FDA cites firms for marketing without proper authorization, failing to maintain sterile environment

The US Food and Drug Administration has cited two manufacturers for marketing drugs without proper authorization and a compounding drug manufacturer for failing to maintain proper sterility requirements.

FDA recently issued warning letters to two drugmakers for marketing products without proper authorization after finding that the product labels made claims that require the agency’s regulatory oversight. In a warning letter dated 7 April to New York-based PMS4PMS, inspectors noted that labeling for its over-the-counter (OTC) Comforté menstrual cramp relief cream claims to temporarily relieve minor cramp pains and other statements that require marketing authorization.

Certain OTC products can be sold without an approved marketing application if they meet the right requirements for external analgesic drug products. However, FDA states that PMS4PMS’ product does not meet those requirements.

“Claims from the product labeling described above related to relief of pain caused by menstrual cramps go beyond merely describing the general intended uses for an external analgesic drug product,” according to the warning letter. “Indications related to relief of pain caused by menstrual cramps are not included in M017 or any other final administrative order in accordance with section 505G [of the Food, Drug and Cosmetics Act].”

PMS4PMS was also cited for not meeting current good manufacturing practices (cGMP), such as proper laboratory testing to ensure the final product conformed to the identity and strength of the active ingredient intended for sale. While the company has already said that it will no longer manufacture the product, the agency said that there are products on the market within the stated expiry date that have not been properly tested.

“Full release testing, including strength and identity testing of the active ingredient, must be performed before drug product release and distribution,” FDA wrote. “Without adequate testing, you do not have adequate scientific evidence to assure that your drug products conform to appropriate specifications before release.”

According to the warning letter, PMS4PMS must notify the agency if it plans to manufacture regulated drugs at the same facility. Before starting production, the company must resolve all the deficiencies cited, ensure that it can meet cGMP requirements, and complete all corrective actions and preventive actions (CAPA).

FDA also said the company failed to establish a stability testing program to support the product expiry claims on its labels. Furthermore, it was cited for not having a quality unit (QU) with appropriate authority to oversee the manufacture of its products.

FDA recommended that PMS4PMS hire a qualified consultant to evaluate its operations and help it meet cGMP requirements if it plans to resume manufacturing products for the US market.

"The qualified consultant should also perform a comprehensive six-system audit of your entire operation for CGMP compliance and evaluate the completion and efficacy of your CAPAs before you pursue resolution of your firm’s compliance status with FDA," the agency added. "Your use of a consultant does not relieve your firm’s obligation to comply with CGMP. Your firm’s executive management remains responsible for resolving all deficiencies and systemic flaws to ensure ongoing CGMP compliance."

On 26 March, FDA sent a warning letter to Naturista Store, an online retailer, for selling pain relief medicines, such as Advance King, which the agency said was being marketed without proper authorization. It noted that the product is sold as an herbal remedy to treat pain, sciatica, uric acid, osteoporosis, arteriosclerosis, and gout. The company also claims the product can strengthen bones, and reduce joint pain, rigidity, and cartilage damage.

FDA obtained samples of Advance King and found that it contained undeclared substances that require regulatory oversight and could have serious side effects. It found diclofenac, a non-steroidal anti-inflammatory drug (NSAID), that could have potentially negative drug-drug interactions and increase risks of cardiovascular events such as heart attacks and strokes. It could also cause serious gastrointestinal damage, such as bleeding, ulcers, and fatal perforations of the stomach and intestines.

Similarly, investigators found that Advance King included the muscle relaxant methocarbamol, which could cause dizziness, low blood pressure, and impair the user’s mental and physical abilities.

FDA noted that on its website, naturistastore.com, which currently seems to be inaccessible to the public, the company sells similar products in the US, such as NatuMex Artri Ajo King, NatuMex Artri King, Royal Honey Sachets, and more.

"Previous FDA lab analyses of products similarly named to those sold on your website revealed these products contained undeclared drug ingredients," the agency added. "While the agency has not sampled and tested these product variations from your inventory to date, this letter also expresses our serious concern about the safety of these products and emphasize that it is your legal responsibility under federal law to ensure that products you sell do not contain any undeclared or potentially harmful ingredients, and that they are marketed in compliance with applicable laws."

In another warning letter on 22 January, FDA cited Nubratori, a California-based compounding drug manufacturer, for failing to maintain proper sterility oversight of its outsourcing facility. Agency investigators found that its products, which were meant to be sterile, were prepared, packed, and held under insanitary conditions. The agency noted that the products could become contaminated and pose serious health risks to patients who use them.

More specifically, FDA said there was a lack of adequate personnel sampling, failure to establish acceptance criteria to sample and test the products, failure to establish proper procedures to prevent contamination, failure to monitor environmental conditions to ensure sterility, and more.

While Nubratori responded to FDA’s concerns and the agency accepted many of the responses as adequate, it said there are still several unresolved issues.

“FDA strongly recommends that your management undertake a comprehensive assessment of operations, including facility design, procedures, personnel, processes, maintenance, materials, and systems,” said FDA. “In particular, this review should assess your aseptic processing operations.

“A third party consultant with relevant sterile drug manufacturing expertise should assist you in conducting this comprehensive evaluation,” the agency added.

Each company was given 15 working days to respond to its warning letter.

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FDA cites firms for marketing without proper authorization, failing to maintain sterile environment

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