Amy Ritter was Scientific Editor, BioPharm International.

Amy Ritter, PhD

	Stem cells are being developed to treat a diverse set of conditions, including spinal cord injury, amyotrophic lateral sclerosis, macular degeneration, Parkinsons disease, and Type I diabetes. But the challenges in moving from the laboratory to the clinic are formidable.  The California-based biotech company, Geron, pioneered clinical trials using embryonic stem cells, with a Phase I trial using oligodendrocyte precursors derived from embryonic stem cells to treat spinal cord injury approved in 2009. In November 2011, however, Geron announced it would be discontinuing all of its stem-cell development work, citing cost and regulatory complexity as factors in that decision.

	At the BIO International Convention, a panel will convene to discuss the current landscape for developing stem cell therapies in a breakout session titled Opportunities and Challenges in Developing Innovative Stem Cell Therapies. 

 spoke with one of the session’s presenters, 

Dr. Armand Keating, Epstein Chair in Cell Therapy and Transplantation, University of Toronto

 about the challenges facing developers.  According to Keating, funding remains the biggest challenge in moving from laboratory to clinic.  He points out that unlike small-molecule development, stem-cell development is still very much rooted in academia. The traditional sources of funding available to academics are ill-suited or inadequate to fund preclinical validation studies, manufacturing scale-up studies, or the clinical trials themselves. While an organization such as the California Institute for Regenerative Medicine is able to provide some funding   for early-stage clinical trials, later-stage trials will be far too expensive to be carried out at academic research centers, he says.

	Clarification of statement in podcast: There have been approximately one million bone marrow transplants performed worldwide since 1959.

Articles

Stem cells are being developed to treat a diverse set of conditions, including spinal cord injury, amyotrophic lateral sclerosis, macular degeneration, Parkinsons disease, and Type I diabetes. But the challenges in moving from the laboratory to the clinic are formidable.

Opportunities and Challenges in the Development of Stem-Cell Therapies

AstraZeneca announced further downsizing in response to an expected period of declining revenues in the face of patent expirations. The company will eliminate 2300 positions in sales and general administration. When combined with the reduction in R&D headcount of 1600 announced earlier this week, and the elimination of 1150 positions related to restructuring of a Phase III workforce announced in February 2012, the new announcement brings the total headcount reduction to approximately 5050 over the 2013–2016 period.

, the company outlined five areas of focus intended to return the company to growth.  The company will focus on capturing market share for its platelet aggregation inhibitor, Brilanta (ticagrelor); partner with Bristol Myers-Squibb to achieve a leading position in the noninsulin diabetes market; invest in emerging markets, particularly China; invest in its on-market respiratory portfolio and accelerate its pipeline of respiratory projects; and capture the potential from its established brands and new launches in Japan.

According to the release, the combined program of changes is estimated to incur $2.3 billion in one-time restructuring charges, of which $1.7 billion are expected to be cash costs. Benefits of approximately $800 million per year are expected by 2016.

AstraZeneca announced further downsizing in response to an expected period of declining revenues in the face of patent expirations. The company will eliminate 2300 positions in sales and general administration.

AstraZeneca Announces an Additional 2300 Layoffs

AstraZeneca announced that it will consolidate its R&D capabilities into three centers located in Cambridge, UK; Gaithersburg, MD in the US; and Mölndal, Sweden.  The move is designed to concentrate R&D near nationally recognized research hubs and to reduce complexity and costs by shrinking the company’s footprint.  The reorganization will lead to the relocation of nearly 2500 positions and an overall estimated reduction in headcount of 1600 positions, according to a company 

. The vast majority of job losses will be in the UK and the US.

AstraZeneca will invest approximately $500 million to establish a new, purpose-built facility in Cambridge that will house the company’s UK-based small molecule and biologics R&D. Cambridge will also become AstraZeneca’s new global corporate headquarters. The consolidation means that R&D will no longer be carried out at the Alderley Park, Cheshire site in the UK. According the release, approximately 1600 positions will relocate from Alderley Park, with the majority going to the new center in Cambridge and the remainder to the company’s nearby Macclesfield manufacturing facility or other AstraZeneca sites overseas. In addition, the majority of corporate and global commercial roles based in London are expected to move to Cambridge, with some going to other AstraZeneca sites. Following the transfer of the company’s headquarters to Cambridge, AstraZeneca’s Paddington office will close by 2016. 

Gaithersburg, which is the site of MedImmune’s headquarters and the primary location for AstraZeneca’s biologics activities, will also become home to much of the company’s US-based Global Medicines Development activities for small and large molecules and will accommodate some global marketing and US specialty care commercial functions, according to the release. 

In the US, the company expects an overall reduction of approximately 650 positions. Wilmington, DE will remain the company’s North America commercial headquarters. However, with the exit of the Global Medicines Development group and the relocation of global marketing and US specialty care commercial roles, Wilmington will lose approximately 1200 positions. There will be a net increase of approximately 300 positions in Gaithersburg and approximately 170 positions will be moved to other AstraZeneca sites in the US or overseas.

AstraZeneca’s site in Mölndal, near Gothenburg, will continue to be a global center for research and development, with a primary focus on small molecules.

AstraZeneca announced that it will consolidate its R&D capabilities into three centers located in Cambridge, UK; Gaithersburg, MD in the US; and M?lndal, Sweden. The reorganization will result in a net loss of 1600 positions, mainly in the UK and the US.

