Chinese Firm Hit With Pandemic's First Remote-Records-Based FDA Drug GMP Warning Letter
Executive Summary
Import alert and warning letter came after Ningbo, China, over-the-counter skin care products firm failed to share requested testing records.
In the first of what could be many as pandemic travel restrictions continue, the US Food and Drug Administration on 22 January issued a drug good manufacturing practices warning letter to a company in China that was based on a remote records request rather than a site inspection.
It was 31 March 2020, two months after the FDA evacuated its China office and two weeks after it suspended travel for all but “mission-critical” foreign and domestic inspections, when the agency issued a request for certain records and other information from Yuyao Yijia Daily Chemical Co. Ltd. in Ningbo, China.
Such requests are allowed in lieu of or in advance of inspections under section 704(a)(4) of the Food, Drug and Cosmetic Act, added by the July 2012 FDA Safety and Innovation Act to enable greater oversight of foreign facilities.
Responses Found Wanting
The response from Yuyao Yijia, a registered over-the-counter drug manufacturer, was underwhelming: instead of the drug product specifications and test methods the FDA asked for, it just gave a list of test equipment used.
A May 8 follow-up request fared little better, with Yuyao Yijia just restating its original response and identifying its third-part testing laboratory. The company also revealed that it did not test active ingredients for identity and strength as required. Nor did the API supplier for a redacted product, upon whose certificate analysis Yuyao Yijia relied, test for identity.
The stability data the company provided for a redacted drug product did not test for API or for microbiological contamination. Also inadequate were its quality systems and the written procedures for its quality unit.
The FDA on 23 September placed the facility on its drug GMP import alert.
A New Twist In The FDA's Sanitizer Saga
The warning letter publicly mentions only one drug product, hand sanitizer, which has been in high demand during the pandemic. The company also makes shampoo, conditioner, shower gel, scrub, hand soap, emulsion and lipstick, according to its website.
Many Mexican hand sanitizer suppliers that popped up early in the pandemic are under import alert because the FDA found toxic methanol in their products during border testing.
Yuyao Yijia’s warning letter based on remote records was a first just like the agency’s 23 July 2020 warning letter to Eskbiochem SA de CV, Celaya, Mexico, based on identification of toxic methanol in border testing of the company’s hand sanitizer. (Also see "The Quality Lowdown: COVID-19's Pressures On Drug Quality" - Pink Sheet, 13 Aug, 2020.)
The Eskbiochem warning letter was the first of 14 that were based on border testing of hand sanitizers from uninspected manufacturers in Mexico last year. (Also see "2020 In Review: Despite Pandemic, The US FDA Issued Just 20% Fewer Drug GMP Warning Letters" - Pink Sheet, 21 Jan, 2021.)
More Records-Based Warning Letters Could Be On The Way
An even greater number of records-based drug GMP warning letters is likely to follow the one to Yuyao Yijia in the coming months.
By the end of August 2020, the agency already had requested records from 547 drug and biologics manufacturing facilities. (Also see "US FDA Assesses Over 500 Biopharma Plants Remotely Via Records Review; Refines Process" - Pink Sheet, 17 Sep, 2020.)
An FDA database shows that in recent years, the agency has classified 10% of the sites inspected under its drug GMP surveillance program as official action indicated. It is generally believed that most OAI sites wind up receiving warning letters.
If during the inspection hiatus, the FDA relies as much on remote records reviews as it did on site inspections to make decisions, there could be dozens more records-based warning letters already in the works.
One difference with remote-records-based enforcement actions like the one against Yuyao Yijia is that the FDA will not record them in its site classification database, the FDA told the Pink Sheet. The site classification process remains focused on site inspections.
Another issue with remote records is the lack of face-to-face communication that can clear up misunderstandings. (Also see "Can We Talk? US FDA Remote Records Review Missteps Worry Industry" - Pink Sheet, 19 Nov, 2020.)