Next meeting ACTIP:

May 26-27-28, 2010, Pueblo Acantilado, El Campello (Alicante), Spain
and is hosted by the ACTIP Steering Committee , Executive Secretary and ACTIP Secretariat.
This meeting, the 20th anniversary of ACTIP, will review science, technology and business aspects in animal cell technology both in the past and in the future. It will also have a session on product and process quality.
For ACTIP member companies and invited guests only.

In this issue:
European News
Vaccine News
Business News
Collaborations and mergers
Biomanufacturing News
Stem cell news
Clinical trials and results
Regulatory News
EDQM and EMEA News
Agenda

European News

Reinvigorating European R&D innovation

Despite its importance to Europe, its pharma industry is not as innovative as it once was and has lost ground to foreign rivals. This shift has been exacerbated by ambivalent attitudes from regional governments towards the industry; on the one hand, governments value the industry's economic contribution and its role in providing medicines, but they are also preoccupied with the rising cost of healthcare. As a result, pharma companies are under pressure to reduce their product prices.
European companies believe that government cost containment measures have damaged the region's competitiveness, and point to R&D investment figures as evidence. In 1990, pharmaceutical R&D investment in the US was less than in Europe; however, R&D investment in Europe now is only approximately 70% of the US figure.1 Between 1990 and 2008, R&D investment in the US grew by 5.6 times compared with 3.5 times in Europe.1 To compound the situation, Europe also faces competition from further afield because of the rapid growth in the research environment in emerging economies, such as China and India. The European Federation of Pharmaceutical Industry Associations (EFPIA) has expressed its concern that this trend has led to the closure of European R&D sites.
Government policies alone, however, cannot be blamed for the difficult R&D conditions. Because of the inherent risks of drug development, many companies have adopted a conservative attitude to using new technologies that may add extra risk to the process, but the steady decline in new drug output suggests that this cautious approach is undermining innovation. However, although there is recognition that bottlenecks exist in the current R&D process, few solutions have been found to ease them.

EFPIA's analysis of the period 2004 to 2008 shows that, while European companies have experienced a decline in new drug output, their US counterparts have become the world leading inventors of new molecules.(1) This trend is worrying — particularly as the US pharma industry has expressed frustration at its own low level of innovation!(2,3) Similarly, the emerging markets of China and India are also considered to be far from optimal environments for R&D. (4,5)
Many in the industry believe that there is no reason why Europe should not be able to keep pace with the US, given the existence of high quality research resources. Many also believe that the way to reinvigorate Europe's R&D lies in a collaborative approach, featuring both public and private parties. This thinking has led to the development of the Innovative Medicines Initiative (IMI), a public–private partnership designed by the European Commission (EC) and EFPIA, to find clear, practical paths to accelerating drug development and stimulate regional R&D.(6)
The operation of the IMI is similar to that of a nonprofit organization, with research grants being awarded to European public–private collaborations. While public money will be used to fund academic and patient participation and support SMEs, large biopharmaceutical companies will fund their own contributions.

Source: www.Pharmtech.com, March , 2010

EU commissioner planning 'step change' in innovation policy

Europe's new Research and Innovation Strategy will be "fundamentally different to what we've done before," EU Innovation Commissioner Máire Geoghegan-Quinn told EurActiv in an exclusive interview.The plan, due to be published in the autumn, will have a holistic definition at its core, according to the Commissioner, who says social innovation, industrial policy, design, and a new method for measuring the impact of R&D spending will be part of the strategy.
Work on earlier drafts of the document began in 2009 at the EU executive's enterprise wing but this has been broadened considerably thanks to input from commissioners responsible for education, regional policy, internal market and others.But despite resistance to research goals and naked opposition to poverty and education targets from EU leaders, the innovation commissioner believes member states are subscribing to the 2020 blueprint.
"I think it is being embraced. Because there's a realization that every country has its own economic difficulties and none can deal with it alone. I think the Greek situation has proven that it's the euro zone that's under attack. It's not just Greece that's under attack. We all have to work together," said Geoghegan-Quinn.
While most countries failed to meet the 3% target that featured in the previous ten-year growth strategy, the commissioner says this time will be different."This time, our services are working with each different member state to define within their circumstances, based on where they are [and] what the actual target should be in their case," she said. This will mean individual targets for each member state and a tailored roadmap on how to ratchet up R&D investment from public and private sources. 
The commissioner is also committed to reaching out to the public. She wants to see greater efforts to engage citizens on scientific matters and to explain how Europe's multi-billion euro research budget is spent.

