Expiration dating period changes

For ANDA s, accelerated studies are carried out for 3 months. Available long-term data are included in the original submission. If a significant change is observed under the accelerated conditions, 12 month data at the intermediate condition or long-term data through the expiration-dating period are required. 

If significant change is observed, 12-month data at intermediate conditions or long-term data through the proposed expiration dating period... 

Failure to complete registration stability studies Failure to include each marketed product in the stability program Stability data not evaluated as part of the annual product review Stability results do not support expiration dating period Batches evaluated under QA requested studies released before sufficient data were available Stability data do not support proposed changes... 

Rationale for bracketing and matrixing Storage conditions Container orientations Test methods Acceptance criteria Retest/expiration dating period Storage conditions for different types of protocols Clinical trial material Registration stability Annual batches Postapproval changes Special studies Test Parameters... 

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. 

Impact of Post-Approval Changes on Expiration Dating Period... 

Unsatisfactory Data If the stability data under the ICH conditions fall outside the acceptance criteria while data from the parallel study under the previously approved conditions or 25°C/ambient humidity, whichever applies, are satisfactory during the previously approved expiration dating period, and the added humidity is determined to be the cause for the stability failure, the product will still be considered to be in compliance with the regulatory specifications approved in the application. If the applicant decides to adopt the ICH conditions, a Changes Being Effected Supplement with a shortened expiration dating period or a Prior Approval Supplement with revised product specifications may be submitted where justified. Other measures (e.g., more protective container and closure or product reformulation) may be considered through a Prior Approval Supplement. 

Additional stability studies (12 months at the intermediate conditions or long-term data through the proposed expiration date) if significant change is seen after 3 months during the accelerated stability study the tentative expiration dating period will be determined on the basis of the available data from the additional study... 

Batches selected for stability studies should optimally constitute a random sample from the population of production batches. In practice, the batches tested to establish the expiration dating period are often made at a pilot plant that may only simulate full-scale production. Future changes in the production process may thus render the initial stability study conclusions obsolete. 

The expiration dating period for an individual batch is based on the observed pattern of change in the quantitative attributes (e.g., assay, degradation products) under study and the precision by which change is estimated. 

For extrapolation beyond the observed range to be valid, the assumed change must continue to apply through the estimated expiration dating period. Thus, an expiration dating period granted on the basis of extrapolation should always be verified by actual stability data as soon as these data become available. 

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. 

NOTE Initial reglsiTBUon period will not be less than 28 months nor more than 39 months. Once your DEA registration is issued, e renewal application rs automatically mailed to you 45 days prior to your expiration date. Any change of address must be reported to the DEA. Renewal applications arc not forwarded. 

Expiration dates of solutions should be respected. Office staff should periodically survey ophthalmic preparations in the office and discard solutions that have reached the expiration date.The use of old solutions can increase liability as well as introduce the risk of potential drug toxicity or iatrogenic infection. Some commonly used ophthalmic solutions, such as proparacaine, may change color, which indicates oxidation (Figure 3-2), whereas others show no visible signs of deterioration. 

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