FDA chastises three US firms for ignoring record requests, inadequate CMO oversight, and shoddy response to fires

Regulatory NewsRegulatory News | 21 October 2021 |  By 

Inadequate oversight of contract manufacturers, failing to address how a fire affected the quality of active pharmaceutical ingredients, and ignoring the agency’s request for electronic records prompted the US Food and Drug Administration (FDA) to issue three warning letters for good manufacturing practice (GMP) violations to an over the counter drug manufacturer, a finished drug manufacturer and an API manufacturer in the US.
The recipients of the warning letters, which were issued in mid-to-late September, include St. Louis, MO-based Marcus Research Laboratory, a manufacturer of active pharmaceutical ingredients (APIs); HealthMEDS Inc, a manufacturer of over the counter (OTC) health and beauty products, including hand sanitizers, in Portland, OR; and drug manufacturer Sircle Laboratories in Madison, MS.
Marcus Research Laboratory failed to address aftermath of fire
FDA’s 30 September warning letter to Marcus Research Laboratory found “significant deviations from current good manufacturing practice (CGMP) violations for active pharmaceutical ingredients (APIs)” in its manufacturing of povidone iodine (PVP-I) used for presurgical preparations. The warning letter followed inspections conducted in May.
The firm failed to adequately investigate the effect of temperature excursions on the quality of an API following a fire and use of an extinguisher.
During production, personnel observed PVP-I in a reactor cabinet that was “smoldering” and responded to an “imminent fire” by using a fire extinguisher. The API was subjected to “inconsistent temperature exposure and additional processing and hold times.” Yet the firm only tested the affected drums to determine the amount of iodine that was still present in the material and released them for further processing.
A similar situation occurred in August 2020 when production personnel observed a “smoking” reactor cabinet in the facility. Production stopped and the materials were “held in unknown conditions,” according to the letter. “Your firm again, solely tested the affected drums of material for percent available iodine and released them for further processing” after this second incident, noted FDA.
“In both instances, your firm created deviation reports but released drugs based solely on composite results of percent available iodine,” wrote the agency. “Your drugs were exposed to excess heat, fire, smoke, and debris. Additional contaminants or other particulates from the use of the fire extinguisher may have also compromised the material.”
The firm did not conduct additional testing on the affected lots “to confirm that the API was not contaminated with harmful particulate matter or other contamination.”
The firm was also cited for having dirty equipment. Inspectors noted that “critical” manufacturing equipment, such as the blender and hopper used to make povidone iodine, was “discolored and rusty.” Additionally, plastic liners wrapping processing trays were “tattered and torn,” resulting in PVP-I being exposed to plastic particles.
Also, plastic liners used to wrap the trays where API was held were “tattered and torn, exposing product to plastic particulate matter.”
Health MEDS refused FDA’s request for records
FDA issued a warning letter to HealthMEDS Inc., an OTC manufacturer that produces ProClean-Pure Atomizer Mist, on 29 September for repeatedly ignoring the agency’s request for records.
The firm failed to respond to the agency’s initial request for records on 1 February and “numerous” telephone calls went unanswered. FDA sent a follow-up written request by certified return-receipt mail on 6 May, and this too failed to elicit a response.
FDA reminded the firm that “it is a prohibited act under section 301(e) of the FD&C Act (21 U.S.C. 331(e)) to refuse to permit access to or copying of any record as required by section 704(a).”
The agency also reminded the company that “since declaration of the COVID-19 public health emergency, a number of hand sanitizer products have been recalled due to quality issues ranging from substitution with other drug substances to subpotency.”
The firm’s failure to respond means that FDA has “no indication of the level of quality assurance for drugs registered as manufactured at your facility.”
The company had 48 hours from the receipt of the letter to confirm or update their registration and drug listing information.
FDA said that the firm’s “continued non-response” may lead FDA to include the company’s product on its list of hand sanitizers that consumers should not use.
Sircle targeted for lax supervision of CMOs
FDA’s 15 September warning letter to Sircle Laboratories criticized the firm’s “inadequate oversight” of its contract manufacturing organization (CMO) following an inspection in mid-April. The letter cited a pattern of Sircle’s “use of sub-standard CMOs” stemming from deficiencies in the firm’s quality unit.
Sircle “lacks appropriate oversight and procedures to manage contract manufacturing organizations (CMOs) …. for the manufacturing, packaging, and distribution of your drug products,” said the warning letter, reminding the company that “you are ultimately responsible for CGMP activities you perform.”
The firm also “failed to review production records for each batch for disposition” in either rejecting or approving batches.
Lastly, the company was criticized for failing to follow its own change control procedures. Since the last FDA inspection in March 2019, the company made changes to how it handled consumer complaints and drug product recalls, and also made labeling changes without following change control procedures.
The firm was reminded that similar GMP violations were flagged in previous inspections conducted in August 2015 and March 2019.
Sircle warning letter
Health Meds warning letter
Marcus Research Laboratory warning letter


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Tags: FDA, GMPs, letters, warning

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