Home | Objectives | Organization | Members | News and Info. | Publications | Products | Interesting Links | Library | Secure |
|
|
ACTIP
Bulletin 36 |
|
|
Next ACTIP meeting
Have you already returned the reply form to register for the ACTIP meeting in Montreux? It will be held in Montreux, Switzerland on
December 11-12, 2003
Central themes are 'serum-free animal cell cultures' and 'toxicogenomics'. As usual, it promises to be a stimulating meeting. See you all in Montreux! - HH
In this issue
ACTIP websiteDespite the summer holidays, the month of August was a good one for the ACTIP website: the number of visitors was very similar to the ones in June and July: in August there were 10,129 visitors, with 2,577 requests to download pages. More than 20% of visitors came from industry (their addresses had a .com ending). Bulletins, organization and secure page were the most popular pages in August. The month of September showed a huge increase in the number of visitors: 32,059 visitors, of which 26,390 came directly from the ACTIP homepage; there were 4,494 requests for page downloads. Of the visitors, 32.4% had a .com ending. The most popular pages in September were links, bulletins, contact and members.
News from the Commission
Council endorses new Innovation PolicyMeeting in May this year, the Competitiveness Council (with among others Commissioner Erkki Liikanen), adopted conclusions from a communication on 'Strengthening European Innovation Policy'. The Council recognized that innovative activity is a key factor stimulating productivity growth and competitiveness, as well as a key factor in achieving sustainable development. Ministers also noted that 'a better understanding of the drivers of innovation in the European contextî is required. The key message was that 'innovation goes beyond technological means and can take many formsî. Furthermore, the 'speed and efficiency of spreading innovation through the economy is critical to productivity, economic growth and job creation. It was also noted that enterprises must be considered as central to innovation in Europe. With regard to actions, the Council calls on both member states and acceding countries to: build and strengthen innovation strategies, ensuring a well-coordinated approach among national and regional authorities;
Source: OJ no C 149 of 26-6-2003, p 4. See also: http://europa.eu.int/eur-lex/pri/en/oj/dat/2003/c_149/c_149200326en00040006.pdf
The 3% targetEurope needs to spend more on R&D and technological innovation if its economy is to be as strong as, or stronger than, that of its main competitors. In March 2002, EU leaders endorsed a target of 3% of GDP for overall R&D spending in Europe. This means that Europe must spend substantially more on R&D, because the average level is 1.9% of GDP, compared to 2.7% for the US and 3% for Japan. This means that the research expenditures in Europe will need to grow at an average annual rate of 8%, shared between a 6% growth rate in public expenditure and a 9% growth rate for private investment. Meeting the objectives is expected to increase GDP by 0.5% per annum after 2010, as well as creating 400,000 new jobs each year. The Commission is currently pressing hard to get implementation of an action plan up and running. Among the measures envisioned are fiscal incentives, availability of risk capital and IPR guidelines for public research institutions. Source: Investing in research &endash; an action plan for Europe. COM(2003)226 http://europa.eu.int/comm/research/era/3pct/index_en.html
Criticism on FP6While preparations for the next calls for proposals for the Sixth Framework Programme are already underway at the Commission, the first calls remain a topic for fervent discussion among stakeholders. One group, the national contact points (NCPs), are particularly concerned by the outcome of the first calls. CORDIS news spoke to three coordinators, from Germany, France and Poland, to find out more about the lessons learned from the results of the first calls, and their thoughts on areas that can be improved for future calls. Paul Jamet is the coordinator the NCP network in France. He told CORDIS News that the results from the first call were better than initially expected with respect to French participation. Around 25 per cent of projects involving French partners were retained, a figure well above the global average. Also, 14 per cent of the projects retained are being coordinated by French consortia. However, despite such encouraging statistics, Mr. Jamet explained that there remains a significant amount of confusion regarding Integrated Projects and Network of Excellence, which has led to rejection of high quality projects. In some priorities the success rate is about five per cent. "This is really frustrating." André Schlochtermeier, coordinator of the German NCP system, also believes that one of the main problems in the first calls was the misunderstanding by applicants of the objective of Network of Excellences. "Not only was it not understood by applicants, I think there were different concepts of the instrument in the Commission depending on the thematic area," he said. "There has also been a reluctance from industry to participate in NoEs because the main aim is not to create results but to overcome the fragmentation of research," explained Dr. Schlochtermeier. 