FDA seeks input on pre-Hatch-Waxman ‘PANDA’ applications

Regulatory NewsRegulatory News | 12 August 2021 |  By 

The US Food and Drug Administration (FDA) on Thursday asked for input from stakeholders on how it should handle certain drugs approved in abbreviated applications before the enactment of the Drug Price Competition and Patent Term Restoration Act (Hatch-Waxman Amendments) in 1984, which created the agency’s modern regulatory framework for generic drugs.
In a Federal Register notice announcing the consultation, FDA refers to such products as “pre-Hatch-Waxman abbreviated new drug applications” or PANDAs. Because these products were submitted and approved under the provisions of section 505(b) of the Federal Food, Drug, and Cosmetic Act, they can be used as both a reference listed drug (RLD) for generic drugs in abbreviated new drug applications (ANDAs) and referenced in 505(b)(2) applications, which are new drug applications (NDAs) containing full reports of investigations of safety and effectiveness that may rely in part on studies conducted by other parties. The consultation applies specifically to PANDAs approved under section 505(b) and, due to their complex regulatory history, excludes antibiotics approved under section 507 of the FD&C Act.
FDA said it is looking for feedback on “several issues related to FDA’s post-approval regulation” of PANDAs and acknowledged that there is “some confusion about the applicability of certain statutory and regulatory provisions to PANDAs.” FDA also notes that such products have traditionally been regulated by the Office of Generic Drugs within the Center for Drug Evaluation and Research.
Products FDA now considers to be PANDAs came about after the enactment of the Kefauver-Harris Drug Amendments, when FDA initiated the Drug Efficacy Study Implementation (DESI) to review drugs approved between 1938 and 1962 solely based on their safety.
“FDA introduced the concept of an ‘abbreviated new drug application’ in 1968 as a vehicle for approval of certain drugs affected by the DESI review, and in 1970, FDA published a final rule establishing a regulatory pathway for submission of abbreviated applications for these drugs,” FDA wrote. When a drug subject to DESI review was determined to be effective, FDA would issue a DESI notice that opened the door for abbreviated applications to be submitted for those products instead of an NDA.
“For approval of PANDAs, FDA relied on the evidence of effectiveness that had been provided, reviewed, and accepted during the DESI process. FDA evaluated the safety of these drug products on the basis of information included in NDAs submitted prior to 1962, as well as the subsequent marketing experience with the drugs,” FDA notes.
FDA further explains that “although the regulations establishing the pathway for PANDAs were similar in some respects to the ANDA pathway … the requirements under the old regulatory pathway … also differed in many respects from current ANDA requirements. For example, although the conditions of use and labeling for PANDA products had to be in accord with the relevant DESI notice (which frequently covered a class of drugs that included multiple products and multiple active ingredients) … PANDA products were not required to have the same labeling as a particular pre-1962 NDA drug product listed in the DESI notice.”
The confusion around PANDAs includes how these products appear in FDA’s Orange Book, which lists patent, exclusivity and therapeutic equivalence information for approved drugs. A recent overhaul of the Orange Book in 2017 “revealed that [for some products] no product is identified as being approved under an NDA (in either the active or discontinued sections of the Orange Book) that could serve as an RLD for a 505(j) ANDA. The lack of an RLD is confusing because the Orange Book reflects that there are approved ANDAs for the drug product, including ANDAs identified as reference standards. One reason for this lack of an RLD is that some of the products listed in the Orange Book and identified as being approved in an ‘ANDA’ are actually drugs that were approved for safety and effectiveness under section 505(c) of the FD&C Act in PANDAs that appeared to have been identified as RLDs before the 2017 update to the Orange Book.”
To make it easier to identify PANDAs, FDA has released a list of such products that are currently included in the Orange Book identified as ANDAs, despite being approved in a PANDA under section 505(c) of the FD&C Act. The list includes hundreds of products approved between 1970 and 1984, when the Hatch-Waxman Amendments were enacted.
FDA also explains that there has been confusion for decades over what regulatory provisions apply to PANDAs, “including with respect to requirements regarding labeling updates, patent listing, eligibility for exclusivity and certain drug safety-related requirements or procedures.”
One example the agency provides is that some PANDA holders have followed procedures for 505(b) applications for labeling updates, while others have followed procedures for 505(j) ANDAs.
“FDA understands … that the holders of some PANDAs may have been following various requirements applicable to 505(j) ANDAs over the years after the enactment of the Hatch-Waxman Amendments, and that for them to instead follow requirements applicable to 505(b) applications could be a change in practice. FDA also understands that PANDAs are a unique category of 505(b) applications and that there could be valid reasons to treat PANDAs differently from other 505(b) applications in certain circumstances, to the extent permitted by the applicable statutory provisions,” the agency wrote.
For the consultation, FDA provides a non-exhaustive list of questions to help it understand some of the questions and issues surrounding PANDAs. Including what factors the agency should consider in determining a reasonable amount of time for PANDA holders to make changes to their practices.
Federal Register notice


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