Source: EurActiv News, May 5, 2010

EU wants researchers 'in the lab, not in the office'

Scientists will face less paperwork under a new bureaucracy-cutting plan outlined by the European Commission on  29 April, which also aims to make it easier for small businesses to tap into European research funds.
EU research represents 5% of overall public spending in Europe. Funding programmes are always oversubscribed but there is concern that world-class researchers think European money comes with too many strings attached. Researchers complain that EU research programmes burden them with too much red tape (EurActiv 24/03/10). This has made European grants less attractive to top scientists who frequently opt for national funding rather than take on the complex task of meeting EU audit criteria. However, the economic crisis has strained public finances across Europe and research budgets are not immune from the cutbacks. With shrinking pots of money available to researchers in EU member states, multi-billion euro R&D budgets may become more attractive.
Another frequent complaint is that small businesses find it difficult to access big EU research programmes. 80% of SMEs applying for European research funding are turned down, a fact which discourages high-tech start-ups from applying for funding in the first place (EurActiv 02/10/09).
Máire Geoghegan-Quinn, EU commissioner for research, innovation and science, says she wants scientists "to spend more time in the lab and less time in the office". Geoghegan-Quinn has launched a detailed proposal designed to make EU-funded research projects more attractive.
She noted that almost 11,000 people had signed a petition demanding that funding be based on trust rather than tick-box auditing. "I agree with every single word. And SMEs are telling us almost the same thing — they want to take part, but some are hesitating over the administrative burden," said the commissioner.

Simplified application and payment systems

Geoghegan-Quinn said some changes are already under way in areas like reducing form-filling, improved IT tools and clearer guidance for applications. She said a new financial regulation, due to be introduced next month, will pave the way for more radical changes.
The Commission wants to pay researchers and companies based on average costs, rather than forcing them to account separately for all of their costs and for each task performed by staff. More flat-rate reimbursements will be used and there will be more cash prizes for scientists, which give more freedom. Geoghegan-Quinn told EurActiv that if the prize money turns out to be more than the cost of the research project, scientists or companies will be allowed tokeep the excess and reinvest it in other R&D projects.

Harmonisation of accounting methods

The new rules will push member states towards greater harmonisation of accounting methods for research funding. The Commission will allow projects to use the same methods for EU schemes as for national funding projects, on the basis that using one accounting method instead of two will save time and reduce errors.
The detailed proposals will require a decision from the European Parliament and European Council, according to the commissioner. She said some of the changes can come into force without delay but others will have to wait until the new framework research programme kicks off in 2014.
The research commissioner has also launched a comprehensive review of all aspects of FP7, led by a group of independent experts. Led by Swedish research expert Rolf Annerberg, the panel will present a report to the EU executive this autumn.

Source: EurActiv News, April 30 and May 17, 2010

EU looks to US model for measuring R&D impact

A major push is under way in the US to work out how to measure the long-term impact of public support for R&D. Policymakers on both sides of the Atlantic believe a common system would make sense given the global nature of science.
A large chunk of US President Barack Obama's stimulus package was devoted to research, but the administration's focus on transparency and accountability has heightened pressure to demonstrate a return on investment in science.Dr Julia Lane, responsible for 'Science of Science & Innovation Policy Design' at the National Science Foundation (NSF) in the US, said there is widespread belief that investment in R&D breeds economic growth but this must be demonstrated using a robust performance measurement.Speaking in the European Parliament on Wednesday 14 April, she said current ways of justifying research spending were too crude and that relying on anecdotal evidence of how science helps society was not good enough. However, Lane acknowledged that systems for addressing this problem are currently not well developed. Filling this gap is a problem common to all developed nations with an interest in innovation, she said, suggesting Europe, the US, Brazil, Japan and others should work together to agree a system for measuring return on investment.
The US is working on a new system known as Star Metrics — Science and Technology for America's Reinvestment: Measuring the Effect of Research on Innovation, Competitiveness and Science.The initial motivation for this is to examine whether job creation has resulted from stimulus spending but Lane wants a more sophisticated system capable of accounting for the knock-on effects of science spending. This could include direct job creation, helping to create a skilled workforce which benefits the private sector, generating patents, improving healthcare and the environment, she said.
Scientists are often reticent when it comes to auditing systems. But the model under development in the US has sparked fears it could hurt basic research and foster a new layer of red tape. This, says Lane, is not what will happen with Star Metrics. She believes there is enough data generated automatically to design an electronic system which "scrapes" the Internet for relevant information about publications, patents, company registrations and details of where science students work after graduation. "Brazil has already done a great deal of work on this automated use of existing information, which minimizes the burden on scientists but captures large amounts of data," Lane told an audience of MEPs and officials from the European Commission.

