General Biotechnology

This is a guest post from Halina Zakowicz, Marketing Specialist at Biovest International, Inc. Do you have a response to Halina’s post? Respond in the comments section below.

Scaling up cell culture production can be a tricky proposition.halina

Generating large amounts of cell-secreted proteins is labor-intensive when utilizing traditional cell culture methods. Quality and yields can be inconsistent; these methods are also prone to contamination due to multiple aseptic manipulations. Making the jump to large-scale systems isn’t easy either, often requiring capital expenditures that are not feasible.

Have you been using petri dishes, plates, flasks or spinner bottles for small-scale production of cell-secreted proteins? Are you looking to scale up your protein manufacturing using alternatives to traditional mammalian and insect cell culture?

If so, you should consider hollow fiber bioreactors.

Scaling up poses many challenges

Small-scale cell culture typically requires little more than individual bottles of media, a tabletop incubator and 30-60 minutes a day from a lab technician. However, generating cell numbers that are 100-10,000 fold higher catches many labs short-handed. Lab technicians are usually not hired to perform cell culture as their full-time job; furthermore, lab space is always at a premium.

There are a number of challenges involved in scaling up cell culture, including the following:

Different cell dynamics

What is frequently taken for granted is how the dynamics of nutrient delivery and waste removal change as a function of scale. When expanding and supporting large-scale cell culture volumes, the maintenance of proper pH and temperature becomes challenging, as does the delivery of adequate oxygen, nutrients and growth factors.

Increased labor requirements

Not only do increased numbers of cells require additional passaging, but once the cell-derived products are ready to harvest, they must be purified and concentrated from large volumes of supernatant. Both the additional cells and their derived products require additional labor.

Increased lab space requirements

Many laboratories scale up their production capacity by investing in entire rooms filled with spinner flasks or roller bottles; other labs purchase large stirred-tank bioreactors. Both of these options take up valuable laboratory space.

Higher costs

When expanding cell culture operations, expense and capital budgets are used to purchase extra media, sera and specialized equipment. Additional technician hours must be allotted and budgeted for.

Hollow fiber bioreactors offer one solution

To address the challenges posed by large-scale cell culture, researchers and commercial manufacturing operations are increasingly turning to an established, yet not well known, technology called the hollow fiber bioreactor. This technology addresses the problems outlined above by reducing the following:

Media

The hollow fiber bioreactor system consists of thousands of semi-permeable capillary membranes arranged in parallel and bundled into small cylindrical polycarbonate shells that typically take up the volume of a 12-ounce beverage can.

As a result, two distinct and separate compartments are generated: an intracapillary (IC) space enclosed within the hollow fibers, and an extracapillary (EC) space surrounding the hollow fibers.

hollow-fiber-bioreactorFigure 1. A standard hollow fiber bioreactor shown with its enclosed intracapillary (IC) and extracapillary (EC) spaces.

The small size of the hollow fiber bioreactor system means that significantly less media is required compared with stirred-tank bioreactors. Also, growth factors and other high molecular weight nutrients are unnecessary in the IC space, resulting in a reduced need for serum.

Oversight

Hollow fiber bioreactor systems can be automated for media flow, pH, temperature and oxygen control, and EC cycling. The automation of these cell culture parameters means that less oversight is required to grow large numbers of healthy cells (>109 cells/ml) and to generate large quantities of cell-secreted proteins.

Space

Stirred-tank bioreactors require additional laboratory space for housing and maintenance. Animals used for ascites production must be housed in specialized rooms. In contrast, hollow fiber bioreactor systems have a very small footprint and in many cases can be stored on a lab bench or inside an incubator.

Downstream processing

Because cell-secreted proteins such as monoclonal antibodies or vaccines remain with the cells in the EC space of the hollow fiber bioreactor, they automatically concentrate and do not need to undergo time-consuming downstream processing, a required step for most protein manufacturing processes.

Enabling efficient, cost-effective protein production

Due to their technological advantages over traditional cell culture methods, hollow fiber bioreactors are being increasingly used by academic and research laboratories and biotech manufacturing plants for mammalian and insect culture-based protein production. They also have been — for decades — the workhorse of companies that manufacture human and veterinary IVD products worldwide.

