- Delivery Method:
- Via Email
Recipient NameMr. Kemal Deniz
- Sudesan Temizlik Urunleri Ve Ambalaj Sanaryi Ticaret Anomin Sirketi
No:5 Petrol Ofisi Caddesi Sehit Komando Onbasi Ugur Hanci Sokak
- Issuing Office:
- Center for Drug Evaluation and Research | CDER
Warning Letter 320-24-05
November 13, 2023
Dear Mr. Deniz:
Your facility is registered with the U.S. Food and Drug Administration (FDA or Agency) as a manufacturer of over-the-counter (OTC) drug products, including Amoray Instant Hand Sanitizer. The FDA has reviewed the records you submitted on March 11, 2022, in response to our August 26, 2021 request for records pursuant to section 704(a)(4) of the Federal, Drug, and Cosmetic Act (FD&C Act) for your facility, Sudesan Temizlik Urunleri Ve Ambalaj Sanaryi Ticaret Anomin Sirketi (hereafter referred to as Sudesan), FEI 3004647124, at No. 5 Petrol Ofisi Caddesi Sehit Komando Onbasi Ugur Hanci Sokak, Avcilar Instanbul.
This warning letter summarizes significant violation of Current Good Manufacturing Practice (CGMP) regulations for finished pharmaceuticals. See Title 21 Code of Federal Regulations (CFR) parts 210 and 211 (21 CFR parts 210 and 211).
Because your methods, facilities, or controls for manufacturing, processing, packaging, or holding drugs as described in your response to our 704(a)(4) request do not conform to CGMP regulations, your drug products are deemed adulterated within the meaning of section 501(a)(2)(B) of the FD&C Act (21 U.S.C. 351(a)(2)(B)).
1. Your firm failed to conduct at least one test to verify the identity of each component of a drug product. Your firm also failed to validate and establish the reliability of your component supplier’s test analyses at appropriate intervals (21 CFR 211.84(d)(1) and 211.84(d)(2)).
Based on the records and information you provided, you have not demonstrated that you are adequately testing incoming lots of components used to manufacture your sanitizer drug products.
For example, in response to our 704(a)(4) requests, you provided a list of testing performed on incoming components. Identity testing did not appear to be adequately performed for any of the components. In addition, you failed to adequately describe the physical and microbiological controls that had been implemented. Furthermore, you provided records showing that testing of incoming ethanol lots started after you shipped these drug products to the United States.
Without adequate testing, you do not have scientific evidence that your raw materials conform to appropriate specifications prior to use in the manufacture of drug products. As a manufacturer, you have a responsibility to sample, test, and examine drug components before use in production to assure adequate quality.
You manufacture drugs that contain ethanol. The use of ethanol contaminated with methanol has resulted in various lethal poisoning incidents in humans worldwide. See FDA's guidance document Policy for Testing of Alcohol (Ethanol) and Isopropyl Alcohol for Methanol at: https://www.fda.gov/media/173005/download.
In response to this letter, provide:
- A comprehensive, independent review of your material system to determine whether all suppliers of components, containers, and closures, are each qualified and the materials are assigned appropriate expiration or retest dates. The review should also determine whether incoming material controls are adequate to prevent use of unsuitable components, containers, and closures.
- The chemical and microbiological quality control specifications established to release each incoming lot of components for use in manufacturing.
- A description of how you will test each component lot for conformity with all appropriate specifications for identity, strength, quality, and purity. If you intend to accept any results from your supplier’s Certificates of Analysis (COA) instead of testing each component lot for strength, quality, and purity, specify how you will robustly establish the reliability of your supplier’s results through initial validation as well as periodic re-validation. In addition, include a commitment to always conduct at least one specific identity test for each incoming component lot.
- A summary of results obtained from testing all components to evaluate the reliability of the COA from each component manufacturer.
2. 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)).
Based on the records and information you provided, you did not conduct adequate finished drug product testing on all drug products.
Specifically, you failed to provide evidence that you performed identity and strength testing for the active ingredient in your Amoray Hand Sanitizers. In response to our request to provide release test specifications, analytical procedures for the analysis of drug products and testing data, you submitted, in part, a procedure stating you evaluated the alcohol concentration and microbiological attributes of your hand sanitizers. However, the COA reports provided indicate your hand sanitizer drug products were only tested for appearance, odor, density, and pH.
Full release testing, including strength and identity testing of the active ingredient, must be performed before drug product release and distribution. Without adequate testing, you do not have adequate scientific evidence to assure that your drug products conform to appropriate specifications before release.
In response to this letter, provide:
- A list of chemical and microbial specifications, including test methods, used to analyze each lot of your drug products before a lot disposition decision.
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.
- 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.
3. 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, you did not provide adequate stability data to demonstrate that your program adequately evaluates appropriate storage conditions and supported expiration dates for the drug products manufactured at your facility that are distributed to the U.S.
Specifically, the COAs provided by your firm stated the expiration date on your drug products was (b)(4). The stability data you provided only covered 12 weeks at controlled room temperature conditions and was limited to drug products manufactured in 2019.
You have not provided data to support the expiry period assigned to your hand sanitizer drug products. Without an adequate stability program, you cannot confirm that your drug products will meet established specifications and all pre-determined quality criteria throughout their shelf life.
In response to this letter, provide:
- 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 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.
CGMP Consultant Recommended
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. The qualified consultant should perform a comprehensive audit of your entire operation for CGMP compliance and also evaluate the completion and efficacy of any identified corrective actions and preventive actions before you pursue resolution of your firm’s compliance status with the FDA.
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 18, 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 re-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 Sudesan at No:5 Petrol Ofisi Caddesi Sehit Komando Onbasi Ugur Hanci Sokak, Avcilar Istanbul 34310 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 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).
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 3004647124 and ATTN: Marva Taylor.
Office of Manufacturing Quality
Office of Compliance
Center for Drug Evaluation and Research