Stability - C.02.027 & C.02.028 

 

Q.1  Do batches have to be tested for preservatives at initial release and then in the continuing stability program? 

A.1  Finished products where antimicrobial agents are added to preparations such as multiple dose injections, topical creams, and oral liquids, an assay with limits should be included in the specifications.

An antimicrobial preservative effectiveness testing is performed during the development phase of the product to establish the minimal effective level of preservatives that will be available up to the stated expiry date, and for which a single regular production batch of the drug is to be tested for antimicrobial preservative effectiveness at the end of the proposed shelf life. Once the minimal effective preservative level has been determined, all lots of any preservative containing dosage form included in the stability program must be tested at least once at the expiry date for preservative content. For sterile drugs, the declaration of preservatives on the label is mandatory and those should be treated as for active ingredients (i.e., tested for preservative content at pre-established control points for those batches enrolled in of the continuing stability program). Where the lower limit of the preservative is less than 90 percent of label claim, the challenge test should be performed on samples at or below the lower limit. The challenge test need not be included in the specifications, provided that an assay for the preservative is included.

 

Q.2  Can it be assumed that United States Pharmacopoeia (USP) chromatographic assay methods are stability indicating?

A.2  No.

 

Q.3  Is it acceptable to place an expiry date on a bottle cap instead of on the bottle label?

A.3  No. Please refer to Section C.01.004(c)(v) of the Food and Drug Regulations. The expiration date must appear on any panel of the inner and outer label.

 

Q.4  When the labelled expiration date states only the month and year does it mean the end of the month? 

A.4  Yes. The product should meet approved specifications up to the last day of the specified month.

 

Q.5  Can accelerated stability data of less than three months be used?

A.5  Accelerated stability studies of any length are considered as preliminary information only and should be supported by long term testing.

The assignment of expiry dates should be based on long term testing.

 

Q.6  Should drugs packaged into kits and subsequently sterilized, be tested for stability?

A.6  Yes. These operations are part of manufacturing. For drugs that are packaged into trays or kits and the resulting package is sterilized prior to being marketed, data should be available to demonstrate that the sterilization process does not adversely affect the physical and chemical properties of the drug. The testing should be sensitive enough to detect any potential chemical reactions and/or degradation, and the test results should be compared with test values obtained prior to sterilization.