- Delivery Method:
- VIA Electronic Mail
Recipient NameMr. Lester Sampath
Recipient TitleChief Executive Officer
- Inopak, Ltd.
24 Executive Pkwy
Ringwood, NJ 07456
- Issuing Office:
- Division of Pharmaceutical Quality Operations I
CMS # 667411
December 15, 2023
Dear Mr. Sampath:
The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Inopak, Ltd., FEI # 1000122232, at 24 Executive Pkwy., Ringwood, New Jersey, from July 24 to August 3, 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 reviewed your August 24, 2023 response to our Form FDA 483 in detail and acknowledge receipt of your subsequent correspondence.
During our inspection, our investigators observed specific violations including, but not limited to, the following.
1. Your firm failed to establish an adequate quality unit and the responsibilities and procedures applicable to the quality control unit are not in writing and fully followed (21 CFR 211.22(a) and 211.22(d)).
Your firm utilizes a contract manufacturing organization (CMO) to manufacture your over-the-counter (OTC) drug products such as SaniGuard SF foam hand sanitizer alcohol 70%. Your quality agreement with your CMO stipulates that you are responsible for reviewing documentation including, but not limited to, formulations, specifications, laboratory results, executed “batch records,” and certificates of analysis (COAs). Your quality unit (QU) failed to adequately review these records to ensure required testing was conducted for methanol1, before acceptance of components for use in drug manufacture. Additionally, you did not ensure that your ethanol had acceptable levels of known impurities such as benzene, acetaldehyde, and acetal.
You also failed to adequately investigate the leaking drug product received from your CMO. You segregated and labeled the product as rejected as established in your procedures. However, your procedures do not adequately establish a requirement to investigate or communicate to your CMO to investigate non-conformances such as leaking drug products.
Your response states that you will use a sampling plan to review representative records for your drug products manufactured by your CMO. You state that prior to approving release, you will review each formulation and specification to verify acceptable ranges on the COAs and test results and review each lot’s COA, “(b)(4),” shipping results, and inspection results. You state that you will revise your standard operating procedures (SOPs) to reflect your current operations as a private label distributor of drug products. You also state that all finished drug products damaged in shipping has been destroyed and removed.
Your response is inadequate because your proposed sampling commitment does not conform with your established procedures and quality agreement with your CMO. Your quality agreement appears to contain ambiguities of responsibilities with your CMO that should be addressed to reflect your current operations as stated in your response. Regardless of your established quality agreement as the owner of your drug products, you are ultimately responsible for the quality of your drug products. You also did not provide an investigation for the leaking drug product or communication to your CMO to conduct an investigation. You provided no documentation supporting the claimed destruction of the leaking drug product.
Your firm’s quality system is 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:
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 lot 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
• Your investigation and communication to your CMO to investigate non-conforming product received from your CMO and supporting documentation of the destruction of the leaking drug product.
2. Your firm failed to assure that the drug product bore an expiration date that was supported by appropriate stability testing (21 CFR 211.137(a)).
You failed to maintain an ongoing stability testing program to support the labeled expiry on your distributed drug products. You utilize a contract testing laboratory to manage your stability testing program and discontinued your ongoing stability program with your contract testing laboratory on January 6, 2023. However, the last lot of drug product manufactured at your facility is labeled with expiration dates through July 29, 2024. There is no assurance that your drug products will remain acceptable throughout their labeled expiry period without an ongoing stability program.
In response to this letter, provide:
• Your plan for continuing stability studies for your drug products through expiry, including detailed timelines. This plan should also include an assessment of the stability of drug product currently on the U.S. market.
• Your action plan to address any product quality or patient safety risks for your drug products in U.S. distribution, including potential customer notifications and recalls.
Use of Contract Manufacturers
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 your drugs regardless of agreements in place with your contract facility. You are required to ensure that drugs are made in accordance with section 501(a)(2)(B) of the FD&C Act to ensure safety, identity, strength, quality, and purity. See FDA’s guidance document Contract Manufacturing Arrangements for Drugs: Quality Agreements at https://www.fda.gov/media/86193/download.
Drug Production Ceased
We acknowledge your commitment to cease production of all drugs at this facility.
If you plan to resume any manufacturing operations regulated under the FD&C Act, notify this office before resuming your drug manufacturing operations. You are responsible for resolving all deficiencies and systemic flaws to ensure your firm is capable of ongoing CGMP compliance. In your notification to the Agency, provide a summary of your remediations to demonstrate that you have appropriately completed all corrective action and preventive action (CAPA).
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 # 667411 and reference: FEI 1000122232.
If you have any questions, contact Compliance Officer CAPT Liatte Closs at Liatte.Closs@fda.hhs.gov.
Deputy Program Division Director
U.S. Food and Drug Administration
OPQO Division I
1 See 21 CFR 211.84; 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.