Madhu Instruments Private Limited

The U.S. Food and Drug Administration (FDA) inspected your manufacturing facility, Madhu Instruments Private Limited FEI 3007317099, at A-260, Okhla Industrial Area, Phase-1, New Delhi, from October 11 to 21, 2022.

FDA determined that (b)(4) manufactured at your facility are adulterated within the meaning of section 501(a)(2)(A) of the Federal Food, Drug, and Cosmetic Act (the FD&C Act), 21 U.S.C. 351(a)(2)(A), in that they have been prepared, packed, or held under insanitary conditions whereby they may have been contaminated with filth, or whereby they may have been rendered injurious to health.

We reviewed your November 11, 2022, response to our Form FDA 483 in detail. Your response is inadequate because it did not provide sufficient detail or evidence of corrective actions to bring your operations into compliance with the FD&C Act.

FDA investigators observed that products intended or expected to be sterile were prepared, packed, or held under insanitary conditions, whereby they may have become contaminated with filth or rendered injurious to health, causing your products to be adulterated under section 501(a)(2)(A) of the FD&C Act. During the inspection, the investigators observed your manufacturing facility of products intended or expected to be sterile was in a state of disrepair, as noted by the following examples:

Peeling paint on the ceilings of your firm’s ISO 7 manufacturing rooms.

A plastic bag covering the high efficiency particulate air (HEPA) filter in the manufacturing area impeding adequate airflow.

Broken tiles along the base of the wall in the manufacturing rooms that were observed to have an (b)(4) residue adhering to them. (b)(4) is (b)(4) in color.

A (b)(4) was used to patch holes in the walls, and masking tape was used to secure (b)(4) and (b)(4) to walls of the manufacturing rooms.

You do not have adequate controls in place to maintain a suitable production environment and prevent contamination of products manufactured at your facility. During the FDA inspection, your manufacturing equipment, including (b)(4) machines were found to be visibly dirty and appeared to be stained with oil or grease residues. The cardboard box used to catch the product (b)(4) after (b)(4) is lined with white masking tape that has become stained and soiled over time. Additionally, the manual operation uses printer paper taped to the work surface on which filling and packaging of the products are performed.

In your response, you acknowledged that your cleaning and sanitization standard operating procedure (SOP) was inadequate, and your facility preventive maintenance plan was not implemented properly. You implemented a new checklist to verify and monitor cleaning and sanitization of the manufacturing areas and revised your SOPs for cleaning.

Your response is inadequate because you failed to conduct a retrospective review and assessment of the risks to product quality, including all potential contamination risks. Previously you had committed to improving your cleaning procedures but thus far have not adequately developed a cleaning and sanitization regimen that minimizes the risk of contamination. Although you terminally sterilize your (b)(4), it is imperative that you adequately design and maintain your facility to prevent the risk of adding contaminants, such as extraneous particulates, to your product.

In response to this letter, provide the following:

Your plan that assesses the vulnerabilities in your equipment cleaning and disinfection processes and practices, as well as facility and equipment design, which develops appropriate remediations to prevent contamination and provides timelines for completion.

Your 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.

Documentation that supports your corrective actions such as work orders, room qualification, photos of any repairs your firm has made to correct the violation, and systemic plans to ensure the manufacturing areas remain adequately designed, controlled, and maintained.

FDA placed your firm on Import Alert 66-40 on May 31, 2023.

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.

If you are considering an action that is likely to lead to a disruption in the supply of the products produced at your facility, FDA requests that you contact the Agency immediately, at drugshortages@fda.hhs.gov, so that FDA can work with you on the most effective way to bring your operations into compliance with the law. Contacting the FDA also allows you to meet any obligations you may have to report discontinuances or interruptions in your product manufacture under the FD&C Act. This also allows FDA to consider, as soon as possible, what actions, if any, may be needed to avoid shortages and protect the health of patients who depend on your products.

Correct any violations promptly. FDA may withhold approval of new applications or supplements listing your firm as a manufacturer until any violations are completely addressed and we confirm your compliance with the Act. We may re-inspect to verify that you have completed corrective actions for any violations.

Failure to address any violations may also result in the FDA continuing to refuse admission of articles manufactured at Madhu Private Limited, A-260, Okhla Industrial Area, Phase-1, New Delhi, India, into the United States under section 801 of the FD&C Act, 21 U.S.C. 381. Articles under this authority that appear to be adulterated or misbranded are subject to detention or refusal of admission.

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 CDER-OC-OMQ-Communications@fda.hhs.gov. Identify your response with FEI 3007317099 and ATTN: Rokhsana Safaai-Jazi