Stability protocol changes

Changes to an approved stability protocol or comparability protocol unless otherwise provided for in this guidance (e.g., Vlll.C, VIII.D, XLC.2). 

Any changes to an approved stability protocol should have a supplemental approval prior to initiation of the stability study. 

Site change (maintaining same specifications) New validation protocol Stability protocol revisions for expanded accelerated and longterm stability Update methods validation Master and batch record revisions Equipment comparability study... 

Marketed product stability studies are required to provide assurance that the drug product continues to exhibit reproducible quality over its shelf life and that accumulated minor changes over time have not adversely affected the product. These studies are initiated annually on one batch of each marketed product in each marketed container-closure system using the approved stability protocol. 

Approved stability protocols are important for the sponsor because they may be used in developing data to support an extension of an approved retest or expiration dating period via annual reports in accordance with 21CFR314.70(d)(5). To change an approved stability protocol or to define one in an application requires a prior approval supplement. 

Products with an Approved Stability Protocol Applicants who have an approved stability protocol may submit the alternate stability protocol in the annual report, reflecting the temperature and humidity as recommended by the ICH. Other changes to the stability protocol generally should be submitted in a Prior Approval Supplement, unless the changes are to comply with the current compendium. 

Products without an Approved Stability Protocol For applications that do not contain an approved stability protocol as defined above, a new or revised stability protocol may be submitted in a Prior Approval Supplement marked expedited review requested. This protocol should encompass 25°C/ambient humidity as the primary long-term storage conditions, and the ICH long-term conditions as the alternate, as well as accelerated stability storage conditions as defined by the ICH Guidance and above, in addition to other recommendations described in this guidance. On approval of the protocol, stability studies may be initiated on annual batches and on batches intended to support supplemental changes. 

Annual reports should include new or updated stability data generated in accordance with the approved stability protocol. These data may include accelerated and long-term studies for each product to satisfy the standard stability commitment made in the original or supplemental application, including the annual batch or batches, and to support postapproval changes. The data should be presented in an organized, comprehensive, and cumulative format. 

Unless a new stability protocol has been adopted via a Prior Approval Supplement before the change is made, stability protocols included in drug applications before the 1985 revisions to the NDA regulations (50 FR 7452) may not support the extension of expiration dating periods through annual reports. If the data are obtained under a new or revised stability protocol, a Prior Approval Supplement under 21 CFR 314.70(b) or (g) or 21 CFR 601.12 should be submitted to extend the expiration dating period. 

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