FDA Sends Warning Letters To Sunscreen Contract Manufacturers

Cosmetic Science Laboratories LLC, Torrance, CA, and Formology Lab Inc., Chatsworth, CA, have been issued Warning Letters by the US Food & Drug Administration (FDA).

In a letter sent to Cosmetic Science Laboratories LLC dated March 10, 2023, FDA cited “significant violations” of Current Good Manufacturing Practice (CGMP) regulations for finished pharmaceuticals, including sunscreens, during an inspection conducted between September 6-20, 2022.

FDA said the company was manufacturing 4-IN-1 Broad Spectrum SPF 50 Sunscreen (NDC 73561-001-01), Daily Protect Sunscreen Moisturizer Broad Spectrum SPF 30 (NDC 73561-100-01), Oil Daily Protect Sunscreen Moisturizer Broad Spectrum SPF 30 (NDC 73561-101-01), and SPF-30 (b)(4)  at its site.

As of March 10, 2023, FDA said had not received updated registration submission from the company, nor had it received a drug listing submission for above-mentioned product called “SPF-30 (b)(4).”

FDA noted that it reviewed an October 5, 2022 response from Cosmetic Science Laboratories, but found that response to be “inadequate because it did not provide sufficient detail or evidence of corrective actions to bring your operations into compliance with CGMP.”

During the inspection, FDA investigators observed specific violations including  failure to conduct at least one test to verify the identity of each component of a drug product. FDA said the company firm also failed to validate and establish the reliability of your component supplier’s test analyses at appropriate intervals. The Agency said the company failed to test incoming active pharmaceutical ingredients (APIs) for identity prior to manufacturing bulk over-the-counter (OTC) drug products, including SPF-50 (b)(4) Sunscreen. Additionally, FDA said Cosmetic Science Laboratories relied on certificates of analysis (COAs) from your suppliers to use incoming APIs without establishing the reliability of the specifications and characteristics of each supplier’s COAs.

FDA said Cosmetic Science Laboratories also failed to establish adequate written procedures for production and process control designed to assure that the drug products it manufactures have the identity, strength, quality, and purity they purport or are represented to possess. FDA said the firm also failed to prepare batch production and control records with complete information relating to the production and control of each batch of drug product produced (21 CFR 211.100 (a) and 21 CFR211.188).

FDA cited a lack of adequate batch records. During the inspection, FDA said the company could not provide investigators with evidence that you have performed cleaning validation and equipment qualification.

The Agency also said the company did not establish that its water system was adequately designed, controlled, maintained and monitored to ensure that it consistently produces water suitable for its intended use.

FDA also said the company’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.

In addition, FDA said the company used hold-time studies to support a expiration date for bulk drug products, such as its SPF-30 Daily Protect Sunscreen, but the hold-time studies do not support a hold time for bulk drug products. The Agency said the company had not determined the impact these inadequate hold-time studies may have had on the stability and quality attributes of its bulk drug products. Additionally, customers may rely on these claims to establish expiration dates on finished drug products, stressed FDA in its letter.

Formolgy Lab's Warning Letter

The Warning Letter sent by FDA to Formology Lab Inc., Chatsworth, CA, was dated March 1, 2023. The agency cited an inspection conducted from August 30 to September 9, 2022. FDA said it had reviewed an Oct. 3, 2022 reponse rom Formology Lab.

The agency said it found “significant violations” of CGMP regulations for finished pharmaceuticals.  During its inspection, FDA said its investigators observed a  failure to conduct at least one test to verify the identity of each component of a drug product. FDA said the company failed to test API prior to use in manufacturing drug products. Specifically, at least (b)(4) drug product batches were manufactured and subsequently released, before identity testing was performed. Component testing is fundamental to drug product quality. Without adequate testing, you do not have scientific evidence that your incoming components conform to appropriate specifications before use in the manufacture of drug products, said FDA in its letter.

According to FDA, in its response, Formology indicated that it is currently developing, reviewing, and updating all quality management system procedures and processes and assessing the roles and responsibilities of all personnel, and it also indicated that procedures around testing and receiving of components will be enhanced. FDA said that the company’s response is inadequate. The revision of the procedure for receiving and testing components lacks details such as timelines for implementation of revised procedures and specific testing to be performed. The use of components and release of the drug products containing these components prior to conducting identity testing, and the qualification of suppliers was not addressed. An impact assessment or investigation into this practice is not provided, nor is there any evaluation if other components were inappropriately utilized.

The Agency said Formology also failed to establish written procedures for production and process control designed to assure that the drug products you manufacture have the identity, strength, quality, and purity they purport or are represented to possess. Specifically, FDA said Formolgy did not provide documentation to show that the manufacturing processes for its over-the-counter (OTC) sunscreen drug products have been validated. In addition, FDA said the firm could not provide data to demonstrate that the water used to manufacture drug products met the United States Pharmacopeia (USP) monograph for (b)(4) water and was fit for pharmaceutical use. Specifically, conductivity and total organic carbon (TOC) testing was not performed.

While Formology had provided to FDA a Master Validation Plan, FDA said the response was inadequate because it lacked sufficient information on the company's planned validation activities, including timelines for completion. Also, your response does not discuss TOC and conductivity testing.

FDA said the company also failed to establish an adequate quality unit and the responsibilities and procedures applicable to the quality control unit are not in writing and fully followed. Specifically, the company’s quality unit (QU) failed to establish procedures describing critical oversight responsibilities including but not limited to, the following: investigations, management of changes, customer complaints, training, corrective actions and preventive actions (CAPAs), deviations, annual product reviews, and written procedures for quality unit operations.

FDA noted that Formology did not have appropriate stability data to demonstrate that the chemical and microbiological properties of the drug products met established specifications and remain acceptable throughout their assigned shelf-life. For example, your firm did not place an appropriate number of batches of each drug product formulation on stability. Additionally, out-of-specification (OOS) viscosity results were obtained for its (b)(4) and (b)(4) formula stability samples. FDA said the compnay failed to conduct an adequate investigation for the OOS viscosity results.

FDA said the company’s response to the issue was inadequate as it did not provide target completion dates for the updated procedures. In addition, it is not appropriate to train personnel without a training procedure in place, stressed FDA.

In both letters, the FDA stated:

“The FDA is aware that many drug manufacturers use independent contractors such as production facilities, testing laboratories, packagers, and labelers. The FDA regards contractors as extensions of the manufacturer. You are responsible for the quality of drugs you produce as a contract facility regardless of agreements in place with product owners. You are required to ensure that drugs are made in accordance with section 501(a)(2)(B) of the FD&C Act for safety, identity, strength, quality, and purity.”