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Animal Cell Technology Industrial Platform  
   last update September 2010


 

 
 


 
 
ACTIP bulletin no. 59 September 2010
 


Next meeting ACTIP:

December 2-3, 2010, in Penzberg/Bad Wiessee, Germany
and is hosted by ACTIP member Roche Diagnostics.
The meeting will focus on 'individualized medicine' and the 'omics', both seen from the perspective of their potential impact on the practice of animal cell culture technology. Only for ACTIP members and invited speakers/guests.

In this issue:

European News
Biomanufacturing News
Vaccine News
Business News
Mergers, acquisitions and alliances
Research News
Regenerative medicine: a review
Stem cell News
Gene therapy News
Clinical Trials and Results
Regulatory News
EMA News
Agenda


European News

2011 budget for FP7 unveiled  

The European Commission has unveiled a 6.4 billion euro package aimed at research and innovation, with a good chunk of the cash being made available to small and medium-sized enterprises specializing in health.

The 2011 budget for the Seventh Framework Programme, which is up 12% on 2010 and 30% in 2009, will see funding made available to 16,000 participants from research organisations, universities and industry, including about 3,000 SMEs. Grants will be awarded through "calls for proposals" and evaluations over the next 14 months and the package is expected to create more than 165.000 jobs.

Over 600 million euros will be dedicated to health and more than 1.3 billion euros are reserved for "the best creative scientists selected by the European Research Council". Mobility grants for 7,000 highly qualified researchers will be provided through 'Marie Curie Actions', worth 772 million euros.

The Commission says that "top priority is given to SMEs, described as “the backbone of the European innovation system, representing 99% of all European businesses". SMEs will receive close to 800 million euros and there will be ring-fenced budgets in several areas, eg in health, "knowledge-based bio-economy, environment and nanotechnologies SME participation must reach 35 % of the total budget for a number of topics".

In health research alone, the Commission noted that around 206 million euros – one-third of the overall budget for 2011 – will be spent on "investigator-driven clinical trials to get new medicines on the market quicker".
Source: www.PharmaTimes, July 20, 2010

ESF boss: Lazy researchers to blame for declining EU science optimism

According to the European Commission, in October 2001, a Eurobarometer survey on science and technology showed a divergence between EU citizens and the desired policy goals set up by the European Union. Policymakers then argued that there was a "need to step up scientific information in order to motivate European citizens to become more involved in science".
A similar poll in 2005 found that progress had clearly been made since 2001 in terms of basic scientific knowledge, but Europeans still considered themselves poorly informed on issues concerning science and technology. A new 2010 Eurobarometer poll shows a similar lack of information among citizens.
The results of the Special Eurobarometer survey were revealed on June 21 in Brussels, following two months of fieldwork in all 27 EU member states earlier this year.
While 79% of citizens said they were very or moderately interested in scientific and technological developments, a lower number of people than in 2005 said they were optimistic about the effects of these developments in society.
Professor Marja Makarow, chief executive of the European Science Foundation (ESF), told EurActiv that this decline, while marginal, was both "surprising and frustrating". Makarow also lamented the fact so few Europeans (11%) feel very well informed about new scientific discoveries and technological development. Only half of those questioned felt they were even moderately informed.
The ESF boss blamed the EU research community for this, arguing that scientists are "often too scared of the public" to undertake the necessary promotion of their work that would make science and tech feature more prominently in mainstream society.
She scathingly went on to claim that many members of the research community are too "lazy and self-contented" to provide this important service. "Talking to the public requires a certain talent that not many scientists have," she said. The solution from the policymakers' perspective, argued Makarow, is to gear EU strategies for "lifelong learning" towards feeding the public desire for more training and knowledge in this area.
The survey also addressed a long-running debate in EU circles, namely the consensus view that women are currently under-represented in the field of scientific research.75% think their government should support specific measures to improve women's representation in the scientific professions, while 63% think that if more women were represented in top research positions, this would improve the way research is conducted. 66% of respondents also thought that their government was not doing enough to stimulate young people's interest in science.Despite these negatives, Makarow identified a number of broadly positive trends arising from the survey. The ESF boss said, for example, that it was "quite satisfying" to see that 79% had an interest in scientific and technical discoveries, and that Europeans overall had a positive view about the image of science and technology. "The full capacity of research endeavours to promote the cultural, societal and economic development of our societies can only be unleashed through a novel pact between researchers, policymakers and society," she concluded.

Source: EurActiv News, June 22, 2010

Wanted: EU chief scientist

The EU executive has yet to appoint a chief scientific advisor, almost one year after European Commission President José Manuel Barroso announced plans to recruit a top scientist to offer advice on controversial issues including climate change and genetically-modified food.
The new job, originally due to be created after the new-look EU executive is sworn in, was part of an ongoing period of major reflection within the Commission, which has been re-organising its directorates in charge of science, research and innovation policy. 
The post - which will come with a salary just shy of €200,000 - has not even been advertised, despite all EU commissioners having formally backed Barroso's plan to create the new position.
Debate has been ongoing over the precise role of the chief scientific advisor, with some in the research sector hoping the position would be independent of political institutions, while others suggesting the scientist would merely be one of many counsellors to the Commission president (EurActiv 09/12/09).
It now seems the latter scenario is more likely. EurActiv has learned that the chief scientist will be given an office in the Commission's Berlaymont building and will slot into the Bureau of European Policy Advisors (BEPA), reporting directly to Barroso.
Although the job has not been advertised and there is no immediate plan to do so, the Commission has agreed that the ideal candidate should have "appropriate professional experience of at least 15 years" and will be paid the same rate as a director-general.
Source: Euractiv News, August 26, 2010

 

Biomanufacturing News

Disposable manufacturing drives CMC’s Seattle expansion plans

A fully-equipped disposable manufacturing facility has been added to CMC Biologic’s Seattle, WA site, as the first stage of a major expansion plan. CMC claim the new facility, supplied with processing equipment under the partnership with Hyclone, will enable early-phase clinical manufacture of biopharmaceuticals, including monoclonal antibodies and other mammalian cell culture-based recombinant proteins.
In order to counter risk of cross-contamination, and to eradicate the need to clean or sterilize the facility, the plant has been fitted with a 100L and two 500L single-use bioreactors (SUBs) and disposable mixers.
"The facility will provide a cost-effective strategy for reducing the speed to market for many biologics."

Gustavo Mahler, company president, believes demand for costly high-volume stainless steel tanks will wane for some products as process yields grow following advances in protein expression, cell culture and purification techniques.
The staged expansion at CMC’s Seattle site is going ahead to increase production capability, and to cater for the rising demand for cGMP manufacture of biopharmaceuticals. As part of this, the company have invested in a second 3,000 L bioreactor train, matching the existing line. Furthermore, client demand has prompted the advancement of plans toward build-out of a pre-existing structure which is set to house two 5000L commercial-ready lines.
The company added that the expansion will eventually involve extending the US workforce by over 30 per cent.
Source: www.In-pharmatechnologist.com, August 26, 2010

DSM: XD scale-up can cut drug production costs

DSM Biologics says successful XD tech expansion paves way for smaller bioreactors that lowers cost of production facilities and, ultimately, of bio-drug manufacture.
The firm, part of DSM Pharmaceutical Products, used off-the-shelf culture media to scale-up its bio-manufacturing technology from 2 to 50L, with densities of 170m cells/ml and titres that are 5 to 10 fold higher than standard fed-batch perfusion processes.
DSM business development spokesman Jeremy Caudill said the project, which employed Chinese Hamster Ovary (CHO) cells, represented a “paradigm shift” in biologic drug production using mammalian lines. Such a cost saving is likely to be attractive to a drug industry facing financial pressure in the economic downturn, particularly those that are focused on the development of biologics rather than traditional small-molecule pharmaceuticals.
Larger contract manufacturers are also likely to be interested in high-yield bio-production capacity as it provides a competitive advantage in what is becoming an increasingly competitive part of the market.
News of the scale-up project came just five days after DSM unveiled plans to combine the extreme density (XD) platform with purification technology acquired from Danish firm Upfront Chromatography.
The announcement is also likely to attract more attention for the new manufacturing facility DSM is building in partnership with the Australian government given that operations at the Queensland site will employ the XD platform.
DSM also said that the next stage of the scale-up project, which is to further expand the XD platform’s efficiency and production capacity, is expected to complete later this year.
Source: www.In-pharmatechnologist.com, May 11, 2010

