- Delivery Method:
- VIA UPS
Recipient NameMr. Lawrence Kalb
- Omega Packaging Corp
55 King Road
Totowa, NJ 07512-2205
- Issuing Office:
- Division of Pharmaceutical Quality Operations I
CMS # 649122
March 20, 2023
Dear Mr. Kalb:
The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Omega Packaging Corp, FEI 2246857, at 55 King Road, Totowa, New Jersey, from October 18 to November 17, 2022.
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 response from your firm for corrective actions to the observations identified during the inspection in our Form FDA 483.
During our inspection, our investigators observed specific violations including, but not limited to, the following.
1. Your firm failed to test samples of each component for identity and conformity with all appropriate written specifications for purity, strength, and quality (21 CFR 211.84(d)(1) and 211.84(d)(2)).
Inadequate API Testing
Your firm contract manufactures ethanol-based over-the-counter (OTC) hand rub1 drug products (also referred to as consumer hand sanitizer). You failed to adequately test your incoming components for identity before using the components to manufacture your OTC drug products, and you relied on certificates of analysis (COAs) from unqualified suppliers. Specifically, you failed to appropriately test your incoming (b)(4) active pharmaceutical ingredient (API) for impurities such as methanol, and your procedures did not ensure that you test glycerin for presence of diethylene glycol (DEG). We also note that the COA for the (b)(4) API you used to manufacture your drug products states that “this material is not considered to be, and is not sold as, an Active Pharmaceutical Ingredient.”
You manufacture multiple 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) to help you meet the CGMP requirements when manufacturing drugs containing ethanol at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/policy-testing-alcohol-ethanol-and-isopropyl-alcohol-methanol-including-during-public-health.
You manufacture products that contain glycerin. The use of glycerin contaminated with DEG has resulted in various lethal poisoning incidents in humans worldwide.
See FDA’s guidance document Testing of Glycerin for Diethylene Glycol to help you meet the CGMP requirements when manufacturing drugs containing glycerin at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/testing-glycerin-diethylene-glycol.
Inadequate Component Water Testing
You use water as a component in your drug products. You failed to provide data supporting the frequency of the testing of your water system for resistivity and microbiological growth. Pharmaceutical water must be suitable for its intended use, and routinely and adequately tested to ensure ongoing conformance with appropriate chemical and microbiological attributes.
2. Your firm 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 (21 CFR 211.100(a)).
Production Process Validation
You failed to validate the processes used to manufacture your drug products.
Process validation evaluates the soundness of design and state of control of a process throughout its lifecycle. Each significant stage of a manufacturing process must be designed appropriately and assure the quality of raw material inputs, in-process materials, and finished drugs. Process qualification studies determine whether an initial state of control has been established. Successful process qualification studies are necessary before commercial distribution. Thereafter, ongoing vigilant oversight of process performance and product quality is necessary to ensure that you maintain a stable manufacturing operation throughout the product lifecycle.
Without adequate process validation, incorporating all manufacturing inputs and parameters that can affect product quality, your firm lacks basic assurance that you can reproducibly deliver products that meet specifications. See FDA's guidance for industry, Process Validation: General Principles and Practices for general principles and approaches that the FDA considers appropriate elements of process validation at https://www.fda.gov/media/71021/download.
Water System Design and Validation
You failed to validate your water system and you lacked written procedures for the validation of the water system. Your firm lacked evidence to demonstrate that you could effectively control, maintain, sanitize, and monitor the system, so it consistently produces pharmaceutical grade water that, at a minimum, meets the Purified Water USP monograph and appropriately stringent microbiological limits. You must design and control your water system to reproducibly yield suitable water for use in production operations.
3. 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 quality unit (QU) did not provide adequate oversight for the manufacture of your drug products. For example, your QU failed to ensure the following:
- Establishment of an adequate cleaning validation program for your non-dedicated equipment (21 CFR 211.67(b)).
- Establishment of an adequate ongoing stability program (21 CFR 211.166(a)).
- Establishment of appropriate data integrity controls (21 CFR 211.68(b)).
- Adequate batch control and production records for your hand sanitizer drug products (21 CFR 211.188).
- Appropriate quality-related procedures were written and approved, such as for finished product release, master batch record review, annual product reviews, recalls, and change control (21 CFR 211.22(d)).
An adequate QU overseeing all manufacturing operations is necessary to consistently ensure drug quality. 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.
Your quality system does not adequately ensure the accuracy and integrity of data to support the safety, effectiveness, and quality of the drugs you manufacture. See FDA’s guidance document Data Integrity and Compliance with Drug CGMP for guidance on establishing and following CGMP compliant data integrity practices at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/data-integrity-and-compliance-drug-cgmp-questions-and-answers.
In response to this letter, provide:
- A comprehensive investigation into the extent of the inaccuracies in data records and reporting, including results of the data review for drugs distributed to the United States. Include a detailed description of the scope and root causes of your data integrity lapses.
- A current risk assessment of the potential effects of the observed failures on the quality of your drugs. Your assessment should include analyses of the risks to patients caused by the release of drugs affected by a lapse of data integrity and analyses of the risks posed by ongoing operations.
- A management strategy for your firm that includes the details of your global corrective action and preventive action (CAPA) plan. The detailed corrective action plan should describe how you intend to ensure the reliability and completeness of all data generated by your firm including microbiological and analytical data, manufacturing records, and all data submitted to FDA.
In response to this letter, confirm whether you intend to continue manufacturing any drugs at this facility or any other facility in the future. If you plan to continue CGMP activities, you are responsible for resolving all deficiencies and systemic flaws to ensure your firm is capable of ongoing CGMP compliance.
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 also perform a comprehensive six-system audit of your entire operation for CGMP compliance and evaluate the completion and efficacy of all CAPAs before you pursue resolution of your firm’s compliance status (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.
Responsibilities as a Contractor
Drugs must be manufactured in conformance with CGMP. FDA is aware that many drug manufacturers use independent contractors such as production facilities, testing laboratories, packagers, and labelers. 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. See FDA’s guidance document Contract Manufacturing Arrangements for Drugs: Quality Agreements at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/contract-manufacturing-arrangements-drugs-quality-agreements-guidance-industry.
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 promptly and adequately address this matter 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.
Send your electronic reply to email@example.com. Your written notification should refer to the Warning Letter CMS # 649122.
If you have any questions, contact Compliance Officer, Liatte Closs at firstname.lastname@example.org. Please identify your response with FEI 2246857.
Program Division Director
U.S. Food and Drug Administration
Office of Pharmaceutical Quality Operations/Division I
1 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. The guidance was withdrawn effective December 31, 2021 (86 Fed Reg at 56960). This guidance communicated the Agency’s temporary policy that we did not intend to take action against firms for CGMP violations under section 501(a)(2)(B) of the FD&C Act if such firms prepared alcohol-based hand sanitizers for consumer use (or for use as a health care personnel hand rub) during the public health emergency, provided certain circumstances described in the guidance are present. These circumstances included preparation of hand sanitizer products using only the ingredients and formulas set forth in the guidance. Because Omega Packaging Corp’s hand sanitizer products are not consistent with the formulations described in these guidances, they do not fall within any temporary Agency policy not to take action against firms manufacturing hand sanitizer products for violations of section 501(a)(2)(B) of the FD&C Act.