A C T I P

ACTIP Bulletin 16

September 1999

On the web

Directory European institutions

An electronic directory of European institutions. You can search by persons, by organization entities (for example, the Office for Offical Publications) or hierarchical (for example: Commission, Secretariat-General of the Commissison, Directorate A etc....). Also available in 9 other languages. I tried it and it is very, very easy and useful. Saves you buying all these heavy volumes!

http://Europa.eu.int/idea/ideaen.html

EC Libraries

Finding so-called 'grey' literature can be quite cumbersome. Try the lists of 400,000 documents stocked in the EC libraries (including the European Commission's central library, the Commission libraries, the Eurolib library and the European Documentation Centres):

http://Europa.eu.int/comm/dg10/libraries/

RTD success stories

A well-arranged site with success stories of articles which appeared in 'Research and results'. Snappy titles make for quick browsing. Visit:

http://europa.eu.int/comm/dg12/success/en/success_en.html

Offical Journal

A reminder: L and C series of the Official Journal of the EU are available free of charge for 20 (in the future 45) days:

http://europa.eu.int/eur-lex

Biotechnology public perception

An extensive site on public perception of biotechnology in Europe:

http://www.kluyver.stm.tudelft.nl/efb/home.htm

Informative site on biotechnology

The Australian Biotechnology Association has established an internet site with a lot of information, such as educational leaflets on animal vaccines, pharmaceutical products, new antibiotics, etc. Also information on Australian Biotech companies, a recruitment section etc. Visit:

http://www.aba.asn.au

Update on the Biological Weapons Convention

From CEFIC/FEBC we received an update about the negotiations for a protocol to the Biological Weapons Convention. Here a short overview of the key points that are of interest to industry:

Declarations:
The declarations to be made annually by relevant companies/agencies depend directly on the criteria that are used. Not all EU members were familiar with the thresholds as proposed by the FEBC, which led to confusion in the EU group of experts.

Random visits (transparency visits)
These are visits to declared facilities that are selected 'at random'. The aim is to promote transparancy, compliance and control of the correctness of declarations. Main opponent states are India and the Russian Federation, who only want visits on a voluntary basis. The US, Japan and Germany only wish to grant minimum access and competencies for inspectors. This position is obviously the least intrusive for industry and a more intrusive visit scheme would certainly jeopardise US ratification. FEBC favours the German position.

Clarification visits
Western countries favour the possibility of clarification visits, also to non-declared facilties.

Investigations
These can be compared with challenge inspections of the Chemical Weapons Convention, i.e. in case of suspected violation of the BWC. Distinction is made between 'facility investigation' in case of suspected development production or stockpiling of biological weapons and filed investigation in case of suspected use or 'accidental releases'.

Timeframe
Progress in the Ad Hoc Group of State Parties is very slow. Nevertheless, it is expected that things may shift to a higher gear by the end of 1999, beginning 2000. An agreement cannot be excluded in 2000 and would have to be reached by the beginning of 2001 at the latest.

Transgenic animals for production of proteins

The use of transgenic animals for the production of biopharmaceutical products has been discussed several times within ACTIP. A recent article summarizes the technological milestones and an overview of selected transgenic protein products in clinical development. For the full article, see the reference below. Here we only give the milestones and products in development.

Technological milestones:

* microinjection technique for gene transfer demonstrated for multiple animal species;
* efficiency of stable transgenesis improved to 10%;
* nuclear transfer techniques demonstrated for multiple animal species;
* multiple heterologous proteins expressed and localized in the mammary glands;
* level of heterologous protein expression in milk demonstated at 1-40 g/L;
* development of purification protocols with 53% yield and 99.999% purity;
* validated removal and inactivation of potential adventitious agents during processing;
* scale up and maintenance of transgenic herds demonstrated;
* the safe use of transgenic products in human clinical trials has been established;
* good agricultural practices have been developed and accepted for commercial production.

