WARNING LETTER
Kor-Chem, Inc.
MARCS-CMS 661280 —
September 11, 2023
Delivery Method:
VIA Electronic Mail
Product:
Drugs
Recipient:
Recipient Name
John E. Fitzwater
Recipient Title
Chief Executive Officer, and Owner
Kor-Chem, Inc.
5800 Bucknell Drive SW
Atlanta
,
GA
30336-2514
United States
Issuing Office:
Division of Pharmaceutical Quality Operations II
United States
DATE: 9/11/2023
Case #: 661280
WARNING LETTER
Dear Mr. Fitzwater:
The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility Kor-Chem, Inc., FEI 3000204701, at 5800 Bucknell Drive SW, Atlanta from April 26 to May 5, 2023.
This warning letter summarizes significant violations 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, 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).
We have not received a detailed response from your firm for corrective actions to the specific observations identified during the inspection and cited on our Form FDA 483. However, we note your correspondence dated August 14, 2023, indicating that you are conducting a review of your operations and developing a remedial plan, and that you had “discontinued” your drug products.
During our inspection, our investigator observed specific violations including, but not limited to, the following:
1. Your firm failed to establish and follow adequate written procedures for cleaning and maintenance of equipment (21 CFR 211.67(b)).
Your firm manufactures topical over the counter (OTC) hand sanitizer drug products. You also manufacture commercial industrial chemical products on the same manufacturing equipment as your OTC drug products. Labels for some of the industrial chemicals that preceded the manufacture of your hand sanitizer drug products state that they are “Corrosive. Causes irreversible eye damage and skin burns. Harmful if swallowed, inhaled, or absorbed through the skin,” and “Causes severe burns and eye damage.” In addition, your equipment usage logs for the shared tanks lacked documentation of cleaning following the manufacture of batches of industrial chemical non-drug products that preceded the manufacture of batches of hand sanitizer drug products.
It is unacceptable as a matter of CGMP to manufacture drugs using the same equipment that you use to manufacture these non-pharmaceutical products due to the risk of cross-contamination.
In response to this letter, provide:
• Confirmation that you will discontinue manufacturing drugs on shared equipment with non-drug products in your facility.
• If you intend to continue manufacturing both pharmaceutical and non- pharmaceutical products at your facility, provide a plan to show how you will maintain dedicated manufacturing equipment and separate manufacturing areas for your pharmaceutical manufacturing and industrial product manufacturing operations.
• A risk assessment for all drugs you have previously produced on equipment shared with industrial products. For each product, assess the risk of potential cross- contamination due to the shared equipment, and provide your plans for addressing the product quality and patient safety risks for any products still in distribution, including potential recalls or market withdrawals.
• Your corrective action and preventive action (CAPA) plan to implement routine, vigilant operations management oversight of facilities and equipment. This plan should ensure, among other things, prompt detection of equipment/facilities performance issues, effective execution of repairs, adherence to appropriate preventive maintenance schedules, timely technological upgrades to the equipment/facility infrastructure, and improved systems for ongoing management review.
2. Your firm failed to test samples of each component for identity and conformity with all appropriate written specifications for purity, strength, and quality. 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 21 CFR 211.84(d)(2)).
You failed to conduct an identity test on each lot of the components (i.e., benzalkonium chloride and glycerin) and failed to conduct adequate identity testing of the active ingredient ethanol, used in the manufacture of your hand sanitizer drug products. You also relied on your suppliers’ certificates of analysis (COA) without establishing the reliability of your suppliers’ test analyses at appropriate intervals.
Products Containing Glycerin
You manufacture drugs that contain glycerin. Glycerin, along with other high-risk components, requires identification testing per the United States Pharmacopeia (USP) to ensure that it meets safety limits for diethylene glycol (DEG) or ethylene glycol (EG). Notably, EG is a component in your tire sealant products. Because you did not perform identity testing on each shipment of each lot using the USP identification test that detects these hazardous impurities, you failed to assure the acceptability of glycerin used in the manufacture of your drug products.
The use of ingredients contaminated with DEG or EG has resulted in various lethal poisoning incidents in humans worldwide. See FDA’s guidance document Testing of Glycerin, Propylene Glycol, Maltitol Solution, Hydrogenated Starch Hydrolysate, Sorbitol Solution, and Other High-Risk Drug Components for Diethylene Glycol and Ethylene Glycol to help you meet the CGMP requirements when manufacturing drugs containing ingredients at high-risk for DEG or EG contamination at https://www.fda.gov/media/167974/download.
In response to this letter, provide:
• A commitment to provide DEG and EG test results, no later than 30 calendar days from the date of this letter, from testing retains for all lots of high-risk drug components used in the manufacture of your drug products. Alternatively, if a retain of a component lot is unavailable, perform retain sample testing of all implicated finished drug product batches for the presence of DEG and EG.
• A full risk assessment for drug products that are within expiry which contain any ingredient at risk for DEG or EG contamination (including, but not limited to, glycerin). Take prompt and appropriate actions to determine the safety of all lots of the component(s) and any related drug product that could contain DEG or EG, including customer notifications and product recalls for any contaminated lots. Identify additional appropriate CAPA that secure supply chains in the future, including, but not limited to, ensuring that all incoming raw material lots are from fully qualified manufacturers and free from unsafe impurities. Detail these actions in your response to this letter.