'It is impossible to expect industry to coordinate all their research with 20 to 30 partners - they will gain nothing. "Some people at the Commission have also warned that these networks are too large and have suggested that to ensure industry participation, the networks should start with a smaller number of partners," said Dr. Schlochtermeier. In addition, there has been a general problem of over-subscription. 'Overall, 12,000 proposals were submitted for the first calls, out of which, less than one in five projects could be supported. The difficulties encountered due to over-subscription, particularly with regard to the projects deploying the new FP6 instruments, are most visible in candidate countries. "Candidate counties are immediately in a weaker position than Member States," said Andrzej Siemaszko, head of Poland's NCP system. He told CORDIS News that the success rate is as low as five per cent in some cases, with candidate counties coordinating only a handful of projects overall. The fact that so many high quality projects have not been retained for budgetary reasons, Mr Siemaszko says, will have a knock-on affect on the second round of calls. "It's clear that proposers will be reluctant to invest their time and money just to have their project rejected." However, despite the negative feedback received by some NCPs, they feel that their concerns are not falling on deaf ears. "The Commission is generally aware of all the problems and that is very positive," explained Dr. Schlochtermeier. "They are listening to NCPs and Member States and they will make some necessary adjustments." The Commission had already proposed a number of measures to turn the situation around. These include:
Asked to pinpoint the most important lesson learned from the results of the first calls, the three coordinators agreed that there should be more emphasis on funding smaller projects and the older instruments, such as specific targeted research projects (STREPs) . "In research as in life, it is wise not put all your eggs in the same basket," said Mr. Jamet. "While big research networks and projects will achieve their objectives, they will not really innovate." Source: CORDIS News
Finalists for 2003 Descartes Prize announcedThe European Commission has announced the eight projects short listed for the Descartes Prize. The one million euro prize will be awarded at a ceremony in Rome on 20 November, following a decision by the Grand Jury. While deciding between eight such diverse and high caliber projects will be no easy task, the list of finalists has already been whittled down from applications involving 900 scientists in 230 research teams. The Commission is keen to highlight the fact that two of this year's short listed projects are coordinated by women. This follows an increased number of entries from projects coordinated by women.
The short listed projects are the following:
Source: Source: CORDIS News, October 1, 2003 , see also www.cordis.lu/descartes
Alternative funding options for rejected FP6 project proposals?EU Research Commissioner Philippe Busquin has spoken of a new idea within the Commission with regard to funding for interesting projects proposed for the Sixth Framework Programme (FP6) that were not selected for EU support. "We have to make it known that these projects are not receiving finance, not because they're not good, but because we don't have the (financial) capacity," said the Commissioner. While there is as yet no concrete proposal, Mr Busquin suggested that "if this could allow Member States to finance these projects, that would be very good." Source: CORDIS News, October 1, 2003
News from the USA
Guidance documents at CDER
The US Center for Drug Evaluation and Research (CDER) has made available several final and draft guidances. The following have been posted: 1. Final Guidances• Guidance for Industry on Part 11, Electronic Records; Electronic Signatures--Scope and Application. www.fda.gov/OHRMS/DOCKETS/98fr/03-22574.pdf and www.fda.gov/OHRMS/DOCKETS/98fr/5667fnl.pdf
• Guidance for Industry on Investigational New Drug Application Exemptions for Studies of Lawfully Marketed Drug or Biological Products for the Treatment of Cancer. http://www.fda.gov/OHRMS/DOCKETS/98fr/03-23510.pdf and http://www.fda.gov/OHRMS/DOCKETS/98fr/5459fnl.pdf
