Wave of Warning Letters to Foreign OTC Drug Manufacturing Facilities Following Remote Records Requests

August 11, 2023By McKenzie E. Cato

On August 3rd, FDA issued 11 warning letters to foreign facilities registered as OTC drug manufacturers.  For each of these facilities, FDA did not conduct an on-site inspection of the facility prior to issuing the warning letter.  Instead, FDA issued a request for records pursuant to Section 704(a)(4) of the Federal Food, Drug, and Cosmetic Act (FDCA).

Section 704(a)(4) was added to the FDCA by the Food and Drug Administration Safety and Innovation Action (FDASIA) in July 2012.  This section grants FDA the authority to request records regarding drug products remotely, without an on-site inspection:

Any records or other information that the Secretary may inspect under this section from a person that owns or operates an establishment that is engaged in the manufacture, preparation, propagation, compounding, or processing of a drug shall, upon the request of the Secretary, be provided to the Secretary by such person, in advance of or in lieu of an inspection, within a reasonable timeframe, within reasonable limits, and in a reasonable manner, and in either electronic or physical form, at the expense of such person. The Secretary’s request shall include a sufficient description of the records requested.

Remote review of records in lieu of an inspection is known as a “paper inspection” or, in FDA guidance, a “remote regulatory assessment.”

Of the 11 warning letters, 6 of the warning letters identified cGMP issues in the records reviewed (see, e.g., Warning Letter to Suhan Aerosol).  As a result of the cGMP issues identified, the 6 firms were placed on Import Alert 66-40, which requires detention of products from “a firm that is not operating in conformity with [cGMP].”  The other 5 warning letters identify the firm’s failure to furnish records after multiple records requests from FDA (see, e.g., Warning Letter to Daxal Cosmetics Private Limited).  These firms were placed on Import Alert 66-79, which applies to “foreign establishments refusing FDA inspection.”

Despite FDA having the authority to conduct paper inspections since the statutory provision was added to the FDCA by FDASIA in 2012, FDA did not issue a warning letter citing Section 704(a)(4) until January 2021.  FDA’s new use of Section 704(a)(4) starting in early 2021 was the result of FDA’s inability to conduct on-site inspections of foreign facilities during the height of the COVID-19 pandemic.  FDA has resumed on-site inspections of foreign facilities focused on current Good Manufacturing Practices (cGMP) but has continued issuing records requests under Section 704(a)(4), which spurred this latest round of warning letters.

In July 2022, FDA issued a draft guidance titled Conducting Remote Regulatory Assessments, which explains that FDA adapted its field operations to continue to provide regulatory oversight of manufacturing facilities during COVID-19, through the use of remote regulatory assessments (RRAs).  The draft guidance defines RRAs to include records requests under Section 704(a)(4).  As described in the draft guidance, FDA learned through its experience during the COVID-19 pandemic that there are “significant benefits in using RRAs” and FDA intends to continue to use RRAs “to assist FDA during and beyond the COVID-19 pandemic.”

The warning letters issued on August 3rd demonstrate that FDA is indeed continuing to take advantage of its authority to conduct paper inspections, even when an on-site inspection may be feasible.  There are obvious efficiencies with remote review of records in conserving agency resources.  It allows FDA to identify manufacturing facilities with flawed cGMP procedures without traveling to a facility for a multi-day inspection.  It may also allow FDA to review the cGMP practices of more facilities than it would otherwise.

However, there is of course the possibility that a firm may have adequate procedures, but is not following those procedures at the facility, which could only be discovered in person.  As FDA continues to issue records requests under Section 704(a)(4) it will be interesting to see if FDA will allow remote records review to replace a routine on-site inspection, or if FDA will follow up on an adequate records review through an on-site inspection.