FDA CRL - HQ Specialty Pharma

The U.S. Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) to HQ Specialty Pharma Corporation for its New Drug Application (NDA 211413) for Cefazolin for Injection USP, 2 g/vial, submitted under section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act. This action followed the company's July 09, 2020, amendment responding to a prior December 26, 2019, action. The FDA determined the application could not be approved in its current form due to significant nonclinical deficiencies related to the safety qualification of leachables from the drug product.

Key issues included a 14-day toxicity study in rats that failed to achieve clinically relevant leachables exposures, with animals receiving significantly less than the estimated maximum human exposure. The company's proposed acceptable intake for leachables also exceeded the FDA’s recommended 5 mcg/day for non-genotoxic substances. Furthermore, the FDA found the methods used for calculating acceptable intake and selecting surrogates for read-across analysis to be inadequate, citing insufficient toxicological data and concerns about structural similarity of the chosen compounds.

To resolve these deficiencies, HQ Specialty Pharma Corporation must conduct an additional general toxicity study for any leachable exceeding the 5 mcg/day safety threshold, ensuring clinically relevant exposures. The FDA strongly recommends submitting a draft study protocol for review before initiating new studies. A detailed leachables assessment plan is also necessary, along with further genotoxicity evaluations, such as (Q)SAR and Ames testing, if new leachables are characterized. Additionally, the company is required to submit a comprehensive safety update and revise the proposed prescribing information according to FDA guidelines.