Celleuxs launches “broad cell line" disposable bioreactor

Cellexus has expanded its disposable bioreactor offering with a unit designed to give biomanufacturers greater flexibility in their choice of cell lines. The new reactor, the CellMaker Plus, features oxygen generation capability, dissolved oxygen (DO) and pH sensors that can be adjusted to enable the use of the “broadest range of cell types.”
This contention is further supported by the wide variety of lines used during the system’s development, which range from laboratory standbys like E.coli and Pichia to “more challenging” insect and mammalian cells.
Compatibility with a large number of cell lines gives Cellexus the biggest possible customer base for the product, which is important given that the disposable reactor market is already highly competitive.
This was highlighted in recent months with the launch of yet another new disposable bioreactor by ATMI and the formation of a reactor-focused development partnership by processing industry heavyweights Pall and New Brunswick.
And in the last few weeks Merck KGaA acquired Millipore which, given that growth in the bio-manufacturing was a key driver for the deal, makes it likely that competition in the bioreactor field will only increase. 
The new Cellexus reactor also uses the firm's range of disposable culture bags, designed to minimise cleaning requirements, as well as a unique airlift aeration technology that the firm said is uniquely beneficial for biomanufacturing.
The CellMaker Plus unit, which is available in 8 and 50 liter versions, is like other products in the range available under the UK processing technology firm’s try before you buy rental plan. The scheme, which was launched in September 2007 for Cellexus’ CellMaker Lite2 technology, enables manufacturers to rent the reactors on a monthly basis allowing them to optimize the system for large-scale production.
Source: www.In-pharmatechnologist.com, July 28, 2010

Pall and New Brunswick partner on disposable bioreactors

Pall and New Brunswick have teamed up to develop and supply new disposable bioreactor technologies, targeting growing demand for products that improve quality and reduce cost of biomanufacturing.
Under the accord Pall will combine its Allergro single-use biocontainer platform with its New Jersey-based partner’s CelliGen bioprocess controller system. The companies, which claim the technology better serves upstream applications ranging from the process development laboratory to the full-scale cGMP production suite, will also co-market it to industry customers.
Bioprocessing is becoming an increasingly important part of Pall’s business in recent times, reducing the impact of a drop in demand for its energy, water aerospace technologies in Q1 of its fiscal year 2010..
Pall’s biomanufacturing business also performed strongly in the following quarter, with operating profit for the division climbing 27 per cent to $62m for the three months ended January 31 on 10 per cent revenue growth.
This has seen the US processing firm undertake a number of expansions of this part of its business in the last six months, with the deal with New Brunswick being just the latest example.
In February for example, Pall launched its PallSep vibrating membrane filtration (VMF) which uses encapsulated hydrophilic 0.2 µm polyethersulfone membrane filter modules to gently separate target proteins from process fluids.
And, prior to that, the firm bought MicroReactor Technologies (MRT) to access its miniature high-throughput process development (HTPD) systems.
Source: www.In-pharmatechnologist.com, June 15, 2010

Xcellerex adding FlexFactory to Massachusetts HQ

Xcellerex is building a second cGMP FlexFactory biomanufacturing facility to support clients transitioning to their own plants and provide contract manufacturing services. Construction of the plant in Marlborough, Massachusetts, US expands the company’s contract manufacturing operation which, in turn, helps drives growth of its FlexFactory business.
Xcellerex already operates a plant at its Marlborough headquarters and is now building another current good manufacturing practice (cGMP) facility. The new site, which is due to be finished in September, allows Xcellerex to meet a “surge in interest”.
Clients installing their own FlexFactory facilities will be provided with transitional biomanufacturing services from the new facility. Furthermore, the facility will provide clients without their own production capacity with contract manufacturing services. Offering contract manufacturing allows Xcellerex to engage with clients at an early stage in their development.
As these clients grow and add in-house capacity Xcellerex can offer them FlexFactory and transition between the sites because process development has been performed.
Xcellerex expects the facility to be operational in September, six months after the project began, and believes the costs involved are significantly lower than for a conventional facility. When operational the facility will provide prospective clients with a hands-on educational tool.
Housed at the new facility are 2,000 litre Xcellerex XDR single-use bioreactors and modular single-use downstream unit operations through bulk-product.
Source: www.In-pharmatechnologist.com, June 10, 2010

Octapharma licenses new BAC purification ligand

Bioprocess purification chromatography tech wins BAC new deal after Swiss protein maker Octapharma licenses it for commercial-scale manufacture. The technology in question, CaptureSelect, uses camelid-derived single domain antibody fragments to produce affinity ligands capable of capturing specific proteins during biomanufacturing.
BAC claims the ligands offer increased stability and broad antigen-specific binding compared to traditional affinity purification methods.
Under the new agreement, Lachen-headquartered Octapharma will use a CaptureSelect affinity ligand it developed in collaboration with BAC to purify recombinant human granulocyte-colony stimulating factor (G-CSF).
Octapharm, which intends to make G-CSF for oncology applications, has already used BAC’s platform to develop purification processes for the production of its recombinant factor IX drug and for its candidate factor VIII.
In a press statement Laurens Sierkstra, BAC CEO, said the deal “confirms the reliability of the CaptureSelect platform to consistently produce highly specific affinity ligands for the purification of any protein.”
BAC has already made more deals with industry for its CaptureSelect technology. In April, for France’s LFB Biotechnologies licensed a new affinity ligand for the large scale production of Factor VIIa (rhFVIIa), expanding on the deal it signed in 2008 .
In February, GE Healthcare also expanded its deal with BAC, licensing an affinity resin for the purification of alpha-1 antitrypsin (AAT) from blood plasma that was developed using the CaptureSelect platform. That deal built on a partnership formed in 2006 which, in 2008, saw CaptureSelect ligand’s supplied to Kirin Pharma’s subsidiary Hematech for the production of human antibodies in transgenic cows.
Source: In-pharmatechnologist.com, August 17, 2010

ATMI doubles bioprocess tech manufacturing capacity

In an announcement on July 28, Connecticut-headquartered firm ATMI said it had significantly increased manufacturing capacity at its plant in Bloomington, Minnesota after a two-year project and investment of $45.5m (€3.4m)
ATMI said that the expansion, which houses a 2,500 sqft Class 1000 cleanroom, applications laboratory and a separate development lab, makes the plant a hub for its single-use bioprocess tech business, including the 2D and 3D vessels it launched earlier this month.
The move doubles ATMI’s global bioprocess vessel production capacity, which is now split between the Bloomington US and its manufacturing facility in Hoegaarden in Belgium.
In a press statement CEO Doug Neugold explained that the expansion was a “direct response to the growing needs of our North American customers for additional single-use bioprocess vessel manufacturing capacity.
ATMI’s investment is an indication of the firm’s desire to build on the gains made by its life sciences business in the second quarter.
The division contributed revenue of $7.5m (€5.7m) for the three months ended June 30, which, although only a fraction of that contributed by its microelectronics business, still represents growth of 27 per cent.
Source: www.In-pharmatechnologist.com, July 29, 2010

Cancer Research UK opens biopharm production unit

Cancer Research UK has established a £18m ($28.4m) biopharm manufacturing unit to produce complex experimental drugs, such as monoclonal antibodies.
Establishing the production unit gives Cancer Research UK the capacity to support scientists as they transition compounds from the laboratory to the clinic. Cancer Research UK began work on the plant in 2007 and the first product manufactured at the site has now entered clinical trials.
The product, an antibody called Chi Lob 7/4, was discovered at the University of Southampton, UK. A Phase I clinical trial, using material produced at the new site in Hertfordshire, UK, is now treating patients who are no longer responding to conventional treatment.
Cancer Research UK has equipped the unit to produce biologics, such as monoclonal antibodies, plasmid DNA and recombinant proteins. Housed at the plant are a 30L continuous fermenter and 100L spinners, as well as downstream processing, cell banking and vial filling capabilities.
The unit is compliant with current good manufacturing practices (cGMP) and licensed by the UK Medicines and Healthcare Regulatory Authority (MHRA) for the manufacture of investigational medicinal products (IMPs).
These capabilities complement Cancer Research UK’s other manufacturing plant in Glasgow. The Glasgow unit, at the University of Strathclyde, develops and manufactures parenteral and oral sold-dose forms for use in clinical trials.
Source: www.In-pharmatechnologist.com, August 4, 2010

Research aims to predict scaled up process performance

Research has been initiated into the prediction of process performance before scale up to help increase yield and efficiency while cutting costs. The research uses ultra-scale down methods, which give data on manufacturing performance but use minimal materials, and a programming framework. By combining these elements the researchers believe they can make predictions about how processes will work on a large scale.
Biopharm Services and University College London’s Innovative Manufacturing Research Centre (IMRC) for Bioprocessing are collaborating on the research having been awarded a knowledge transfer secondment by the UK Engineering and Physical Sciences Research Council (EPSRC).
Commercial application of the method is also being worked towards. For individual operations commercial use could occur in 12 months. Work on all operations will take a little longer and reach commercial clients in 12 to 24 months.
The first step of the research focuses on how to measure engineering properties of biological materials used in bioprocessing by IMRC ultra scale-down methods. For instance, the research will look at how an antibody breaks up when certain manufacturing processes are performed.
Gaining an understanding of the properties of a molecule allows the researchers to feed parameters, such as sensitivity to shearing, into the programming framework developed by Biopharm Services.
By linking the data generated using ultra scale-down methods to the programming framework, called BioSolve, the researchers believe they can predict full process sequence scenarios.
Source: www.In-pharmatechnologist.com, July 13, 2010