Source: EurActiv News, April 16, 2010

Vaccine News

Vaccines that can beat the heat

Mixing virus-based vaccines with sugars and allowing them to dry on a simple filter can keep them stable for four months, even at tropical temperatures. The process, developed and tested by scientists at Nova Bio-Pharma Technologies and the University of Oxford, could provide an inexpensive way to streamline vaccine storage and delivery, reduce waste, and improve vaccine efficacy.
The new technique could make vaccines cheaper and more accessible in areas lacking modern infrastructure. Existing live vaccines must be refrigerated between 4 °C to 8 °C to remain effective. In countries like England and the United States, maintaining this "cold chain" costs up to $200 million a year and increases the cost of vaccination by 14 percent to 20 percent, according to the World Health Organization. In poor countries, the refrigerated transports and even electricity at medical clinics is often missing altogether, making vaccination impossible.
Nova has previously shown that the technique can stabilize various types of vaccines, as well as protein-based drugs. The new study, published in Science Translational Medicine, is the first time a live-virus vaccine has been kept potent after exposure to high temperatures.
The Oxford team showed that it could preserve the two vaccine viruses by mixing the viruses with sucrose—common table sugar—and trehalose, a sugar found in plants and mushrooms and used as a stabilizer in processed foods. The team then dripped the mixture onto a membrane made of glass fibers and dried it at room temperature in a low-humidity chamber. This allowed the sugars to form a noncrystalline solid around the fibers of the membrane, immobilizing the virus so that nothing could interact with it. To release the vaccine, the researchers flushed the membranes with saline, which dissolves the sugar almost instantaneously. Based on tests done in mice, the team found that they could store the two different vaccines on sugar-stabilized membranes at a tropical 45 °C for as long as six months without any degradation. The vaccines could be kept for over a year and more at body temperature—37 °C—with only tiny losses in effectiveness.
Nova Bio-Pharma holds the patent on the drying technique, and it has also developed a small, plastic cartridge into which the filter is sealed. The cartridge has a hole at either end, one of which fits a sterile syringe and the other a disposable needle. When the vaccine is administered, a nurse or technician would pass sterile saline through the cartridge, pushing it out slowly. This instantly rehydrates the vaccine.
The company already has an aseptic manufacturing process in place that can produce quantities that would be needed for clinical trials. The next steps are to show that the process can be scaled up to industrial manufacturing levels and demonstrate that it works with a standard or newly licensed human vaccine.

Source: MIT Technology Review, February 18, 2010

Merck & Co joins biosecurity vaccine facility coalition

Merck & Co has joined a coalition to build a vaccine facility which is capable of simultaneously manufacturing multiple products and can quickly switch in response to a crisis. Bioterrorism and pandemic influenza have increased scrutiny of biosecurity in the US and the coalition, called 21st Century Biodefense (21CB), expects the government will allocate funds to ensure the nation is protected. 21CB will compete for this funding and use it to build a vaccine development and production facility. The plant would operate as a public-private partnership under the direction of the federal government, helping to keep production focused on threats to biosecurity in the US.
Discussing biosecurity President Obama outlined plans to create “a business model that leverages market forces and reduces risk to attract pharmaceutical and biotechnology industry collaboration with the US government”. It is unclear exactly how and when this plan will be implemented. Consequently, 21CB is yet to establish a timeline for the vaccine facility but expects its initiative will create 1,000 jobs directly.
Source: www.In-pharmatechnologist.com, March 15, 2010

Business News

Contract Manufacturing bucks economic downturn

The biopharmaceutical industry’s capacity pendulum has taken wide swings over the past decade—from shortfall to overcapacity—as companies built up production for projected pipeline products that failed to materialize. In the ramping-up process, the industry has made major investments in facilities, equipment, technology, and staff. 
Most CMOs in this industry experienced a drop in business the first quarter of last year. As a result, CMOs became much more cost sensitive and competitive in their service delivery. There was also some minor price erosion. That has now been stabilized, and starting in Q4 of last year business picked up.”
The recent financial pinch on CMOs appears to have been short-lived. Yet the lessons learned may be here to stay—continuously streamlined operations, keeping costs competitive, and ensuring service delivery is consistent with industry demands are signs of operational maturity. CMOs are increasing service quality; capacity gaps are being filled, including 2,000 L and 5,000 L; and customer needs are being considered more now than in the past as the economic crunch has compelled many to redouble efforts to operate more collaboratively and cost effectively.
Part of the reason for optimism is that virtually all biopharmaceutical developers sooner or later use the services of CMOs, whether for manufacture of clinical or commercial supplies, process development, testing, or for fill-finish operations. So, drug developers have a vested interest in the health of this sector. 

