Pinnacle Transplant Technologies, LLC — FDA Warning Letter Findings

Failure to establish an adequate system for cleaning and disinfecting the room to produce aseptic conditions [21 CFR 211.42(c)(10)(v)]. Your cleaning validation is inadequate. For example, at the time of the inspection, you failed to validate the efficacy of the disinfectants used to clean and disinfect your cleanroom.

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, your firm failed to adequately validate the aseptic process used to manufacture over (b)(4) units of PalinGen® (b)(4) and PalinGen® (b)(4) since your manufacturing operations began in March 2020. More specifically, it was observed during record reviews that the media fill simulations did not follow your commercial manufacturing process for the products. Additionally, critical manufacturing steps were not simulated during the validations. Your products are purported to be sterile and are expected to be sterile.

Failure to establish laboratory controls that include scientifically sound and appropriate specifications designed to assure that drug products conform to appropriate standards of identity, strength, quality, and purity [21 CFR 211.160(b)]. For example, your finished product testing is limited to sterility testing and endotoxin testing as measurements of product attributes, and such testing does not demonstrate, for example, the identity and/or strength of your products.

Failure to maintain equipment and utensils at appropriate intervals to prevent contamination that would alter the safety, identity, strength, quality or purity of the drug product [21 CFR 211.67(a)]. For example, your firm performed HEPA filter integrity testing (b)(4) on your ISO- (b)(4) , despite the detection of a gross leak in the HEPA filter during (b)(4) testing. 2 Your ISO- (b)(4) are used to aseptically process your (b)(4) products which are purported to be sterile…

Failure to have an adequate system for monitoring environmental conditions in an aseptic processing area [21 CFR 211.42(c)(10)(iv)]. Specifically, environmental monitoring samples within your ISO- (b)(4) are not positioned in critical areas that pose the most microbiological risk to your products during aseptic processing operations. During the inspection, FDA investigators observed passive (b)(4) positioned on a (b)(4) , within the (b)(4) portion of the ISO- (b)(4) , during aseptic filling operations. This practice is insufficient to demonstrate control of the critical manufacturing areas during aseptic processing.

Failure to thoroughly investigate any unexplained discrepancy or the failure of a batch or any of its components to meet any of its specifications whether or not the batch has been already distributed [21 CFR 211.192]. Specifically, between July 2020 and February 2022, your firm failed to investigate 8 sterility failures. While you identified the contaminating organisms, you did not conduct an investigation to determine the root cause of the failures or implement corrective and preventative actions. Examples of contaminating organisms include (b)(4) .