Products in clinical development:

* alpha-1 antitrypsin (PPL): phase 1 for emphysema, phase II for cystic fibrosis;

* alpha-glucosidase (Pharming): Phase I/II for Pompe's disease;

* antithrombin III (GTC): phase III for coronary artery bypass grafting;

Products in preclinical stages:

* bile salt stimulated lipase (PPL): preclinical for cystic fibrosis and acute pancreatitis;

* C-1 esterase inhibitor (Pharming): preclinical, acute myocardial infarction
* collagen type I and II (Pharming): tissue repair (I) and rheumatoid arthritis (II);

* superoxide dismutase (PPL): reperfusion injury, acute respiratory distress syndrome;

* factor VII (Pharming, PPL): bleeding conditions;

* factor IX (Pharming, PPL): hemophilia B;

* fibrinogen (Pharming, PPL): tissue glue for trauma and surgery;

* lactoferrin (Pharming) prevention of gastrointestinal tract infections;

* protein C (PPL): prevention of deep vein thrombosis;

* salmon calcitonin (PPL): osteoporosis;

Source: Genetic Engineering news, May 1999

Calls for Proposals

New deadlines for project proposals

On August 12, 1999, the European Commission published a corrigendum concerning the call for proposals for RTD actions under the specific programme for research, technological development and demonstration on the 'Quality of Life' programme (Official Journal, 12.8.99, C 229/13).

The amendment concerns page 16 of the call for proposals of March 6, 1999 (reference OJ C 64/13 6.3.99) and reads as follows:

1. The website of point 3 is replaced by:

http://www.cordis.lu/life

2. The address indicated in the second indent of point 5 is replaced by the following:

European Commission
Quality of Life and Management of Living Resources programme
Research Proposals Office (ORBN 8)
Square Frère Orban 8
B-1000 Brussels, belgium

Thus, for delivery by hand or courier, use the Frère Orban address.

3. The evaluation dates '11 October 1999' and 10 February 2000' in the Annex to the call for proposals, concerning research infrastructures, are postponed to 15 November 1999 and March 2000 respectively.

There is also an amendment on page 19:

1. As above

2. As above

3. The three deadlines for submitting proposals '4 October 1999', 11 October 1999 and 18 October 1999 in the Annex to the call for proposals are postponed to the single date of November 15, 1999.

Thus, new deadline is: November 15, 1999

RTD calls open until November 15, 1999

The following areas are open for calls for proposals, with a deadline of November 15, 1999:

Key actions:

Key action 2, Control of infectious diseases:
2.2. New strategies for treatment and prevention
2.3. Public health issues

Key action 3, the cell factory: bioprocesses and products combining ecological, industrial and consumer advantages:
3.3.1. Cellular and molecular characteristics
3.3.4. Metabolic and genetic diversity

Generic RTD activities:

7. Chronic, degenerative and rare diseases: 7.2/7.3: Evaluation of therapies, databases, registries, sample banks

8. Genomes and diseases of genetic origin:
8.3/8.4: Novel expression systems; biophysics, statistics and computation

9. Neurosciences
9.3/9.4: Brain development; behaviour, cognition and functional mapping

10. Public health and health services research:
10.1 Improving of health systems

11. Research relating to the disabled
12. Biomedical ethics and bioethics
13. Socio-economic aspects

Contact the European Commission for help/information regarding submitting a proposal. Either Irene Norstedt (irene.norstedt@dg12.cec.be, tel 00 32 2 296 95 27; fax 00 32 2 299 1860) or for general questions the helpdesk: life@dg12.cec.be

Calls for experts

First we would like to repeat the call for experts to evaluate research proposals. If you have not already filled in the application forms, please do so soon. The Commission still needs industrial experts and in particular women.