The Situation Today

Although some innovators and CMOs are experiencing excess capacity, biopharmaceutical manufacturing demands for available capacity, including that of CMOs, appear relatively balanced overall. Preliminary data from BioPlan’s 7th Annual Report and Survey show that only 18% of biomanufacturers today are experiencing anything greater than minor capacity bottlenecks at the clinical stage and 30% at the commercial scale. This compares with 32% for clinical stage and 39% for commercial scale last year.
Some of the larger biopharmaceutical companies are cutting back on the number of products they have in development, often resulting in idle manufacturing capacity. As a result, some of these innovator companies are now offering CMO services and joining the ranks of contract manufacturers. 
So far, this has not caused any apparent market disruption for mainstream CMOs, with demand for CMO services remaining rather steady.

One common issue that CMOs appear to be having is that smaller companies are continuing to cancel contracts, due to problems with financing. But this loss of business is being offset by increased business from big pharmas.
The biopharmaceutical CMO industry overall appears to be doing rather well. Growth has paralleled that of the biopharmaceutical industry. Many CMOs are now rather mature and many, if not most, offer a wide range of manufacturing, testing, discovery, screening, regulatory, and other services. Current annual industry revenues have been variously estimated at over $2 billion, with this projected to grow rapidly by 2014.
This assessment is consistent with the data on services segment growth from BioPlan’s 6th Annual Report, which recognized 14% annual growth in services over the past three years (since 2007). The biopharmaceutical CMO industry is likely now approaching $3 billion in revenue, taking in about 2.4% of all biopharmaceutical product sales revenue.

Current and Future Trends

CMOs are expecting cost savings from innovations, including expanded use of disposable equipment and increased yields from improved expression systems and cell lines. This complements trends among drug innovators, particularly larger ones, which are becoming increasingly risk- and cost-averse.
The biopharmaceuticcal industry is also outsourcing projects at an increasing rate, which contributes to the future prospects for CMOs. Despite this additional business, CMOs continue to be a competitive bunch, as they vie for projects to keep their facilities running. The ongoing credit crunch could end up slowing major expansion projects, forcing both innovator companies and CMOs to implement technological fixes to further increase capacity. 
New CMOs continue to enter the market, both in developed and developing countries, with many countries offering lower costs but having limited requisite expertise, facilities, and quality programs to manufacture at FDA/EU cGMP standards. The market for CMOs will continue to expand as dozens of companies enter the biosimilars/biogeneric markets. 

Future Capacity Bottlenecks

CMOs are currently experiencing relatively few problems, with little CMO capacity idle. BioPlan’s survey shows that most manufacturers of monoclonal antibodies are reporting yields typically just over 2 grams/L, while yields using newer mammalian cell culture technologies are now typically 10 gram/L or more. These results indicate that many of the future CMO and innovator expansions in manufacturing capacity may well come from implementing improved processes, rather than more costly and time-consuming building and certification of new manufacturing facilities.
As one would expect, with only about one in ten pipeline products moving through each major stage in product development, most contract manufacturing projects involve drugs produced at smaller scale for clinical trials, not large-scale manufacture for commercial sales. However, the major opportunities for CMO profits, including long-term supply contracts, involve large-scale manufacture for commercial sales. 

