Regulatory Routes - Biopharmaceuticals

REGULATORY ROUTES

From a regulatory perspective, a copy of a biophar-maceutical product can be identified as a generic product. But in practice it is unlikely, due to additional complexity, particularly safety issues. The copy of a biopharmaceutical product is required to have a similar safety and efficacy profile as the brand name/innovator product, and therefore it is referred to as “biosimilar”. Biosimilar products are non-interchangeable.

According to the U.S. Food, Drug and Cosmetic Act, the approval process can follow one of two routes: New Drug Application (NDA) with two sub-classes, and Abbreviated New Drug Application (ANDA)

Section 505(b)(1): Full reports of investigations of safety and efficacy are needed. This results in a full NDA, with right of reference. This means that information about safety and efficacy can be used by others to document safety and efficacy of the product.

Section 505(b)(2): This requires clinical studies, without the right of reference, e.g., NDA for rDNA. Most of the biosimilar products fall into this category.

Section 505(3): This is the route for ANDA applications. This requires the dosage form to be pharmaceutically equivalent and requires only bioequivalent studies. It does not require clinical or pre-clinical studies. This is the route normally followed for small molecule generic products.

Biosimilar products are different from second generation biopharmaceuticals (Table 2). The second generation biopharmaceuticals have improved phar-macological properties/biological activity compared to an already approved biopharmaceutical product which has been deliberately modified. The second generation products are marketed with the claim of improved clinical superiority. The second generation biopharmaceuticals require a full New Drug Appli-cation and are not interchangeable with the brand name product.

Two “types” of equivalence can be envisioned.

·           Within a manufacturer—changes in the manufac-turing process, changes in the formulation or a change in manufacturing site by a given manu-facturer. This requires assurance of pharmaceutical equivalence. At times, depending upon the nature of the change, a comparability study (see below) may be required. The FDA Guidance on Com- parability is summarized in the insert box.

·           Between manufacturers—This falls in the category of a biosimilar product and it requires confirma-tion of pharmaceutical equivalence as well as bioequivalence.