Another interesting call is the call for experts to monitor the 5th FP and the Specific Programmes and Key Actions. The EC asks for people with an overview and enough knowledge of the details in research. Experts are asked to assess the progress of implementation of FP5 and whether the objectives, priorities and financial resources are still appropriate. The experts will be asked for their personal skills.
Deadlines: 15/09 in the years 1999, 2000, 2001 and 2002. More details at:

http://www.cordis.lu/expert-monitoring/home.html

There are also vacancies at the EU for candidates for temporary research posts (closing date 30/06/2002). For forms, see:
http://www.cordis.lu/nppr-candidature/home.html

Finally, there is a call (no deadline) for expression of interest for the provision of assistance in relation to industrial affairs, e.g. legal, economic and/or statistical analysis in biotechnology, or food production or medicinal products for human and veterinary use. A list of companies and individuals will be made, to be invited to respond to calls for tenders which are not published separately in the OJ. Information by fax: + 32 2 299 38 62.

Viral vaccines in plants

ProdiGene, Inc. of College Station, Texas, received a patent for vaccines made in plants. The ProdiGene patent covers viral disease vaccines, for hepatitis and the swine disease transmissible gastroenteritis, that are
produced in plants. They could be delivered either in edible form or as injectables. According to Dr. Carol Tacket of the Center for Vaccines Development at the University of Maryland, "Plant-based vaccines are an
exciting and novel new strategy for the development of oral vaccines. These
vaccines may be very safe and inexpensive to produce and deliver to target populations." Dr Jose Luis Di Fabio of the Pan American Health Organization said, "This new technology will contribute to global vaccine programs and will have a dramatic impact on health care in developing countries. (July 20)

News on BSE/TSE

Three BSE Tests with 100% effectiveness

In order to determine the potential of BSE tests for official uses, the European Commission published, in May 1998, an open Call to participate in a comparative Community evaluation programme. Ten tests were submitted in response to the call, four of these were selected for detailed evaluation by a
group of independent scientists: Enfer Technology Limited (Ireland), Prionics AG (Switzerland), Commissariat à l´Energie Atomique (CEA/France) and E.G.&Wallac Ltd. (United Kingdom). All the tests are based on the detection of prion proteins.

Three tests, Prionics, Enfer and CEA showed all a sensitivity and specificity of 100%, when tested on 1400 mixed contaminated and non-contaminated samples. The French test was able to detect the prion at the lowest concentrations. The tests take from four hours (Enfer) to 24 hours (CEA). The Wallac test did not perform as well as the others, but developmental work on this test is still ongoing.

The evaluation programme was managed by the Directorate General for Consumer Policy and Consumer Health Protection (DG XXIV) with a financement of nearly 1 Mio Euro. As the evaluation used positive samples from clinically diseased animals only, it is not yet possible to conclude whether the tests also could detect the BSE prion in animals in the early stages of the disease before clinical signs are present.

A report on "The evaluation of tests for the diagnoses of transmissible spongiform encephalopathy in bovines" will be published by the Commission in a leading scientific journal as soon as possible.

See for the statement of the Scientific Steering
Committee:
http://europa.eu.int/comm/dg24/health/afh/index_en.html <BR>

More news on rapid tests for BSE

Paradigm Genetics has agreed to collaborate with Prionics AG of Zürich to develop innovative diagnostics for rapid detection of bovine spongiform encephalopathy and Creutzfeld-Jacob disease. Prionics has developed proprietary antibodies that recognize and differentiate the disease-specific form of prion protein. Paradigm will develop a rapid and high-throughput test format, in return for royalties on assays performed with the technology. The first diagnostics are expected to be available for
testing on cattle next year. Human diagnostics will take longer depending on the length of the regulatory process.

TSE Conference

A potentially interesting conference is being organized in Washington DC from October 27-28, 1999. Simply called 'Transmissable Spongiform Encephalopathies', it will have sessions on:
* new data on the agent and its transmissability;
* risk analysis, safety and regulatory insights;
* TSE clearance, prophylaxis and testing (including validation processes).

Full agenda available from the ACTIP secretariat. See also the agenda on how to contact the organizers directly.