Source: Eric S. Langer In GEN News Highlights, February 15, 2010

Munich gets €94M to build personalized medicine cluster

The region around Munich already has a lot of what it takes to compete as a successful biotechnology centre. Besides some 120 biotech companies located in and around the metropolis, with companies such as MorphoSys, MediGene and Micromet numbering among the success stories, the area has also seen a growing pharmaceutical presence over the past decade. 
Novartis moved Sandoz, its generic drugs arm, from Vienna to the Munich suburb of Holzkirchen in 2005, for example. Roche has set up a biotechnology centre in Penzberg, that produces enzymes, proteins, monoclonal antibodies and hormones. Completing the picture are research institutions such as the Ludwig Maximilian University (LMU) and the Technical University of Munich (TUM), which cooperate in the Centre of Integrated Protein Science. Then there are Max Planck Institutes for Biochemistry, Psychiatry and Extraterrestrial Physics, the Helmholtz Research Centre for Environmental Health, and the German Gene Centre at the biotech centre in Martinsried, southwest of Munich. Together, Munich’s biotech and pharma companies generate annual revenues of about €10.5 billion, and, along with research institutes, employ around 30,000 people, according to a study carried out in 2008 by the local Chamber of Commerce and BioM, a consultancy and services company that represents Munich’s biotech cluster.
But there is still untapped potential in the region, believes Horst Domdey, managing director of BioM. “We want to address some of the deficits in coordination between academia and industry, building a real campus here,” he says. This is part of a vision for the future of Munich’s biotech sector, developed by BioM over the last year as part of a government competition for Germany’s top technology clusters.
This work bore fruit last month when the cluster was named one of the top five in Germany by the German Ministry for Education and Research. The prize is €94 million in funding. About €40 million will come from the federal government, another €40 million as matching donations from industry partners within the cluster, and the remainder from the Bavarian government. Bio-M’s concept centers on transforming the cluster into one focused on personalized medicine, which it loosely defines as the development of diagnostics and medicines tailored to those who can most be helped by them.  BioM’s proposal to win the grant funding set out 40 potential collaborations and seven structural projects to bridge the gap between academia and industry.  Just which of these ideas will come to fruition has yet to be decided.  
One of the most important proposals is the development of a centre where companies can carry out Phase I and II clinical trials. Although the LMU and TUM both have clinical trials units, the newly proposed M4 Trial Centre would better coordinate and direct such activities. Currently, many companies in the cluster undertake trials elsewhere.  The M4 centre will also house a tissue bank, where local companies will have access to blood and tissue samples for research. Again, Domdey notes, such resources exist now, but it is difficult for companies to locate and gain access to them.

Source: Science Business, February 18, 2010

Collaborations and Mergers

DSM buys Upfront's Rhobust chromatography tech

DSM Biologics says combining its XD platform with newly-acquired Rhobust chromatography platform will create high yield, low cost bio-manufacturing option.
The US-based DSM unit has had its eye on the platform since September 2007 when it provided former owner, Danish purification technology specialist Upfront Chromatography, with funding to further its development.
Financial terms of the acquisition have not been disclosed although it is understood that DSM will continue to work with customers that already use the technology.
Rhobust is an expanded-bed absorption (EBA) technology in which cross-linked tungsten carbide and agarose beads create a purification surface designed to improve recovery yields during bio-processing.
The enhanced purification capacity offered by Rhobust has significant application in the field of high density bio-production. The XD platform’s ability to operate at densities of 200m cells per ml and produce, for example, up to 27 grams of antibody per litre has created a need for downstream technologies able to match this capacity.

Source: www.In-pharmatechnologist.com, May 5, 2010

Roche expands position in insulin delivery systems market
Roche and Elron Electronics Ltd.  announced today that they have signed an agreement under which Roche will acquire 100% of Medingo Ltd., a majority-owned subsidiary of the Elron group. Medingo Ltd. is engaged in the development of a semi-disposable insulin patch pump. Daniel O’Day, Chief Operating Officer Roche Diagnostics, said: “Diabetes has become a real epidemic that affects more than 285 million people worldwide. Roche Diabetes Care, a global leader in blood glucose monitoring and insulin delivery systems, is committed to improving the quality of life for people with diabetes. With this acquisition we will broaden our portfolio of innovative insulin delivery technologies and strengthen our position as a leading player in the diabetes care business”.  more

Source: press release Roche Group Media Relations, April 13, 2010

Merck KGaA to buy Millipore for €5bn

German pharmaceutical firm Merck KGaA says proposed Millipore acquisition will transform its chemicals unit and give it a more balanced business profile. According to Merck chairman Karl-Ludwig Kley, merging the firms makes strategic sense.
Merck’s chemicals business, which makes a wide range of products ranging from active pharmaceutical ingredients (API) and cosmetic ingredients to liquid crystals for high-tech televisions, brings in about 25 per cent of the firm’s annual €9bn revenue. The German firm aims to increase this contribution to around 35 per cent by combining the unit with Millipore to create a €2.1bn business that offers pharma and biopharma customers “integrated solutions beyond chemicals.” Merck also said it “plans to build on Millipore’s talented workforce and intends to retain its senior management,” and predicted that the combined business will generate annual cost synergies of €75m in three years.

