The above observation was given because of the following reasons;
1. The firm lacked stability data to support the expiration dates for the drug product which was in distribution.
2. This was a repeat observation from your 2016 FDA inspection. Instead, to support the two-year expiration date of the drug product, the firm provided data from a different formulation of (b)(4) that failed its long-term stability study and was stopped at the three-month time point because of changes in viscosity. The long-term stability test report determined the need for reformulation.
3. In the firm's response, the firm explained that because a retained sample of (b)(4) drug product passed microbiology and assay testing, the two-year expiration date was justified for the drug product.
However, the retain sample tested was the formulation that failed its long-term stability study for viscosity. Further, the firm did not provide testing to ensure the retained sample met all specifications required during your stability studies such as odor, pH, and viscosity.
4. The firm's response was inadequate because it failed to provide a report that ensures adequate stability studies have been conducted for all drug products.
Without an adequate stability program, you cannot confirm that your drug products will meet established specifications and all pre-determined quality criteria throughout their shelf life.
The above observation has been given to the firm because of the following reasons;
1.The firm has assigned a two-year expiration date to your products without adequate data regarding the stability characteristics of the products.
2.For example, the shelf-life study performed, completed on September 27, 2021, only included sterility and endotoxin testing as part of the stability protocol.
3.The corrective actions described in the response are not adequate to address the above-noted violations. FDA noted that certain of their planned corrective actions cannot be evaluated because of a lack of supporting documentation.
4. Additionally, the response does not address the firm’s continued manufacture and distribution of the products under the violative conditions outlined above or the plans for the disposition of the product inventory that may still have at the facility. FDA noted the products carry a two-year shelf life.
5. While the firm asserts that its products should be regulated solely under section 361 of the PHS Act, as explained above, the available evidence shows that the products do not meet all the criteria in 21 CFR 1271.10(a) for regulation solely under section 361 of the PHS Act and the regulations in 21 CFR Part 1271.
6. The firm's response also does not adequately address its failure to have an IND in effect to study its products addressed in this letter or the firm's lack of an approved BLA to lawfully market its products.
7. As noted above, to lawfully market a drug that is a biological product, a valid biologics license must be in effect [42 U.S.C. 262(a)]. Such licenses are issued only after showing that the product is safe, pure, and potent. While in the development stage, such a product may be distributed for clinical use in humans only if the sponsor has an IND in effect for that product, as specified by FDA regulations, that covers such clinical use [21 U.S.C. 355(i); 42 U.S.C. 262(a)(3); 21 CFR Part 312].
8. Neither this letter nor the observations noted on Form FDA 483, which were discussed with the firm at the conclusion of the inspection, are intended to be an all-inclusive list of deficiencies that may be associated with its products. It is the firm's responsibility to ensure full compliance with the FD&C Act, PHS Act, and all applicable regulations.
9. This letter notifies the firm of the FDA's findings and provides the firm an opportunity to address them.
Failure to adequately address these matters may lead to regulatory action without further notice. Such actions include seizure and/or injunction.