FDA’s document-based inspections prompt warning letters for GMP violations

The US Food and Drug Administration (FDA) on 13 April warned South American active pharmaceutical ingredient (API) manufacturer Proquimes SA Productos Quimicos Especializados SA for a multitude of good manufacturing practice (GMP) violations. The letter joins three others the agency has issued since the beginning of the year that are based solely on a records review and not onsite inspections.
 
The warning letters signal the agency’s increasing reliance on a review of records supplied by firms as investigators cannot get to sites in the midst of the coronavirus pandemic.
 
In July 2020, months after halting most inspections amid the coronavirus disease (COVID-19) pandemic, the FDA said it planned to resume on-site domestic inspections on a limited basis and would depend on the data about the virus’ trajectory in each state and locality. (RELATED: FDA looks to resume domestic inspections this month, Regulatory Focus 10 July 2020)
 
The warning letters illustrate how FDA investigators are using the agency’s authority under Section 704(a)(4) of the FD&C Act to review records remotely when they cannot get to sites to perform physical inspections.
 
The April warning letter to the firm, based in Cali, Colombia, targeted the firm’s inability to demonstrate that its manufacturing processes can reproducibly manufacture an API. Such processes, said the FDA, were “determined to be critical to the quality and purity of the API.”
 
The FDA told the firm that “without process validation documentation, you cannot determine that your manufacturing process can consistently produce API that meet predetermined quality attributes.”
 
The agency also criticized the firm’s failure to qualify critical equipment and ancillary systems. FDA said that “the continued and suitable performance of manufacturing equipment is important to ensure batch-to-batch consistency during the manufacturing of API.”
 
The firm was also blasted for its failure to test the identity of each batch of incoming production materials. The firm blamed its inability to conduct such testing on a “lack of resources.”
 
The FDA placed all drugs manufactured by the firm on an import alert.
 
Dibar Nutricional
 
FDA also issued a warning letter on 10 March to Dibar Nutricional S. de R.L. de C.V., a manufacturer of over-the-counter drugs in Morelia, Mexico, for similar GMP problems related to inadequate equipment maintenance and testing of incoming components.
 
The firm failed to have an installation qualification and operation qualification in place for its manufacturing equipment.
 
In terms of component testing, the firm said it only collects “random samples” of drugs and does not perform routine testing of incoming raw materials.
 
Foshan Biours Bioscience
 
FDA issued a warning letter on 10 March to Foshan Biours Bioscience, a manufacturer of over-the-counter (OTC) drugs based in Foshan, Guangdong, China for inadequate cleaning procedures for equipment used to manufacture and package OTC products, and for not testing finished products.
 
Yuyao YiJia Chemical
 
Earlier this year, on 22 January, FDA issued a fourth warning letter, also based solely on a records review, to Yuyao YiJia Daily Chemical, a manufacturer of OTC drugs in Ningbo, China. The firm was reprimanded for not adequately testing the final product and not testing the incoming materials used to make the drugs.
 
After halting most foreign and domestic inspections in March 2020, the FDA said last May that it was working with the Centers for Disease Control and Prevention (CDC) on a phased plan for resuming on-site surveillance inspections and that it will continue to rely on “alternative inspection tools and approaches” as it postpones most routine surveillance inspections. (RELATED: FDA plans phased approach to restarting surveillance inspections, Regulatory Focus12 May 2020)