Source: In-pharmatechnologist.com, March 1, 2010

 (Bio)manufacturing News

Genzyme addresses impurity problem at Ireland Cerezyme plant

US drugmaker Genzyme has detected an impurity in one vial of the Gaucher’s disease drug Cerezyme produced at its manufacturing facility in Waterford, Ireland. According to media reports Genzyme found a chemical called 2,4 dichlorobenzoic acid (2,4 DBCA) in one Cerezyme vial during a routine inspection last month and has already notified regulatory authorities and patients.
In a statement on its website Genzyme said that: “Based on review of the medical literature and the Cerezyme safety database, any risk to patients from this impurity is considered to be remote. “The Cerezyme batch in question meets all routine quality release standards and therefore has been released for use. The overall safety profile of Cerezyme remains unchanged.”
The source of 2, 4 DCBA, silicone tubing used during vial filling operations at the Waterford facility, has already been replaced with platinum tubing.

Source: www.In-pharmatechnologist.com, March 16, 2010

ATMI introduces disposable bioreactor

ATMI  has recently launched the Integrity PadReactor, a disposable bioreactor designed to provide a highly scalable entry point in its line of mixing and process manufacturing systems. The system accommodates volumes ranging from 20L to 1,000L and is portable at all sizes. ATMI highlighted the system’s swifter set-up times, with installation taking “well under an hour”, and minimal facility requirements compared to stationary, stainless steel systems. These attributes, combined with the system’s scalability, make it ideal for producing vaccines, monoclonal antibodies and other secreted proteins.

Source: www.In-pharmatechnologist.com, April 22, 2010

Wacker opens €18m expansion of biologics site

Wacker Chemie AG has expanded its biologics production facility, adding GMP manufacturing capacity and a process development building in response to customer demand. Faced with pricing pressures from emerging markets and rising demand for biologics, some chemical companies, including Wacker and Lonza, have expanded production for higher margin products. Wacker’s expansion includes an €18m ($24.5m) investment in its biologics production facility in Jena, Germany. The final phase of the expansion, which doubled the capacity of the existing good manufacturing practice (GMP) production facility, officially opened this week.
Also included in the second phase of expansion is a new facility for product purification. Wacker claims the new site can achieve up to three times higher product yield per batch and meets US Food and Drug Administration (FDA) and European Medicines Agency (EMA) GMP standards.
The facility will use Wacker’s proprietary technologies, Esetec and Densetec, which can make biologics production simpler, more cost-effective and boost yields, according to the company. Esetec uses the patented Escherichia coli (E. coli) K12 strain during fermentation to secrete recombinant proteins into the culture broth. Taking this approach eliminates the refolding stage and facilitates cleanup of recombinant products, making production more cost-effective, according to Wacker. This will be used in conjunction with Densetec, a high-cell-density process for fermenting E. coli. Wacker claims the combination of these technologies makes production more efficient.

Source: www.In-pharmatechnologist.com, March 9, 2010

iBio licences plant-based technology for H1N1 vaccine production

iBio has agreed in principle to license its iBioLaunch platform, which uses Nicotiana to produce therapeutics, to G-Con for the development and manufacture of plant-expressed influenza vaccines.
Plant-based production has been proposed as a rapid response, low cost alternative with the ability to massively scale up. G-Con’s GreenVax Project intends to show proof-of-concept for a large-scale vaccine production facility using Nicotiana plants grown in a controlled environment.
The project will initially look at producing H1N1 vaccines. iBio believes its platform is particularly suited to producing vaccines in response to pandemics because of the speed advantages it offers over egg-based manufacture.
Non-genetically-modified plants used in iBioLaunch have short growing cycles and this, coupled to the transient nature of the gene expression technology, helps cut the time from isolating the strain to production. When manufacture begins it can be quickly scaled-up by simply growing more plants in the contained growth facilities. G-Con will perform this process on a secure, 21-acre site at the Texas A&M Health Science Center in Bryan, Texas, US. A 145,000 sq ft bio-production facility capable of producing 100m doses a month is being constructed at the site. The facility has been designed to complete the GreenVax Project but can be expanded without interrupting core operations.
H1N1 is the target of the GreenVax Project but iBioLaunch can be applied to seasonal influenza, other infectious diseases or cancer.

