WARNING LETTER Yibin Lihao Bio-technical Co., Ltd. MARCS-CMS 592503 — FEBRUARY 13, 2020
1. Failure to prepare and use production and control records for each intermediate and API batch.
Your site produces crude heparin for purification into finished API. During a pre-inspectional call on July 10, 2019, your firm stated to FDA that you had not manufactured any materials for months. At the start of the FDA inspection on July 31, 2019, your firm stated to the investigator that you were not manufacturing crude heparin and were only per forming equipment testing.
During a walkthrough of your warehouse, the investigator observed a warehouse employee leaving the warehouse with a fiber drum and inquired about the contents of the drum. Your firm stated that the drum contained (b)(4) bags. However. inspection of the drum revealed two batches of crude heparin manufactured just a few days before the FDA inspection (CU190726, (b)(4), manufacturing date July 26, 2019, and CU 190727, (b)(4), manufacturing date July 27, 2019). When asked about manufacturing and testing records pertaining to these two crude heparin batches, your firm told us that you do not have records for the two crude heparin batches....
2. Failure to establish, document, and implement an effective system for managing quality that involves the active participation of management and appropriate manufacturing personnel.
During the inspection, the investigator observed your firm did not adequately control critical documentation pertinent to the traceability of crude heparin manufactured at your facility. During the walkthrough on July 31, 2019, our investigator observed numerous records on the floor, desks, and cabinets of the Quality Assurance (QA) Office on the third floor of the office building. Some of these records included batch production records for heparin.
During the inspection, one of your employees stated that these records were generated to support an application for government funding, but the crude heparin batches specified in the records had not actually been manufactured. However, later during the inspection, on August 2, 2019, your firm stated that all the records in the QA Office were in fact associated with genuine crude heparin batches.
Additionally, even though your Crude Heparin Sodium Inventory and Distribution Record indicated your firm manufactured (b)(4) batches of crude heparin (CU190601 to CU190730) from June 1, 2019, to July 30, 2019, your firm was only able to provide complete batch records for two batches, CU190728 and CU190730.
Traceability of crude heparin is a critical part of managing quality. You must ensure that a complete contemporaneous record of each batch of drug manufactured is retained for CGMP purposes. Your system for managing quality is inadequate and calls into question the traceability of all drugs, including crude heparin. manufactured at your facility...
Data Integrity Remediation
Your quality system does not adequately ensure the accuracy and integrity of data to support the safety, effectiveness, and quality of the drugs you manufacture. See FDA's guidance document Data lntegrily and Compliance with Drug CGMP for guidance on establishing and following CGMP compliant data integrity practices at https://www.fda.gov/media/97005/download.
We strongly recommend that you retain a qualified consultant to assist in your remediation...
