Complex Drugs and Biologics: Scientific and Regulatory Challenges for Follow-on Products

Since the passage of the Health Care Reform Act, the Food and Drug Administration has been working to develop consistent regulations for the approval of biosimilar drugs. However, there has been little public discussion of the scientific challenges associated with approval of follow-on versions of non-biologic complex drugs (NBCDs), which more closely resemble biologics than small-molecule drugs. Abbreviated new drug applications (ANDAs) are appropriate for low-molecular-weight, well-characterized drugs. In contrast some complex drugs, including synthetic proteins and polypeptides, are not characterizable or amenable to therapeutic equivalence testing. Essential to new regulations for biosimilars are guidelines for the necessary degree of similarity to the innovator drug, and the extent of testing needed to demonstrate safety and efficacy of the follow-on product. These issues also apply to follow-on NBCDs, as exemplified by experience with members of the glatiramoid class. As the FDA and Congress develop legislation for biosimilars, regulatory guidelines for follow-on versions of NBCDs should be addressed.