Mr Mark A. Elengold, United States of America

The regulation of products by the Food and Drug Administration (FDA) in the USA is based on sound science, law and public health impact. Biological products are regulated by the Center for Biologics Evaluation and Research (CBER). The cornerstone for our regulatory efforts is research. We serve the functions of both evaluator, enforcement authority, and standards and control authority over biological products in theUnited States. In order to do that, we have a robust mission-related research programme that allows us to learn about these cutting-edge products, and at the same time retain highquality staff, which is key to regulating these emerging technologies.

The aim of research and development is to shepherd the production of safe and effective products from bench to bedside, and ultimately to the marketplace, based on safety and quality. In 2000, the Pharmaceutical Research and Manufacturers Association estimated that there were 369 products resulting from developments in biotechnology. Cancer and related conditions are the number one target for this research. The US human genome project began in 1990 with a short-term goal of diagnosis and prevention of diseases. In the long run, the study of the gene may lead to the development of drugs such as small-molecular drugs, therapeutic protein drugs, and pharmacogenomics. In the USA, new offices are being set up to regulate various new tissues, cells and related therapies such as:

- conventional bank tissues for transplantation,
- gene therapy,
- reproductive cells for assisted reproductive therapy,
- human reproductive and therapeutic cloning,
- somatic cell therapies, e.g. stem cells,
- xenotransplantation.

Control of human reproductive cloning presents a great challenge to FDA. Regenerative medical techniques, such as stem cell manipulation and tissue engineering, raise public expectation that, in time, many human parts - heart, lungs, eyes, skin, etc. - will be available. CBER’s proposed approach to human cellular and tissue-based products is a risk-based stratified approach. Most tissue-based products are regulated solely under the Public Health Service Act Sec:361, the primary purpose of which is to prevent disease transmission. Such cellular and tissue-based products include musculoskeletal, ocular and cellular products, haematopoietic stem cells, reproductive tissue, heart valves, dura mater, etc.

“Kicked-up” products that do not meet the criteria of PHS Act Sec:361, but that raise concerns about safety and/or effectiveness other than those associated with conventional use of tissues, will be regulated as drugs, biologicals or devices. In relation to xenotransplantation, the following initiatives have been taken:

- Xenotransplantation Action Plan,
- Secretary’s Advisory Committee on Xeno (SACX), second meeting, July 2001,
- Xeno Sub-Committee of the Biological Response Modifiers Advisory Committee,
- National Xenotransplantation Registry and Database-Pilot Phase,
- Xenotransplantation and Gene Therapy Disclosure, published 18 January 2001.

Transgenics is another promising area that raises regulatory issues that are only now becoming apparent. Plants and animals are being used to make products such as vaccines, monoclonal antibodies and therapeutic proteins. New techniques, including recombinant DNA technology, open up exciting prospects for developing a range of new vaccines such as DNA vaccines, tumour vaccines and new live attenuated vaccines. New technology has led to advances in genomics, proteomics, metabonomics, cellonomics and bioinformatics. The microarray technology promises to bring about a better understanding of the complex causes of hitherto unconquered human diseases. Research in these new technologies contributes to the discovery of innovative medicines, vaccines and the provision of new diagnostic tests.

Oligonucleotide microchips can be used for surveillance or detection of both naturally occurring pathogens and those that might be used in biological warfare. The microchips can also be used in vaccine quality control and vaccine development.

There are some potential impacts of proteomics. Research is likely to lead to the development of new disease markers for early detection, new therapeutic targets, and new markers for therapeutic efficacy and for toxicity. New regulations will therefore need to take into account the new target pool, new markers for toxicity, new endpoints for efficacy, new endpoints for potency, and new bioassays for, e.g. identity and purity.

Last, but not least, here are some challenges for the future:

• New discoveries through biomedical research and technology:

- gene therapy,
- stem cell products,
- genomics and proteomics,
- transgenic plants and animals,
- xenotransplantation,
- new vaccines.

• New analytical methods:

- three-dimensional nuclear magnetic resonance,
- microarray technology,
- proteomics,
- fluorescent cell imaging,
- MALDI-TOF spectroscopy,
- PERT assays.