A C T I P

ACTIP Policy Statement on
Somatic Gene Therapy

ACTIP was established in 1990 in Brussels at the initiative of the European Commission. To date it comprises 28 companies representing a substantial cross-section of European Industry engaged in the in- vitro use of animal cell technology. The member companies are responsible for a significant proportion of the research, development and production efforts in this area of life sciences within Europe. The Membership is composed of representatives from the following industries:

Pharmaceuticals.
Diagnostics.
Equipment Manufacturers.
Quality Assurance / Safety Testing.
Associated Representatives of the European Commission and Academic Institutions.

The Platform provides a forum where the members meet at regular intervals to discuss common issues relevant to animal cell technology, its application and industrial use. It acts in an advisory capacity to the European Commission on current and future publicly funded research themes and generates opinions and actions concerning industrial policies. Other major objectives are the identification of problems or obstacles to the implementation of new methodologies or technologies as applied to the commercialisation of in-vitro animal cell culture and to propose solutions. This particularly relates to responsible research, development and production, environmental and consumer protection, intellectual property and harmonisation of relevant European regulations and guidelines. Also to inform the public of the beneficial effects and positive contribution that biotechnology in general, and animal cell technology in particular, can make in the prevention or treatment of human or animal disease or infirmity.

Somatic Gene Therapy and the production of gene therapy products use molecular and cell biological methods. The techniques used for the in-vitro cultivation of cells in the manufacture of biologics, as practised by ACTIP companies are comparable to those used to generate cell populations expressing a particular gene of interest for use in gene therapy. When this gene has a potential therapeutic application, it follows that regulatory requirements and guidelines (together with other aspects) will be based or judged on similar issues and standards as used for the animal cell technology industry.

Through the rapid advancement of methods based on recombinant-DNA technology in the 1980's the revolutionary idea to transfer genes to human somatic cells as a means of therapy for genetic disorders became a reality. In 1990 the first treatment of patients with a genetic deficiency for the expression of the enzyme adenosine deaminase was successfully performed in the USA. Since then many protocols for other genetic disorders like cancer, cystic fibrosis and cardiovascular disease have been proposed both in the USA and in Europe.

The emerging technique of nucleic acid vaccination (NAVAC) raises issues that are similar and often identical to those raised by somatic gene therapy; this technique also raises great hopes for the future of new vaccine development.

While the work performed in this area has not gone beyond the preclinical stage yet, it is foreseen that clinical trials will be conducted in the near future.

The members of ACTIP have:

A strong positive scientific interest in these cutting edge technologies.
A well established safety and regulatory expertise.
A partial or individual company involvement in their own right.
No desire to act as a 'watch dog' committee but as an industrial 'sounding board' or discussions forum.
A willingness to provide expertise or helpful advice in the interpretation or establishment of harmonised regulation or guidelines.
A particular interest in the development of an environment that will continue to ensure that no adverse or improper use of this technology occurs.

The members of ACTIP therefore support present and future research, development and potential commercialisation of these fundamental scientific principles in their application to the relief of animal or human suffering.

Rotterdam, December 1994

ACTIP position paper
on
unconventional agents of spongiform encephalopathy

Background

The nature of the transmissable agents that cause spongiform encephalopathies, such as scrapie or bovine spongiform encephalopathy (BSE) in animals, or Kuru, Creutzfeldt-Jakob disease (CJD) and Gerstman- Straussler-Scheinker disease (GSS) in man, is still controversial. Several lines of evidence indicate that the transmissable agents consist of a modified form of the normal host protein, PrPc, that is devoid of any nucleic acid. However, due to the number of distinct strains of the agent with distinct phenotypes, it has been suggested that a nucleic acid must be a component of the agent; however, no specific nucleic acid has sofar been detected.

These agents persist in infected individuals without being detectable and only after an incubation period of several years do they cause clinical signs as the progressive neurodegenerative disease finally leads to a fatal outcome.

BSE has been confirmed in several countries such as the UK, Switzerland, France, the Republic of Ireland, Italy, Canada and Portugal. The incidence of new cases, however, is decreasing. Scrapie, on the other hand, has been diagnosed in all five continents. Spongiform encephalopathy disease has now been confirmed in many other animal species.

Despite extensive epidemiological studies there is no evidence for the transmission of scrapie to humans. However, the possibility exists that the species barriers to BSE may be different and therefore due prudence is warranted when biological materials from species susceptable to these diseases are used in the production of medical products.

Concern and suggestions of Animal Cell Technology Industrial Platform

1. Rapid, sensitive, diagnostic test development

It is essential to develop diagnostic tests which are rapid and sensitive, to enable the pharmaceutical industry to assess the safety of products derived from materials of animal origin, or in the use of animal products such as serum, for their manufacture. In addition, such tests are essential for the agricultural industry to diagnose disease in animals. The current bioassays in mice and hamsters are sensitive but take one to two years to detect low levels of the agent.

2. Host range

The potential for different causative agents of spongiform encephalopathies to cross the species barrier must be actively researched. These studies will give a better insight into both the biology and the potential risk of these agents.

3. Fundamental research - establish and identify the nature of the agent

It is critical that future work is conducted to establish the nature of these agents. This will require a programme of fundamental research, focused on the cellular protein, PrP, which appears to play a key role in the development of these diseases.

First edition of this position paper: Rotterdam, January 1992

First update of this position paper: Rotterdam, April 1996

Summary

Scheme for handling of bovine material in the pharmaceutical industry

Scheme drafted by the German Health authority

The following six areas have to be observed when material of bovine origin is used in the pharmaceutical industry. In each of these six areas points can be scored. The lower the risk, the more points are awarded. If the product obtains 20 or more points, it is considered safe.

Six areas to be observed:

country of origin of the bovine material, plus mode of rearing and of feeding the donor animals;
age of the donor animals;
source of the material (from which organ is it derived);
kind of process for the production of the final pharmaceutical product (are inactivation or removal steps involved?);
amount of original bovine material used per daily dose;
length of time of application;
mode of application.

Note:

The approval for all drugs, containing bovine material of risk that have not scored 20 points or more in the above scheme, have been suspended in Germany. Initially this will last until the end of September 1997.

ACTIP, Rotterdam, April 1996