Cheaper insulin production proposed for emerging markets

Diabetes is increasingly prevalent in emerging markets, notably India, and lowering the cost of production is viewed as one way to ensure these patients have access to insulin.
A team of researchers from Germany, Italy, India and Pakistan believe a paper they published in the journal Microbial Cell Factories can help further these efforts. Details of the manufacturing process have been published in an open access journal to ensure information is freely available.
The new manufacturing method produces insulin precursor in Pichia pastoris. Other methods of insulin production involve expression by Escherichia coli or in a yeast-based system using Saccharomyces cerevisiae.
Using Pichia pastoris to express insulin precursor offers several advantages over the more established yeast-based system, Saccharomyces cerevisiae, according to the researchers.
Firstly, stable and high levels of recombinant protein production are supported by Pichia pastoris’ capacity to reach high cell densities using simple cultivation strategies. Also, Pichia pastoris secretes few of its own proteins, making isolation of insulin precursor easier.
Recognising these benefits the researchers sought to boost the yield of insulin derived from precursor expressed by Pichia pastoris. To achieve this, a two-phase process using a glycerol batch and constant methanol fed-batch phase was used for the secretory precursor production.
Adopting this system increased precursor levels to more than 200 per cent of the highest previously reported yield from Pichia pastoris. To maximise insulin precursor capture from the culture supernatant the researchers used immobilised metal ion affinity chromatography (IMAC).
Using this novel approach the researchers recovered 95 per cent of the secreted product with a purity of 96 per cent. The purified precursor was trypsin digested, transpeptidated, deprotected and further purified to achieve 1.5g of 99 per cent pure insulin per litre of culture broth.
Source: www.In-pharmatechnologist.com, May 31, 2010

Cellectis and Lonza form biomanufacturing partnership

Lonza is to collaborate with France’s Cellectis SA for the development and commercialisation of a bioengineered cell line.
The partnership continues an ongoing trend within the industry that is seeing a greater emphasis on the importance of biomanufacturing. As large-scale manufacturing continues to gain momentum, biotechnology firms are faced with limited resources. Biotechnology firms are now looking to form partnerships or outsource to contract manufacturing organisations (CMO) in order to promote and develop technology.
Under the terms of the agreement, genome engineering specialists Cellectis, will use its technology to deactivate ("knock-out") the glutamine synthetase (GS) in CHOK1SV, a host cell line for manufacturing recombinant antibodies.
The GS System has already been used to generate therapeutics for use in clinical trials and eventual commercialisation. Femta Pharmaceuticals’ used the GS System to facilitate the development and current good manufacturing practice (cGMP) production of FM101. FM101, is a monoclonal (MAb) antibody that targets an immunomodulatory cytokine, this is involved in the damaging autoimmune response characteristic of rheumatoid arthritis RA.
Celectis’ will direct its genome customisation tool that uses meganucleases to induce unique site-directed double-strand breaks in the genome of organisms. Meganucleases specifically target gene integration, gene knock-out as well as of gene function modulation in for example, plants for agricultural and nutrition applications. Meganucleases, the most specific endonucleases, represent ideal tools for targeted genome editing, or genome surgery. They can induce up to 20 per cent of gene insertion into chosen human genes.
Other biotechnology firms experimenting with the meganucleases as a genome tool include Precision Biosciences. Its Directed Nuclease Editor (DNE) uses its own engineered endonuclease technology to essentially customise select genome, inserting, removing, modifying, and regulating genes in mammalian or plant cells.
In May last year, the technology was awarded the 2009 Genomics Technology Innovation of the Year award by Frost & Sullivan.
Source: www.In-pharmatechnologist.com June 9, 2010

 

Vaccine News

Pandemic vaccine production time could be halved in 3 years

Efforts to manufacture a H1N1 vaccine revealed a number of production bottlenecks which led to unanticipated delays. In response, the President’s Council of Advisors on Science and Technology (PCAST) was asked to look into how the US government can improve the situation.
Primarily PCAST sought to answer one question: “How can the federal government help to reduce the time required for the nation to supply effective vaccine to its population when the next influenza pandemic occurs?”
A document answering this question has now been sent to President Obama. In the document PCAST details a number of measures the US government should take, including some short-term actions which could have a significant impact without fundamental changes to manufacturing.
PCAST regards fill and finish as a “major hurdle” in efforts to respond to a pandemic threat. To tackle this “costly and laborious phase of manufacturing”, which is often “a major rate-limiting step”, PCAST recommends undertaking a comprehensive six month review focused on this area.
The review should assess use of existing facilities or the creation of new plants which could be used in the event of a pandemic. However, PCAST acknowledges that costs for additional facilities “will not be readily adsorbed by the manufacturers”.
An alternative is the adoption of facilities and equipment that can process different vaccines at different times of year. Widespread use would require guidance from regulators to avoid safety violations and production delays.
PCAST also suggests machinery could be improved. To drive innovation in this area the review recommends government incentives are considered, especially if the resulting technology would have applications beyond pandemic response.
Greater use of multi-dose vials is another suggestion. This could save several weeks but also increases the risk of contamination or failure to change needles between doses. Furthermore, multi-dose vials generally require greater use of preservatives.

Other short-term measures
* Improving potency assays “should be a high-priority effort”. Adoption of new methods, such as isotope dilution mass spectrometry, could make vaccines available four to eight weeks sooner.
* Changes to sterility testing could cut pandemic response times in half by adopting new methods.
* Alternatives such as PCR and shotgun DNA sequencing could be performed in parallel with the current standard to assess sensitivity and validity. This should be supported by FDA guidance on development and implementation.
* Development of influenza vaccine seed strains. By developing and disseminating a panel of viral backbones PCAST believes vaccine production could be accelerated.

E coli production an option for affordable conjugate vaccines

Use of conjugate vaccines for combating infectious diseases in the developing world is currently limited by production costs. Production in recombinant Escherichia coli (E coli) is potentially a simpler, more cost-effective method that would make vaccination campaigns economically viable.
Writing in the journal Microbial Cell Factories, researchers describe producing potential vaccines against shigellosis, a disease responsible for 1m deaths a year in the developing world, using recombinant E coli.
Glycosylation of carrier proteins occurred in E coli cultivated in 2.5L or 3.5L fed-batch bioreactors. Using this process the researchers produced bioconjugates that are potential vaccines against shigellosis.
“In this work it was demonstrated for the first time that glycosylated proteins can be produced in recombinant E coli at a larger scale in fed-batch culture”, wrote the researchers. However, time-space-yields for glycoconjugates are still low compared to methods using recombinant proteins.
Despite this current shortcoming the researchers believe the technique has potential. Amounts of glycoconjugate needed per vaccination are relatively low and applying different methods could increase yields. For instance, the researchers suggest process modifications could result in more complete glycosylation of carrier proteins. Alternative strains of E coli hosts could also increase yields, as could optimization of the sequence context of glycosylation sites in carrier proteins. Identification of metabolic bottlenecks and subsequent molecular engineering of host strains is also on option. Finally, protein engineering could be used to improve functional expression or catalytic efficiency.
Successfully increasing the yield could make in vivo production a viable alternative to the multi-step process which is currently used to manufacture conjugate vaccines.
Source: www.In-pharmatechnologist.com, August 18, 2010

Abbott exploring sale of vaccines unit

Abbott Laboratories has confirmed it is considering the sale of the vaccines unit it gained with the €4.5bn ($6.2bn) acquisition of Solvay Pharmaceuticals in February. The business, which is headquartered in Brussels, Belgium, manufacturers a range of products including the seasonal influenza sub unit vaccine Influvac and, according to Stoffel, generated revenues of €162m in 2009.
Unsubstantiated media reports suggest that Abbott has put a €500 million price tag on the business, although the US health care major has not yet confirmed the speculation.
While Abbott did not give reasons for the move, observers suggested that the business lacks the scale needed to compete effectively against industry leaders like GlaxoSmithKline (GSK), Sanofi Pasteur and Novartis. The Wall Street Journal reported that GSK is among the potential bidders, suggesting that the unit’s presence in the Eastern European vaccine market would be an attractive growth option for the firm.
Datamonitor agreed, suggesting that: “Abbott's cell-based manufacturing technology could provide an incentive to GlaxoSmithKline, which is lagging behind other flu vaccine players with regards to cell-based manufacturing.” However they also suggested that GSK may face competition from UK rival AstraZeneca who may table a bid to bolster the existing vaccines business operated by its MedImmune subsidiary.
Source: www.In-pharmatechnologist.com, July 6, 2010