In light of the recent influenza outbreaks, for example, there has been particular interest in using hollow fiber technology to rapidly produce viral vaccines not tainted by allergy-inducing animal proteins. Likewise, both price and ethical concerns over using mouse ascites have situated the hollow fiber bioreactor as a more humane method for large-scale in vitro generation of monoclonal antibodies and other cell-secreted proteins.

Because the hollow fiber bioreactor offers a compact, efficient, economical and long-lived method for protein generation, this technology is becoming increasingly employed across laboratories, and especially laboratories that wish to find an easy and cost-effective method for scaling up their production capacities.

About the author:
As marketing specialist at Biovest International, Inc., Halina helps customers understand how hollow fiber bioreactors can be used to scale up traditional cell culture and facilitate novel in vitro applications like vaccine production. Biovest also uses hollow fiber technology in its upstream protein manufacturing and downstream processing services when working with academic, research and pharmaceutical customers.

Journal of Commercial Biotechnology This paper is part of the free Open Access archive of the Journal of Commercial Biotechnology

Biotechnology in India: Public–private partnerships

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ABSTRACT: As the purpose of this study was a survey of public sector–private industry collaborations of the biotechnology sector in India, an organisational and functional overview of this sector was needed. Therefore, rather than studying a hypothetical biotech sector in India, the focus of this work was to study the public–private partnerships (PPP) that are occurring in India in the area of modern biotechnology...

The Journal of Commercial Biotechnology is a unique forum for all those involved in biotechnology commercialization to present, share, and explore new ideas, latest thinking and best practices, making it an indispensable guide for those developing projects and careers within this fast moving field.

Each issue publishes peer-reviewed, authoritative, cutting-edge articles written by the leading practitioners and researchers in the field, addressing topics such as:

  • Management
  • Policy
  • Finance
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For more information, see the Journal of Commercial Biotechnology website

Journal of Commercial Biotechnology This paper is part of the free Open Access archive of the Journal of Commercial Biotechnology

Assessing the history and value of Human Genome Sciences

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ABSTRACT: Human Genome Science (HGS) aspired to dominate the emergent field of genomics by discovering expressed gene sequences and developing therapeutic and diagnostic products based on proprietary genes. While HGS’ accomplishments fell short of their own lofty expectations, by the time HGS was acquired by GlaxoSmithKline, the company had extensive intellectual property and had launched a product with >$1 billion market potential...

The Journal of Commercial Biotechnology is a unique forum for all those involved in biotechnology commercialization to present, share, and explore new ideas, latest thinking and best practices, making it an indispensable guide for those developing projects and careers within this fast moving field.

Each issue publishes peer-reviewed, authoritative, cutting-edge articles written by the leading practitioners and researchers in the field, addressing topics such as:

  • Management
  • Policy
  • Finance
  • Law
  • Regulation
  • Bioethics

For more information, see the Journal of Commercial Biotechnology website

Drug Patent Expirations for March 2015

Tradename Applicant Generic Name Patent Number Patent Expiration
SUSTIVA Bristol Myers Squibb efavirenz 5,663,169*PED Mar 2, 2015
ATRIPLA Gilead efavirenz; emtricitabine; tenofovir disoproxil fumarate 5,663,169*PED Mar 2, 2015
DEPOCYT Pacira Pharms Inc cytarabine 5,723,147 Mar 3, 2015
AGENERASE Glaxosmithkline amprenavir 5,723,490 Mar 3, 2015
DEPODUR Pacira Pharms Inc morphine sulfate 5,723,147 Mar 3, 2015
KYNAMRO Genzyme Corp mipomersen sodium 6,222,025 Mar 6, 2015
ENABLEX Warner Chilcott Llc darifenacin hydrobromide 5,096,890 Mar 13, 2015
ADENOSCAN Astellas adenosine 5,731,296 Mar 24, 2015
IPRIVASK Marathon Pharms Llc desirudin recombinant 5,733,874 Mar 31, 2015
MIACALCIN Sebela Ireland Ltd calcitonin salmon 5,759,565 Mar 31, 2015
ONEXTON Dow Pharm benzoyl peroxide; clindamycin phosphate 5,733,886 Mar 31, 2015
MIACALCIN Sebela Ireland Ltd calcitonin salmon 5,733,569 Mar 31, 2015
ACANYA Dow Pharm benzoyl peroxide; clindamycin phosphate 5,733,886 Mar 31, 2015
*Drugs may be covered by multiple patents or regulatory protections. See the DrugPatentWatch database for complete details.

