BioWorld International Correspondent

BRUSSELS, Belgium - Continuing a flurry of consultation over implementing recent changes in EU rules on pharmaceuticals, a draft guideline released Dec. 16 focused on assessing the clinical superiority of similar medicines in the framework of Europe's scheme to promote orphan drugs - and demonstrated the complexity of evaluating competing medicines in the biotechnology sector.

The aim was to clarify eligibility for orphan drugs and the 10-year market exclusivity provided against authorization of a similar product - unless that similar product is "safer, more effective or otherwise clinically superior."

The judgment has to be made by the EU's principal scientific body, the Committee on Human Medicinal Products. To assist, the EU envisages a procedure for tracking potential similarity issues, for assessing similarity and, when necessary, for assessing whether "clinical superiority" applies to a competing product. Sixty days will be allowed for the procedure, with a possible extension by 30 days, to include - if appropriate - advice from the EU's specialist working party on biotechnology. An applicant for the second product would have to provide appropriate documentation on its position regarding similarity and clinical superiority. That would have to cover mechanism of action, structural similarity and evidence of better safety, efficacy or other clinical superiority, based on a comparison of the products with results of clinical studies and from scientific literature.

For instance, the draft guideline suggested, in the context of the orphan drug rules, interferon betas would be considered similar and interferon alfas would be considered similar, but an interferon beta normally would be considered to be different from an interferon alfa. Somatropin and methionyl human growth hormone would be considered to be similar. Pegylated and non-pegylated versions of proteins would be considered similar. And the same protein, whether produced by biotechnology or by synthesis, would be considered similar. Two monoclonal antibodies targeting the same antigen also would normally be considered similar.

Differences in the gene sequence would need to be significant for two genes not to be considered similar. For example, two genes coding for two pharmacologically related proteins of the same group would be considered similar; thus two genes coding for an interferon alfa would be considered similar (either coding for the same amino acid sequence by using different codons, allelic variants, or coding for an interferon alfa of different amino acid sequence). The same gene placed in a different vector or transfer system (such as a retrovirus, adenovirus or liposomes) also would be considered similar. So, too, would cell therapy products based on islets of Langerhans cells for diabetes.