FDA Updates Orange Book and Rules for Complex Generics
​[Thursday, January 31, 2019}

FDA would create special criteria for complex drugs that are hard to genericize so generics could be created for them. Also, FDA would require manufacturers to provide timely and accurate updates to Orange Book information. Last year was a record year for generic drug approvals. FDA has repeatedly demonstrated that it wants to make it easier to create generic versions of drugs to increase competition and manage the drug prices. The two new announcements this week attempt to address common issues with generic drug. Complex drugs are those “that, by nature of their formulation, delivery systems or the complexity of their active ingredients, for example, are harder to “genericize” under traditional approaches. As a result, these complex drugs often face less competition.” Although many of these drugs are no longer protected by patents, they have no or few generics. About an year and half ago, FDA published a list of drugs with few or no generics despite lack of patent protection. Many of those were complex drugs. FDA’s publicized list did little to help create generic version of these due to the complication of doing the same. FDA’s new initiative addresses this issue by creating special exceptions for complex drugs where the generic manufacturers could establish bioequivalence through alternate methods such as establishing API equivalence only or in vitro assays for bioequivalence. FDA plans to release several new guidance documents in the coming months for these complex generics. Another issue hindering generic development is the inaccurate description of marketing status of drugs in the Orange Book. Manufacturers will now need to update the current marketing status of their drugs in a timely manner. NDA and ANDA holders will need to notify FDA at least 180 days prior to withdrawing a product from sale or if a newly approved drug will not be available for sale within 180 days of approval. Also, manufacturers will need to notify FDA within 180 days if their drugs included in the active section of the Orange Book were available for sale or if one or more of their drugs in the active section had been withdrawn from sale or had never been available for sale. These notifications apply to drugs withdrawn from market due to non-safety reasons. The notifier will also need to inform FDA of the reason for the market withdrawal.