2. Draft Guidances• Guidance for Industry: Comparability Protocols--Protein Drug Products--Chemistry, Manufacturing, and Controls Information. www.fda.gov/OHRMS/DOCKETS/98fr/03-22577.pdf and www.fda.gov/OHRMS/DOCKETS/98fr/protcmc.pdf
• Guidance for
Industry on Formal Dispute Resolution: Scientific
and
Technical
Issues Related to Pharmaceutical Current Good
Manufacturing
Practice. www.fda.gov/OHRMS/DOCKETS/98fr/5804dft.pdf
• Guidance for Industry: Process Analytical Technology--A Framework for Innovative Pharmaceutical Manufacturing and Quality Assurance. www.fda.gov/OHRMS/DOCKETS/98fr/03-22578.pdf and www.fda.gov/OHRMS/DOCKETS/98fr/5815dft.pdf
•Guidance for Industry on Sterile Drug Products Produced by Aseptic Processing. www.fda.gov/OHRMS/DOCKETS/98fr/03-22576.pdf and www.fda.gov/OHRMS/DOCKETS/98fr/1874dft.pdf
•International Conference on Harmonization; Guidance on E2D Postapproval Safety Data Management: Definitions and Standards for Expedited Reporting. www.fda.gov/OHRMS/DOCKETS/98fr/03-23508.pdf and www.fda.gov/OHRMS/DOCKETS/98fr/5827dft.pdf Source: Ron Wilson, Director of Small Business Assistance
Research News
Heart repair by bone marrow stem cellsMesenchymal stem cells isolated from bone marrow have been used to repair a heart damaged by a heart attack. This approach had been attempted before, but the success rate was low because the stem cells died soon after transplantation. Recently, USA researchers (Dzau et al) succeeded, using an approach whereby a gene for a survival-promoting signal molecule, Akt, was inserted into the mesenchymal stem cells. These transformed stem cells were injected into rats shortly after heart attacks had been induced in these rats. The stem cells were found to migrate towards the injured myocardium and developed into cardiomyocyte-like cells that formed connections with native myocytes. The modified stem cells returned cardiac performance to near normal. Source: Nature Medicine, 9, pp 1195-1201, 2003
Japan's first ES cellsOn May this year, the Japanese group of Norio Nakatsuji in Kyoto announced that they had successfully derived Japan's first line of human embryonic stem cells. These were cultured from donated human embryos left over from fertility treatments. As a result, Japanese scientists will no longer need to pay licensing fees to the patent owner of foreign cell lines. It is expected that 40-50 Japanese groups and companies will want to avail of this cell line. The scientists plans to develop another 3-4 cell lines over the coming months. Source: Nature Biotechnology, vol 21, 7, 2003
Zebrafish screeningIncreasingly, zebrafish are found to be very good model systems for the study of the effects of small drug molecules on vertebrate development and disease. Zebrafish are permeable to small molecules, are amenable to visualization of embryogenesis, have large clutch sizes and can be maintained at high population densities. Recently, Australian scientists (Love et al) described how the combination of gene expression with zebrafish screens complemented existing whole organism studies currently used in drug discovery projects. Source: Nature Biotechnology, vol 21; 8, August 2003, pp 879-883
Improved procedure to pinpoint phosphorylationThe common procedure to pinpoint phosphorylation sites involved protein digestion followed by purification of the phosphopeptides and sequencing by tandem mass spectrometry. Recently, Californian scientists (Shokat et al) found a way to improve this cumbersome procedure. Lacking proteases specific for phosphorylation, they used a chemical method to convert phosphoserine and phosphothreonine into lysine analogues, which can then be digested by lysine-specific proteases. Phosphorylated proteins on the resulting protein fragments can then be identified without sequencing from the masses of the phosphopeptides alone. Source: Nature Biotechnology, vol 21; 9, September 2003, pp 1047-1054
Improved protein activityScientists at Amgen, USA succeeded in improving therapeutic protein activity by increasing the level of glycosylation of these compounds. The approach consisted of introducing N-linked carbohydrates at specific protein sites where N-linked glycosylation amino acid sequences had been inserted. The authors demonstrated that it is possible to improve the duration and activity of three different glycosylated proteins: rec EPO, mpl ligand, and leptin (respectively N-glycosylated, O-glycosylated and non-glycosylated). Source: Nature Biotechnology, vol 21, April 2003, pp 414-421
Yeast to identify antiprion compoundsIdentifying compounds that inhibit aggregation of normal prions with diseased ones is a first step towards designing therapeutic approaches for fighting prion diseases. Taking advantage of the presence of prions in yeast, a group of French researchers (Blondel et al) have designed a high-throughput, yeast-based screening method for identifying novel prion inhibitors. Using this method, the authors identified a family of compounds, the kastellpaolitines, which elicits prion clearance. The authors also suggest that biochemical pathways controlling prion formation and/or maintenance are conserved from yeast to human. Source: Nature Biotechnology, Vol 21; 9, pp 1075-1081