Xcellerex’ technology key to US rapid vaccine production

The US biomanufacturing technology firm Xcellerex, and partners Pfenex, BioPharm Services and deltaDOT, were able to produce purified “swine flu” H1 hemagglutinin just 42 days starting with the protein’s amino acid sequence.
The project combined Xcellerex’ microbial PDMax process development and FlexFactory technology with expression, analysis and data modelling platforms to create a rapid-response vaccine production platform.
The co-developed production platform, which Xcellerex said had better "the goal for rate of production by at least 10 fold and exceeded all product quality specifications," has obvious application in the production of vaccine in the event of another influenza pandemic.
This point was stressed by the US Defense Advanced Research Projects Agency (DARPA) and Defense Threat Reduction Agency’s Transformational Medical Technologies Initiative (TMTI), which co-funded the work.
“The test demonstrated the speed and capability of the platform in producing a real-world vaccine, in this case swine flu H1 within 12 weeks of receipt of an unknown target amino acid sequence.
“The team succeeded in developing a strain and bioprocess, and fully characterizing the purified product in less than six weeks and at a cost, that scaled to manufacturing would be less than $0.50 per dose.”
Source: www.In-pharmatechnologist.com, May 18, 2010

 

Business News

GSK provides free access to data on 13,500 compounds with potential against malaria

GlaxoSmithKline (GSK) hopes to give the global fight against malaria a boost by making scientific data on some 13,500 relevant compounds from its library freely available online to researchers worldwide. The initiative will provide screening data on compounds that have shown strong inhibition of the Plasmodium falciparum parasite. Information being made accessible includes chemical families that GSK is currently investigating against malaria along with mechanisms of action for compounds that it has previously tested for other indications.
The initiative has been made possible through a collaboration between GSK, the European Bioinformatics Institute (EMBL-EBI), the United States National Library of Medicine (NLM), and Collaborative Drug Discovery (CDD), a U.S.-based informatics service provider. EMBL-EBI will act as the primary repository for the data through its ChEMBL resource and will index and format new information as it is added by GSK and other scientists working on the compounds. GSK says the resources are easily accessed by researchers, and specialist research tools on the site are also being made available to scientists at no extra cost. 
GSK claims that it is the first company to make the structures of so many of it compounds publicly available as part of the search for new drugs against malaria.
Source: GEN News Highlights, May 20, 2010

Pfizer to close 8 sites, cut ops at 6 more; 6,000 jobs to go

Pfizer plans to close eight manufacturing sites and reduce operations at a further six by the end of 2015, leading to 6,000 job losses, as part of its reorganisation after acquiring Wyeth.
Buying Wyeth swelled Pfizer’s manufacturing network to 78 sites, having aimed pre-takeover to have 41 facilities in 2010, and details of the expected cuts have now been released. As well as reducing overall capacity and overheads the cuts reflect increased interest in biologics at Pfizer.
Of the sites to be closed, three, in Caguas, Puerto Rico; Loughbeg, Ireland; and Rouses Point, New York, US, manufacture solid-doses. Furthermore, solid-dose is to be phased out at a site in Guayama, Puerto Rico and reduced at plants in Newbridge, Ireland and Illertissen, Germany.
Pfizer believes these cuts will eliminate excess capacity, making supply more closely aligned with demand, and give it the efficient production network needed to support its growth in biologics.
However, despite increased focus on biopharm, Pfizer is also making cuts to its vaccine and large-molecule network. Sites in Shanbally, Ireland and Pearl River, New York, US are due to close and Sanford, North Carolina, US; Andover, Massachusetts, US; and Havant, UK face cuts.
Aseptic production facilities in Carolina, Puerto Rico and Dublin, Ireland are also due to close and consumer healthcare manufacturing will be eliminated from Richmond, Virginia, US. The closure of the Pearl River site will also reduce consumer healthcare capacity.
Product transfers from the affected sites will lead to the expansion of the roles of a number of other production sites. Also, the site in Guayama, where solid-dose is being phased out, will expand its consumer healthcare operations.

Making the cuts
Pfizer plans to close the sites by 2015 and this, coupled to reductions at other facilities, will result in 6,000 of its 33,000 manufacturing employees being laid off. Timing of exits depends on operational complexity, the period needed for product transfers and other business requirements.
Attempts will be made to divest the sites but Pfizer warned that the success of this will depend on a number of factors, such as present demand for pharma manufacturing facilities. In the past divested sites have had supply agreements to ensure Pfizer receives products for several years.
Pfizer is also evaluating its animal health manufacturing sites, with recommendations expected in June, and will also begin assessing its nutrition and emerging markets plant networks later this year.
Source: www.In-pharmatechnologist.com, May 19, 2010

Sanofi to set up new facility in Saudi Arabia

Sanofi-Aventis will build a new manufacturing plant in King Abdullah Economic City (KAEC) in Saudi Arabia through an agreement with the Emaar development company (ECC).
The 35,000 sqm facility will produce oral anti-diabetics and cardiovascular drugs for the local market, which is estimated to be worth over $400m (€328m) a year according to a recent Zawya survey.
Sanofi’s decision to locate the plant in KAEC is a big win for the ECC and the Saudi Arabian General Investment Authority (SAGIA) who have been actively courting investment from the global drug industry.
Sanofi’s move, which fits with the general trend for Big Pharma firm’s to invest in emerging pharmaceutical markets, is unlikely to be its last deal in the region according to company senior VP Antoine Ortoli.  He explained that: “We are looking for all public and private partnerships across the Middle East that will open doors to new solutions for better health outcomes and strengthen our leadership position in those fast growing Markets.”
Source: www.In-pharmatechnologist.com, June 30, 2010


Mergers, acquisitions and alliances

SAFC and Novozymes Biopharma extend partnership in exclusive growth hormone distribution

SAFC and Novozymes Biopharma have agreed to extend their partnership by ten years for the exclusive distribution of LONG R3 growth factor, used for industrial cell culture applications.
The joint agreement allows SAFC to retain exclusive marketing and distribution rights which, according to SAFC spokesman Michael James, ensures customers in the biotech, pharmaceutical and vaccine industries of consistent supply minimizing operational, regulatory and manufacturing risks.
James told in-PharmaTechnologist that, when added to cultures of CHO clones, HEK 293, Vero, PerC6, MDCK, fibroblasts and other compatible cell types, the factor works by specifically targeting and activating the type I IGF Receptor (IGF-IR). This results in greater activation of downstream signalling cascades responsible for proliferation and inhibiting apoptosis. Greater activation of these key pathways results in increased cell density, higher viability, and extended cell culture productivity.
Several US Food and Drug Administration (FDA), European Medicines (EMA) and Japanese Ministry of Health Labour and Welfare (MHW) approved therapeutics already on the market are produced using cultures containing LONG R3. Source: In-pharmatechnologist.com, August 19, 2010

Sanofi-aventis and Scripps Genomic Medicine enter Personalized Medicine Alliance

Sanofi-aventis and Scripps Genomic Medicine have formed a strategic alliance designed to advance R&D initiatives in individualized medicine. Under terms of the alliance announced today, a Sanofi-aventis Group subsidiary, Sanofi-aventis Recherche & Development, will fund up to three Discovery Innovation Grants per year. The grants are intended to offer flexible financing for innovative research proposals from investigators at Scripps Genomic Medicine, a division of Scripps Health, the private not-for-profit community health system based in San Diego.
In return, Sanofi-aventis will be granted non-exclusive rights to any research tools developed through these grants, as well as preferred access to Scripps laboratory facilities for work conducted in support of sponsored research agreements and technologies, or discoveries in the field of personalized medicine. Also, Sanofi-aventis will have access to Scripps research programs that can contribute to the company's priority areas through ongoing scientific exchange and collaboration efforts – including an annual research symposium to be jointly organized by Sanofi-aventis and Scripps, the partners said.
Source: www.genomeweb.com, August 10, 2010

 

Research News

New Cancer Drug Gets Dramatic Results

Researchers call the experimental drug a major success for targeted cancer therapies.
An experimental drug designed to block the effects of a genetic mutation often found in patients with malignant melanoma significantly shrank tumors in about 80 percent of those who carried the mutation. The findings, published in the New England Journal of Medicine, signal a major success for so-called targeted cancer therapies.

shrinking tumors-1 shrinking tumors-2 Shrinking tumors: A PET scan of one melanoma patient shows a significant decrease in the size and number of tumors (shown in black) 15 days after treatment with an experimental drug.
Credit: Peter MacCallum Cancer Centre/Plexxikon

