New FDA Warning Letters

The FDA has issued warning letters to a US-based contract testing lab and an OTC/cosmetics producer in India.

Advanced Botanical Consulting and Testing Inc., Tustin, CA, was sent a letter following an FDA inspection in November 2018 in which the agency found “significant violations of current good manufacturing practice (CGMP) regulations for finished pharmaceuticals. See 21 CFR, parts 210 and 211” and the company responded on Dec. 4, 2018. 

According to FDA, during its inspection, an investigator observed specific violations including, but not limited to, the following:
Failure to establish and document the accuracy, sensitivity, specificity, and reproducibility of its test methods (21 CFR 211.165(e)).  On multiple occasions, FDA said the firm used test methods to perform microbiological testing for drug products salicylic acid and lidocaine, but lacked assurance that the methods were adequate. You lacked suitability testing to determine whether these methods were appropriate for testing each drug product.
 
In addition, FDA said the firm failed to ensure that laboratory records included complete data derived from all tests necessary to ensure compliance with established specifications and standards (21 CFR 211.194(a)). Specifcally, notebooks and worksheets for the analysis of “Brd Spect SPF 50” lacked documentation of lot numbers and expiration dates of standards. 
 
In its response, the testing company stated that it updated notebooks and worksheets to “document the Lot Numbers and Expiry Date for the Standards and CRM used in Tests at all times.” 
 
“Your response is inadequate because it is unclear whether you performed a global review of all your procedures related to notebooks and worksheets to determine if there is any additional missing information,” said FDA in its letter.
 
This violation is a repeat observation from a 2012 inspection, noted FDA.
 
FDA stated the the company failed to routinely calibrate, inspect, or check according to a written program designed to assure proper performance of and to maintain adequate written records of calibration checks and inspections of automatic, mechanical, electronic equipment, or other types of equipment, including computers, used in the manufacture, processing, packing, and holding of a drug product (21 CFR 211.68(a)). FDA said many pieces of equipment that you used for drug product testing were out-of-calibration or not validated. 
 
FDA said it considers contractors as extensions of the manufacturer’s own facility. 
 
“Your failure to comply with CGMP may affect the quality, safety, and efficacy of the drugs you test for your clients. It is essential that you understand your responsibility to operate in full compliance with CGMP, and that you inform all your customers of any out-of-specification results or significant problems encountered during the testing of these drugs,” wrote FDA.
 
A second letter was sent to Glint Cosmetics Pvt. Ltd., a company based in India, following FDA’s inspection of the company’s drug manufacturing facility in Maharashtra in December 2018. FDA said found significant violations of current good manufacturing practice (CGMP) regulations for finished pharmaceuticals, rendering its drug products as adulterated.

According to FDA, Glint Cosmetics is manufacturing Wish Vaporizing Chest Rub (4 oz) and Wish Blue Therapeutic Ice Gel (8 oz) that are unapproved new drugs in violation of section 505(a) of the FD&C Act, 21 U.S.C. 355(a). FDA said that introduction or delivery for introduction of such products into interstate commerce is prohibited.

FDA also said that Glint-manufactured products AmeriDerm Ointment with Vitamins A&D (15 oz), MedPRIDE Zinc Oxide Ointment (1 oz), GeriGentle Bacitracin Ointment USP (1 oz), GeriGentle Zinc Oxide Ointment (1 oz and 2 oz), GeriGentle Vitamin A&D Ointment (4 oz, 4 oz (12 tubes), and 5 g), geri gard (4 oz), MedPRIDE Vitamins A&D Ointment (4 oz and 1 oz), MedPRIDE En-Shield (3.5 oz), MedPRIDE White Petrolatum (720 g), AmeriDerm PeriShield (3.5 oz), and Wish products (original, cocoa butter, baby, aloe, and lavender (6 oz and 12 oz) are are misbranded under section 502 of the FD&C Act, 21 U.S.C. 352. Introduction or delivery for introduction of such products into interstate commerce is prohibited under section 301(a) of the FD&C Act, 21 U.S.C. 331(a), wrote FDA.

FDA said it reviewed correspondence from Glint in January 11, 2019, that the company had  “decided to suspend exports to the USA until all corrections have been made.” 
FDA said, however, that Glint’s drug products were shipped to the United States after this response via your distributor.

The agency placed Glint on Import Alert 66-40 on April 17, 2019. 

During FDA’s inspection, the investigator observed specific violations including, but not limited to CGMP Violations 

FDA said  Glint’s quality control unit failed to exercise its responsibility to ensure drug products manufactured are in compliance with CGMP, and meet established specifications for identity, strength, quality, and purity (21 CFR 211.22).

During the inspection, an FDA investigator observed that Glint’s quality unit did not provide adequate oversight for the manufacture of over-the-counter (OTC) drug products, and the also firm failed to clean, maintain, and, as appropriate for the nature of the drug, sanitize and/or sterilize equipment and utensils at appropriate intervals to prevent malfunctions or contamination that would alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements (21 CFR 211.67(a)).

FDA said that Glint uses non-dedicated equipment to manufacture multiple topical OTC drug products without a validated cleaning process for drug product changeover to prevent cross-contamination between products. 
 
FDA said its investigator also observed that employees pre-filled and signed logbooks for cleaning and falsified the recorded duration of equipment cleaning. For example, the cleaning of two “scoops” was documented at the exact same time, and for a duration of each day from September to December 2018, despite the facility being closed on some of those days. 
 
FDA also pointed out label claims made on Wish BLUE THERAPEUTIC ICE GEL (8 oz), which is a “drug” as defined by section 201(g)(1)(B) of the FD&C Act, 21 U.S.C. 321(g)(1)(B), because it is intended for the diagnosis, cure, mitigation, treatment, or prevention of disease, and/or under section 201(g)(1)(C) of the FD&C Act, 21 U.S.C. 321(g)(1)(C), because it is intended to affect the structure or any function of the body. Specifically, this product is intended as an external analgesic. In addition, FDA said it was  not aware of any adequate and well controlled clinical trials in the published literature that support a determination that Wish BLUE THERAPEUTIC ICE GEL (8 oz) is generally recognized as safe and effective for its labeled indications. Additionally, we are not aware of a similar OTC product as formulated and labeled that was available in the United States market on or before the inception of the OTC Drug Review.

FDA also took issue with misbranded drugs due to product labels that did not meet requirements:  AmeriDerm Ointment with Vitamins A&D (15 oz), MedPride Zinc Oxide Ointment (1 oz), GeriGentle Bacitracin Ointment USP (1 oz), GeriGentle Zinc Oxide Ointment (1 oz and 2 oz), GeriGentle Vitamin A&D Ointment (4 oz, 4 oz (12 tubes), and 5 g), geri gard (4 oz), MedPride Vitamins A&D Ointment (4oz, 5 g, and 1 oz), MedPride En-Shield (3.5 oz), MedPride White Petrolatum (720 g), AmeriDerm PeriShield (3.5 oz), and Wish products (original, cocoa butter, baby, aloe, and lavender (6 oz and 12 oz)).