innovation. Indian companies simply cannot compete with the financial resources at the disposal of their Western counterparts. TRIPS implementation essentially signals the initiation of a race that is unfair.<br /><br />A potential best-case strategy is evident from the Daiichi-Ranbaxy, transformational deal. To enter the Indian biopharmaceutical market or strengthening a current presence is to merge with one of the larger Indian generics companies, thus entering the Indian market from the low end and high end simultaneously. This approach removes a significant generic competitor for newly launched products in the Indian market, provides entry into all tiers of Indian healthcare, and, depending on the company size, and offers worldwide generic distribution and access to highly qualified, cost-effective Indian R&D staff. As a first test of this model, future results of the recent acquisition of Ranbaxy by Daiichi Sankyo, Japan will provide insight into possible success.<br /><br /><span style="font-weight: bold;">4. All-time-good domestic-demand-driven biotechnology market opportunity</span><br /><br />However, even as global markets are non-growing for many Indian players, domestic healthcare markets prove to be an anchor with steady growth at a volatile time. Domestic market proved to be an anchor for Indian Pharma in a time of a global slowdown. The companies like Piramal, Lupin, Cipla, and Ranbaxy are strongly focused on local segments and managed to stay firm in the falling markets. Therapeutics remain the thrust in Indian R&D, with human insulin being the most common area of research. Plasma proteins are an emerging market in India. Over 100,000 people in India suffer from haemophilia (25 per cent of the world’s haemophiliac population). India has been sourcing plasma proteins from MNCs such as Baxter. There is Market potential for manufacturing plasma proteins locally and indigenously. mAbs is a fast-growing market-especially in oncology and auto-immune diseases. India has 3 million cancer patients and 700,000 new cases every year.<br /><br />Please feel free to post your comments or write to virenkonde at gmail dot com for your suggestions!<br /><br /></div>Viren Kondehttp://www.blogger.com/profile/18090726614388750732noreply@blogger.com0tag:blogger.com,1999:blog-701594073146171910.post-51091374577425109562009-02-10T18:50:00.007+05:302009-02-11T10:52:11.477+05:30Indian Bio-Scenario in the Current Economic Meltdown (Q408-Q109) - Part I<div style="text-align: justify;">The analysis of Indian Bio-Scenario in the current economic downturn is based on the opinion of industry experts, analysts, and market news and it is divided into three parts. <a href="http://biotechmanage.blogspot.com/2009/02/indian-bio-scenario-in-current-economic.html">Part I discusses about the current investment trends in the Indian biotechnology sector</a>; <a href="http://biotechmanage.blogspot.com/2009/02/indian-bio-scenario-in-current-economic_10.html">Part II talks about the current business trends of the Indian biotechnology industry</a>; and <a href="http://biotechmanage.blogspot.com/2009/02/indian-bio-scenario-in-current-economic_6690.html">Part III provides strategies to improve the current Indian biotechnology scenario</a>.<br /><br /><span style="font-weight: bold;">Part I. Investment trends in the Indian biotechnology sector</span><br /><br />It is considered that, the worldwide financing environment in 2009 will be extremely challenging. Capital markets in India might remain turbulent during the first half of 2009 although in the second half of the year the capital markets might stabilize and biotechnology sector might benefit from this. Keeping fingers crossed! The biotechnology industry is mainly dependent on private equity and venture capital funds. Hence the after effects of the global meltdown could be observed over a period of few months. Experts from financial institutions and analysts have varied opinions about the inflow and outflow of monetary funds into the industry.<br /><br />It is believed that, start-up health care and drug technology firms would be struggling to attract funding as venture capital and private equity firms shy away from high-risk projects with long gestation periods in the wake of the global economic downturn. Also, the lack of confidence in riskier projects might lead venture capital and private equity firms to shift their focus to established companies to take advantage of their current low valuations. Investors can gain from the low valuations, but only if they are able to identify technologies that can give significantly big returns after taking the high risk and waiting for long. Innovation in the pharma and biotechnology space is going to be impacted heavily owing to lack of funding from venture capital and private equity companies. However, some believe that, as far as the global meltdown is concerned, the early stage companies would not be affected because they are not much dependent on market dynamics from the beginning. If companies really need to attract investment funds, they need to have some very good science and promoters should have a good track record. New funding is going to be tough for start-up companies now, unless the entrepreneurs are ready to either grossly undervalue their companies or ensure easy exit options. Nobody can predict which companies with “out-of-the-box business models” would be favored, but it appears that several global investors are evaluating Indian biotechnology startups’ intellectual property assets. While more mature companies may wait till their valuations improve, younger companies will continue to raise funds through the private equity route. Companies that planned to launch its IPO last year left scouting because of the lack of funding to support its product pipeline due to the downturn effect. The capital availability for small-to-mid size development stage life sciences companies will lag the broader market and these industries will remain under funding-pressure for a significant period of time.<br /><br />Some industry experts believe that there won’t be shortage of funding coming in for bio-services-led businesses in India. Experienced entrepreneurs trying to set up companies [CRAMS (clinical research and manufacturing services) and CROs (clinical research organizations)] in India might find it easier to get funding. The risk capital is going to be very hard to find. For the supported bio-services-led businesses it’s not really risk capital because it’s fairly low risk. So, a lot of capital would be flowing into the services businesses. They are going to find it very interesting because there is a natural hedging opportunity for them because companies are looking for more affordable ways. It might be more difficult to get funding for a newbie entrepreneur who is trying to get into the CRO space. On the other hand, some experts are of the opinion that, far from registering a robust growth- as was being projected earlier- there are also fears of a dramatic fall in the number of clinical trials being outsourced to India. If the recessionary trends do not subside, there could be an impact on clinical trials and data management projects coming towards India. There is a growing perception that expenditures on clinical trials will be significantly lower. This is because pharmaceutical and biotechnology companies of all sizes in the US and European markets are trimming their portfolios, making tough decisions on compounds in the pipeline. Only few would receive continued investment. Only the time would decide, if the projections on the Indian clinical trials market to become $1 billion by 2010, as projected.