Unlike chemotherapy, which can affect both healthy and cancerous cells and often triggers serious side effect‘s, genetically targeted drugs act selectively on cancer cells that carry the mutation. Only a handful of such drugs have been approved by the U.S. Food and Drug Administration, and most target rare mutations. The BRAF mutation, in comparison, is common. Discovered in 2002, the mutation disrupts regulation of the BRAF protein, making it continually active. The drug in the current study is under development by Roche and Plexxikon, a startup based in Berkeley, CA. The drug is just one of a number of BRAF inhibitors currently in clinical tests.
The two currently available drugs work in only about 10 to 20 percent of patients. According to the new findings, 37 of 48 patients with the mutation responded to the new experimental drug, with their tumors shrinking by more than 30 percent. Tumors completely disappeared in three of those patients. About 30 percent of patients who took the drug the longest developed a specific type of squamous cell carcinoma, a tumor that usually doesn't spread and typically resolves on its own.
Further studies are needed before the drug can be approved by the FDA. But because scientists can use genetic testing to select the patients for whom the drug is most likely to be effective, they require much smaller trials to show the drug works.
The new drug candidate does have limitations. Many patients develop resistance anywhere from three months to two years after beginning treatment, a problem that has occurred with other targeted cancer therapies as well. Scientists hope to overcome this problem by combining the drug with other compounds, an approach that worked with Gleevec, a targeted cancer drug used to treat some kinds of leukemia.
The benefits of BRAF inhibitors are likely to extend beyond melanoma; the mutation is found in approximately 7 to 8 percent of all cancers, and tests of the drug in colorectal cancer are now underway.
Source: MIT Technology Review, August 25, 2010

Microarray study reveals tuberculosis blood gene signature

In a paper which appeared online in Nature, an international research team reports that they have identified a gene signature linked to active tuberculosis infection and a subset of latent TB cases.
The researchers used microarray and other analyses to find a gene transcript pattern in the blood of individuals with active TB infections that's not detected in healthy individuals. A fraction of individuals with a latent or dormant form of infection with TB-causing bacteria have the same signature, they explained, fueling speculation that the signature may eventually help find those at risk of developing active TB.
The researchers used Illumina HumanHT-12 v3 BeadChip arrays to assess gene transcript patterns in blood samples from 42 individuals recruited in London, including 13 participants with active TB, 17 with latent TB, and a dozen healthy controls. By doing this study in London, the scientists were able to involve individuals from a really wide range of backgrounds and diverse ethnicity and, thus, make the findings more widely applicable to this global disease than is sometimes the case. Indeed, the team found a 393-gene signature linked to active TB infection that was independent of factors such as age, sex, or ethnicity.
They subsequently verified their findings by looking at 21 active and 21 latent TB cases and a dozen controls from the UK and a second validation set from South Africa that included 20 individuals with active TB and 31 individuals with latent TB. The findings made in London were generalized to a different population living in different circumstances on the opposite side of the world.
The signature, which showed up in around 10 percent of individuals with latent infection, seemed to reflect the severity of TB disease, researchers noted, disappearing with successful TB treatment. Based on these findings, they suggested that the signature may serve as a tool for both classifying individuals with latent infections and monitoring treatment response.
Among the genes up regulated in the blood, meanwhile, were those induced by gamma interferon, a signaling pathway thought to protect against TB, and type 1 interferon, which helps combat viral infections but can aggravate some bacterial infections. Type 1 interferon-induced genes were particularly elevated in neutrophils, immune cells not previously implicated in TB infection.
Along with the initial signature, the team also identified another 86-gene signature that's seen in blood samples from individuals with TB but not those with other types of infections, such as those caused by Streptococcus and Staphylococcus bacteria. That signature was detected in active TB cases and in the same latent TB cases picked out by the original signature.
Source: GenomeWeb Daily News, August 18, 2010

 

Regenerative medicine: a review

Defining Regenerative Medicine

Regenerative medicine is not one discipline, but several emerging and sometimes related fields. They can be defined as a group of biomedical techniques which restore the function of organs or tissue. This could be achieved by transplanting engineered tissue or cells as a replacement, or by inducing the body to regenerate itself, or by using medical devices to assist organ functions.

Cell therapies
This involves the injection of stem cells or progenitor cells (for specific cell types). Therapies can be either ‘autologous’ - using the patient’s own cells or ‘allogeneic’ using donated cells.

Tissue engineering
Transplantation of in vitro grown organs and tissues. The best known example of this is the growing of a new trachea for a patient in June 2008. A section of trachea was taken from a donor, which then had all of its living cells removed in a repeated ‘washing’ process. Two types of cells were then used to line the trachea to make it bio-compatible with the patient. Epithelial cells were taken from the patient’s existing trachea for the inner surface of the scaffold while chondrocytes (cartilage cells) were derived from stem cells from the patient’s bone marrow for the outer surface. The operation was a success, and no immune-suppression was needed because the cells were the patient’s own.

Biomedical engineering
The pacemaker, which helps to regulate the heartbeat, and was first used by patients in 1958, is an early example of biomedical engineering. Technological advances mean that an artificial pancreas is now being developed. The first artificial limbs which can be controlled by thought are among the exciting cutting-edge ideas in the field now being tested in patients.

Gene therapy
The insertion of genes into a cell or tissue of a patient to treat a disease with a genetic basis.
A handful of companies have pioneered gene therapy. One of these is Genzyme, which launched its first enzyme replacement therapy Ceredase (algucerase) for type I Gaucher disease in 1991. The technology could in theory be applied to cancer to replace genes which cause tumours to develop

Regenerative medicine: company involvement

The concept of being able to repair, restore and regenerate human tissue and organs directly was once the stuff of science fiction, but is now becoming reality. If stem cell therapy and other regenerative medicine techniques and technologies can realize their potential, they could offer radical new treatments for conditions such as cardiovascular disease, stroke, neurodegenerative disorders, blindness and diabetes.
Despite the promise, progress has not been quick in the field, and indeed public hope and media hype around stem cells have raised expectations far beyond what has been achieved so far.

Stem cells
The field of stem cell research, is of course, the focal point of the regenerative medicines. Geron and ReNeuron are among the pioneering companies now embarking on clinical trials of stem cell therapies.
In January 2009, the FDA approved the world’s first phase I clinical trial of a stem cell therapy - Geron’s use of human embryonic cell to treat patients with spinal cord injury. However, just a few months in, the FDA called a halt to the trial after some patients developed cysts, and the trial has yet to gain clearance to resume. Meanwhile, in April this year ReNeuron began a UK trial of its ReN001 in 12 patients who have suffered an ischaemic stroke. The treatment involves implanting neural stem cells directly into the brain with the hope of reversing the disabling effect of stroke.
There are various sources of stem cells, including human embryonic stem cells, adult stem cells (mainly sourced from bone marrow) and the recently discovered induced pluripotent stem cells (iPSCs). These offer the pharmaceutical industry three possible types of application.
First, most companies are now developing and validating various stem cell-based assays for drug discovery and development, particularly for hepatoxicity and cardiotoxicity. Of most interest, perhaps, is the prospect of disease-specific cell lines from iPSCs.
Second, there is the possibility of using stem cells themselves as a therapy, either sourced from the patient (autologous) or from a donor (allogeneic). Recent advances in stem cell biology show that the cells often act as more than just a replacement - they secrete growth factors and other molecules which stimulate the body’s endogenous stem cells and tissue repair process, acting in many ways like a small molecule drug.
The latter opens up the third possibility - of discovering small (or large) molecules, perhaps from within a pharma company’s own libraries, which can target the repair process by stimulating the repair processes of endogenous stem cells.
It is predicted that an allogeneic ‘off the shelf’ stem cell product will be easiest for the industry to develop and bring to the clinic. Induced pluripotent cells and human embryonic stem cells show great potential, but there are currently too many hurdles involved in their development, so this will take longer.