Bacteria as anti-HIV condomNew Scientist reports that scientists at Stanford University in California are developing genetically modified bacteria able to excrete an anti-HIV protein. Following insertion into the vagina, these bacteria are supposed to colonise the vagina and effectively form a living condom against HIV. The used bacterium, Lactobacillus jensenii, excretes the human protein CD4, a protein capable of binding to HIV viruses. In the laboratory, these genetically modified bacteria were successful in preventing infection of human cells by HIV viruses. Currently, the scientists are investigating whether a non-genetically modified strain of these bacteria is capable of colonising the vagina of rhesus monkeys. Source: 'Living condom could block HIV', New Scientist 90-09-03, www.newscientist.com/news/news.jsp?id=ns99994141
Business news
BioReliance acquires Q-One BiotechOn September 23 last, BioReliance Corporation announced that it has completed its previously announced acquisition of Q-One Biotech. BioReliance paid the purchase price of approximately §42 million in cash, subject to post-closing adjustments and excluding transaction costs. The combined international company will operate under the BioReliance name worldwide, with offices in Glasgow and Stirling in the U.K., in Worcester and Rockville in the U.S., and in Heidelberg in Germany. From all of us at ACTIP: congratulations BioReliance, and congratulations Malcolm! Source: Press release BioReliance, Sept 23, 2003
EPO adverse effects: cause foundDutch scientists have found that aggregates of small molecules (micelles) in the formulation of erythropoietin alpha (EPO), sold as Eprex in Europe, were responsible for an immunogenic reaction that triggered severe side effects (pure red cell aplasia or PRCA). The producer of Eprex, Ortho Biotech USA, had removed human derived proteins from the formulation on request of the EMEA. The firm decided to replace it usual stabilizer Human Serum Albumin with sorbitol 80. However, it has now become clear that the high concentration of sorbitol led to the formation of micelles, which were found to cluster with EPO in a form that triggers an immunogenic reaction. As a result, at least ten companies that are now competing to receive approval for a follow-on biogeneric version of EPO may need to prepare for a more stringent focus by the regulatory authorities on immunogenicity during clinical trials and stricter postmarketing regulatory requirements Source: Nature Biotechnology, vol 21; 9, September 2003
Biogen building in DenmarkBiogen broke ground on a large-scale manufacturing facility in Hillerod, Denmark. It will be one of the largest facilities in the world with 90,000 liters of bioreactor capacity. It will also be Biogen"s first major international manufacturing plant. Biogen expects that actual construction will start in late 2005. The Danish site will complement the newly, FDA approved, 6x15,000 Liter production site in the Research Triangle Park facility in North Carolina, USA. Currently, Biogen's total capacity for mammalian cell products amounts to 106,000 Liters. Source: PharmaTEC International, 1-2003
EAPB Regulatory & Guidelines GroupThe European Association of Pharma Biotechnology (EAPB) has announced that it has just founded a Special Interest Group )SIG) 'Regulatory & Guidelines'. The mission of the EAPB is to be the representative and central network to promote and develop Pharma Biotechnology in Europe, linking academia, industry and regulatory bodies. For contacts, please contact the SIG"s chairman, DR. Axel Wenzel at axel.wenzel@p-ss-t.de. On www.new-drugs.com you will be able to:
Source: NewDrugs, summer 2003
What are biotech drugs?For many it might not always be clear what is meant with 'biotech drugs'. In the European Union, the following definition is used (see Council Regulation EEC 2309/93): Biotechnological processes are those which use:
More troubles for alternative production technologiesOn June 18, PPL Therapeutics announced it was postponing trials of its lead therapeutic protein, alpha1-antitrypsin. This signifies another setback for the approval of a drug in a transgenic animal system. PPL Therapeutics will focus on fibrinogen, derived from human plasma. This illustrates the daunting economic and regulatory uncertainties of manufacturing proteins in the milk, blood or eggs of genetically modified animals or in the tissue of plants. So far, no protein produced in a transgenic animal has been taken all the way through regulatory approval and commercialization. The following products are in the developmental pipeline:
