- Delivery Method:
- VIA UPS
Recipient NameMr. Selim Yesil
- Delta Kozmetik Sanayi Ve Ticaret-Selim Yesil
N.12 Istanbul Endustri Ve Ticaret Serbest
Bolgesi Aydinli Sb Mahallesi, 6. Sokak
- Issuing Office:
- Center for Drug Evaluation and Research
Warning Letter 320-21-51
July 8, 2021
Dear Mr. Yesil:
Your firm is registered as a human drug manufacturer. The U.S. Food and Drug Administration (FDA) conducted testing of a consumer antiseptic hand rub drug product (also referred to as a consumer hand sanitizer), labeled as (b)(4). This drug product was listed to be manufactured at your facility, Delta Kozmetik Sanayi Ve Ticaret-Selim Yesil, FEI 3010166780, at N.12 Istanbul Endustri Ve Ticaret Serbest, Bolgesi Aydinli Sb Mahallesi, 6. Sokak, Tuzla, Istanbul. Following an attempt to import (b)(4) into the United States, it was detained and refused admission at the border.
The results of the FDA laboratory testing of a batch of this product detained at the border demonstrate that this drug product listed to be manufactured at your facility is adulterated within the meaning of section 501(c) of the Federal Food, Drug, and Cosmetic Act (FD&C Act or Act), 21 U.S.C. 351(c), in that its strength, purity, or quality falls below that which it purports or is represented to possess. In addition, this product is adulterated within the meaning of section 501(a)(2)(B) of the FD&C Act (21 U.S.C. 351(a)(2)(B)), in that the subpotency demonstrates that the quality assurance within your facility is not functioning in accordance with Current Good Manufacturing Practice (CGMP) requirements.
(b)(4), listed to be manufactured at your facility, is labeled to contain (b)(4)% volume/volume (v/v) of the active ingredient ethyl alcohol (ethanol). However, FDA laboratory testing of a batch of this product detained at the border found that the drug product contained an average of only 59% v/v ethanol. This hand sanitizer drug product is adulterated under section 501(c) of the FD&C Act in that the active ingredient of ethanol is present at levels in the product lower than that which is declared on its labeling.
CDC recommends1 that, if soap and water are not readily available, consumers use an alcohol-based hand sanitizer that contains not less than 60% alcohol (ethanol). This is the minimum active ingredient concentration of ethanol specified in the 1994 Tentative Final Monograph (1994 TFM) for Health-Care Antiseptic Drug Products (59 FR 31402), as further amended by “Safety and Effectiveness of Consumer Antiseptics; Topical Antimicrobial Drug Products for Over-the-Counter Human Use; Proposed Amendment of the Tentative Final Monograph; Reopening of Administrative Record,” Proposed Rule, 81 FR 42912 (June 30, 2016) (Consumer Antiseptic Rubs Proposed Rule). FDA testing of a batch of your product detained at the border found a level of ethanol that is below that specified in the 1994 TFM, as further amended by the Consumer Antiseptic Rubs Proposed Rule, and below the CDC recommendation of at least 60% ethanol content in this drug product.
On March 19, 2021, FDA held a teleconference with you and your registered U.S. Agent. During the call, we requested additional information concerning your CGMP operations, including test methods for your incoming active pharmaceutical ingredient (ethanol) and finished product. In your response, you provided your test methods and documentation of your associated laboratory test equipment. However, the methods you submitted did not include an appropriate identity test for ethanol, nor did the methods include testing for methanol, as required under 21 CFR 211.84. In addition, your test methods did not include appropriate assay testing for finished product as required per 21 CFR 211.165. Without adequate testing of incoming raw materials and finished product you cannot assure that your drug products conform to appropriate standards of identity, strength, quality and purity.
While the drug product detailed above was shipped to the United States, information available to FDA demonstrated that all of your hand sanitizers were detained and refused admission at the border and did not enter the United States. Therefore, FDA did not recommend that you remove this product from the market.
In response to this letter, provide the following:
• A detailed investigation into how the hand sanitizer drug product described above, which was labeled as containing (b)(4)% ethanol, in fact contained an average of 59% ethanol.
• A list of all raw materials used to manufacture your hand sanitizer drug products, including the suppliers’ names, addresses, and contact information.
• A list of all batches of any hand sanitizer drug products shipped to the United States by your firm, and a full reconciliation of all material you distributed.
• Copies of the complete batch records for all batches distributed to the United States.
• A complete, comprehensive, and 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.
The subpotency of hand sanitizer drug products listed or labeled as manufactured in your facility, in addition to the deficiencies in your response to the information we requested during the March 19, 2021 teleconference, demonstrate that the quality assurance within your facility is not functioning in accordance with CGMP requirements under section 501(a)(2)(B) of the FD&C Act.2
CGMP Consultant Recommended
Based upon the nature of the violations we identified at your firm, we strongly recommend engaging a consultant qualified as set forth in 21 CFR 211.34 to evaluate your operations and to assist your firm in meeting CGMP requirements if your firm intends to resume manufacturing drugs for the U.S. market. We also recommend that the qualified consultant perform a comprehensive audit of your entire operation for CGMP compliance and that the consultant evaluates 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 associated with your drug products. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations.
Note that FDA placed all drugs and drug products manufactured by your firm on Import Alert 66-78 on May 17, 2021, as the methods used in and controls used for the manufacture, processing, packing, or holding of these products do not appear to conform to current good manufacturing practices within the meaning of section 501(a)(2)(B) of the FD&C Act. Drugs and drug products that appear to be adulterated may be detained or refused admission without physical examination.
All drugs and drug products manufactured by your firm may remain listed on this import alert until there is evidence establishing that the conditions that gave rise to the appearance of a violation have been resolved, and the Agency has confidence that future entries will be in compliance with the FD&C Act. This may include an inspection prior to the Agency considering the appearance of adulteration to be addressed.
If you decide you want to manufacture drugs for the United States in the future, request a Regulatory Meeting to discuss corrective actions.
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 do so 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.
Please identify your response with FEI 3010166780 and ATTN: Bryce Hammer.
Office of Manufacturing Quality
Office of Compliance
Center for Drug Evaluation and Research
Registered U.S. Agent
Mark M. Yesil
2 Due to an increased demand for alcohol-based hand sanitizers during the COVID-19 pandemic, FDA published the Guidance for Industry: Temporary Policy for Preparation of Certain Alcohol-Based Hand Sanitizer Products During the Public Health Emergency (COVID-19) on March 19, 2020, and subsequently updated the guidance several times, most recently on February 10, 2021. This guidance communicates the Agency’s temporary policy that we do not intend to take action against firms for CGMP violations under section 501(a)(2)(B) of the FD&C Act if such firms prepare alcohol-based hand sanitizers for consumer use (or for use as health care personnel hand rubs) during the public health emergency, provided certain circumstances described in the guidance are present. These circumstances include preparation of hand sanitizer products using only the ingredients and formulas set forth in the guidance. In addition to the violative testing results detailed above that demonstrate the subpotency of hand sanitizer products listed as manufactured at your facility, a review of the purported formulations on the drug product’s labeling further indicates that this product is not prepared consistent with FDA’s temporary policy set forth in the guidance. Therefore, this product does not fall within the Agency’s temporary policy not to take action against firms manufacturing hand sanitizer products for violations of section 501(a)(2)(B) of the FD&C Act.