Continuing our plan to detail the regulatory and fundamental quality responsibilities that all brand manufacturers (especially online-only brands) need to embrace, this piece offers a short discussion about another responsibility/accountability gap that often exists in the industry with the use of expiration or shelf-life determinations.
Introduction:
Expiration dating is not required as part of the Food and Drug Administration’s final rule of Current Good Manufacturing Process (“cGMP”). The cGMP Code of Federal Regulations (“CFR”) 21CFR Part 111 (72FR 34572 at 34856) definitively states that a shelf life or expiration date is not required, but if the company decides to use an expiration date, it must be supported by substantiating data.
That’s only part of the issue though. Companies could, in theory avoid expiration dating and the entire hassle of measuring product stability over time. However, many retailers do require an expiration date as a term of sale. Some brands still elect to not place an expiration date on their products and some others place a manufacture date on the product instead of an expiration date. Consumers also expect to see an expiration date so one can question the logic from a business perspective of companies who dodge this issue.
Issue:
Expiration dating is a “mostly required” data point for sale of dietary supplements. Because the FDA does not specifically have a requirement for shelf life or expiration dating, many variations of the data are provided in the marketplace. Expiration dates are also not clearly definable at the onset of a product introduction. The benchmark for shelf life is often a “reasonable expectation” as provided by substantiation of information. This vague language can easily, but not rightfully, be altered to fit the wishes of the seller.
Relevance:
The FDA is clear in stating that if an expiration date, or anything similar, is used to sell a product, the date must be substantiated with documentation. The Federal Register document 34855 states the FDA declines to require expiration dating because it is known that accurate and definable analytical testing methods are often not agreed upon. The document describes a lack of sufficient scientific information to determine the biological activity of certain dietary ingredients used in dietary supplements. The FDA concluded its comments by stating:
“Because the final rule does not require that you establish an expiration date, we decline to offer guidance on the type of data that are acceptable to support an expiration date, other than to repeat that any expiration date that you place on a product label should be supported by data.”
The required substantiation used by many sellers has ranged from accelerated stability studies on product not released to the market to expectations established through analysis of single ingredient(s) used to manufacture the product. Many FDA warning letters have addressed this issue, but no warning letter has clearly defined what expectation for substantiation is required to meet the FDA standard. Furthermore, most FDA warning letters separate any discussion regarding expiration dates as “comments” outside of the general information of the letter.
Stability testing is an acceptable method of substantiation, but no frequency of testing is mandated. A skip lot method of testing at manufacture date, half-life and full-life is a popular method of substantiation for expiration dates. Fundamentally, the substantiation must be a part of a documented SOP which can be referenced upon request. Another factor for consideration when substantiating an expiration date is the obligation that the company has an make the rationale for determination of expiration date available should it be requested.
Relevance:
While the FDA has not made it clear that a specific requirement is set for expiration dates or shelf life determination, the requirement of the marketplace for this information places the responsibility for accurate information on the brand owner.
Example:
VitaCare Pharma LLC 3/7/16 Warning Letter
https://www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm490871
Comment:
- Your firm includes expiration dates on the labels for your dietary supplement products. For example, the labels on your dietary supplements: Monster Xplosion capsules and HerDiet Pink capsules have a 3 year shelf life. Similarly, the label on your dietary supplement Stimuloid US Capsules has a 2 year shelf life.
Any expiration date and storage conditions you place on a product label should be supported by data that demonstrates the product’s shelf life under the recommended storage conditions [See 72 Fed. Reg. 34752, 34856 (Jun. 25, 2007)]. Please note that the term “expiration date” includes shelf life dating as well as ‘‘best if used by’’ dating [See 72 Fed. Reg. 34912, 34856 (Jun. 25, 2007)].
We note that your written response provided a blank template that you provide to your clients that ask them to verify the shelf life dating; however, no supportive documents were provided to explain the justification for the expiration date.
There are a number of Warning Letters that provide this type of response from the FDA. The summary and consistency of the wording in each of these letters is found in the sentence:
Any expiration date and storage conditions you place on a product label should be supported by data that demonstrates the product’s shelf life under the recommended storage conditions.
What you can do:
It is prudent business practice to include the expiration date on your product labels. To help ensure those dates are substantiated, we recommend the following:
- Ask your suppliers about known ingredient deterioration
- Perform stability studies on finished products
- Test and evaluate retained inventory in a pre-determined and documented manner
