RenatiLabs Inc. — FDA Warning Letter Findings

In response to FDA-483 Observation 3, you state that storage of sterility samples at (b)(4) not affect detection of microbial contamination. FDA disagrees. There is no assurance that microorganisms, which may be weakened by the manufacturing process, would survive freezing and be reliably detected by sterility testing.

Drug products failing to meet established standards or specifications and any other relevant quality control criteria are not rejected [21 CFR 211.165(f)]. For example: You failed to reject WJMAX™ lot REN20210205 after this lot failed sterility testing, due to contamination with Staphylococcus epidermidis , according to the final report from your contract laboratory dated March 22, 2021. Your Quality Representative and Management with Executive Responsibility approved this lot for release for distribution on June 14, 2021, and June 22, 2021, respectively. You have sold numerous vials of this lot, as recently as (b)(4) .

Failure to establish and follow a written testing program designed to assess the stability characteristics of drug products and to use results of such stability testing to determine appropriate storage conditions and expiration dates [21 CFR 211.166(a)]. For example: You assigned a four-year expiration date to batches of WJMAX™ without supporting stability testing data. FDA has reviewed your written response, dated September 1, 2022, to the inspectional observations on the Form FDA-483 issued at the conclusion of the inspection. The corrective actions described in your response are not adequate to address the above-noted violations. We note that some planned corrective actions did not include a timeline for completion and cannot be evaluated because of a lack of supporting documentation. Our concerns regarding your response to specific FDA-483 observations include but are not limited to, the following…

Failure to establish written procedures for production and process control designed to assure drug products have the identity, strength, quality, and purity they purport or are represented to possess [21 CFR 211.100(a)]. For example: The manufacturing process for WJMAX™ has not been validated with respect to identity, strength, quality, and purity.

In response to FDA-483 Observation 2, your proposal to “perform the tissue dispersion or reduction purely (b)(4) ” or “quantify total protein” “if deemed necessary” would not alter the regulatory status of your product as a drug and biological product. Moreover, the method suitability test referenced in your response is insufficient to assure that your product has the identity, strength, quality, and purity it purports or is represented to possess as required by 21 CFR 211.100(a).

Failure to prepare batch production and control records for each batch of drug product produced that include documentation that each significant step in the manufacture, processing, packing, or holding of the batch was accomplished [21 CFR 211.188(b)]. For example: a. Your batch records do not include documentation of all investigations made according to 21 CFR 211.192. For example: i. Your batch record for WJMAX™ lot REN20210205 does not include documentation of any…

In response to FDA-483 Observation 5, you stated that you have a “robust system for environmental monitoring which is documented in [your] SOPs” and it was developed with (b)(4) , a third-party microbiology lab. You also stated that your firm “intends to adhere to [your] robust environmental monitoring for future tissue processing” and that testing would be conducted (b)(4) . Your environmental monitoring procedure provided during the inspection, QP 195.102 Air, Surface, &…

Failure to establish and follow appropriate written procedures designed to prevent microbiological contamination of drug products purporting to be sterile, including procedures for validation of all aseptic and sterilization processes [21 CFR 211.113(b)]. For example: a. Your firm failed to validate the aseptic process used to manufacture WJMAX™ (i.e., by performing media fill simulations). By the nature of its route of administration, and per your product labeling, your product purports to be sterile and is expected to be sterile. b. You failed to conduct environmental monitoring for any of the (b)(4) processing runs of WJMAX™ in the aseptic processing areas.

Failure to establish laboratory controls that include scientifically sound and appropriate specifications, standards, sampling plans, and test procedures designed to assure that components, drug product containers, closures, in-process materials, labeling, and drug products conform to appropriate standards of identity, strength, quality, and purity [21CFR 211.160(b)]. For example: a. Sterility samples of WJMAX™ are stored at (b)(4) prior to sterility testing. Freezing in this manner has the potential to destroy any microbial content in the samples before testing; therefore, contamination, if present, may not be detected. b. You have not collected and tested sterility samples that are representative of the lot size. You have tested (b)(4) vials for sterility regardless of lot size, which may consist of as many as (b)(4) vials.