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Global Biotechnology InventorsI was just notified of a fascinating paper citing my research from DrugPatentWatch.com.

Briefly, I found two surprising results: Firstly, pharmaceutical innovation has been essentially immobile — it remains almost completely rooted in the United States and Western Europe. Secondly, there is virtually no innovation coming out of so-called emerging economies such as India and China (i.e. <1% as many patent inventors as the US).

Going further, Hu et al published a social network analysis of pharmaceutical innovation. They found that the network of international collaboration developed from a star-like US-centric network in the late 1990s to a more distributed network with a diminished centrality of the US in the late 2000s. Importantly the decrease is US centrality is due to increase collaboration between European neighbors, rather than due to a rise among emerging economies.

This is a guest post from Susan K Finston, President of Finston Consulting. Do you have a response to Susan’s post? Respond in the comments section below.

Susan Kling FinstonFor the next chapter in this continuing series, let’s turn back to India and the draft National IPR Policy currently under debate in New Delhi. A great deal of digital ink has been spilled on the constitution of the IPR Think Tank that produced the draft Policy, with less attention given to the importance of the detailed recommendations to improve the environment for creation, commercialization and management of IP in India, with particular attention to the IP challenges of Micro-Small & Medium Enterprises or MSMEs.

With regard to the appointments to the IP Think Tank, IPR academics,  NGOs and assorted IP-skeptics are aggrieved by the appointment of actual IP practitioners with experience in corporate affairs, industrial R&D, patent litigation, WIPO and the Courts, preferring that the Centre Government leave IP policy to the PhDs to avoid ‘potential conflict of interest.’ These criticisms are available online here and here.

In the event, the Modi Government chose a broader, gender-diverse range of experts for the IP Think Tank, appointing a venerable former Judge of the Madras high court, Justice Prabha Sridevan as Chairperson, and including two of India’s leading female litigators, Senior Advocate Ms. Pratibha Singh and Advocate Ms Punita Bhargaval. Rounding out the group are Dr. Unnat Pandit of Cadila Pharmaceuticals Ltd., Shri Rajeev Srinivasan, Director, Asian School of Business, Thiruvananthapuram, and Shri Narendra K. Sabharwal, Retired Deputy DG, World Intellectual Property Organization (WIPO) and now Chair of the FICCI-IPR Committee as the final member and Convenor. The Modi Government also provided opportunities for public comment by stakeholders including both before and after the IPR Think Tank’s submission of the draft document, and posted the draft National IPR Policy online.

Apart from persistent ad hominem attacks on IPR Think Tank Members – because only professors can be ‘IP experts’ –  the primary substantive complaint relating the draft IPR Policy is the threadbare assertion that there is no link between IP, innovation and assimilation of novel technologies for creation of economic and social value. This is an issue that also figured prominently in an earlier ill-fated IP Policy Baseline Draft submitted to the Modi Government by Professors Shamnad Basheer and Yogesh Pai.

Before circling back to the linkages between IP protection and enterprise development, it may be helpful to review the origins on the Basheer/Pai Document, where the Modi Government had earlier tasked three Ministry of Human Resource Development (MHRD) IP chairs – Professors Prabuddha Ganguli, Shamnad Basheer and Yogesh Pai – with submitting a draft IP policy. At some point Prabuddha Ganguly, the senior member of the team with perhaps the greatest expertise on the strategic importance of IP for enterprises, left the group. The remaining two like-minded academes Shamnad Basheer and Yogesh Pai apparently did not seek advice from the Government on how to – or even whether to – proceed, and subsequently submitted a beautifully drafted if highly impractical document.
(In full disclosure: I have known Prabuddha Ganguly and Shamnad Basheer for many years. I respect and admire them both. While I do not know Shri Yogesh Pai personally, as he is Shamnad’s close colleague I am sure he is also brilliant.)