<br /><br />In the last year or two the capital has been flowing into discovery- or innovation-led businesses and that might dry up. The venture capital or private equity investors would be highly reluctant to fund any risky business. So innovation companies are going to find it difficult because they are going to need the next round of funding and the private investors are not going to support companies with even phase I clinical data. They know that, even when the potential drug candidate goes to phase II or III, it may fail. So they won’t have the risk appetite to fund these companies. The incremental investments once over phase I clinical trials are also huge. So this financial funding crisis is going to remain for some time. There might be very innovative companies being acquired for a very low valuation or they will fold up because no one is investing in them. If they are working on something unique, big pharma companies might step-in. Many companies in biotechnology sectors have used external sources of financing to fund their research efforts and to enhance or support their claims to being ‘profitable’. However, with banks and financial institutions collapsing and the need for liquidity to manage their own businesses being amplified; the lending process has come to an abrupt halt or is being managed at much higher interest rates. Thus, those companies that have already worked up large debts are under pressure to return these as quickly as possible or have to sustain these debts at much higher interest rates – this situation is threatening the very existence of these companies.<br /><br />The regulatory requirements of the life sciences sector is the biggest hurdles because the gestation timelines are long, the predictable outcome matrix is not very favorable and that’s why it makes it very high risk. Therefore, when investors talk about return on investment (ROI) in this kind of economic downturn, they don’t want to invest in these types of uncertain sectors. A new council to help coordinate efforts between academics and biotechnology companies and a new regulatory body has been created by the Indian government. India has a shortage of trained regulators, but the FDA/USA has stepped in to help train personnel in India. There are recent reports of the opening of US HHS/FDA offices in New Delhi and Mumbai to improve safety and quality of the biotechnology products, which will facilitate the smooth flow of trade. Through these offices, these HHS/FDA personnel will provide technical advice, conduct inspections of facilities that export to the U.S., and work with Indian government agencies and the private sector to develop certification programs to allow the efficient flow of safe HHS/FDA-regulated goods between the U.S. and India.<br /><br />Private equity companies might consider companies following de-risking strategies. They might be interested investing in medical devices, drug discovery, and diagnostics. Diagnostics for instance has a lot of prospects for potential growth in the future because of a lot of innovation churning up. Govt. is planning a new legislation on medical devices to regulate the quality of medical equipment being marketed in the country. The new regulation will help standardization of the quality of medical devices manufactured in India. Because of the fact that, most of the medical equipments in India are imported and the medical devices industry in India has not grown much, the government is working on medical devices legislation, in order to standardize the quality of Indian manufactured medical devices.<br /><br />The biotechnology sector might be struggling a lot, not just in India but globally, in terms of investment in innovation. With the current liquidity crisis, the government has stepped in to support research. And that’s where the government’s initiatives [like, SBIRI (Small Business Innovative Research Initiative) as an early stage support scheme, and Biotechnology Industry Partnership Programme (BIPP), as a later stage support scheme to concentrate on big science, big innovations, where governments job would be to reduce or cover the risks] are for rescue, filling the funding gap. The government has approved the proposal under BIPP, which is an advanced technology science scheme envisaged as a government partnership with industries for high risk discovery and innovation. An investment of US$ 73.24 million budgeted under the 11th Five-Year-Plan will be made for the programme. Also, under the new legislation, the country's Department of Biotechnology would be setting aside 30 per cent of its annual budget to fund public-private collaborations on new drug development. That’s how governments all across the World will have to fund innovation at least until times are better.<br /><br />Please feel free to post your comments or write to virenkonde at gmail dot com for your suggestions!<br /><br /></div>Viren Kondehttp://www.blogger.com/profile/18090726614388750732noreply@blogger.com0tag:blogger.com,1999:blog-701594073146171910.post-92095794279656706522008-11-07T10:42:00.004+05:302008-12-03T15:05:19.419+05:30Biotechnology Business Models: An Indian Perspective<div style="text-align: justify;"><span style="font-weight: bold;">Abstract</span><br /><br />A typical business model consists of three components – value proposition, value chain structure and revenue generation. These components are used to give a general description of a business. The biotechnology industry is not really characterized by specific business models and neither is there one single model for success. The sector is not only characterized by an enormous diversity, but is also driven by innovations, which makes the prediction of future development rather difficult. The enormous flexibility of biotechnologycompanies is a strength that has helped them survive in times of economic difficulties. In years of crisis, companies have managed to reorient themselves, change their business plans, or even switch markets. Several Indian firms have focused their businesses on the development, manufacturing and marketing of biopharmaceuticals and providing services. The Indian companies appear well positioned to leverage their cost-effective manufacturing capabilities to corner some of the market share and compete on a global scale. This paper discusses the various business models and strategies adopted by the biotechnology companies that directed the growth of the biotechnology industry in the country based on the techno-economic dynamics and the key challenges faced by these firms.<br /><br />To receive a post-peer-review, pre-copyedit version of the article accepted by the <a href="http://www.palgrave-journals.com/jcb/journal/vaop/ncurrent/abs/jcb200852a.html">Journal </a><a href="http://www.palgrave-journals.com/jcb/journal/vaop/ncurrent/abs/jcb200852a.html">of Commercial Biotechnology</a>, please send me an <a href="email:virenkonde@gmail.com">email</a>. The definitive publisher-authenticated version is available online at: <a href="http://www.palgrave-journals.com/jcb/journal/vaop/ncurrent/abs/jcb200852a.html">http://www.palgrave-journals.com/jcb/journal/vaop/ncurrent/abs/jcb200852a.html</a>.