The stem cell market

An estimate of the market for stem cells technology is at $2,680 million in 2012 and $5,100 million in 2014. The market could very much be like that for monoclonal antibodies, which took 25 years to mature
So far, Pfizer is the only one of the big pharma firms to set up a research unit specifically dedicated to regenerative medicine. Set up in late 2008, Pfizer Regenerative Medicine employs around 50 full-time scientists at centres in Cambridge UK (neural, sensory disorders) and Cambridge, US (cardiac, endocrine disorders).
Pfizer recently set up a deal with stem cell company Athersys to develop and commercialise the latter’s MultiStem technology for  inflammatory bowel disease. MultiStem is a patented and proprietary cell therapy product that consists of a class of stem cells obtained from the bone marrow of healthy adult donors. As such, it is the type of stem cell therapy that big pharma is likely to be most comfortable with. The deal is worth $6 million upfront, with milestone payments and royalties to follow.
Pfizer has another agreement with University College London (UCL) on developing a stem cell-based therapy for age-related macular degeneration (AMD), which is a leading cause of blindness in older people and for which there is currently no really effective therapy. Pfizer will fund the development of therapies for AMD and other related retinal diseases. They have a further agreement with Novocell, which is developing a hESC-based therapy for diabetes, hoping to supply pancreatic cells that make insulin.
Meanwhile, GlaxoSmithKline signed a five-year $25 million deal with the Harvard Stem Cell Institute (HSCI) in late 2008, with projects in cardiovascular, obesity, oncology, neurology, muscle, and immunology now underway. HSCI represents one of the world’s largest concentrations of biomedical researchers, bringing together the University, the Medical School and 11 teaching hospitals and research institutions including Massachusetts General Hospital, Joslin Diabetes Center and the Dana Faber Cancer Institute. Meanwhile, GSK brings its compound libraries, high throughput screening, regulatory knowledge, and drug development expertise to the table.
Regenerative medicine is also an area of significant and developing interest at AstraZeneca. The company is pursuing regenerative medicine projects through both internal work and external collaborations that are aligned to existing areas of disease interest such as respiratory and inflammation, cardiovascular and metabolic and neuroscience and that offer the opportunity to address unmet medical need in different patient populations. The company’s New Opportunities Group can pursue potentially fruitful regenerative medicine approaches in areas outside AstraZeneca’s core interests, such as bone, muscle and ophthalmic disease.
While these projects principally are directed at modulation of stem cells, the company is also interested to understand the progress being made in cell-based regenerative approaches to disease.

Barriers

However, many barriers remain before regenerative medicine and stem cells become part of big pharma’s mainstream activity. In the absence of clear proof of efficacy, it is difficult to predict which would be the best market to aim for.
Probably best would be to tackle a large indication which is an unmet medical need, like chronic obstructive pulmonary disease. The COPD market was about $7 billion in 2008 but there is no specific therapy for the disease, which is treated with drugs that are meant for the treatment of asthma. In COPD, cells have the [conceptual] potential to regenerate and it might be easy to deliver a therapy that can assist this process into the lungs. Diabetes might be another promising area for a therapy that could replace insulin-producing beta cells.
However, with cardiovascular disease - another potentially promising indication - the costs of clinical trials may be prohibitively high and there would also be competition with existing medical therapies.
Another possibility is to go for the smaller or orphan market, where Genzyme, for instance, has been successful. Regenerative therapies for inflammatory conditions like Crohn’s disease might be feasible in this context.
Regenerative medicine companies always mention regulatory as one of their main hurdles, for this is uncharted territory, with the therapies being neither a medicinal product nor a medical device. Geron’s application for its hESC therapy was the largest IND the FDA had ever had, and their phase I is currently on clinical hold while they carry out further studies. ReNeuron also had a long and winding path to approval, turning to the UK after a series of setbacks and delays at the FDA.
One key issue for regulators is where stem cells go once they are in the body, and what are they doing where in vivo imaging and tracking systems for cells will be very important. Hopefully, however, the introduction of the EU’s Advanced Therapies Medicinal Products Regulations may help progress regenerative therapies into the clinic. Scale up and manufacturing is another potential barrier in regenerative medicine, for cell-based therapies are inherently more complex than small molecule.
Cost of goods is a significantly higher part of the sales cost than it is for, say, a tablet. Regenerative medicine will fail if the cost bar is too high to offer treatments to those who need them. One company that has tackled many of these technical problems, including scalability, is Lonza, the largest contract manufacturing organisation (CMO) for cell-based therapies. At their dedicated facility in Walkersville, Maryland, they now produce 100 billion cells per batch which allows for 50-100 million cells per dose. In the UK, Angel Biotechnology is manufacturing the neural stem cells for ReNeuron’s clinical trial.
As for the future of regenerative medicine, it is believed that there will be several clinical trials underway in the next five to ten years, but it will be at least 10 years before the hoped-for large scale indications are ready.
Source: www.Inpharm.com, August 16, 2010

 

Stem Cell News

The US stem cell story continues: in short

The stem cell debate is back in the limelight after a federal district judge put the brakes on the Obama administration's expanded support of embryonic stem cell research. Congress should act quickly to prevent any lull in the important research that's already taking place around the country, including in Michigan.
U.S. District Judge Royce Lamberth recently halted President Barack Obama's 2009 executive order expanding embryonic stem cell research. The White House is considering an appeal among other options.
The Washington, D.C.-based judge ruled that the administration's stand breached the Dickey-Wicker Amendment, which bans the federal financing of embryo destruction. The administration does not see this as a conflict since federal funds are allocated towards research once stem cell lines are created, not for the actual destruction of embryos. But the judge saw this as a case of semantics since you can't have one without the other. Thus, Lamberth endorsed a strict reading of the amendment, to the delight of Pro-life groups. Supporters of stem cell research though point to the abundant possibilities for research to determine causes and treatments for a range  of diseases.
Congress is called to act on a parallel track, step up to the plate, end any confusion and clarify the situation in a way that allows embryonic stem cell research to go forward.
Source: The Detroit News, August 31, 2010 www.detnews.com/article

Step 1: Court temporarily blocks federal funding of ESCs

A federal district judge has put a temporary block on federal funding for human embryonic stem cell (ESC) research, which was okayed by the Obama administration last year. The judge agreed with plaintiffs in a lawsuit contending that such research is illegal because it destroys embryos.
In August 2009, a number of Christian groups filed a lawsuit against the HHS and the NIH, charging that the Obama administration's ESC policy violated the Dickey-Wicker Amendment. The law, passed annually by Congress, bans federal financing for any “research in which a human embryo or embryos are destroyed, discarded, or knowingly subjected to risk of injury or death.” The suit was dismissed because the court felt that the plaintiffs had no real chance of winning.
Since 1999, defendants determined that the Dickey-Wicker Amendment was not applicable to ESC research because ESCs are not embryos. They also made the distinction that derivation of ESCs from embryos results in destruction of embryos but research on ESCs did not. This argument was once again leveraged by the NIH and HHS. They also argued that the term “research” in the Dickey-Wicker Amendment is ambiguous.
Judge Lamberth, however, found that the distinction between ESC research and embryo destruction could not be made. “ESC research is clearly research in which an embryo is destroyed. To conduct ESC research, ESCs must be derived from an embryo. The process of deriving ESCs from an embryo results in the destruction of the embryo. Thus, ESC research necessarily depends upon the destruction of a human embryo,” judge Lamberth noted.
He also ruled that there was nothing ambiguous about the word “research” in the Dickey-Wicker Amendment. “Contrary to defendants’ argument, the term ‘research’ as used in the Dickey-Wicker Amendment has only one meaning, i.e., a systematic investigation including research, development, testing, and evaluation designed to develop or contribute to generalizable knowledge.”
Source: GEN News Highlights, August 24, 2010

Step 2: NIH Halts all internal Embryonic Stem-Cell Research

The National Institutes of Health, the US's largest biomedical funding agency, halted all ongoing research at the agency that involves human embryonic stem cells. The order comes in response to a federal injunction issued last week blocking use of federal funding for the research.
According to a furious NIH staffer who read the e-mail to ScienceInsider over the telephone, the message from NIH intramural research chief Michael Gottesman states: "HHS [the Department of Health and Human Services] has determined that the recent preliminary injunction ... is applicable to the use of human embryonic stem cells in intramural research projects. In light of this determination, effective today, intramural scientists who use human ES cell lines should initiate procedures to terminate these projects. Procedures that will conserve and protect the research resources should be followed."
The agency has eight research projects that use hESCs, most if not all of which use lines approved under the Bush Administration, say NIH officials. It also has a unit that characterizes lines added to the NIH registry of approved hESC lines.
The shutdown is the first immediate halt to research since Lamberth issued the preliminary injunction. NIH Director Francis Collins has said that extramural researchers can continue their projects for now and that the injunction will affect only future grant payments. ("Intramural" means researchers in labs on the NIH campus; "extramural" refers to researchers at universities and other outside institutions who receive NIH grants.). But some biomedical research lobbyists worry that that interpretation of the ruling may have been too optimistic, and a shutdown of all ongoing NIH-funded hESC research could be imminent.

