Posted on September 21, 2021 | Through
The U.S. Food and Drug Administration’s Center for Drug Evaluation and Research (FDA’s CDER) on Monday released draft guidelines that provide generic drug applicants with answers to frequently asked questions in the area of drug quality. medications. The new guidelines are designed to provide an immediate response to these questions to reduce the number of controlled matches on identical topics.
The guidelines, which are in the form of questions and answers, cover FDA policies on quality-related scientific and regulatory topics that “appear frequently” in vetted correspondence submissions from CDER’s Office of Pharmaceutical Quality. The intent of the guidelines is to help industry “move forward with certain generic drug development activities without the need to submit controlled correspondence to the FDA,” according to an email from the agency. September 20.
Under the Generic Drug User Fee (GDUFA II) changes, manufacturers who submit a question through the controlled match mechanism may wait up to 60 or 120 calendar days for a response, depending on the type of controlled correspondence, as the agency reiterated in its final version. guidance released last December (RELATED: Generics: FDA Finalizes Controlled Match Guidance, Regulatory guidance December 17, 2020).
The nine questions and answers contained in the guidelines to date are “derived from numerous vetted match submissions” and cover parenthesizing and mastering expectations, container closure changes, dissolution, testing for endotoxins, the number of lots of exhibits needed and the scoring and testing of split tablets. .
Some of these frequently asked questions and the answers from the FDA are as follows:
Bracketing and mastering
The FDA has clarified that a bracketing approach is acceptable for a multi-strength drug product, as long as the active and inactive ingredients are proportional to the dose.
The agency was responding to a question about whether it is acceptable to use a bracketing approach for manufacturing voucher lots of a generic drug with multiple strengths produced from granulations or bulk blends currents, and whether all of these batches should be placed on a stability program.
The guidelines specify that sponsors should produce three separate intermediate bulk batches, with one batch representing all proposed concentrations, one batch reflecting the lowest concentration, and one batch reflecting the highest concentration. For more information, sponsors should consult the May 2014 FDA guidance titled “ANDA: questions and answers on stability testing of drug substances and products.”
Container closing systems
A proposed generic drug need not have the same container closure system (CCS) as the reference product, the agency said in response to a question about whether a generic drug could be packaged in a bottle if the RLD is packaged in an ampoule.
The guide provides answers to two questions related to bacterial endotoxins. The first answer relates to how an acceptance criterion for endotoxin testing should be determined for a finished pharmaceutical product. Here, the FDA directs generic developers to General Chapter 85 of the American Pharmacopoeiawhich defines the maximum endotoxin exposure for drugs in general and for topical and intrathecal drugs.
Topical ophthalmic drug products do not have to be tested for bacterial endotoxins, the FDA said, answering a second question about whether it is acceptable to omit bacterial test limits for these products. However, endotoxin testing may be required if the product is to be used on an abraded eye or used during surgery.
The FDA has advised industry to consider these matters before submitting controlled correspondence on these topics. The agency intends to add additional questions and answers as needed to address any frequently asked questions that may arise.
FDA Guidelines on Controlled Correspondence
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