What to Expect and How to Prepare
FDA’s renewed focus on foreign and domestic inspections via onsite routine surveillance inspections, unannounced inspections and remote regulatory assessments continues to climb across all FDA-regulated industries. Following a pandemic pause, foreign inspections are particularly on the rise with an estimated 1,636 facilities already investigated this year following a sharp decline in 2019-2022. While inspection elements vary for each industry, FDA’s inspection philosophy remains the same for foods, supplements, cosmetics, drugs and devices: to confirm compliance with current Good Manufacturing Practice (cGMP) requirements, to ensure product quality, and to mitigate issues that would trigger public health risk or patient harm.
For food products, top citations include failure to develop and/or implement a Foreign Supplier Verification Program (FSVP), sanitation monitoring, food safety hazards, critical control points, and lack of effective pest exclusion. Top citations for medical devices include lack of or inadequate procedures, including lack of receiving procedures and complaint procedures, and inadequate procedures relating to supplier evaluation, and equipment calibration and inspection. For drugs, top citations include procedures not in writing and not being fully followed, lack of investigation of discrepancies and failures, inadequate control procedures to monitor and validate performance, and inadequate testing and release procedures. While cosmetic GMPs are currently voluntary, FDA is known to conduct inspections of cosmetic facilities for compliance. Additionally, the newly implemented Modernization of Cosmetics Regulation Act (MoCRA) provides for enforceable cosmetic GMPs, with FDA expected to issue a proposed rule on cosmetic GMPs by December 29, 2024.
It is important to note that facilities that are required to register with FDA and list their products are subject to routine cGMP surveillance inspections based on FDA’s risk-based model, which prioritizes manufacturing sites and/or facilities based on compliance history, inherent product risk, facility type, time since the last inspection, hazard signals and risk exposure. If warranted by compliance information, facilities may also be subject to “For Cause” inspections.
So, what is an inspection all about, really? FDA has routinely advised that an inspection verifies a firm’s adherence to good manufacturing practice standards, which is then documented in an Establishment Inspection Report (EIR) to reflect the firm’s operations and state of control. Items that are routinely covered during FDA inspections include investigation reports, equipment qualification, validation of the manufacturing process, testing of incoming raw materials and finished products, and adequate analytical methods. During a recent FDA webinar on inspections, FDA advised that drug inspectors, for instance, focus on drug quality conditions that may affect persons using the product. Key points of concern include quality, facilities and equipment (specifically water systems), materials inspection and handling, product production, packaging and labeling and laboratory controls. Any observed deficiencies that are in violation of cGMP requirements are provided in an FDA-483, to which a firm typically has 15 business days to respond with corrective and preventative actions.
Companies relying on foreign manufacturing sites should ensure their facilities are GMP compliant or consider alternative sites for key materials. Although FDA does not conduct pre-launch inspections as a condition to market launch, cGMP compliance with the requisite regulations (e.g. 21 CFR Part 117, 21 CFR Part 820) should be in place prior to launching a product to the U.S. market and prior to facility registration, as a facility’s registration with the FDA signifies consent to an FDA inspection. While independent third-party certifications (e.g. BRC, ISO, etc.) are advisable and often-times required by B2B purchasers or others, compliance with these standards is not dispositive of cGMP compliance. All SOPs and recordkeeping will need to be in place and available for inspection.
In terms of post-inspection enforcement, FDA continues to utilize enforcement tools such as warning letters and import alerts, many of which are focused on product quality issues that are reviewed during inspections. While the decline in FDA inspections in recent years may have created a lack of immediacy at some sites and/or the failure to implement corrective and preventative actions, we recommend manufacturing sites and facilities take steps now to timely close quality investigations to avoid FDA scrutiny during inspections and whistleblower risks, particularly considering the marked post-pandemic increase of foreign and domestic inspections.
In preparing for FDA inspections, we recommend businesses take the following steps:
- Assess inspection readiness of key sites, including conducting a gap assessment and creating or updating policies relating to FDA record requests.
- Ensure equipment, processes and test methods are qualified or validated, where required.
- Confirm supplier compliance via documented supplier evaluations.
- Consider third-party audits and demonstrate the efficacy of corrective and preventative actions.
- Conduct thorough investigations of compliance concerns raised by employees, and document the identification and outcome of such issues.
- Identify and train appropriate staff to receive, accompany and address questions with FDA inspectors.
- Practice management of unannounced inspections, conduct regular “mock audits” and document reviews to stay inspection-ready.
For any questions on FDA inspections, including conducting a mock FDA audit, preparing for an inspection, or post-inspection compliance including responding to 483s or Warning Letters, please contact us at info@garg-law.com.