Step 3: ....and litigation battles

The Obama administration says it will appeal the court ruling which invalidated the president's new rules on stem cell research, the New York Times reports. The ruling puts millions of federal grant dollars into question, and is leaving many researchers wondering what will become of their work to find treatments for diseases ranging from diabetes to Alzheimer's. "Beyond human embryonic stem cell studies, research on vaccines, viruses and lung disease could also be affected, experts said, because cells commonly used in such research were derived from either aborted fetuses or destroyed embryos," the Times' Sheryl Gay Stolberg and Gardiner Harris say. Researchers could find themselves in a quandary if the Justice Department's appeal doesn't pan out – scrambling to find work outside the US or private funding, or will have to delay the research in hopes of finding another approach. The Wall Street Journal's Gautam Naik reports that NIH has abandoned a planned review of 50 new grant applications and second-level reviews of about 12 applications worth $15 million to $20 million. There was also a review of another 22 grant applications worth $54 million planned for September, which will also be frozen. However, Naik says, Francis Collins has assured researchers who have already been granted some $130 million in grants that they can continue working until the money runs out.
But the consequences of the decision run even deeper, says Keith Robison at Omics! Omics! The two researchers who brought the suit — and who work with adult stem cell lines — say that the new rules for embryonic stem cell research mean they will have to compete for research funding to do their work. The danger now, Robison says, is that every time there is a change in federal funding, litigators could see an opportunity for themselves. "Wind down project X to fund project Y? LAWSUIT!" he says. "Either this will dissuade funding from the ebb and flow which is necessary, or a far worse than zero sum game ensues in which funding for science instead funds litigation." Jonathan Moreno at Science Progress points out that the two researchers' argument about their funding being in jeopardy is nonsense anyway, because there is no cap on stem cell research funding. "The NIH will give grants based on the quality of the proposed work, not on the materials to be used," he says. "In fact, adult stem cell research has received three times as much funding as embryonic. Over the past decade funding for adult stem cells has increased, not declined, and it has done so partly because of the greater understanding of stem cell biology gained from work with embryonic stem cells." Basically, Moreno adds, these scientists are using the courts to get rid of the competition.
Source: www.Genoweb.com, August 25, 2010

Synthetic surface enables Stem Cell Growth for up to three months

MIT chemical engineers, materials scientists, and biologists have devised a synthetic surface that includes no foreign animal material and allows stem cells to stay alive and continue reproducing for at least three months. It is also reportedly the first synthetic material that allows single cells to form colonies of identical cells, which is necessary to identify cells with desired traits and has been difficult to achieve with existing materials.
The experiments are detailed in Nature Materials in a paper titled "Combinatorial development of biomaterials for clonal growth of human pluripotent stem cells."
Scientists who work with human pluripotent stem cells have had trouble growing large enough quantities to perform certain experiments. Furthermore, most materials now used to grow human stem cells include cells or proteins that come from mice embryos, which help stimulate stem cell growth but would likely cause an immune reaction if injected into a human patient. Current growth surfaces, consisting of a plastic dish coated with a layer of gelatin and then a layer of mouse cells or proteins, are notoriously inefficient, according to Krishanu Saha, Ph.D., who works at the Whitehead Institute for Biomedical Research.
Previous studies had suggested that several chemical and physical properties of surfaces, including roughness, stiffness, and affinity for water, might play a role in stem cell growth. The researchers created about 500 polymers that varied in those traits, grew stem cells on them, and analyzed each polymer's performance. After correlating surface characteristics with performance, they found that there was an optimal range of surface hydrophobicity, but varying roughness and stiffness did not have much effect on cell growth. They also adjusted the composition of the materials including proteins embedded in the polymer. They found that the best polymers contained a high percentage of acrylates, a common ingredient in plastics, and were coated with a protein called vitronectin, which encourages cells to attach to surfaces.
Using their best-performing material, the researchers got both embryonic and induced pluripotent stem cells to continue growing and dividing for up to three months. They were also able to generate cells in the millions.
Source: GEN News Highlights, August 23, 2010

Beike opens China stem cell storage and processing site

Beike Biotechnology has opened a stem cell storage and processing facility at the 20,000 sq m regenerative medicine base in China, furthering the nation’s development in the field.
China has identified stem cell research as an area that it can become a global leader in and is willing to invest to make this happen. Beike is a beneficiary of this policy, receiving support from Jiangsu government-backed China Medical City (CMC) to establish the stem cell site.
The 20,000 sq m site, called the Stem Cell Regenerative Medicine Industrial Facility of National Bio-Industry Base (NBPD), forms part of a multi-stage project to give China a central research zone.
Industry partnerships form part of this strategy. The NBPD gives Beike the capacity to process and store 1m stem cell samples, making it the largest facility of its type according to the company. This represents a significant expansion on Beike’s earlier 1,800 sq m, 100,000 sample site.
Beike broke ground on the new site in April 2009 and now it is operational, ahead of schedule, researchers will begin work. Using the processing, storage and clinical application development capabilities Beike intends to “produce the highest quality stem cell therapies” in the world. 
To advance stem cell research three main goals have been established for the site. Firstly, the facility will be involved in adult stem cell collection and storage. This will be supported by the establishment of international standards, such as ISO9001 certification.
By forming these working processes and infrastructure the site can work towards its third main goal – to patent and develop stem cell therapies into clinical practice.
Source: www.In-pharmatechnologist.com, May 12, 2010

 

Gene Therapy News

Scientists in Denmark use gene therapy as possible cure for epilepsy

David Woldbye of Copenhagen University, in collaboration with researchers from Lund University in Sweden, has been able to stop attacks of temporal lap epilepsy by using gene therapy. Testing the treatment on rats, the researchers exchanged the genes in the virus cells with so-called therapeutic cells and injected these into the affected part of the brain, which then stopped the attacks on the tested animals.
Temporal lap epilepsy is the hardest form of epilepsy to treat. Some 30 percent of sufferers have an adverse reaction to normal epilepsy medicine and are unable to take it. The researchers now hope that their discovery will lead to gene therapy being approved as a treatment for temporal lap epilepsy, and that it might lead to gene therapy being used to treat other diseases or conditions based in the brain, such as Parkinson’s disease.
There are currently 55,000 people in Denmark who suffer from epilepsy. Although most are able to avoid attacks, the medicine many of them take has serious side effects.
Source: the Copenhagen Post online, August 17, 2010


Clinical results

Study demonstrates TB-402 superior antithrombotic activity to enoxaparin

BioInvent International AB and ThromboGenics NV announced that the positive results from a Phase II trial of TB-402 (Anti-Factor VIII antibody) were presented at the 21st International Congress on Thrombosis (ICT) in Milan, Italy. TB-402 is a novel, long acting anticoagulant that is being developed as a single injection for the prevention of venous thromboembolism (VTE) following orthopaedic surgery.
The Phase II results showed the superior antithrombotic activity of TB-402, when compared to enoxaparin (Lovenox®: sanofi-aventis). The study showed that the two drugs had comparable safety. Enoxaparin is currently the standard treatment to prevent VTE in this setting. VTE encompasses both deep venous thrombosis (DVT) and pulmonary embolism (PE).
The Phase II trial was a multicenter, dose-escalating, randomised, open-label trial, evaluating TB-402 against enoxaparin for the prophylaxis of VTE after knee surgery.
Source: BioInvent Press Release, July 9, 2010

Testing for Human Papillomavirus genotypes 16 and 18 detects cervical pre-cancer missed by Pap Test

Roche announced that data from the ATHENA (Addressing THE Need for Advanced HPV Diagnostics) U.S. registration trial of over 47,000 women demonstrate that two human papillomavirus genotypes, HPV 16 and HPV 18, can identify those women with cervical pre-cancer missed by cytologic examination with a Papanicolau (Pap) test. In the trial, 1 in 10 women age 30-years and older, who tested positive for HPV genotypes 16 and/or 18 by the cobas 4800 HPV Test had cervical pre-cancer, although their Pap test was normal. The data demonstrate the importance of HPV genotyping to increase the accuracy of assessing cervical cancer risk, especially by screening for the two highest risk HPV genotypes (16 and 18), and underscore the limitations of relying upon cytology (Pap) testing alone in identifying women with cervical pre-cancer. The data were presented by Thomas C. Wright Jr., M.D. of Columbia University at the 26th International Papillomavirus Conference in Montréal, Canada. more
Source: Roche Group Media Relations, July 8, 2010

MabThera doubles likelihood of progression-free survival in patients with follicular lymphoma

Roche announced data from the Phase III PRIMA study. The data showed that continuing MabThera (rituximab) for two years in patients who responded to initial treatment with MabThera plus chemotherapy, doubled the likelihood of them living without their disease worsening, known as progression-free survival (PFS), compared to those who did not receive maintenance. The study enrolled patients with previously untreated advanced follicular lymphoma. No new safety signals were observed in this study and the safety profile was consistent with previous experience with MabThera. more
Source: Roche Group Media Relations Press Release, May 20, 2010


