Changes to an Approved NDA / ANDA
Recommendations are provided for postapproval changes in
(1) components and composition,
(2) manufacturing sites,
(3) manufacturing process,
(4) specifications,
(5) container closure system, and
(6) labeling, as well as
(7) miscellaneous changes and
(8) multiple related changes
Reporting categories
Major change / Prior Approval Supplement
A major change is a change that has a substantial potential to have an adverse effect on the identity, strength, quality, purity, or potency of a drug product as these factors may relate to the safety or effectiveness of the drug product. A major change requires the submission of a supplement and approval by FDA prior to distribution of the drug product made using the change. This type of supplement is called, and should be clearly labeled, a Prior Approval Supplement
The following are examples of changes considered to have a substantial potential to have an adverse effect on the identity, strength, quality, purity, or potency of a drug product as these factors may relate to the safety or effectiveness of the drug product.
- Changes requiring completion of studies in accordance with 21 CFR part 320 to demonstrate equivalence of the drug product to the drug product as manufactured without the change or to the reference listed drug
- Addition of a stability protocol or comparability protocol.
- Changes to an approved stability protocol or comparability protocol unless otherwise provided for in this guidance (e.g., VIII.C, VIII.D, XI.C.2).
- An extension of an expiration dating period based on (1) data obtained under a new or revised stability testing protocol that has not been approved in the application or (2) full shelf life data on pilot scale batches using an approved protocol.
- Changes to a drug product under an application that is subject to a validity assessment because of significant questions regarding the integrity of the data supporting that application
Moderate change / Supplement – Changes Being Effected in 30 Days
A moderate change is a change that has a moderate 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. There are two types of moderate change. One type of moderate change requires the submission of a supplement to FDA at least 30 days before the distribution of the drug product made using the change. This type of supplement is called, and should be clearly labeled, a Supplement – Changes Being Effected in 30 Days
The following are examples of changes considered to have a moderate potential to have an adverse effect on the identity, strength, quality, purity, or potency of a drug product as these factors may relate to the safety or effectiveness of the drug product.
- Supplement – Changes Being Effected in 30 Days
Reduction of an expiration dating period to provide increased assurance of the identity, strength, quality, purity, or potency of the drug product.
Extension of an expiration date that has previously been reduced under this provision should be submitted in a changes-being-effected-in-30-days supplement even if the extension is based on data obtained under a protocol approved in the application. - Supplement – Changes Being Effected
No changes have been identified
Minor change
A minor change is a change 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. The applicant must describe minor changes in its next Annual Report
The following are examples of changes considered to have a minimal potential to have an adverse effect on the identity, strength, quality, purity, or potency of a drug product as these factors may relate to the safety or effectiveness of the drug product.
- Addition of time points to the stability protocol or deletion of time points beyond the approved expiration dating period.
- A change from previously approved stability storage conditions to storage conditions recommended in International Conference on Harmonisation (ICH) guidances.
- Non-USP reference standards:
• Replacement of an in-house reference standard or reference panel (or panel member) according to procedures in an approved application.
• Tightening of acceptance criteria for existing reference standards to provide greater assurance of drug product purity and potency.
Final Year B Pharm Notes, Syllabus, Books, PDF Subjectwise/Topicwise
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