Cerci Kozmetik Ve Otel Ekipmanlari Pazarlama Ic Ve Dis Ticaret Limited Sirketi

Your facility is registered with the U.S. Food and Drug Administration (FDA) as a manufacturer of over-the-counter (OTC) drug products. FDA has reviewed the records you submitted in response to our June 16, 2022, and July 6, 2023 requests for records and other information pursuant to section 704(a)(4) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) for your facility, Cerci Kozmetik Ve Otel Ekipmanlari Pazarlama Ic Ve Dis Ticaret Limited Sirketi, FEI 3017978054, Aytop Sanayi Sitesi B2 Block, 14-15-16 Battalgazi Mahalle, Istanbul (Anatolia).

This warning letter summarizes significant violations of Current Good Manufacturing Practice (CGMP) regulations for finished pharmaceuticals. See Title 21 Code of Federal Regulations, parts 210 and 211 (21 CFR, parts 210 and 211).

Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, your 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)).

Following review of records and other information provided pursuant to section 704(a)(4) of the FD&C Act, significant violations were observed including, but not limited to, the following:

1. Your firm 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)).

Your firm manufactures an OTC drug product, (b)(4). Your response to our request for records and other information under section 704(a)(4) indicates that you distributed this drug product into the United States without adequate finished drug product testing. Specifically, in response to our request to provide release specifications of U.S. products and the test methods used to evaluate them, you submitted a certificate of analysis (COA) for your OTC (b)(4). The COA did not include testing for identity and strength of the active ingredient, as required prior to release per 211.165(a).

Without adequate testing, there is no scientific evidence to assure that your drug product conforms to appropriate specifications before release.

In response to this letter, provide the following for all drug products imported to the United States prior to and after our 704(a)(4) request:

A list of chemical and microbial test methods and specifications used to analyze each batch of your drug product before making a batch disposition decision, and the associated written procedures.

o An action plan and timelines for conducting full chemical and microbiological testing of retain samples to determine the quality of all batches of drug product distributed to the United States that are within expiry as of the date of this letter. o A summary of all results obtained from testing retain samples from each batch. If such testing reveals substandard quality drug products, take rapid corrective actions, such as notifying customers and product recalls.

A comprehensive, independent assessment of your laboratory practices, procedures, methods, equipment, documentation, and analyst competencies. Based on this review, provide a detailed plan to remediate and evaluate the effectiveness of your laboratory system.

(b)(4) test results for all batches of (b)(4) shipped to the United States within expiry.

2. Your firm failed to establish and follow an adequate written testing program designed to assess the stability characteristics of drug products and to use results of stability testing to determine appropriate storage conditions and expiration dates (21 CFR 211.166(a)).

Based on the records and information you provided for stability, you did not demonstrate that the chemical properties of your drug products remain acceptable throughout the labeled expiry period of 24 months.

The stability test results you provided were limited to pH, density, appearance, smell, color and strength. You failed to provide data for testing of impurities, and microbiological attributes (total counts and free of objectionable microorganisms).

Without appropriate stability studies, you do not have scientific evidence to support whether your drug products meet established specifications and retain their quality attributes through their labeled expiry.

In response to this letter, provide the following for all drug products imported to the United States prior to and after our 704(a)(4) request:

A comprehensive, independent assessment and corrective action and preventive action (CAPA) plan to ensure the adequacy of your stability program. Your remediated program should include, but not be limited to:

o Stability indicating methods o Stability studies for each drug product in its marketed container-closure system before distribution is permitted o An ongoing program in which representative batches of each product are added each year to the program to determine if the shelf-life claim remains valid o Detailed definition of the specific attributes to be tested at each station (timepoint)

All procedures that describe these and other elements of your remediated stability program

While you state that you perform identity testing, we note that in response to our initial 704(a)(4) requests for information on identity testing for each lot of components, you did not provide evidence of such testing. Without these test results, you have not demonstrated that you are testing incoming lots of the active pharmaceutical ingredient (API) used to manufacture your OTC drug products to determine their identity. Refer to 21 CFR 211.84(d)(1) and (d)(2).

Based upon the nature of the violations we identified at your firm, you should engage a consultant qualified as set forth in 21 CFR 211.34 to assist your firm in meeting CGMP requirements if your firm intends to resume manufacturing drugs for the U.S. market. The qualified consultant should also perform a comprehensive audit of your entire operation for CGMP compliance and evaluate the completion and efficacy of your corrective actions and preventive actions before you pursue resolution of your firm’s compliance status with FDA.

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.

The violations cited in this letter are not intended to be an all-inclusive list of violations that exist at your facility. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations.

FDA placed your firm on Import Alert 66-40 on October 27, 2023.

Correct any violations promptly. FDA may withhold approval of new applications or supplements listing your firm as a drug manufacturer until any violations are completely addressed and we confirm your compliance with CGMP. We may inspect to verify that you have completed corrective actions to any violations.

Failure to address any violations may also result in the FDA continuing to refuse admission of articles manufactured at Cerci Kozmetik Ve Otel Ekipmanlari Pazarlama Ic Ve Dis Ticaret Limited Sirketi, Aytop Sanayi Sitesi B2 Block, 14-15-16 Battalgazi Mahalle, Istanbul (Anatolia), into the United States under section 801(a)(3) of the FD&C Act, 21 U.S.C. 381(a)(3). Articles under this authority that appear to be adulterated or misbranded may be detained or refused admission, in that the methods and controls used in their manufacture do not appear to conform to CGMP within the meaning of section 501(a)(2)(B) of the FD&C Act, 21 U.S.C. 351(a)(2)(B) and are misbranded under section 502 of the FD&C Act, respectively.

This letter notifies you of our findings and provides you an opportunity to address the above deficiencies. After you receive this letter, respond to this office in writing within 15 working days. Specify what you have done to address any violations and to prevent their recurrence. In response to this letter, you may provide additional information for our consideration as we continue to assess your activities and practices. If you cannot complete corrective actions within 15 working days, state your reasons for delay and your schedule for completion.

Send your electronic reply to CDER-OC-OMQ-Communications@fda.hhs.gov. Identify your response with FEI 3017978054 and ATTN: Chhaya Shetty.