<br /></div>Viren Kondehttp://www.blogger.com/profile/18090726614388750732noreply@blogger.com0tag:blogger.com,1999:blog-701594073146171910.post-3026445975967489322008-11-03T22:42:00.009+05:302008-11-03T23:30:47.504+05:30Biotechnology Regulations in India: Progress-so-far<div style="text-align: justify; color: rgb(0, 0, 0);">India’s biotechnology regulatory system has experienced a number of changes since the Rules for the Manufacture, Use, Import, Export and Storage of Hazardous Microorganisms/Genetically Engineered Organisms or Cells 1989 (Rules, 1989) were first notified under the Environment (Protection) Act, 1986, including the elaboration of aseries of guidance documents published by the Department of Biotechnology (DBT) in 1990, 1998 and 1999. The extraordinary growth of the Indian biotechnology sector has significant implications for policy in the area of regulation, and two specific reports were commissioned by the Ministry of Agriculture and the Ministry of Environment and Forests to evaluate the regulatory framework for products of agricultural biotechnology and recombinant pharmaceuticals, respectively.<br /><br />The 2004 Report of the Task Force on the Application of Agricultural Biotechnology chaired by Prof. M.S. Swaminathan recommended the establishment of an “autonomous, statutory and professionally-led National Biotechnology Regulatory Authority” (NBRA) that would have “two separate wings – one dealing with food and agricultural biotechnology, and the other with medical and pharmaceutical biotechnology.” The Report recommended that the “NBRA is essential for generating the necessary public, political, professional and commercial confidence in the science based regulatory mechanism in place in the country.”<br /><br />The 2005 Report of the Task Force on Recombinant Pharma chaired by Dr. R.A. Mashelkar similarly supported the establishment of a National Biotechnology Regulatory Authority/Commission “providing a professionally managed single window mechanism for giving various clearances including biosafety issues.” A model for the NBRA was proposed that “would comprise of four wings namely: a) Agricultural products / Transgenic Crops; b) Pharmaceutical/ Drugs and Industrial Products; c) Transgenic Foods/Feed; and d) Transgenic Animals/ Aquaculture” and that “alternate models of how a National Biotechnology Regulatory Authority can be created also needs to be examined.” The Mashelkar Report additionally provided a series of recommendations to streamline the existing regulatory system for recombinant pharmaceuticals until the feasibility of establishing a NBRA could be evaluated.<br /><br />In 2005, DBT published a draft National Biotechnology Development Strategy which elaborated a ten year vision for the future of biotechnology in India. Key policy recommendations and approaches to implement these were established through a process of multi-stakeholder consultations that focused on cross-cutting issues of relevance to allsub-sectors of the biotechnology community. Under the topic of regulatory mechanisms, the National Biotechnology Strategy recommended “a competent single National Biotechnology Regulatory Authority be established with separate divisions for agriculture products/transgenic crops, pharmaceuticals/drugs and industrial products; and transgenic food/feed and transgenic animal/aqua culture. The authority is to be governed by an independent administrative structure with common chairman. The inter-ministerial group will evolve suitable proposals for consideration of the government.”<br /><br />The National Biotechnology Development Strategy was approved by the Government of India in November, 2007 after a two year consultation period with multiple stakeholders including concerned ministries, universities, research institutes, private sector, civil society, consumer groups, non-government and voluntary organizations and international bodies. As regards the regulation of biotechnology, the Strategy states that the NBRA will be established as an “independent, autonomous and professionally led body to provide a single window mechanism for biosafety clearance of genetically modified products and processes”. DBT has been given the responsibility to set up the NBRA and until such time as the NBRA is fully functional, biotechnology regulation will continue under the existing regulatory framework.<br /><br />The NBRA will be an independent, autonomous, statutory agency established by the Government of India to safeguard the health and safety of the people of India and to protect the environment by identifying risks posed by, or as a result of, modern biotechnology, and managing those risks through regulating the safe development and deployment of biotechnology products and processes. GM foods are regulated by the Food Safety and Standards Authority under the Food Safety and Standards Act, 2006 (FSSA, 2006). Product safety, efficacy, clinical trials and market authorization of recombinant drugs are regulated by the Drug Controller General of India (DCGI) under the authority of the Drugs and Cosmetics Rules 1945 (Rules, 1945) of the Drugs and Cosmetic Act 1940. The NBRA would be responsible for the GM food safety assessment and any subsequent authorization of the GM food as safe, all other rules and regulations that pertain to food (e.g., conventional safety provisions related to adulterants, extraneous matter and unhygienic/unsanitary processing or manufacturing of food) would still apply to the GM food as regulated by the FSSA and any other authority in India. The NBRA will also be responsible for regulating genetically modified organisms with applications in human and veterinary health and a sub-set of products derived from these. This will include the regulation of recombinant biologics such as DNA vaccines, recombinant gene therapy products, recombinant and transgenic plasma derived products like clotting factors, and veterinary biologics but will exclude all other therapeutic proteins derived from recombinant organisms, which will continue to be regulated by the DCGI.<br /><br />In order to establish and empower the NBRA, DBT is considering promulgating new legislation, “National Biotechnology Regulatory Act (NBR Act)”. Elements of biotechnology regulation are currently spread over multiple acts and some of these would be amended to establish and operate the NBRA. Drafting new legislation would provide an opportunity to consolidate and enhance the efficiency and effectiveness of biotechnology regulation, increase collaboration with state governments in this area, promote public confidence in the regulatory system, and facilitate international trade.<br /></div>Viren Kondehttp://www.blogger.com/profile/18090726614388750732noreply@blogger.com0tag:blogger.com,1999:blog-701594073146171910.post-44860960533173641982008-06-30T13:11:00.003+05:302009-03-02T10:29:02.842+05:30Biotechnology Business Models: Snapshot<div align="justify">Biotechnology companies definitely need a business plan to convey the winning idea while being coherent, comprehensive, rational and defensible. Many new biotechnology companies have learnt the importance of business models and sophisticated business plans the hard way. A typical business model consists of three components – value proposition, value chain structure and revenue generation. These components are used to give a general description of a business. The biotechnology industry is not really characterized by specific business models and neither is there one single model for success. The sector is not only characterized by an enormous diversity, but is also driven by innovations, which makes the prediction of future development rather difficult. The enormous flexibility of biotechnology companies is a strength that has helped them survive in times of economic difficulties. In years of crisis, companies have managed to reorient themselves, change their business plans or even switch market. Business models have to be continuously adapted to internal and external conditions. This means in practice, companies occasionally follow one particular business model in preference to others in order to adapt to prevailing financing mechanisms as well as to changing market demands.