• 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 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 revalidation. In addition, include a commitment to always conduct at least one specific identity test for each incoming component lot. In the case of glycerin, propylene glycol, and certain additional high-risk components we note that this includes the performance of parts A, B, and C of the USP monograph.
• The chemical quality control specifications you use to test each incoming lot of high- risk drug components to determine acceptability for use in manufacturing.
• 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.
• A summary of results obtained from testing all components to evaluate the reliability of the COA from each component manufacturer. Include your standard operating procedure (SOP) that describes this COA validation program.
Products Containing Ethanol
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, Including During the Public Health Emergency (COVID-19) at: https://www.fda.gov/media/145262/download.
3. Your firm failed to conduct, for each batch of drug product, appropriate laboratory testing, as necessary, required to be free of objectionable microorganisms (21 CFR 211.165(b)).
You failed to test your hand sanitizer drug products for microbiological attributes. Without testing each batch prior to release, you lack scientific evidence that all your drug product batches were free of microbial contamination that is objectionable in view of their intended use.
In response to this letter, provide a list of chemical and microbial test methods and specifications used to analyze each lot of your drug products before making a lot disposition decision, and the associated written procedures.
4. Your firm’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).
Your firm failed to establish an adequate quality unit (QU) with the responsibilities and authority to oversee the manufacture of your drug products. For example, your QU failed to ensure:
• Validation of drug product manufacturing processes, as well as validation and monitoring of your firm’s
(b)(4)
water system (21 CFR 211.100(a)).
• Validated analytical methods are used for drug product testing (21 CFR 211.160(b)).
• Adherence to an adequate stability program (21 CFR 211.166(a)).
Your firm’s quality systems are inadequate. See FDA’s guidance document Quality Systems Approach to Pharmaceutical CGMP Regulations for help implementing quality systems and risk management approaches to meet the requirements of CGMP regulations 21 CFR, parts 210 and 211 at: https://www.fda.gov/media/71023/download.
In response to this letter, provide a comprehensive assessment and remediation plan to ensure your QU is given the authority and resources to effectively function. The assessment should also include, but not be limited to:
• A determination of whether procedures used by your firm are robust and appropriate.
• Provisions for QU oversight throughout your operations to evaluate adherence to appropriate practices.
• A complete and final review of each batch and its related information before the QU disposition decision.
• Oversight and approval of investigations and discharging of all other QU duties to ensure identity, strength, quality, and purity of all products.
• Also describe how top management supports quality assurance and reliable operations, including, but not limited to, timely provision of resources to proactively address emerging manufacturing/quality issues and to assure a continuing state of control.
Drug Production Ceased
We acknowledge your commitment to cease production of drugs at this facility. In response to this letter, clarify whether you intend to resume manufacturing any drugs at this facility in the future. If you plan to resume manufacturing drugs, notify this office prior to resuming your operations.
Drug Registration and Listing
A query of FDA’s drug registration and listing database determined that Kor-Chem, Inc.’s establishment registration is current and is associated with two active drug listings, Instant Hand Sanitizer (62881-001) and Handy San (62881-003). Under section 510(j)(1) of the FD&C Act, 21 U.S.C. 360(j)(1), and 21 CFR 207.41, all drugs manufactured, prepared, propagated, compounded, or processed for U.S. commercial distribution must be listed with FDA.
If you discontinue the manufacture of any of your products, you must review and update your drug listing information in June or December after the change, submitting the date you discontinued the manufacture and providing the expiration date of the last lot manufactured, repacked, relabeled, or salvaged (21 CFR 207.57(b)(ii)). Although updates to drug listings are required in June or December after a change to the listed drug occurs (including discontinuation), registrants are encouraged to update listing information as soon as the change occurs (21 CFR 207 207.57(c)). Additionally, if you no longer plan to manufacture drug products for U.S. commercial distribution, FDA requests that you deregister as a drug manufacturing establishment (21 CFR 207.29).
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 evaluate your operations and to assist your firm in meeting CGMP requirements. The qualified consultant should also perform a comprehensive six-system audit
1
of your entire operation for CGMP compliance and evaluate the completion and efficacy of your CAPA 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.
Conclusion
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.
Correct any violations promptly. Failure to address this matter promptly and adequately may result in regulatory or legal action without further notice including, without limitation, seizure, and injunction. Unresolved violations may also prevent other Federal agencies from awarding contracts.
Failure to address violations may also cause FDA to withhold issuance of Export Certificates. 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 address any violations.
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.
Your written notification should refer to case #
661280
.
Please electronically submit your reply, on company letterhead, to Rebecca Asente, Compliance Officer, at ORAPHARM2_RESPONSES@fda.hhs.gov, and copy Ronda Loyd-Jones, Director, Compliance Branch at ronda-loyd-jones@fda.hhs.gov.
If you have questions regarding the contents of this letter, you may contact Ms. Asente via (504) 846-6104 or Rebecca.asente@fda.hhs.gov.
Sincerely,
/S/
Monica R. Maxwell
Program Division Director
Office of Pharmaceutical Quality Operations,
Division II
______________________
1
i.e., Quality System, Facilities & Equipment System, Materials System, Production System, Packaging & Labeling System, and Laboratory Control System per FDA’s guidance document
Quality Systems Approach to Pharmaceutical CGMP Regulations
.
Content current as of:
09/19/2023
Regulated Product(s)
Drugs