Source: In-pharmatechnologist.com, March 1, 2010

Sandoz opens Slovenian biosimilars production plant

Lek has opened a 430m2 modified protein manufacturing facility in Slovenia to produce epoetin alfa drug substance for use in the biosimilars marketed by its parent company, Sandoz. Construction of the facility allows Sandoz to boost production of epoetin alfa, a drug originally marketed by a Johnson & Johnson subsidiary, which was among the first biosimilars to be marketed in the European Union. To ensure supply of the drug Sandoz has invested $3.75m (€2.77m) into Lek’s site in Menges in central Slovenia. These funds have been used to build a 430m2 production plant that will become a global supply point for Sandoz modified proteins.
Lek’s expertise in this field has been strengthened by the €45m investment Sandoz and parent company Novartis have made in biopharmaceutical development and production in Slovenia. This investment has led to Menges becoming one of Sandoz’ leading biopharmaceutical development and production centres, with particular expertise in cell culture and modified protein technology.
In total Sandoz and Novartis claim to have invested €900m in Slovenia over the past seven years. This includes a €13m packaging centre which opened last year to supply European markets.

Source: www.In-pharmatechnologist.com, February 25, 2010

Stem Cell News

Benefits of Osiris’ mesenchymal stem cell therapy confirmed in late-stage studies against SR-GvHD

Osiris Therapeutics’ stem cell product Prochymal showed significant benefits as a treatment for steroid-refractory acute graft vs. host disease (SR-GvHD) in both adults and children, according to Phase III trial results. Prochymal comprises a preparation of expanded mesenchymal stem cells (MSC) derived from the bone marrow of healthy young adult donors. The stem cells are formulated for intravenous administration.
Data from a Phase III trial (Protocol 280) in adults were presented at the 2010 BMT Tandem Meeting. The study included 244 patients with GvHD, who were treated using either Prochymal or placebo in addition to standard-of-care therapy. Overall results showed that the addition of Prochymal resulted in a 76% response rate among patients with steroid-refractory liver and an 82% response rate for patients with gastrointestinal GvHD. For individuals with GvHD affecting the skin, liver, and gastrointestinal tract, treatment with Prochymal produced a 63% overall response rate. None of the placebo-treated patients in this group responded.
The pediatric trial (Protocol 275) showed that Prochymal therapy resulted in a 64% overall response rate compared with 36% for the placebo group. Treatment with Prochymal also more than doubled the complete response rate to 64% and halved disease progression to 21%.
Prochymal is currently undergoing Phase III trials against steroid-refractory GvHD, acute GvHD, and Crohn disease. The treatment is the first stem cell product to receive FDA expanded access approval, Osiris points out. Phase II trials with Prochymal are also under way for the treatment of acute myocardial infarction, pulmonary disease, and type 1 diabetes.

Source: GEN News Highlights, February 24, 2010

Clinical trials news

Roche Begins new clinical study with TB-403

BioInvent International AB and ThromboGenics NV announced that their partner Roche will begin an imaging study with the novel anti-cancer antibody TB-403 (RG7334) in patients with metastatic, treatment-refractory, colorectal and ovarian cancer. BioInvent and co-development partner ThromboGenics will receive a milestone payment of €10 million from Roche under the terms of the strategic alliance agreement signed in June 2008. ThromboGenics, which discovered TB-403, receives 60% and BioInvent 40% of all revenue from the alliance with Roche for this anti-cancer antibody.
This trial is a multi-centre, open-label (monotherapy), dose-finding study with intravenous TB-403. The primary objective of the study will be to establish the TB-403 concentration-pharmacodynamic (PD) effect relationship using DCE-MRI (dynamic contrast-enhanced magnetic resonance imaging) and to identify the minimally PD effective dose. The trial will recruit up to 50 patients across three European sites.
With the start of this study, Roche will assume responsibility for all future development of TB-403, continuing the work started by BioInvent and ThromboGenics. A Joint Steering Committee made up of representatives from Roche, BioInvent and ThromboGenics will continue to oversee research and development activities. In addition, Roche will continue to provide funding to BioInvent and ThromboGenics for research activities related to TB-403.
A Phase I trial found that TB-403 was well tolerated with no reported dose limiting toxicity.

