Background
Today, most drug therapies are based on small molecules; they, and new ones developed in the future, will continue to be widely used because they are relatively effective and easy to manufacture. But, many conditions, especially the chronic degenerative diseases of old age and some serious genetically pre-disposed conditions of the young, are poorly addressed, if at all, by existing drugs and surgical practices.

Biotechnology’s techniques have opened up the prospect of a range of new therapies which may address some of these conditions. Protein based drugs, such as recombinant insulin, are of value in many conditions despite the problems of products that cannot be taken orally. Additionally, most protein-based products and many prospective antibody products suffer, like small molecules, from the need for regular administration of small doses, frequently for many years in the case of some essentially prophylactic products.

We believe that biotechnology will produce many new types of therapy in the future, some of which will make a permanent improvement to a patient’s condition with only a single application or a short programme. They will achieve this by harnessing the exquisitely accurate and efficient mechanisms that nature has itself devised. We also believe that regulatory systems designed for the examination and approval of small molecule drugs, and adapted somewhat for biopharmaceuticals, are not yet attuned to the cell- and gene-based products that can now be envisaged, and which are beginning to enter clinical environments.

This position paper identifies some potential therapies based on Cell Therapies and Tissue Engineering and comments on the regulatory developments that may be needed to address them.

Possible Therapies
Artificial organs using animal cells
Xenotransplantation
Cloning
Gene re-programming
Immune System Activation
Neurological Re-construction

Regulatory Considerations
The safety and efficacy considerations applied by regulatory agencies to small molecule drugs are complex and demanding but the essentials of the process are widely understood; in other words, the questions that have to be answered are well known and generally agreed. In recent years, there has been considerable harmonisation of approach to data requirements and to the assessment of manufacture, quality, safety and efficacy through the ICH programme.

This is anything but the case in the context of the new types of therapies under discussion in this paper. Safety and efficacy will of course remain paramount but it is not completely clear what these terms mean in the context of a therapy based on living cells. We are still largely at the stage of "guidelines", "notes" and "points to consider". Moreover, standard practice, such as positive controls and double-blind trials for efficacy assessment, will often be impractical. And, some diseases for which orphan drugs will be used have insufficiently large populations for statistical significance to be assessed by standard methodologies.

In only a few countries has there been adequate preparation of the regulatory systems to the extent that it is clear about what questions have to be answered before a therapy can be approved, and which regulatory bodies should be approached. Indeed, in some countries there is no specific "competent authority" (one which has legal status and empowerment to make judgements on this type of product) and establishing one may be part of the political process. In the UK for example, the possibility of xenotransplantation identified the fact that the necessary capabilities lay outside the remit of any existing regulatory body; as a result UKXIRA was rapidly convened with some guidelines issued by the government. But, the new body was obliged to spend its first several months of existence trying to define the processes that it considered relevant to its task, with consequent delay to interested parties.

MRL Experience
Through working with several leading-edge companies in this field, our principal associates (Alan Williams, Meredith Lloyd-Evans and Richard Kruger) have a wealth of experience that is relevant to the development, evaluation, approval and commercial assessment of products of this type, both in North America and in the major countries of Western Europe. Alan and Meredith are based in Cambridge UK; the former focuses on strategic and commercial issues while the latter has in-depth experience of the existing and developing regulatory systems (Meredith has also managed networks of EU-wide R&D co-workers in tissue engineering and biomaterials). Richard, based in the USA near Boston, has unparalleled experience of steering cell- and tissue-based products and hybrid medical devices through FDA, in industry and latterly as a consultant.

As a result, MRL is extremely well placed to assist companies with such novel therapies, even more so when they address regulatory and market issues, including reimbursement, in more than one jurisdiction. In this sense, Europe may seem unified but there are differences of procedure and philosophy between different countries that can surprise the unwary. MRL’s aim is to protect its clients from the adverse impacts of such variations and smooth the path to market entry.

MRL at BIO 2002
We invited a prestigious panel of experts from the industrial and public sectors the USA and the UK to make presentations in a seminar entitled "Cell Products - The Science and the Regulation" under the Chairmanship of Richard Kruger.

Full details of the seminar

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