Zhejiang Huahai Pharmaceutical – FDA 483, May 19, 2017

The FDA Form 483 inspection revealed significant deficiencies in quality control, analytical testing, and equipment maintenance. The facility failed to implement appropriate controls over Quality Control instruments, leading to compromised analytical testing integrity. Anomalies in testing were not investigated, and assay testing for Active Pharmaceutical Ingredients (API) was repeatedly performed to achieve satisfactory results, violating SOP QC-024-5 which limits replicate sample differences. Specific examples include retesting API batches (b)(4) and (b)(4) without investigation after initial out-of-specification or out-of-trend results due to large differentials between replicate injections. Repeat testing for (b)(4) and (b)(4) showed average assay result differentials of approximately (b)(4)% and (b)(4)% respectively, without substantive explanation from the Quality Control Director.

Impurities during analytical testing were not consistently documented or quantitated. Unidentified "ghost peaks" in Liquid Chromatography-Mass Spectrometry for (b)(4) control batches (b)(4) and (b)(4) were not investigated. Impurity testing for (b)(4) batches (b)(4) showed a coalescing peak with the primary (b)(4) peak, but the impurity was quantitated as desired API without investigation.

Furthermore, facilities and equipment were not maintained to ensure drug product quality. Multiple pieces of equipment, including (b)(4) V-305, J09-805,