<br /><br />On the road to success, many biotechnology companies have adopted several different business models in order to be able to successfully operate under national and international conditions. Although business models in the biotechnology sector are not homogeneous, they are roughly divided into the Platform, Product, Vertical, and Hybrid models based on the value chain structure of the biotechnology industry. Typically, the Platform-based companies develop a set of tools or integrated technologies and provide these for use in different applications. One advantage of this business model is that revenue is generated relatively quickly. In addition, cost and time-savings are made in relation to product approval. The Product or drug developing companies offer products manufactured with new, own or already known technologies. This includes classical items like drugs and diagnostic products, but also new groups such as tissue engineering products. In FIPCO (fully integrated pharmaceutical company) or Vertical business model, the drugs are developed up to end of clinical studies or up to approval, meaning that the creation of value is pursued as far as possible. On the other hand, VIPCOs (virtually integrated pharmaceutical companies) only have a small number of employees that are focused on a specific area; other business areas are outsourced to external partners. It is simply an office-based company, dealing exclusively with project management and outsourcing all steps along the practical value creation work, from ADME tests (absorption, disposition, metabolism and elimination) to animal experiments and clinical studies. Contract research or service companies offer their services on the basis of known technologies, in the form of contract research or contract production. The combination of these business models leads to what is known as ‘hybrid or dual models’ in which technology platforms are combined with services and the creation of products.<br /><br />The entrance of domestically manufactured products into the marketplace and the local competition has benefited Indian citizens in terms of price reduction from that of the imported products. Looks like, Indian companies appear well positioned to leverage their cost-effective manufacturing capabilities to corner some of the market share and compete on a global scale. Several Indian firms have focused their businesses on the development, manufacturing and marketing of biopharmaceuticals and providing services. Multinational companies have already established a presence in India in areas such as equity participation, contract manufacturing, research relationships, joint product development, commercialization and manufacturing relationships, and product/technology in-licensing and out-licensing. In the context of the size and growth of the current Indian biotechnology market in relation to the global markets, it is clear that India promises great potential to become one of the most significant players on the global arena by 2010. However, the product development capabilities of India's nascent biotechnology sector and the strategies used by private firms to survive and grow are among the innumerable challenges related to operating in a developing world’s context. The Indian biotechnology industry like its global counterparts is dominated by the healthcare sector having its roots in the pharmaceutical industry. The important characteristics of Indian biotechnology business lies in examining their evolution, structure and growth based on their products, technologies and the services provided by them. Though there has been a slow transition to Product model by Indian biotechnology companies, India is still a generic market. To achieve global presence, Indian firms need to have product focus and should come up with blockbuster drugs. In conclusion, there exist boundless opportunities for pharmaceutical and biotechnology firms to find innovative ways of working together by leveraging the committed government support in terms of public-private partnerships.<br /><br />The article on 'Biotechnology business models: An Indian Perspective' accepted by the <a href="http://www.palgrave-journals.com/jcb/journal/vaop/ncurrent/abs/jcb200852a.html">Journal </a><a href="http://www.palgrave-journals.com/jcb/journal/vaop/ncurrent/abs/jcb200852a.html">of Commercial Biotechnology</a>, is available online at: <a href="http://www.palgrave-journals.com/jcb/journal/vaop/ncurrent/abs/jcb200852a.html">http://www.palgrave-journals.com/jcb/journal/vaop/ncurrent/abs/jcb200852a.html</a>.<br /><br /></div><div align="justify"> </div>Viren Kondehttp://www.blogger.com/profile/18090726614388750732noreply@blogger.com0tag:blogger.com,1999:blog-701594073146171910.post-62224985488870768072008-02-14T14:19:00.004+05:302008-03-12T11:21:47.608+05:30Drug Pricing Strategies in India<p class="MsoNormal"><o:p> </o:p><b style="">1. Cost-based pricing:<o:p></o:p></b></p> <p class="MsoNormal" style="text-align: justify;"><o:p></o:p>The Indian cabinet ministry proposed to control the prices of 354 essential medicines by taking into account their cost of production. Today 1/4<sup>th</sup> of Rs. 23,000 crores domestic pharma market is controlled. The ministry has not accepted the industry’s offer to lower the current prices of essential drugs by 5-10%, because the revised policy will prevent companies escaping price control by adding new ingredients to drugs and going out of the essential drugs list. Without such measures, drug makers may add vitamins and other unnecessary components, leading to risky irrational combinations besides defeating the purpose of price control. </p> <p class="MsoNormal" style="text-align: justify;"><o:p></o:p>The essential therapeutic drugs constitute the painkillers, antibiotics, psychotic drugs, cancer and HIV drugs. The companies making essential drugs are given 150% margin of production cost, whereas price controlled drugs are given 100% margin for the post manufacturing expenses. </p> <p class="MsoNormal"><b style="">2. Value-based pricing:<o:p></o:p></b></p> <p class="MsoNormal" style="text-align: justify;">Biotech industry has been accused of the excessive prices that have been emphasized on the cost of R & D, years of lab and clinical trials, innumerable failures for each successful product and imperative to reward investor’s high risks with commensurately high rewards. </p> <p class="MsoNormal" style="text-align: justify;">Cost-based justification of high biotech drug prices is based on 2 nontrivial problems. 