FDA reprimands OTC drugmaker for inadequate ingredient testing, contamination
The US Food and Drug Administration (FDA) has reprimanded an over-the-counter manufacturer of children’s homeopathic medicines for multiple good manufacturing practice (GMP) violations in a warning letter posted on 15 August. Such violations included an inadequate investigation after a machine lubricant was detected in product batches, failure to investigate the source of foul odors, and failure to test ingredients for Diethylene Glycol (DEG) and Ethylene Glycol (EG).The warning letter to contract manufacturer Denison Pharmaceuticals of Lincoln, RI, follows several other letters to drugmakers citing the issue and amid a period of increased scrutiny of firms’ ingredient testing programs. (RELATED: FDA issues blitz of warning letters over testing violations and refusing records requests, Regulatory Focus 9 August 2023)
FDA said Denison failed to launch an adequate investigation after some batches were found to be contaminated with a machinery lubricant. FDA states that “your investigation into the contamination of [redacted] with [redacted] lubricant, a non-food grade lubricant not intended for ingestion, concluded that only Lot [redacted] was impacted and was rejected. However, your investigation did not consider other potentially affected drug products manufactured in the same mixing tank, and indicated that no corrective action and preventive action (CAPA) was required.”
Safety data from the manufacturer indicated that the lubricant is “unsuitable for pharmaceutical purposes” and says health hazards tied to the product include skin and respiratory irritation, genetic defects and cancer.
The firm also failed to investigate “multiple foul odor complaints,” which was later tied to “too numerous to count” (TNTC) results for yeast and mold. The investigation found that the organism which caused the odor, Staphylococcus epidermis, “posed an unacceptable risk to public health, yet you failed to take any market action.”
The firm also failed to test its purified water system after detecting “multiple microbiological excursions.” The company “failed to consider how flaws in design, control, and maintenance of your water system contribute to these excessive microbial counts.” Also, sampling and testing procedures lacked a mechanism to trigger an investigation to respond to severe microbiological excursions.
The company was also faulted for failure to test each “high-risk” component lot of glycerin and propylene glycol for DEG and ethylene glycol contamination in the drug products and lacked a specific identity test to conduct such testing.
FDA reminded the company that “as a drug manufacturer, you are responsible for performing specific identity tests for all incoming shipments of component lots prior to determining suitability for release for use in manufacturing” and that “without appropriate testing of components and ingredients, you cannot ensure the quality and safety of your drug products.”
FDA said that “the use of ingredients contaminated with DEG or EG has resulted in various lethal poisoning incidents in humans worldwide.”
The firm also did not validate its rapid microbiological methods for detecting objectionable microorganisms. “You failed to demonstrate that that the [redacted] system is appropriate for total count testing of or detection of objectionable microorganisms, such as Burkholderia cepacia, in your drug products.”
FDA also said the company was marketing its “Colic Calm” its Colic Calm+” and “Nauzene Kids” products as drugs even though the firm had not sought new drug marketing approval.
FDA advised the firm to promptly correct the violations, and to hire a GMP consultant. Failure to address these problems may cause the agency to withhold export certificates.
The firm was advised to hire a GMP consultant.
Denison
×
Welcome to the new RAPS Digital Experience
We have completed our migration to a new platform and are pleased to introduce the updated site.
What to expect: If you have an existing login, please RESET YOUR PASSWORD before signing in. After you log in for the first time, you will be prompted to confirm your profile preferences, which will be used to personalize content.
We encourage you to explore the new website and visit your updated My RAPS page. If you need assistance, please review our FAQ page.
We welcome your feedback. Please let us know how we can continue to improve your experience.