AstraZeneca to Cut 1600 Positions in R&D Reorganization

INTERPOL and 29 of the world’s largest pharmaceutical companies have joined forces in an initiative to battle counterfeit drugs. INTERPOL announced the creation of the Pharmaceutical Crime Programme to further build on the work of its Medical Product Counterfeiting and Pharmaceutical Crime (MPCPC) unit. The program is funded by $5.9 million (EUR $4.5 million) from pharmaceutical industry partners. According to a 

, the program will focus on the prevention of all types of pharmaceutical crime, including branded and generic drug counterfeiting as well as the identification and dismantling of organized crime networks linked to drug counterfeiting.

“Both brand-name and generic pharmaceuticals are susceptible to counterfeiting, putting patient lives at risk,” said Haruo Naito, president and CEO of Eisai, in the release. “This is why we have joined our colleagues across the biopharmaceutical industry to partner with INTERPOL and expand the work of its Medical Product Counterfeiting and Pharmaceutical Crime Unit. We fully support INTERPOL's decision to establish a comprehensive initiative that will enhance its efforts to prevent medical product counterfeiting and pharmaceutical crime. Ultimately, this is about protecting patients around the world.”

INTERPOL and 29 of the worldâ€™s largest pharmaceutical companies have joined forces in an initiative to battle counterfeit drugs.

INTERPOL and Pharma Collaborate to Fight Counterfeiting

 that it has signed an agreement to acquire the generic injectables unit Agila Specialties from Strides Arcolab for $1.6 billion in cash.  The acquisition will significantly expand and strengthen Mylan’s global injectables platform and provide entry into new, high-growth geographic markets, according to a company press release. The transaction is expected to close in the fourth quarter of 2013, subject to regulatory approvals and certain closing conditions.

Agila is based in Bangalore, India, and currently holds a portfolio of more than 300 products marketed in 70 countries, including 61 products approved by FDA.  In addition, Agila’s pipeline contains 350 filings pending approval, including 122 filed in the US. The company currently produces products across nine manufacturing facilities in India, Brazil, and Poland, eight of which have been approved by FDA. Its manufacturing capabilities include vials, prefilled syringes, ampuls, lyophilization, cytotoxics, and antibiotics. Agila’s portfolio complements Mylan’s existing injectables business, which consists of more than 500 products marketed globally.

Mylan CEO Heather Bresch says in the release, "The addition of Agila to our existing injectables platform will immediately create a new, powerful global leader in this fast-growing, attractive market segment and accelerate our target of becoming a top-three global player in injectables. Further, the acquisition of this unique asset delivers on several of Mylan's strategic growth drivers by further expanding and diversifying our product portfolio and geographic reach, strengthening our presence in the institutional channel, and positioning us to maximize our generic biologics portfolio. Agila's broad product portfolio and pipeline, which is very complementary to Mylan's, is the result of best-in-class research and development and an industry-leading track record of securing product approvals. Importantly, Agila will bring us one of the most state-of-the-art, high quality injectables manufacturing platforms in the industry. Our significantly expanded manufacturing capacity will allow us to vertically integrate our injectables platform and fast-track our ability to pursue additional product opportunities and partnerships to facilitate long-term growth. We are excited to welcome the Agila employees to our growing global team and anticipate a seamless and rapid integration of the Agila business."

Mylan announced that it has signed an agreement to acquire the generic injectables unit Agila Specialties from Strides Arcolab for $1.6 billion in cash.

Mylan Acquires Generic Injectables Unit From Strides Arcolab

	In January, 2011, FDA released its guidance, Process Validation, General Principles and Practices, describing process validation practices based on quality-by-design principles. At the IBC Biopharmaceutical Development and Production conference held this week in Huntington Beach, California, scientists described how their companies have been working toward implementing the guidance for the production of biopharmaceuticals.
	Vijay Chiruvolu, director of corporate validation at Amgen discussed his company’s current process validation practices. Amgen, he explained, was somewhat ahead of the game, having worked toward implementing a data-driven and risk-based approach to process validation before the guidance was finalized. For the past 10 years, Amgen has taken a lifecycle approach to process validation, by beginning to plan process validation strategies during the early phases of process design and by continuing to update the plan throughout the lifecycle of the product. Process validation, he explained, is not a once-and-done activity, but should be adjusted as process understanding improves over time, or as expected or unexpected process changes require additional validation.
	Peter Calcott, president of Calcott Consulting, weighed in with what the guidance means for small companies. Big biotechs like Amgen can devote a lot of resources towards risk assessment, process understanding, and developing a risk-based process validation plan, but smaller entities that outsource some or all of their process development and manufacturing activities will likely not have the staff or knowledge necessary to implement the guidance on their own. Calcott said he is commonly asked how much effort a company should spend in implementing the new guidance, and his advice, he says, depends on what the company’s business model is and where in the development cycle they are. For example, companies in early stages of development that expect to sell the compound to a larger entity for development need not concern themselves with the guidance, with the expectation that process validation will fall to someone else. A company that expects to manufacture and perhaps market the compound itself, however, should invest the time and resources to develop a compliant process validation plan.

In January, 2011, FDA released its guidance, Process Validation, General Principles and Practices, describing process validation practices based on quality-by-design principles.