1) Biotech companies do not base prices on the cost. 2) The industry is beginning to realize that it does not want public to think that the prices are based on the cost. </p> <p class="MsoNormal" style="text-align: justify;">The price for new product must cover the incremental expenditures on manufacturing and marketing but there is no logic to quantify past expenditures on R & D. Rather, prices are based on what the market will bear. These prices may or may not reimburse past efforts and investments, but their social purpose is to encourage future efforts and future investments. The prices for today’s products finance research for tomorrow’s products either directly through the retained earnings of biotech firms or indirectly by enriching investors who remain attached to the sector rather than moving their money elsewhere. </p> <p class="MsoNormal" style="text-align: justify;">So, biotech companies now promote the language of ‘value-based pricing’ for their products; which offers the virtue of honesty. With this, we need face these questions: How to define value in healthcare, how do we measure it? Or is it only about value and not cost.</p> <p class="MsoNormal" style="text-align: justify;"><b style="">The link between innovation and market-based pricing:</b> Innovation in the biotech industry is created and driven by multiple factors: the existing market-based pricing, size of the biopharma companies’ R & D budget, level of venture capital investment and level of government intervention in market. The recent history has shown that threat of price control drives investors out and dries up the resources those researchers must have to develop tomorrow’s medical miracles.</p><p class="MsoNormal" style="text-align: justify;"><br /></p>Viren Kondehttp://www.blogger.com/profile/18090726614388750732noreply@blogger.com0tag:blogger.com,1999:blog-701594073146171910.post-68868389008152417012008-01-12T22:06:00.000+05:302008-01-12T22:10:30.722+05:30Price Control of Biotech Drugs: Potential Impact on the Biopharma Industry<p class="MsoNormal" style="text-align: justify;">Life saving, less expensive biotech drugs, isn’t a good deal for consumers?</p> <p class="MsoNormal" style="text-align: justify;"><b style=""><o:p></o:p></b>The large public outcry or critics about the biopharmaceutical drugs are very expensive and that the biopharma industry is so greedy in making profits. The prices are so high because of the labour intensive, long term process involved, from the hypothesis that a drug might work to actually getting it through the testing and approval and getting it on the market. It takes a lot of money to do that, and of course the drug companies do make a lot of money, but it’s a win-win situation, where they make a lot of money and we get these fantastic life saving drugs. The advancements that are being made are absolutely astonishing. Do we really want to kill the goose that lays golden eggs by putting in price controls? There has to be some incentives for the investors and the biopharmaceutical companies.<span style=""> </span>Again, although a good idea, the drug companies invest so heavily on bringing a drug to market, ideally the market forces should dominate or decide the price of the drug.<o:p><br /></o:p></p> <p class="MsoNormal" style="text-align: justify;">Drug importation is a major obstacle. People buy drugs on the internet, from overseas to get it in low prices. These drugs are sold under the international treaty to price control countries with low prices. They are not supposed to be sent it back to the original countries from where they are innovated. Thus, buying drugs overseas introduces price control into the original country, which is undesirable.<o:p><br /></o:p></p> <p class="MsoNormal" style="text-align: justify;">Government should stay away from any issue concerning the price control of drugs. The biopharma industry needs to be innovative, creative, energetic and astonishing. A great deal of excited anticipation is required as to what kind of drugs will be coming up in the future. This is only possible, if the biopharma industry can operate in an environment where they can be profit incentive. Thus, Government control of science or negotiating Government purchase of drugs does not guarantee or encourage creating innovative drugs.<o:p><br /></o:p></p> <p class="MsoNormal" style="text-align: justify;">When we talk about price control, we are taking the oxygen out of the system. That might not worth the investment and that might stop breathing. Look around and ask a question, how many countries that have the price control system in place have actually innovated new drugs, and the answer is ‘basically almost none’.<o:p><br /></o:p></p> <p class="MsoNormal" style="text-align: justify;">Unlike Unites States, many developed countries like <st1:country-region><st1:place>Canada</st1:place></st1:country-region> or <st1:country-region><st1:place>England</st1:place></st1:country-region> or much of the <st1:place>Europe</st1:place> have price control systems for drugs. Let us not overlook the fact that more than 90-95 percent drugs are innovated in <st1:country-region><st1:place>U.S.</st1:place></st1:country-region> compared to the rest of the world comprising price control countries. The price controls presents a major disincentive to create a new medication.<o:p><br /></o:p></p> <p class="MsoNormal" style="text-align: justify;">With the Government’s intervention, if the health insurance companies like Medicare negotiates the drug prices with the biopharma industry? It’s a very bad idea. That would create a monopoly but in reverse. Basically, that would allow the largest purchaser of drugs to negotiate the prices with the sellers. This will force down the price of drugs. Although, initially sounds like a good deal to consumers, ultimately would create disincentives to drug companies to actually invest in innovative drugs. </p> <p class="MsoNormal" style="text-align: justify;"><o:p></o:p> </p><p class="MsoNormal" style="text-align: justify;">Some might argue that, the Government agencies like research institutions are actively involved in discovering new molecular entities that are later licensed to biopharma companies. There is a huge difference in investing, marketing and profiting new approved drugs verses the basic research. In contrast, the pharma companies actually create the pharmaceutical product drug. The venture capitalists need to get repaid too for their efforts and contribution, don’t you think so?</p>Viren Kondehttp://www.blogger.com/profile/18090726614388750732noreply@blogger.com0tag:blogger.com,1999:blog-701594073146171910.post-56087026389312007622007-12-25T23:38:00.000+05:302008-01-24T12:35:30.992+05:30Biotechnology Management: The science and the business<p style="text-align: justify;" class="MsoNormal">There are so many definitions of biotechnology exists today that we do not feel inclined to add to them. Not that the definitions are wrong but they do not necessarily convey the very realistic ideas of the subject. Biotechnology is no more just an innovative academic activity, but rather an intense industrial and commercial involvement. This monograph is an attempt to provide you with a variety of issues, their relative importance and their interrelatedness in managing commercial biotechnology. By understanding the factors influencing biotechnology companies it is possible to select opportunities and position for a rewarding career. Examining existing biotechnology firms can reveal desirable credentials for careers. Many companies list the academic qualifications of their senior management. Job postings also describe necessary qualifications for specific positions. The key to a career in biotechnology, regardless of educational background or expertise, is to appreciate the unique challenges faced by biotechnology companies.