No transmission through milk

The Scientific Steering Committee (SSC) sees no evidence for transmission of BSE through milk.The higher infection rate of calves from BSE-infected cows of between 5-15% is rather to be found in other routes of contagion. The definite mechanisms for vertical transmission still need to be clarified. However, as a precaution, milk from BSE-affected cows should be taken out, although this milk is not proven to be contagious.

The Committee also recommended that animals and SRMs with TSE or suspected of being so, should be incinerated or burned after rendering and not be recycled for any direct or indirect use, inclusing use in cosmetics, pharmaceutical or medical products and devices. The opinion can be found on:
http://europa.eu.int/comm/dg24/health/sc/ssc/outcome_en.html

Opinion on Prevention and Control of certain TSEs and scrapie

The European Economic and Social Committee (EcoSoc) adopted in July last an opinion on the Commission's proposal for a Council Regulation on the prevention and control of certain TSEs and scrapie.
The debate focused on the case for banning the use of animal-based meal in feedstuffs.

The Committee:
* advocates a ban on animal-based meal in feedstuffs;
* questions the effectiveness of checks and the use of the precautionary principle regarding animal feedstuffs;
* serious organisational shortcomings must be overcome in all tiers of authority, as regards monitoring and evaluation and punishment of infringements;
* is concerned about insufficient coordination between Commission departments and member states;
* approves of the approach to differentiate specified risk materials according to geographical risk;
* a 7-year period of information as the basis for decisions is considered too short; the Committee proposes 14 years;
* takes the view that human health is more important than ruminant health and rherefore calls for an EU wide ban on the marketing of all products that are considered to pose a potential BSE transmussion risk to humans. This is in line with WHO recommendations;

Publications

Biomed publications

The following publications are available from the Biomed programme:

* Recommendations for the management of HIV infected women and their infants - a European consensus (28 pp) EUR 18851;

* Research on Bioethics: AIDS - Ethics, justice and European policy (234 pp) - EUR 17789;

* Cancer research suppported under BIOMED 1 (395 pp) IOS Press ISBN 90 5199 4109;

* Human Genome Analysis supported under Biomed 1 (477 pp) IOS Press ISBN 90 5199 4095;

Requests for publications to: European Commission, fax: 00 32 2 299 18 60, email: life@dg12.cec.be

Annual Industry report

Ernst & Young published its biotechnology industry annual report: "1999 Bridging the gap". While USA based biotechnology companies suffer financial chill, Europe's entrepreneurs were spoiled with the surge in new biotech funds. European governments strive to stimulate entrepreneurial activity. However, two crucial European demands have still not been met: a positive fiscal climate and a clear regulatory framework. For further information, see:

http://www.ey.com

Bioentrepreneurship

Available from the ACTIP Secretariat: a copy of a special of Nature Biotchnology on 'Bioentrepreneurship - maintaining financial stability', including a nice article about 'financing biotech ventures in Scandinavia'. The issue is available from the ACTIP Secretariat upon request.

Biotechnology & Finance Forum

Recently we received the summary report of the '2nd Conference of the Biotechnology & Finance Forum', held in Lyon on March 26-29. Below are the 10 key messages distilled from the Conference discussions:

* link the ability to discover to the ability to produce;
* provide young entrepreneurs with appropriate tools such as business plan training;
* set up a nurturing environment (e.g. entreprise incubator) for the new generation of European entrepreneurs;
* link bio-valleys or entreprise incubators at a European level, as both are needed by start-ups;
* although Venture Capital in Europe is no longer difficult to find, seed capital, which is essential, remains scarce;
* therefore the need for transparancy and mutual understanding between early stage investors and entrepreneurs is vital;
* find the right mix of managerial and technical skills;
* make scientists aware of the importance of intellectual property rights;
* avoid IPO pitfalls (wrong timing, difficulties in valuing biotech companies);
* find the right market.

The full report is available upon request from the ACTIP Secretariat.