Regulatory News

EMA and FDA co-operate to reduce GMP inspections burden

The European Medicines Agency and the U.S. FDA are once again calling for pharmaceutical manufacturers to apply to them for joint good manufacturing practices inspections for medicines. But while the initiative is aimed at reducing the burden of inspections for drug companies and the agencies, companies aren't queuing up for the service.
The agencies issued an initial announcement in March 2009 in order to address companies' concerns about waiting periods between inspections, which often led to delays in the manufacturing process. The first announcement focused on EU and U.S. manufacturing only. The latest reiteration expands the offer to manufacturing facilities in third countries.
The joint GMP inspections would rely on greater international collaboration to better distribute inspection capacity. As the pharmaceutical market becomes more global, companies rely less on the U.S. and EU as production sites and increasingly turn to countries outside the traditional pharma markets, in which they can manufacture products more cheaply. Inspection delays in these expanded territories, however, have become a problem for production schedules. According to industry sources, FDA and the EMA are the most active regulators inspecting outside their territories.
The new measure will allow the agencies to eliminate duplicate efforts and monitor more sites faster and at less cost to companies. The EMA points out that the majority of national regulatory authorities in the EU by law have systems in place to verify the GMP status of drug manufacturers that sell products locally. The same is true of most "developed" countries - Japan, South Korea, Australia and New Zealand included. But countries differ in their approaches to requiring inspections outside a national territory.
Companies' plans for new product approval submissions to both agencies trigger pre-authorization/pre-approval inspection in either the U.S. or European Economic Area. Manufacturers in the midst of this process may contact FDA and/or EMA to express an interest in a joint inspection. The agencies then decide whether a joint inspection is feasible. In turn, they guarantee confidentiality relating to the information provided. They will also consider requests from manufacturers who may be expecting to host routine surveillance inspections from both agencies in a similar time frame.
Despite wide industry support for this initiative, it has gotten off to a slow start - for reasons that no one seems to fully understand. "When we announced the initiative, the message did not really get through and so we are calling attention to this once again," said Monika Benstetter, spokesperson for the EMA.
Furthermore, a request for a joint inspection does not guarantee that such an inspection can go ahead. Scheduling conflicts and lack of available resources may lead one or both of the agencies to decline to participate. "Another reason for perhaps not agreeing to a joint inspection could be related to the product," suggested Benstetter, adding that joint inspections may not work for facilities that are producing complex molecules.
The agencies insist, however, that rejections will not affect the outcome of a submission which is ultimately processed separately by each agency. Where a major disagreement on the conclusion of the inspection arises between the agencies, they will proceed separately and conclude the inspection in accordance with their own national procedures.
If an inspection receives a negative result, the FDA and EMA will liaise with each other to ensure a common understanding and, if possible, an agreed conclusion before closing out the inspection process.
Source: EuroPharmaToday, August 25, 2010

UK to set up new clinical trials agency

The UK government is to set up a single agency to supervise clinical trials, in a bid to cut through the bureaucracy that has led to a flight of academic clinical research from the country.
The formation of the new agency is proposed at the same time as the axe is taken to quangos and other arms-length agencies across all other areas of government. This includes plans to close 15 agencies that support the National Health Service (NHS), leaving only three existing agencies intact. The new clinical trials body will be in addition to these three.
In the UK a bewildering number of bodies from local ethics committees to primary care trusts, and the Human Tissue Authority, to the Gene Therapy Advisory Committee, and others, have responsibility for different aspects of research regulation. The picture in regenerative medicine is so complicated that the Department of Health has published a route map to guide companies wishing to set up trials of products such as stem cell therapies.
“There is a strong argument for rationalising this and creating greater strategic coherence around research by placing responsibility for these different aspects of medical research regulations within one arm’s length body,” the Department of Health said in a review of the 18 existing NHS agencies. Such a body would perform the single technical function of regulating clinical research with the aim of streamlining the process of getting permission to stage trials. In particular, the review recognised that the burden of regulation is deterring small-scale academic trials and says one aim of the new agency should be to make is easier for universities to carry out clinical studies.
Health bodies facing the chop include the Human Tissue Authority, which oversees the European Union Advanced Tissue Products legislation and the Human Fertilisation and Embryology Authority, which is responsible amongst other things for awarding licenses for human cloning for embryonic stem cell research.
The proposed clinical trials agency is presented as the route around the red tape that has engulfed clinical research since the coming into force in April 2004 of the EU Clinical Trials Directive. This was intended to harmonise clinical trials activity across Europe, but is widely acknowledged to have had the opposite effect, with different member states implementing its requirements more, or less, stringently.
UK participation in global clinical trials dropped from 6 per cent in 2002, to 2 per cent in 2006.As yet, the shape of the new clinical research oversight body is undecided. The increase in costs and the flight of trials elsewhere is happening across western Europe. The European Commission has acknowledged the adverse impact of the Directive and is currently consulting on how it should be changed, with a promise to bring in new legislation by November 2011.
Source: Science Business, News Alerts, August 5, 2010

Roche submits application to FDA for trastuzumab-DM1

Roche announced that the company submitted a Biologics Licence Application (BLA) to the U.S. Food and Drug Administration (FDA) for trastuzumab-DM1 (T-DM1) in people with advanced HER2-positive breast cancer who have previously received multiple HER2-targeted medicines and chemotherapies. This submission is based on the results of a Phase II study which showed T-DM1 shrank tumours in one-third of women who had received on average seven prior medicines for advanced HER2-positive breast cancer. T-DM1 is the first antibody-drug conjugate in Roche’s pipeline to be submitted to the FDA. more
Source: Roche Group Media Relations, July 7, 2010

 

EMA News

New EMA website

The European Medicines Agency unveiled its new corporate website at www.ema.europa.eu. The site has been completely redesigned and rebuilt to optimize usability for the Agency's key online audiences and build on existing activities to improve openness and transparency.

The Agency website now receives an average of half a million unique visits per month and is a key resource for patients, healthcare professionals, regulators and those interested in the regulation and safety of medicines in
the European Union.

Some of the website's new features include:

  • Quick medicine searches: Allows you to search for human and veterinary medicines by name and active substance and for herbal medicinal substances by name
  • An online library: Enables you to search for all Agency documents currently online through a search on title and date published online.
  • Improved navigation: More intuitive labelling and improved organisation of content so that browsing is quicker for all audience groups
  • Audience landing pages: Flags information of specific value to different key users
  • Online calendar and news search: Allows you to keep up to date with the latest news and events at the Agency
  • RSS feeds: Brings information straight to you as soon as it is published online.

Source: www.ema.europa.eu

Draft guideline on Quality

The European Medicines Agency has published a draft Guideline on quality, non-clinical and clinical aspects of medicinal products containing genetically modified cells (EMA/CHMP/GTWP/671639/2008).

This draft guideline defines scientific principles and provides guidance for the development and evaluation of medicinal products containing genetically modified cells intended for use in humans. Its focus is on the quality, safety and efficacy requirements of genetically modified cells developed as medicinal products.

The document is available on the following webpage:
www.ema.europa.eu/pdfs/human/genetherapy/67163908en.pdf

Comments should be provided using this template
www.ema.europa.eu/pdfs/human/regaffair/submitcomment.doc
The completed comments form should be sent to GTWPsecretariat@ema.europa.eu

Please note that the deadline for comments is 30 November 2010.
Source: EMA, June 22, 2010

Draft position statement on CJD

The EMA has published a Draft CHMP/CAT position statement on Creutzfeldt-Jakob disease (CJD) and advanced therapy medicinal products.
The document considers the risk of transmitting CJD or variant CJD agents in advanced therapy medicinal products.
The draft position statement is available for consultation on the  following webpage:
www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2010/07/WC500095069.pdf

Comments should be provided using this template
www.ema.europa.eu/docs/en_GB/document_library/Templates_and_Form/2009/10/WC500004016.doc
.
The completed comments form should be sent to alberto.ganan@ema.europa.eu.

Please note that the deadline for comments is 30 September 2010.
Source: EMA email, August 4, 2010

EDQM: new monographs

For more information on new monographs adopted at the last  European Pharmacopoeia Commission click here: http://www.edqm.eu/site/News_and_General_Information-43.html

Source: www.edqm.eu , July 5, 2010

 

AGENDA

BIOSPAIN
Sept 30 - Oct 2, 2010
Pamplona, Spain

7th Annual Biosimilars Conference
Optimising commercial strategies to develop Biosimilars and Biobetters
5th - 7th October 2010, BSG Conference Centre, London, UK
Information: jana.jankova@vgpharma.com 

BIOTECHNICA
05 - 07 October 2010, Hannover, Germany
 

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

francine.baumgarthen@edqm.eu

Advances in Metabolic Profiling
09 - 10 November 2010, Florence, Italy


Recombinant protein production 6
16 - 19 February 2011, Vienna, Austria
Information: EFB SEction Microbial Physiology
www.rpp2011.at

 


 

medimmune2

 

pfizer3


 

   
 
      © 2010 ACTIP