<o:p><br /></o:p></p><div style="text-align: justify;"> </div><p style="text-align: justify;" class="MsoNormal">Broadly speaking, the path to commercialization of a new technology may be identified by three phases of evolution: phase one (<i style="">science-driven</i>), where primary emphasis is placed on scientific research; phase two (<i style="">technology-driven</i>), with primary emphasis on technology development and standardization; and phase three (<i style="">commercialization</i>), with primary emphasis on commercial development and application. Modern biotechnology perhaps provides an exemplar of a new form of knowledge production where academia-industry collaboration has been evident in all three phases of this evolution since its inception, driven largely by scientific and commercial requirements. Biotechnology management is a model based on multidisciplinary approaches and problem solving in the context of business applications. This model is characterized by the convergence of a diverse set of skills from a variety of disciplines.<o:p><br /></o:p></p><div style="text-align: justify;"> </div><p style="text-align: justify;" class="MsoNormal">The ultimate test of corporate strategy occurs in the marketplace. The biotechnology industry is finally starting to bring products to market. Most of the biotechnology companies are establishing links with larger, more established drug companies to give them the financial and marketing muscle they need for the next stage of their development. Marketing and sales experts are needed to study and develop markets and ultimately enable the delivery of products to consumers. The significant negative impact of patent expirations on sales represents a great opportunity for individuals who can successfully develop strong brand positions for pioneers to help them sustain sales post-expiration. The more you can explain and demonstrate the understanding of the market, the increasing levels of confidence investors have in the concept and ultimately the firm.<o:p><br /></o:p></p><div style="text-align: justify;"> </div><p style="text-align: justify;" class="MsoNormal">Biotechnology is a very capital intensive business. The manager of a biotechnology start-up faces the challenge of fostering a transition within the founding team from science-oriented to commerce-oriented thinking and action. The central role of funding and financial management in biotechnology establishes a demand for individuals with proven financial expertise. Furthermore, the potential for substantial financial returns has attracted great interest for biotechnology in public markets, creating a demand for analysts, venture capitalists, and investment bankers with an understanding of biotechnology-related financial issues. The major challenge for the biotech manager is the timely acquisition of funding to picking up a financial partner in the strategic business.<o:p><br /></o:p></p><div style="text-align: justify;"> </div><p style="text-align: justify;" class="MsoNormal">Likewise, the primary resource of any technology enterprise is its people. Attracting, motivating and retaining these highly trained individuals are the key concerns of the human resource manager. However, keeping those hearts and minds loyal to the cause is no easy feat. Today's biopharmaceutical projects have a high degree of complexity. In order to properly utilize staff and other resources like suppliers and internal groups, a manager must be able to clearly visualize the desired goal. Human resources constitute an increasingly critical function in any biotechnology company, particularly in an industry that's in an increasing state of inflation. Middle managers and human resources experts are needed for their specialized abilities.<o:p><br /></o:p></p><div style="text-align: justify;"> </div><p style="text-align: justify;" class="MsoNormal">All businesses have to keep ahead of the competition and there is no business activity more dependent on innovation than biotechnology. The creation of innovations in a knowledge intensive biotechnology sector had a profound impact on the biopharmaceutical sector. Considering the prospectus of patenting new drugs and diagnostics both the inventor and a manager of an invention-intensive business will need to understand to make meaningful decisions on the subject. Because of the importance of intellectual property protection in biotechnology, the life science graduates with technical and legal expertise are needed to write and defend patents and assist in the collection and evaluation in the competitive biotechnology industries.<o:p><br /></o:p></p><div style="text-align: justify;"> </div><p style="text-align: justify;" class="MsoNormal">Although, an attempt is made to touch upon all the major aspects – marketing, finance, human resource, intellectual property, etc. - that are part of the business, it would be impossible to cover biotechnology management in one such write-up. In such a rapidly changing environment much of the technology and managers will appear very different next year, next month, and even tomorrow. What an exciting industry it is! It is risky and deeply rewarding. It is fascinating and frustrating but never dull. For all that excitement, you must become, like me, part of the experiment.<o:p><br /></o:p></p><div style="text-align: justify;"> </div><p style="text-align: justify;" class="MsoNormal">References:</p><div style="text-align: justify;"> </div><ol style="margin-top: 0in; text-align: left;" start="1" type="1"><li class="MsoNormal">Konde, V. (2007). <a href="http://biotechmanage.blogspot.com">Biotechnology Management Blog</a>.<br /></li><li class="MsoNormal">Konde, V. (2008). <a href="http://www.palgrave-journals.com/jcb/journal/v14/n1/full/3050079a.html">Biotechnology in <st1:country-region><st1:place>India</st1:place></st1:country-region>: Public-private partnerships.<i style=""></i></a> <i>Journal of Commercial Biotechnology</i> (2008) <b>14,</b> 43–55. doi:10.1057/palgrave.jcb.3050079; published online 27 November 2007 <o:p></o:p></li></ol>Viren Kondehttp://www.blogger.com/profile/18090726614388750732noreply@blogger.com0tag:blogger.com,1999:blog-701594073146171910.post-75657181891866508162007-12-03T11:30:00.000+05:302007-12-03T11:44:40.934+05:30Crisis Management - A lesson to learn in Corporate Communication<div style="text-align: justify;"><span style="font-size:130%;"><span style="font-weight: bold;"> All businesses mess-up on occasion</span></span> </div><p style="text-align: justify;" class="MsoNormal"><o:p></o:p><b>What to do when it (all) goes wrong?</b></p><div style="text-align: justify;"> </div><ul style="text-align: justify;"><li><!--[if !supportLists]-->Growing Up Is Hard to Do </li><li><!--[if !supportLists]-->Crisis need not strike a company purely as a result of its own negligence or misadventure.</li><li><!--[if !supportLists]-->Often, a situation is created which cannot be blamed on the company - but the company finds out pretty quickly that it takes a huge amount of blame to hit the ball in its response. </li><li><!--[if !supportLists]-->Clearing the Hurdles & Accelerating the Business</li></ul><div style="text-align: justify;"> </div><p style="text-align: justify;" class="MsoNormal"><b>High-profile incidents in the bio/pharmaceutical industry</b></p><div style="text-align: justify;"> </div><ul style="text-align: justify;"><li><!