Source: BioInvent Press Release, May 17, 2010

Regulatory News

FDA guide offers more cultured approach to vaccine production

The US FDA wants to boost the production of cell-based viral vaccines and says new guidance will help manufacturers. While the H1N1 pandemic may not be as severe as first thought, the difficulty drugmakers faced in trying to build vaccine stockpiles using egg-based production methods did highlight the need for new manufacturing technologies. The US Food and Drug Administration (FDA) believes its new guidance document, available here , can make it more straightforward for vaccine makers to use cell culture methods, and accelerate production.
The guidelines cover the characterization and qualification of the mammalian and insect cell substrates used in vaccine production as well as some of the technical hurdles to be overcome in this type of manufacturing. Topics include methods used to measure vaccine purity or identify potential sources of contamination, through to good manufacturing practice requirements and the appropriate use of control cultures.
The agency explained it developed the guidance after a decade long research programme to outline “best practices using current and emerging science to safely expand the types of cells that may be used to produce vaccines.” The Food and Drug Administration (FDA) added that the information supplements the recommendations already detailed in International Conference on Harmonization (ICH) documents Q5A and Q5. Agency Commissioner Margaret Hamburg said: “The availability of this final guidance is an important tool to help manufacturers advance the development and production of cell-based vaccines against infectious diseases.”

Source: www.In-pharmatechnologist.com, March 3, 2010

EMEA approval for Xelox for adjuvant treatment of early colon cancer

Roche announced that Xeloda (capecitabine) in combination with oxaliplatin (a combination known as XELOX) has been approved by the European Medicines Agency (EMEA) for the adjuvant (post-surgery) treatment of patients with early colon cancer. The approval was based on results from the pivotal NO16968 (XELOXA) study, one of the largest studies of patients with stage III (early) colon cancer, which showed that patients taking XELOX immediately after surgery lived disease-free for longer compared to those treated with chemotherapy regimen 5-fluorouracil/leucovorin (5-FU/LV). The 3 year disease-free survival (DFS) for patients receiving XELOX was superior to the 5-FU/LV arm (71.0% versus 67.0%, HR 0.80, p=0.0045). more

Source: Roche Group Media Relations, March 30, 2010

EDQM and EMEA News

Reflection paper on stem-cell based medicinal products

The European Medicines Agency has published a Reflection paper on stem cell-based medicinal products (EMA/CAT/571134/2009). The aim of this reflection paper is to cover specific aspects related to stem cell-based medicinal products, and is relevant to all medicinal products using stem cells as starting material.


The document is available on the following webpage:

www.ema.europa.eu/pdfs/human/cat/57113409en.pdf


Please provide any comments you may have on this document to
veronika.jekerle@ema.europa.eu using the following template:

www.ema.europa.eu/pdfs/human/regaffair/submitcomment.doc

Deadline for comments is 30 June 2010.

EDQM: 10 new monographs adopted

(26/3/10) In its 136th session, the European Pharmacopoeia Commission
adopted 10 new monographs, including three monographs on active substances
which were elaborated under the P4 Procedure and two new general chapters.
During its session, the Commission elected Dr. Marianne Ek as Chair for a
term running from June 2010 to June 2013.

For more information: www.edqm.eu/en/Whats-new-525.html

AGENDA

ACTIP 20th anniversary meeting
May 26-27-28, 2010, Pueblo Acantilado, El Campello (Alicante, Spain)
Only for ACTIP members and invited guests
Info: actip-secretariat@telefonica.net

20th Anniversary World Congress on Biosensors,
May 26-28, 2010, Glasgow, UK

Physiology of Yeast and Filamentous Fungi
1-4 June, 2010, Rotterdam, The Netherlands
Information: EFB

The 3rd International Multi-Conference on Engineering and Technological Innovation: IMETI 2010  
June 29-July 2, 2010 ~ Orlando, Florida, USA          
Info: www.2010iiisconferences.org/imeti                    

EDQM Training Course on European Regulatory System/monographs etc.
12-13 July 2010, Strasbourg, France
Information: nadia.bontinck@edqm.eu

Bioprocess Engineering Course
19-26 September 2010, Brac, Croatia
Information: EFB efb@efb-central.org

14th International Biotechnology Symposium and Exhibition
14-18 September, 2010, Rimini, Italy
Information: IBS2010 secretariat or EFB efb@efb-central.org

BIOSPAIN,
Sept 30-Oct 2, 2010, Pamplona, Spain

Quality of medicines in a globalised world: dreams and reality
October 14-15, 2010, Prague, Czech Republic
Information: European Directorate for the Quality of Medicines & HealthCare (EDQM), Council of Europe
francine.baumgarthen@edqm.eu

Recombinant protein production 6
17-19 February 2011, Vienna, Austria
Information: EFB