The warning letters were addressed to Pure Sourece, LLC; Proandre SL; and Shadow Holdings LLC (dba Bocchi Laboratories).
The letter to Pure Source LLC, Doral FL followed an inspection of its drug manufacturing facility conducted from Feb. 8 to March 1, 2018, noting that there were significant violations of current good manufacturing practice (CGMP) regulations for finished pharmaceuticals. Because methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, Pure Source’s drug products are adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 351(a)(2)(B), according to FDA.
The inspection also revealed that the firm manufactures and distributes misbranded drugs labeled as homeopathic under section 503(b)(4) of the FD&C Act, 21 U.S.C. 353(b)(4).
Pure Source, according to FDA, firm failed to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed (21 CFR 211.192). FDA said it quality unit did not initiate an out-of-specification (OOS) investigation for a raw material with excessive microbial growth. In addition, it did not conduct a thorough investigation for drug products with failing assay results.
For example, FDA said Pure Sourece, LLC used a raw material lot with a too-numerous-to-count result for total aerobic microbial count. The firm, according to FDA, was using the material in an acne treatment it was making for a customer. FDA said the firm failed to thoroughly investigate the excessive microbial contamination and distributed finished product made with the highly contaminated raw material.
FDA said it released the failed lot of raw material, which was used in the manufacture of the finished drug product and failed to provide adequate corrective actions and preventive actions (CAPA). FDA alledges that the company did not identify the microorganisms to determine whether any were potentially pathogenic and failed to evaluate the consumer hazard posed by this microbial contamination, and that it decided that this ingredient batch did not need to conform to a microbial specification because it is from a natural mineral source.
FDA also wrote in the letter addressed to Pure Source: “Notably, you also told our investigator that you informed the product owner about the failing result and the owner insisted on using the failing (b)(4) ingredient. Insistence from a customer does not relieve you from your obligation to follow CGMP regulations.”
In addition, FDA said the firm’s quality unit released OOS drug products for distribution without conducting a thorough investigation, including avobenzone sunscreen drug product (Lot C06Z9), which had a failing assay result of 0.85%; and bulk in-process material Pain Relief Gel Lot which had a failing assay result of 2.47% w/w.
FDA also issued a letter to Proandre SL of Barcelona, Spain following an section of its drug manufacturing facility in June 2018 for significant violations of CGMP regulations for finished pharmaceuticals. FDA also said that as formulated and labeled, the OTC drug products Proandre Antibacterial Soap Liquid and Proandre Hand Sanitizer Liquid are misbranded.
FDA said Proandre failed to have, for each batch of drug product, appropriate laboratory determination of satisfactory conformance to final specifications for the drug product, including the identity and strength of each active ingredient, prior to release (21 CFR 211.165(a)). It said the firm released Proandre Antibacterial Soap Liquid without testing for identity and strength. Our investigator documented that you only test your finished drug products for specific gravity, pH, refraction value, and microbiological tests.
FDA also addressed the firm’s failure to follow an adequate written testing program designed to assess the stability characteristics of drug products.
In a third letter, FDA said it conducted an inspection of Shadow Holdings LLC, dba Bocchi Laboratories of Santa Clarita, CA in response to an outbreak of Burkholderia cepacia associated with Medline Remedy Essentials Cleanser No-Rinse Foam, which the firm akes for use in hospital settings, and to determine your firm's compliance with the Federal Food, Drug, and Cosmetic Act (the Act). Based on its inspection, FDA said found significant violations of the Act.
In its letter, FDA wrote: ‘Your firm is a contract manufacturer for various products, including no-rinse cleanser foam, face wash, lotion, moisturizer, hair styling cream, shampoo, and conditioner. These products that you manufacture, pack, and label are intended to be applied to the human body for cleansing, beautifying, promoting attractiveness, or altering the appearance, and as such, they are cosmetics within the meaning of section 201(i) of the Act [21 U.S.C. 321(i)]. The microbial contamination of the Medline Remedy Essentials Cleanser No-Rinse Foam product causes this product to be adulterated within the meaning of section 601(a) of the Act [21 U.S.C. 361(a)], as described further below. Furthermore, the conditions observed during the inspection cause Medline Remedy Essentials Cleanser No-Rinse Foam and other cosmetics manufactured in your facility to be adulterated within the meaning of section 601(c) of the Act [21 U.S.C. 361(c)], as described further below. It is a violation of Section 301(a) of the Act [21 U.S.C. 331(a)] to introduce or deliver for introduction into interstate commerce an adulterated cosmetic.”
The Medline Remedy Essentials brand Cleanser No-Rinse Foam is adulterated, according to FDA. Under section 601(a) of the Act [21 U.S.C. 361(a)], a cosmetic is adulterated if it bears or contains any poisonous or deleterious substance which may render it injurious to users under the conditions of use prescribed in the labeling thereof, or under such conditions of use as are customary or usual. FDA’s investigator collected samples of the Medline Remedy Essentials brand Cleanser No-Rinse Foam from lots Mo7247 and Mo6691 and these samples were found by FDA laboratory analysis to contain the pathogen Burkholderia cepacia, which may render the product injurious to health.
FDA said that it acknowledged that company had recalled several cosmetics products due to potential microbiological contamination. (The firm initiated a recall on March 28, 2018, for Medline Remedy Essentials Cleanser No-Rinse Foam due to potential contamination with Burkholderia cepacian and also issued a second recall on May 8, 2018, for nineteen cosmetic products due to potential contamination with Burkholderia cepacia. Itinitiated a recall for Super Sculpt Glaze on December 11, 2018, for potential contamination with Burkholderia cepacia.)
According to FDA, on March 29, 2018, April 23, 2018, April 26, 2018, and May 3, 2018, the FDA collected environmental swabs from the production area and product contact areas, as well as water samples. FDA laboratory analysis of these samples found contamination with Burkholderia cepacia, Pseudomonas aeruginosa, Pseudomonas putida, Pseudomonasfiuorescens, Pseudomonas oryzihabitans, other Pseudomonas spp., Enterobacter gergoviae, and several other microbiological organisms. These microorganisms in the water, production area, and other product contact areas could contaminate your cosmetic products, which may render them injurious to health.
FDA said the firm released finished cosmetic products such as Remedy Essential No-Rinse Cleansing Foam that did not meet your finished product specification limits for Aerobic Plate Count (APC) of "(b)(4) cfu/ gm" and Yeast & Mold (Y&M) of "(b)(4) cfu/gm". Specifically, your test results showed "TNTC" [Too Numerous to Count] for both Aerobic Plate Count and Yeast & Mold for two lots of Remedy Essential No-Rinse Cleansing Foam, but you released those two lots and did not investigate or identify the source of the elevated microbial counts.
The warning letter also summarized significant violations of current good manufacturing practice (CGMP) regulations for finished pharmaceuticals, including Acne Shave Cream, Acne Shave Moisturizer and X-Jow Pain Gel. These products, according to FDA, are "drugs" as defined by section 201(g)(1)(B) of the Act [21 U.S.C. 321(g)(1)(B)] because they are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease, and/or under section 201(g)(1)(C) of the Act [21 U.S.C. 321(g)(1)(C)], because they are intended to affect the structure or any function of the body.
The letters can be accessed here.