--[if !supportLists]-->Product integrity is constantly challenged, from patent infringement to counterfeits to life-threatening side effects during first-in-human clinical trials. </li><li><!--[if !supportLists]-->Each step of the product life cycle, from idea inception to post-marketing surveillance and product retirement, raises potential legal, commercial, financial and ethical risks. </li><li><!--[if !supportLists]-->Product protection risks should be managed through an anticipatory, proactive approach employing mechanisms found to be successful in monitoring, controlling, and correcting vulnerabilities throughout the product’s life cycle. </li></ul><div style="text-align: justify;"> </div><p style="text-align: justify;" class="MsoNormal"><b>Johnson & Johnson and Tylenol Poisoning</b></p><div style="text-align: justify;"> </div><ul style="text-align: justify;"><li><!--[if !supportLists]-->In 1982, Tylenol - 35 % of the <st1:place st="on"><st1:country-region st="on">US</st1:country-region></st1:place> over-the-counter analgesic market - represented 15 % of the company's profits.</li><li><!--[if !supportLists]-->Unfortunately, at that point one individual succeeded in lacing the drug with cyanide. Seven people died as a result, and a widespread panic ensued about how widespread the contamination might be.</li><li><!--[if !supportLists]-->By the end of the episode, everyone knew that Tylenol was associated with the scare. The company's market value fell by $1bn as a result. </li></ul><div style="text-align: justify;"> </div><p style="text-align: justify;" class="MsoNormal"><b>Cost and benefit analysis<o:p></o:p></b></p><div style="text-align: justify;"> </div><ul style="text-align: justify;"><li><!--[if !supportLists]-->The cost was a high one. In addition to the impact on the company's share price when the crisis first hit, the lost production (destroyed goods) and public law suits as a result of the recall were considerable. </li><li><!--[if !supportLists]-->Within five months of the disaster, the company had recovered 70% of its market share for the drug - and the fact this went on to improve over time showed that the company had succeeded in preserving the long term value of the brand.<o:p><br /></o:p></li></ul><div style="text-align: justify;"> </div><p style="text-align: justify;" class="MsoNormal"><b><o:p> </o:p>What did the company do?<o:p></o:p></b></p><div style="text-align: justify;"> </div><ul style="text-align: justify;"><li><b><o:p> </o:p></b><span style="">They acted quickly, with complete openness about what had happened, and immediately ordered recall from every outlet - not waiting for evidence to see whether the contamination might be more widespread <o:p></o:p></span></li><li><!--[if !supportLists]--><span style="">They showed themselves to be prepared to bear the short term cost in the name of consumer safety. That more than anything else established a basis for trust with their customers <o:p></o:p></span></li><li><!--[if !supportLists]--><span style="">Developed better product protection- tamperproof packaging that would make it much more difficult for a similar incident to occur in future. <o:p></o:p></span></li><li><!--[if !supportLists]--><span style="">They achieved the status of consumer champion. <o:p></o:p></span></li></ul><div style="text-align: justify;"> </div><p style="text-align: justify;" class="MsoNormal"><i style=""><span style="">What the company didn't do was to avoid responsibility. </span><o:p></o:p></i></p><div style="text-align: justify;"> </div><p style="text-align: justify;" class="MsoNormal"><b>Vital Communications: <span style=""> </span>Internal & External</b></p><div style="text-align: justify;"> </div><ul style="text-align: justify;"><li><!--[if !supportLists]-->On all media interviews, expressed sympathy and regret for all those affected and immediately promised that the company would pay all medical costs. </li><li><!--[if !supportLists]-->Conducted regular company-wide conference calls on a daily basis, giving employees the chance to ask questions and get the latest information. This approach proved so popular that the practice of quarterly calls survived the crisis. </li><li>Within 24 hours, the company had an explanatory web site (its first) that received 20,000 hits in 48 hours. The company spoke to the press, appeared on TV and carried out direct advertising with the website address. All possible attempts were made to provide up to the minute, accurate information.</li><li>There were critics who refused to credit the company with any integrity whatsoever - but was considered that as an exercise in crisis management<span style=""> </span><o:p> </o:p></li></ul><div style="text-align: justify;"> </div><p style="text-align: justify;" class="MsoNormal"><b>What can other businesses learn from such a biotech blow-up? <o:p></o:p></b></p><div style="text-align: justify;"> </div><ul style="text-align: justify;"><li><!--[if !supportLists]-->Could J&J have done anything differently? </li><li><!--[if !supportLists]-->Present-day threats and potential costs associated with recalls have never been higher -- one recall can put you out of business. As companies seek to increase their control and in turn, minimize their risks, they discover that varied activities within and outside the organization must be considered, and operations up and down the supply chain must be addressed. </li><li><!--[if !supportLists]-->When potential issues are identified, you can quickly determine the underlying cause, make the necessary corrections, and provide supporting documentation. </li></ul><div style="text-align: justify;"> </div><p style="text-align: justify;" class="MsoNormal"><i style="">Please <a href="mailto:virenkonde@gmail.com">share</a> your thoughts over this case! <o:p></o:p></i></p>Viren Kondehttp://www.blogger.com/profile/18090726614388750732noreply@blogger.com0tag:blogger.com,1999:blog-701594073146171910.post-12913128229640039222007-11-18T21:52:00.000+05:302007-11-19T08:30:37.680+05:30Crisis Management –Technology competent, product license terminated Biotech Company<p style="text-align: justify;" class="MsoNormal">There are many examples to quote for the major challenge faced by the world’s most successful as well as start-up biotech companies: how to overcome the crisis of technologically competent, product license terminated situation of biotech companies. The question is with little or no money situation, how to generate the sufficient clinical data for the re-evaluation of the drug by the regulatory bodies and how to stay alive until the supporting clinical data is generated! Here, the three best possible options are addressed to overcome this situation and you are welcome to add more to it!</p><div style="text-align: justify;"> </div><p style="text-align: justify;" class="MsoNormal">The <span style="font-weight: bold;">‘Tripod’ business model</span> offers a solution:</p><div style="text-align: justify;">1. Seek government funding for the better development of the drug and the technology.<br /><br /><span style="font-style: italic;">If the public health is a major concern, government would most likely to take initiative to support funding a clinical programme and the associated technology development with the industry in collaboration. This way the company can pursue the government agency as a licensing partner in the similar areas of clinical development and generate revenue.</span><br /><br />2. Develop the next-stage technology platform and license it for multiple techno-based applications.