BioWorld International Correspondent

BRUSSELS, Belgium - Concerns are exaggerated about the decline in applications and authorizations of new medicines, according to a new European study of the pharmaceutical sector, which finds that new technologies such as gene therapy are contributing to a growth in products in early stages of development.

The study, commissioned by the European Union to assess whether there is a worldwide crisis in innovation, predicts a recovery in authorizations in 2004-05, and a gradual increase in marketing authorizations in the foreseeable future. However, it added, it is unlikely that biotech products will represent a significant number of applications or authorizations over the next five years, because of the lengthy development process for new high-technology products.

Global R&D expenditure has risen over the past decade without generating a significant increase in the number of new products - largely because of the shift to more complex products, and because new technology has increased the costs of research and development in the short term, according to the study. But it expects the costs of technology "to be reversed in the future, when the impact of biotechnology on innovative output will come through."

The report urged giving assistance to drug companies to accelerate moving products from Phase II to the market, and closer communication between the authorities and pharmaceutical companies. It suggested an agreement on using advances in applied sciences as surrogate endpoints for a particular product, or focusing a product's development on a narrower area of therapy to speed the review process.

"A failure to focus effort in Europe is likely to lead to even less European-led pharmaceutical innovation, particularly in the burgeoning areas of genome sciences and biotechnology," it warned. It also called for improved access to venture capital in Europe, complemented by public funds to "make the industry less risky and more attractive for private venture capital."

EU Builds Biotech Generics Policy

The European Union is creating the first comprehensive framework for regulating generic copies of biotechnology-derived medicines. The aim is to bring greater clarity into what has been a gray area until now - the rules around bringing biotech copies to the market.

The standard procedures for obtaining a marketing authorization for a chemical-based copy product are not sufficient for biologicals, the European Medicines Agency acknowledged in its announcement last week. Abridged applications based on references to a similar product already on the EU market are in theory acceptable, but the applicant has to demonstrate the similar nature of the two biological medicinal products in terms of quality, safety and efficacy.

Because of the molecular complexity of products derived from recombinant DNA and from gene and cell therapy, it often is difficult to characterize the reference product and demonstrate an adequate degree of similarity of a copy.

"Moreover, parameters such as the 3-dimensional structure, the amount of acido-basic variants or post-translational modifications, such as the glycosylation profile, can be significantly altered by changes, which may initially be considered to be minor' in the manufacturing process," the agency said.

It might be possible to demonstrate biosimilarity through comparability studies for highly purified products that can be thoroughly characterized, but it is more difficult to apply to other biological medicines that by their nature are more difficult to characterize, such as gene and cell therapy products for which little clinical and regulatory experience has been gained.

The draft guideline urged a case-by-case approach for the nonclinical/clinical data package, dependent on the state of the art of analytical procedures, the manufacturing processes employed, and clinical and regulatory experience. But the agency has deferred consideration of generics in gene or cell therapy.

"These products are of a complex nature and will be considered in the future in light of the scientific knowledge and regulatory experience gained at the time," it said.

The agency's initiative also is a follow-up to the major package of new pharmaceutical legislation agreed by the 25 member states in March, which envisaged specific guidance. An extended consultation is to be held, lasting until February, on a set of guidelines to define how the new policy is to be put into effect.

Plans For Conditional Marketing Authorization

The European Union has released draft new rules for another of the innovations introduced by the March 2003 pharmaceutical package, which was particularly requested by the European biotechnology industry: conditional marketing authorizations.

The concept of a conditional marketing authorization, while familiar at a national level, has not before been defined at the EU level. It has been created to standardize the approach to early clinical use of valuable medicines in development. It will be available for medicines that aim at the treatment, prevention or medical diagnosis of chronically or seriously debilitating or life-threatening diseases, particularly orphan medicines and medicines for public health threats.

The applicant will have to demonstrate the public health interest of the product, and a presumed positive benefit-risk balance. Ongoing studies - or new studies - will have to be conducted to verify that the benefit-risk balance is positive. Successful applications will receive a conditional marketing authorization valid for one year, but which can be renewed. Product information will have to make clear that only a conditional marketing authorization has been granted.

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