- Delivery Method:
- VIA Electronic Mail
Recipient NameRuben De Quesada
Recipient TitleGeneral Manager
- Omega & Delta Co., Inc.
Carr. 887 Km 0 Hm 8
Julio N. Matos Ind. Park Bldg #10
- Issuing Office:
- Division of Pharmaceutical Quality Operations II
Case #: 636606
Dear Mr. De Quesada:
The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Omega & Delta Co., Inc., FEI 2650091, at Carr. 887 Km 0 Hm 8, Julio N. Matos Ind. Park Bldg. #10, Carolina, Puerto Rico, from April 25 to May 6, 2022.
Your hand sanitizer drug products are adulterated under section 501(a)(2)(A) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 351(a)(2)(A), in that they have been prepared, packed, or held under insanitary conditions.
This warning letter also 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 FD&C Act, 21 U.S.C. 351(a)(2)(B).
We reviewed your response dated May 26, 2022, to our Form FDA 483 in detail.
Your hand sanitizer drug products are adulterated under section 501(a)(2)(A) of the FD&C Act because they were prepared, packed, or held under insanitary conditions. FDA investigators observed your facility to be in a state of disrepair, poorly cleaned, and maintained as evidenced by insects, cobwebs, and unexplained spills in your drug manufacturing and raw material storage areas. In addition, a portion of the raw materials warehouse for drug products was exposed to the external environment. You do not have adequate controls in place to maintain a clean production environment and prevent contamination of drug products. Similar facility conditions were observed during the 2017 FDA inspection.
During our inspection, our investigators observed specific violations including, but not limited to, the following.
1. 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 is currently registered as a drug manufacturer. Your quality unit (QU) lacked adequate personnel responsible for the quality oversight for the manufacture of your over the counter (OTC) drug products, including alcohol-based hand sanitizers. 1 During the inspection, you stated that you needed to hire additional personnel, including one additional person in the quality unit. For example:
• Your Quality Manager stated that he is not always present during the execution of manufacturing activities when he signs under “verified by” on manufacturing batch records.
• Our investigators reviewed three investigation reports that lacked oversight and approval by your QU. The reports were generated by your consultant and approved by you, the General Manager. Further, two of those investigation reports were generated and approved a year after the events occurred.
In your response, you stated that you will “identify, hire, and train new resources” for the QU, and that all employees will be retrained on applicable QU procedures. Additionally, you stated that your investigation handling procedure will be updated to include QU approval. Your response is inadequate as you did not fully describe how your QU will be enabled to exercise proper authority and/or sufficiently implement its responsibilities.
Additionally, you did not adequately describe your interim plans to ensure there is proper quality oversight over the drug products until you are able to hire and train new employees.
Your inspectional history indicates that your QU is not able to fully exercise its authority and/or responsibilities. Your firm must provide the QU with the appropriate authority and sufficient resources to carry out its responsibilities and 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.
In your 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:
o A determination of whether procedures used by your firm are robust and appropriate
o Provisions for QU oversight throughout your operations to evaluate adherence to appropriate practices
o A complete and final review of each batch and its related information before the QU disposition decision
o Oversight and approval of investigations and discharging of all other QU duties to ensure identity, strength, quality, and purity of all products
• A complete assessment of documentation systems used throughout your manufacturing and laboratory operations to determine where documentation practices are insufficient. Include a detailed corrective action and preventive action (CAPA) plan that comprehensively remediates your firm’s documentation practices to ensure you retain attributable, legible, complete, original, accurate, contemporaneous records throughout your operation.
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 211.84(d)(2)).
You failed to perform an identity test on samples of each component lot used in the production of your drug products, including the active ingredient (i.e., isopropyl alcohol). Additionally, you relied on certificates of analysis (COAs) from suppliers and failed to establish the reliability of each of your suppliers’ COAs for component specifications and characteristics. This is a repeat observation from the 2017 FDA inspection.
In your response, you stated that you have identified three laboratories to perform identity tests on your raw materials (components). Your response is inadequate as you did not provide details on your interim plans to ensure the identity of your drug components until you have identified a laboratory to perform testing, nor did you provide details on how you will establish the reliability of your suppliers’ COA.
Identity testing is required for (b)(4) to the use in drug product manufacturing, and you can only rely on a COA for other component attributes through validation of supplier’s test results at appropriate intervals.
