Whenever an applicant wishes to register their follow-on medicinal product, be it a generic product or a biosimilar, the applicant has to include in their dossier a comparison between the newly-developed product with a previously-approved and registered medicine. For “standard” generic products evidence, such as the approved product’s dosage form, strength, excipient and content can be obtained from published information and further “proof” is generated by such things as dissolution profiling and bioequivalence studies. However, there is always a question as to whether the comparison product (usually the originator’s product) is the same internationally. For example, it is possible that the same active ingredient in the same dosage form could have been formulated differently from country to country, either as a result of differing timing of the drug’s development and launch or on purpose to create artificial barriers, such that the follow on products will be more complex to develop. Of course, the difficulty of having what outwardly appears to be the same product, but inwardly is significantly different, creates potentially dangerous problems for both doctors and patients. Clearly, if a patient travels across borders and needs to refill their prescription, it could result in real problems, if the apparent same drug and dosage form act differently biologically.
Health authorities around the world now work much more closely together and confidential information about their registered and approved products can be passed between them, such that differences in formulations that affect bioavailability would be available to them and thus will be alert to possible issues. For a company making a follow-on product, however, this information is not available. As a result, companies wishing to make a generic product have to carry out extra studies as outlined above to investigate the differences from country to country and carry out bioequivalence studies against a local reference product.
Biological medicines are medicines that are made by or derived from a biological source. They can consist of relatively small molecules, such as human insulin or erythropoietin, or complex molecules, such as monoclonal antibodies. Biosimilar products are, thus, far more complex and need far more studies to show similarity, requiring a large number of clinical trials, as opposed to the bioequivalence studies that generic products undergo. Given the difficulty in developing, testing and registering new biological, it may well be that, unlike non-biological medicines, biological products may well be the same product internationally.