Source: Nature Biotechnology vol 21; 9, September 2003
Looming problems with clinical trial directiveIn 2001, the EU passed the new clinical trial directive, which harmonizes provisions governing clinical research across Europe. The directive must be transposed into national laws by May 2004. The directive standardizes GMP, GLP, clinical trial requirements, and procedures for reporting and recording adverse drug reactions. It also gives rules for the import and labeling of drugs. Unfortunately, the directive allocates all responsibility for initiating, funding and managing the risk and quality of trials to a "single" sponsor organization, that will carry the full legal liability for the trial (and thus will need to buy insurance). Thus, the directive is not set up to accommodate publicly funded trials, which are often organized by several partners, including charities and hospitals. The law is further expected to affect small companies at the approval stage for products, because the time for regulatory approval procedures might take as much as six months for reviews of cell and gene therapies, a field in which smaller companies are very active. Source: Nature Biotechnology, Vol 21;8,pp 838, 2003
Bayer offers contract manufacturingBayer Pharma Biotechnology is offering contract manufacturing facilities to produce monoclonal antibodies and recombinant proteins for start-up biotechnology companies and for universities interested in using them for research. In this, Bayer is joining Boehringer-Ingelheim, which has already been offering this service for some time. A growing number of companies around the world are starting similar contract out facilities. According to a spokesman from Boehringer-Ingelheim, big pharma are motivated by the potential to foster relationships with, and eventually in-license technologies from, small biotech firms and academia. Source: Nature Biotechnology, vol 21; 8, 2003, pp 841
Biopharmaceutical benchmarks
During 2000-2003, regulators in North America and Europe approved a total of 64 biopharmaceuticals for human use. The approved drugs include hormones, blood factors, thrombolytics, vaccines, interferons, mAbs and therapeutic enzymes. All of these are protein-based drugs. In total, four humanized mAb products were approved, including Humera, the first human monoclonal antibody created using phage display technology. In total, there are now 24 therapeutic antibodies on the market. An increasing number of the newly approved products have undergone some form of genetic engineering. To date, no gene therapy drug has gained marketing approval. Neither has a new antisense-based product gained approval since 1998. During the same period, an estimated 50 new chemical entities (NCEs) were approved in the EU and 64 in the US. However, excluding duplicates, only 80 genuinely different NCEs have come to market. These data suggest that during the past three years over a quarter of all new drug approvals were biopharmaceuticals. Notable target indications for newly approved medicines include diabetes, hemophilia, myocardial infarction and various cancers, largely reflecting the major killers of Western society. Hepatitis remains the most frequently targeted indication of newly approved medicines, reflecting its global significance with 2 billion perople affected worldwide. A complete table, containing all biopharmaceuticals approved in the US and the EU, is available as a fold-out with the benchmark review. Source: Nature Biotechnology, vol 21, August 2003, 8, pp 865-870
Web pitfalls
A team of internet specialists has analyzed 57 biotech websites for design consistency, organization and information delivery. Overall, new scientific companies scored poorly. Of the studied companies, 54% allowed poor design to undermine their work and repouations. Here some advice distilled from the study on how to avoid common pitfalls:
Source: The homepage report: a study of the latest croip of Biotechs. Mark.williams@jwt.com
AGENDAA number of interesting conferences and workshops is coming up. Of all the events mentioned here, the detailed programmes and registration/application forms are available from the ACTIP secretariat.
Patinnova
'03 11th
Annual Meeting of the European Society of Gene
Therapy Advances
in Cell Culture Processing CORDIA-EuropaBio
Convention 2003 Protein
arrays, protein expression, human proteome and
protein process development Management
of innovation processes in pharmaceutical
organizations BioSquare
2004 The
Williamsburg BioProcessing Conference Europe, 1st
Annual Meeting 3rd
Recombinant Protein Production - A comparative view
on host physiology
ACTIP bulletin no. 36, November 2003
|
Home | Objectives | Organization | Members | News and Info. | Publications | Products | Interesting Links | Library | Secure