In your response to this letter, provide:
• The chemical and microbiological quality control specifications you use to test and release (b)(4) lot of component 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 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 (b)(4) re-validation. In addition, include a commitment to always conduct at (b)(4) specific identity test for (b)(4) component lot.
• A summary of your program for qualifying and overseeing contract facilities that test the drug products you manufacture.
3. Your firm failed to establish adequate 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, and to follow all of your written production and process control procedures (21 CFR 211.100(a) and 211.100(b)).
You failed to adequately design your water system to ensure that it was suitable for producing water used in the formulation of your drug products. Your (b)(4) systems “(b)(4)” and “(b)(4)” appear to have multiple dead-legs,2 which can foster the development of biofilms.
In addition, your firm has not demonstrated that you can effectively control, maintain, sanitize, and monitor your water systems to ensure that they consistently, at a minimum, meet the USP monograph for (b)(4) water and appropriate chemical and microbiological limits. For example, your firm lacked a written and validated test method to perform your (b)(4) microbiological testing for coliforms and enumeration.
Your response stated that you have contacted the manufacturer of your water system to provide the necessary parts to replace the dead-legs and your microbiological testing procedures included the established acceptance limits. Additionally, you stated that you were reviewing several proposals for the validation of your water system, and that you would start the validation by July 2022.
Your response is inadequate. You failed to assess the impact of using water from these unvalidated water systems on the quality of drug products you manufacture. Further, you did not address the adequacy of your overall design to ensure that the system consistently produces water meeting (b)(4) water USP monograph specifications and appropriate microbial limits. Additionally, you did not provide a detailed plan for validating your water systems nor did you provide interim measures in place to ensure your water meets quality attributes until the systems consistently produce water of appropriate quality and they are validated.
Pharmaceutical water must be suitable for its intended use and (b)(4) tested to ensure ongoing conformance with appropriate chemical and microbiological attributes.
In response to this letter provide:
• A comprehensive remediation plan for the design, control, and maintenance of the water system.
o Validation report for the water system obtained after all identified design issues have been fully corrected and any maintenance repairs have been completed. Include the system validation protocol, the complete test results, and the final validation report.
• Your total microbial count limits to monitor whether this system is producing water suitable for the intended uses for each of your products.
• A detailed risk assessment addressing the potential effects of the observed water system failures on the quality of all drug product lots currently in U.S. distribution or within expiry. Specify actions that you will take in response to the risk assessment, such as customer notifications and product recalls.
• A procedure for your water system monitoring that specifies (b)(4) microbial testing and chemical attribute testing of water to ensure its acceptability for use (b)(4) batch of drug products produced by your firm.
• A procedure governing your program for ongoing control, maintenance, and monitoring that ensures the remediated system consistently produces water that meets (b)(4) Water, USP monograph specifications and appropriate microbial limit.
Repeat Observations at Facility
In a previous inspection dated January 2017, FDA cited similar CGMP observations. You proposed specific remediation for these observations in your response. Our current inspection identified multiple failures to implement your specific corrective actions.
These repeated failures demonstrate that executive management oversight and control over the manufacture of drugs is inadequate. Explain how you intend to assure your commitments are fulfilled and corrective actions are effective and sustainable.
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 also perform a comprehensive audit of your entire operation for CGMP compliance and evaluate the completion and efficacy of any identified corrective actions and preventive actions before you pursue resolution of your firm’s compliance status with 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.
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.
Your written notification should refer to case # 636606.
Please electronically submit your reply, on company letterhead, to Rebecca Asente, Compliance Officer, at ORAPHARM2_RESPONSES@fda.hhs.gov. In addition, please submit a signed copy of your response to Rebecca.firstname.lastname@example.org and email@example.com.
If you have questions regarding the contents of this letter, you may contact Rebecca Asente via (504) 846-6104 or Rebecca.firstname.lastname@example.org.
Monica R. Maxwell
Program Division Director
Office of Pharmaceutical Quality Operations, Division II
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. A review of the formulations of the drug products indicates that such products are not prepared consistent with FDA’s temporary policy set forth in the guidance. Because Omega & Delta Co., Inc.’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 505 of the FD&C Act.
2 High Purity Water System (7/93) | FDA