Amendments vs Supplements | USFDA

Both amendments and supplements are important tools in the USFDA’s regulatory process with some key differences.


Initiated by the company or requested by the USFDA to make a change to an unapproved application/PAS/tentatively approved application. There are three categories of amendments: major, minor, and unsolicited.

Major amendments are changes that have a significant impact on the safety, efficacy, or labeling of a product and are often required in response to complete response letter (CR) identified by the FDA and require significant time and resources.

Example: manufacturing a new batch of the drug product, performing a new BE study, or developing new analytical procedures.

Minor amendments are an important part of the drug approval process, as they allow for necessary changes to be made without delaying the approval of a drug and can be resolved through an information request (IR) or discipline review letter (DRL).

Example: These amendments are typically used to address minor deficiencies in the DMF, incomplete dissolution data, or labeling issues.

Unsolicited amendment is a type of amendment submitted to the FDA without being requested. These amendments can be classified as either major or minor, depending on the content of the amendment. The FDA has specific guidelines and processes in place for reviewing and addressing unsolicited amendments to ensure the safety and effectiveness of drugs on the market.

Requests for final approval with no new data, information, or other changes to the ANDA must be submitted at least 90 days prior to the date on which the applicant seeks final approval.


Request by a company to add new information or data to an approved application. Unlike amendments, supplements do not involve changes to the product itself. There are three types of supplements: annual reports, CBE-0, and CBE-30.

Annual reports are submitted every year with changes that has “minimal potential to have an adverse effect” on the identity, strength, quality, purity, or potency of the drug product as these factors may relate to the safety or effectiveness of the drug product.

CBE-0 (Changes Being Effected) supplements are submitted to the USFDA for minor changes that are intended to improve the product’s safety, efficacy, or labeling. Changes subject to this type of supplement contain changes for which distribution can occur when FDA receives the supplement.

CBE-30 (Changes Being Effected – 30) supplements are submitted for moderate changes. Changes that fall into this category require the submission of a supplement that must be made to the FDA at least 30 days before the changed drug product is distributed.

PAS (Prior Approval Supplement) is a type of supplement that is submitted for major changes to an already approved application. These changes require prior approval from the USFDA and cannot be implemented until approval is received.

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Resource Person: Bharathi Kodali

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