The Basheer/Pai draft is a lyrical document, coming close to poetry in parts, with majestic, soaring language, like the following:

“While India will continue to draw on foreign precedent from jurisdictions that have had a longer and more sophisticated history with intellectual property, it will not blindly adopt their norms. Rather it will seek to adapt them to the local conditions in a bid to promote and protect national interest. Much in line with words of wisdom from the father of the nation, Mahatma Gandhi who once said: “I do not want my house to be walled in on all sides and my windows to be stuffed. I want the cultures of all lands to be blown about my house as freely as possible. But I refuse to be blown off my feet by any.’“ (p. 2)

However earnestly felt, the Basheer/Pai document reads like an IP manifesto rather than a national IP policy, lacking specific, detailed policy recommendations needed by Indian Industry for IP administration, adjudication, or training.  Basheer and Pai dispose of IP enforcement issues in the closing paragraph in 4 sentences (and one fragment)(p. 11). While touching on traditional knowledge, the paper makes no recommendations for improving access to IP rights for R&D-intensive MSMEs, despite growing recognition that innovative MSMEs face the greatest challenges in gaining needed IP protection in India.

In the final analysis,  the challenges facing India’s innovative MSMEs may provide the best response to IP-skeptics on the important connection between IP protection and innovation.

Unlike many larger firms, R&D Intensive MSMEs rely to a much greater degree on their innovative capacities and the ability to protect their creations – whether these are copyrighted works, trademarked products or patentable inventions. MSMEs in OECD-member states like Israel and the United States that have a greater ability to protect and commercialize their technologies, have a track record of creating substantial economic and social benefit in the process.

In fact the original third HRD IP Expert, Prabuddha Ganguly, has undertaken critical research in this area in his role as a WIPO consultant.  He has presented compelling data on the importance of IP protection for MSME enterprises at WIPO events around the globe, as in this paper for a 2004 regional WIPO event in Oman.

Beyond any research, my ongoing work as co-founder of emerging Indian biotech Amrita Therapeutics and consulting (transactional) work for innovative MSMEs provides daily reminders of the causal relationship between the ability of MSMEs to protect their creative works, process and/or products through IP protection, and the effective diffusion and assimilation of new technologies for creation of social and economic value.

Comparing the Basheer/Pai manifesto side by side with the Draft National IPR Policy underscores the wisdom of the Modi Government’s reboot, and calls to mind the old saw:  those who can do, those who can’t teach.  However much we may benefit from IP-Skeptics who keep challenging our IP assumptions, it may better for the rest of us if they are not charged with actual policy making in the meantime!

About the author:
President of Finston Consulting LLC since 2005, Susan works with innovative biotechnology and other clients ranging from start-up to Fortune-100, providing support for legal, transactional, policy and “doing business” issues. Susan has extensive background and special expertise relating to intellectual property and knowledge-economy issues in advanced developing countries including India and South Asia, Latin America and the Middle East North Africa (MENA) region. She also works with governments, and NGOs on capacity building and related educational programs through BayhDole25. Together with biotechnology pioneer Ananda Chakrabarty, she also is co-founder of Amrita Therapeutics Ltd., an emerging biopharmaceutical company based in India with cancer peptide drugs entering in vivo research. Previous experience includes 11 years in the U.S Foreign Service with overseas tours in London, Tel Aviv, and Manila and at the Department of State in Washington DC. For more information on latest presentations and publications please visit finstonconsulting.com.

Journal of Commercial Biotechnology This paper is part of the free Open Access archive of the Journal of Commercial Biotechnology

What will it take to get institutional investors interested in life sciences again?

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ABSTRACT: With the European biotechnology market nearing a crisis state, companies must try to attract and maintain interest from institutional investors. In this article, a brief outline of who companies should be trying to appeal to and how these investors view the sector is followed by an assessment of the areas that management must focus on to attract investors...

The Journal of Commercial Biotechnology is a unique forum for all those involved in biotechnology commercialization to present, share, and explore new ideas, latest thinking and best practices, making it an indispensable guide for those developing projects and careers within this fast moving field.

Each issue publishes peer-reviewed, authoritative, cutting-edge articles written by the leading practitioners and researchers in the field, addressing topics such as:

  • Management
  • Policy
  • Finance
  • Law
  • Regulation
  • Bioethics

For more information, see the Journal of Commercial Biotechnology website

Journal of Commercial Biotechnology This paper is part of the free Open Access archive of the Journal of Commercial Biotechnology

Growth of Indian biotech companies, in the context of the international biotechnology industry

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ABSTRACT: The paper discusses the evolution and growth of Indian biotech companies in recent years. It focuses on the alternative business models key players in the industry have adopted and highlights the activities and achievements of some of the globally competitive companies across various segments of the market...