<o:p></o:p><br /><br /><span style="font-style: italic;">The main interest of this strategic management would be to progress the marketing of products based on the technology platform. It would build future values in the form of royalties and potential royalty payments could generate future profits for the company in question. This would ultimately build the company’s own manufacturing capacity. </span><br /><br />3. Drive the revenues by selling the drug-associated research reagents and increase recognition of the company.<span style=""> </span><br /><br /><span style="font-style: italic;">The technology-related research reagents could be added to the company’s portfolio. This would generate revenues and create awareness and acceptance of the next-stage technology. In addition to building a strong customer base, it would lead to licensing and partnership opportunities.</span><br /><br />All the above strategies could go hand-in-hand by partnering with other biotech companies for a secure and manageable future of the company.<br /><br />Please drop <a href="mailto:virenkonde@gmail.com">me</a> a line to have your say on this issue.<br /><br /></div>Viren Kondehttp://www.blogger.com/profile/18090726614388750732noreply@blogger.com0tag:blogger.com,1999:blog-701594073146171910.post-63722508270043336202007-11-03T16:04:00.001+05:302007-11-03T16:08:56.068+05:30Risk-reduced cost management practices (No. 5)<div style="text-align: justify;" xmlns="http://www.w3.org/1999/xhtml"><b>5. Drug-Device hybrid model<br /><br /></b><p class="MsoNormal"><o:p>The biotech investments are volatile in nature considering the probability that the drug would fail during clinical trials phase II or III, after much of the time and money has been spent. It is characterized by high risk, in terms of capital commitment and probability of success, and high reward, in terms of profit potential and exit scenarios.</o:p><br /></p><p class="MsoNormal"><o:p>For example, in India, the diabetic drug insulin is manufactured by Torrent Pharmaceuticals, under licence from Novo Nordisk India, and distributed by Abbott India verses the blood glucose measuring device called ‘AccuCheck’ is manufactured and marketed by Roche diagnostics alone. In this scenario, although the cost or risk is reduced the profit is also shared.</o:p><br /></p><p class="MsoNormal"><o:p>The best way to describe the drug-device hybrid is to look at one of the most successful examples set forth by Johnson & Johnson, who created the market opportunity for the drug coated stents used in the coronary artery diseases. As a result, start-up device companies have been formed to develop drug coated stents, or are adapting their strategies to do so. The prospective for the biotech market indicates that the drug-device combination products will experience a promising future and this drug-device hybrid companies would impact the investment allocations by decreasing the cost and lowering the risk. </o:p></p></div>Viren Kondehttp://www.blogger.com/profile/18090726614388750732noreply@blogger.com0tag:blogger.com,1999:blog-701594073146171910.post-13181426582144534082007-10-31T10:35:00.000+05:302008-01-24T12:32:46.878+05:30Biotechnology in India: Public-Private Partnerships<p class="MsoNormal" style="text-align: justify;">My recent article on 'Biotechnology in India: Public-Private Partnerships' has been published by the <a href="http://www.palgrave-journals.com/jcb/journal/v14/n1/full/3050079a.html">Journal of Commercial Biotechnology</a>, published from UK. Please take a look at the abstract below.<br /></p><p class="MsoNormal" style="text-align: justify;"><b style="">Abstract<o:p></o:p></b></p> <p class="MsoNormal" style="text-align: justify;">The purpose of the study being a survey of public sector- private industry collaborations of the biotechnology sector in <st1:place st="on"><st1:country-region st="on">India</st1:country-region></st1:place>, an organizational and functional overview of this sector was needed. Therefore, rather than studying a hypothetical biotechnology sector in India, the area of this work confined to study the public-private partnerships (PPP) that are occurring in India in the area of modern biotechnology. The Indian Government has been playing an important role in the development of biotechnology sector from the very beginning and there are large numbers of R&D institutions (Scientific, Medical, Industrial and Agricultural) which have been set up by the Government during the past two-three decades. Indian Biotechnology industry is advancing towards new heights in alignment with the growth and progression observed globally. The past performance of the industry indicates that it has surpassed the growth rate of many other industries.<span style=""> </span>This paper also highlights the favorable national policies undertaken to strengthen the Indian biotechnology industry. It is in this context that the paper shows that these collaborations are an expression of more general trends towards a changing role for the country in economic production.<br /></p> <p class="MsoNormal" style="text-align: justify;">In case, you are interested reading further on this topic, please send me an <a href="mailto:virenkonde@gmail.com">email</a> to receive the preprint copy of it.<br /></p>Viren Kondehttp://www.blogger.com/profile/18090726614388750732noreply@blogger.com0tag:blogger.com,1999:blog-701594073146171910.post-12689317318508179292007-10-29T13:22:00.000+05:302007-10-29T13:34:36.094+05:30Risk-reduced cost management practices (No. 4)<p class="MsoNormal" style="text-align: justify; font-weight: bold;">4. Outsourcing (CROs)</p> <p class="MsoNormal" style="text-align: justify;"><o:p></o:p>While most attention is paid for reducing the risk and the cost of drug development, from the clinical perspective, contract research organizations (CROs), in order to manage successfully require flexible and efficient management team. Considering the managerial issues, the ‘Monitor closely, Work closely’ team approach proves to be the most accepted across the globe. The basic principle followed by the FIPCOs is certainly based on ‘Inspect, what you expect’ formula.<span style=""> </span>In order to minimize the cost, what needs to be delivered needs to be expected early in the developmental pipeline. Issues like, the increasing attrition rate in CROs, often indicate that the people you end up with are not the people who started the work. The most important thing for any bio/pharma company is to have their communication channels well equipped in terms of rules and regulations that needs to be followed. The middle level product manages required to be rightly placed at the right time in order to monitor the progress efficiently in the hierarchical manner. </p> <p class="MsoNormal" style="text-align: justify;">From drug discovery to selling, the bio/pharmaceutical industry needs new solutions. Outsourcing provides the small pharmaceutical company the ability to take new drugs through clinical trials by avoid the investment in infrastructure which would normally be necessary. These companies are mostly looking at collaborative research outsourcing work to be done out of <st1:country-region st="on"><st1:place st="on">India</st1:place></st1:country-region>. Another theme on collaborative research outsourcing (CRO) is likely to become the next big wave after contract research outsourcing. </p>Viren Kondehttp://www.blogger.com/profile/18090726614388750732noreply@blogger.com0