Recently, the U.S. Food and Drug Administration released a guidance to explain how assessment goals are set for amendments to either abbreviated new drug applications (ANDAs) or prior approval supplements (PASs). According to the FDA, every submission attached to an application under review is considered an amendment.
Each type of amendment has to fulfill specific assessment goals. These goals are determined according to the kind of assessment subjected (standard or priority) and the type of amendment. Assessment goals are also impacted by the need for pre-approval inspections and by whether the applicant submitted pre-submission facility correspondence (PFC) in a timely and complete manner.
Depending on the content, each submission is classified and issued goals and deadlines set in relation to its amendment type. In this article, we provide an overview of the different types of amendments as well as some examples.
Major Amendments
This type of amendment applies to significant actions such as manufacturing a new batch of drugs, performing a new bioequivalence study, carrying out new analytical tests, and providing complete validation data. This classification is not correlated to the time the applicant spent addressing a complete response letter (CRL), information requests (IRs), or discipline review letters (DRLs).
Some of the reasons why manufacturers decide to submit a new batch of drugs include:
Composition changes.
Reformulation.
Change in the source of active substances.
Change of manufacturing facility.
Significant change in the manufacturing process.
New in vitro studies.
New strength.
Unacceptable impurities.
Unacceptable excipients.
Failed stability data.
Change in the container-closure system.
In addition, the FDA has the authority to classify submissions as major amendments, even if they are not specific examples listed in Appendix A of the aforementioned guidance.
Minor Amendments
This classification applies to submissions not considered as major amendments or related to a deficiency that can be more easily addressed and require less FDA involvement in its review. Some examples of these amendments include:
Small drug substance deficiencies.
Incomplete dissolution data.
Labeling deficiencies.
Unsolicited amendments
These submissions encompass amendments with information not requested by the FDA, except for those considered routine and that do not require scientific review, such as final ANDA approval requests, patent amendments, and general communication. Based on their significance, unsolicited submissions can be classified as major or minor amendments.
Ultimately, understanding the types of amendments is crucial for applicants navigating the regulatory pathway for generic drug approvals. Each amendment type: major, minor, or unsolicited, carries specific requirements and deadlines. By knowing in advance which kind of amendments they are submitting, manufacturers can work on including all the information necessary, adjust their timelines according to the assessment goals, and improve the likelihood of a successful application.
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