The Journal of Commercial Biotechnology is a unique forum for all those involved in biotechnology commercialization to present, share, and explore new ideas, latest thinking and best practices, making it an indispensable guide for those developing projects and careers within this fast moving field.

Each issue publishes peer-reviewed, authoritative, cutting-edge articles written by the leading practitioners and researchers in the field, addressing topics such as:

  • Management
  • Policy
  • Finance
  • Law
  • Regulation
  • Bioethics

For more information, see the Journal of Commercial Biotechnology website

Drug Patent Expirations for January 2015

Tradename Applicant Generic Name Patent Number Patent Expiration
ENTOCORT EC Astrazeneca budesonide 5,643,602*PED Jan 1, 2015
VISUDYNE Valeant Pharms Inc verteporfin 5,770,619 Jan 6, 2015
SILENOR Pernix Theraps Llc doxepin hydrochloride 5,725,884 Jan 9, 2015
SILENOR Pernix Theraps Llc doxepin hydrochloride 6,103,219 Jan 9, 2015
SILENOR Pernix Theraps Llc doxepin hydrochloride 6,217,909 Jan 9, 2015
SILENOR Pernix Theraps Llc doxepin hydrochloride 5,866,166 Jan 9, 2015
SILENOR Pernix Theraps Llc doxepin hydrochloride 5,585,115 Jan 9, 2015
SILENOR Pernix Theraps Llc doxepin hydrochloride 5,948,438 Jan 9, 2015
LIPOFEN Cipher Pharms Inc fenofibrate 5,545,628 Jan 10, 2015
RISPERDAL Janssen Pharms risperidone RE39181*PED Jan 11, 2015
RISPERDAL Janssen Pharms risperidone 5,453,425*PED Jan 11, 2015
SPORANOX Janssen Pharms itraconazole 5,707,975 Jan 13, 2015
NORVIR Abbvie ritonavir 5,648,497*PED Jan 15, 2015
KALETRA Abbvie lopinavir; ritonavir 5,648,497*PED Jan 15, 2015
RISPERDAL Janssen Pharms risperidone 5,648,093*PED Jan 15, 2015
NORVIR Abbott ritonavir 5,648,497*PED Jan 15, 2015
PREMPRO Wyeth Pharms Inc estrogens, conjugated; medroxyprogesterone acetate 5,547,948 Jan 17, 2015
PREMPHASE 14/14 Wyeth Pharms Inc estrogens, conjugated; medroxyprogesterone acetate 5,547,948 Jan 17, 2015
CYMBALTA Lilly duloxetine hydrochloride 5,508,276*PED Jan 18, 2015
DALIRESP Forest Res Inst Inc roflumilast 5,712,298 Jan 27, 2015
ESTRASORB Medicis estradiol hemihydrate 5,629,021 Jan 31, 2015
*Drugs may be covered by multiple patents or regulatory protections. See the DrugPatentWatch database for complete details.

Subscribers have access to valuable datasets, including:

  • Clinical trial information
  • International patent families
  • International patent priority and PCT information
  • Patent maintenance
  • Full-text patent downloads
  • Sales data (top 200 drugs)
  • Paragraph IV challenges
  • Tentative approvals
  • Dynamic search capabilities with data export
  • More…
See the Database Preview and Plan Comparison.
Contact Us with any questions.

Journal of Commercial Biotechnology This paper is part of the free Open Access archive of the Journal of Commercial Biotechnology

Technology transfer in the biomedical sciences: The Medical Research Council approach

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ABSTRACT: This paper describes why the UK Medical Research Council participates in exploitation (an integral part of its mission), the objectives for exploitation (primarily to serve public food through contributions to the health and wealth of the UK) and how the organisation of exploitation is structured...

The Journal of Commercial Biotechnology is a unique forum for all those involved in biotechnology commercialization to present, share, and explore new ideas, latest thinking and best practices, making it an indispensable guide for those developing projects and careers within this fast moving field.

Each issue publishes peer-reviewed, authoritative, cutting-edge articles written by the leading practitioners and researchers in the field, addressing topics such as:

  • Management
  • Policy
  • Finance
  • Law
  • Regulation
  • Bioethics

For more information, see the Journal of Commercial Biotechnology website