The US Food and Drug Administration (US FDA) has updated two Compliance Program Guides (CPGs) on GMP inspections. CPG’s are primarily for US FDA staff and assist them in evaluating and enforcing regulations for the industry. Many details and interpretations are found there that are not covered by existing US FDA laws, regulations or guidance. CHAPTER 46-New Drug Evaluation deals with pre-approval inspections (PAI) and CHAPTER 56-Drug Quality Assurance with routine surveillance inspections.
The background is possible alternatives to on-site inspections, improvements in the control of nitrosamine impurities, but also adaptations during the adoption of the ICH Q9 guideline on quality risk management (EMA/CHMP/ICH/24235/2006), ICH Q10 on pharmaceutical quality systems (EMA/CHMP/ICH/214732/2007) and ICH Q12 on technical and regulatory considerations for pharmaceutical product lifecycle management (EMA/CHMP/ICH/804273/2017).
- Revised CHAPTER 56 explains how US FDA can use MRA’s (Mutual Recognition Agreements) and RRA’s (Remote Regulatory Assessments) to support decisions, better plan inspections, and review certain information submitted to the agency.
- Revised CHAPTER 46 describes four inspection objectives for PAIs with strategies to be adapted, depending on the risk assessment of the facility; objective 1: Readiness for Commercial Manufacturing, objective 2: Conformance to Application, objective 3: Data Integrity Audit, objective 4: Commitment to Quality in Pharmaceutical Development.
Among other points, “Attachment A: Remote Regulatory Assessments” also describes possible alternative tools for conducting a PAI. For example, the US FDA can conduct remote regulatory assessments (RRAs). However, it is emphasised that RRAs do not constitute an inspection under section 704(a)(1) of the Federal Food, Drug, and Cosmetic Act (FD&C Act). Thus, RRAs are conducted to support the objectives of the compliance programme. With the PAI document, US FDA describes another type, a voluntary Remote Interactive Evaluation (RIE) to assess a company’s compliance and/or conformance with a submitted application. Various techniques can be used for this purpose, such as livestreaming of operations, teleconferencing, screen sharing, etc. With respect to the compliance programme, an RIE may be conducted in lieu of or in advance of a PAI to assist in the evaluation of a pending application or supplement.