Inspections, Compliance, Enforcement, and Criminal Investigations
Performing Subsystem Inspections
The Guide to Inspections of Quality Systems provides instructions for conducting medical device quality system/GMP inspections. It is to be used in conjunction with the compliance program entitled Inspections of Medical Device Manufacturers (7382.845). The guide was prepared by the Food and Drug Administration (FDA) Office of Regulatory Affairs (ORA), and the Center for Devices and Radiological Health (CDRH). It provides guidance for inspecting medical device manufacturers against the Quality System Regulation (21 CFR Part 820) and related regulations.
This process for performing subsystem inspections is based on a "top-down" approach to inspecting. The subsystem approach is designed to provide you with the key objectives that can help determine a firm's state of compliance. The process was designed to account for the time constraints placed on field investigators when performing device quality system inspections. If you can focus your effort on key elements of a firm's quality system, you can efficiently and effectively evaluate that quality system.
When you begin an inspection by looking at one or more instances of quality problems, such as nonconforming device reports, and work your way back through the firm's quality system, you are doing a "bottom-up" inspection. This method has been helpful in zeroing in on specific problems, and evaluating the firm's actions relating to those problems. However, with the "top-down" approach, we are looking at the firm's "systems" for addressing quality before we actually look at specific quality problems. In the "top-down" approach, we "touch bottom" in each of the subsystems by sampling records, rather than working our way from records review backwards towards procedures.
The "top-down" approach begins each subsystem review with an evaluation of whether the firm has addressed the basic requirements in that subsystem by defining and documenting appropriate procedures. This is followed by an analysis of whether the firm has implemented the requirements of that subsystem.
The illustration provided inside the front cover of this book shows the seven subsystems, along with related satellite programs. Based on discussions between the device industry and the agency, we have chosen four major subsystems that are the basic foundation of a firm's quality system. Those four major subsystems are Management Control; Corrective and Preventive Actions (CAPA) (with satellites Medical Device Reporting, Corrections and Removals, and Medical Device Tracking); Design Controls; and Production and Process Controls (P&PC) (with satellite Sterilization Process Controls). We have provided a suggested technique for inspecting each of these four subsystems. In addition, following the chapter of the related subsystem we have provided suggested techniques for inspecting the satellite programs.
The satellite programs were included in the QSIT Inspection due to their correlation in the inspection process with the related subsystem. For instance, the CAPA subsystem is the logical "jumping-off" point to begin inspecting for Medical Device Reporting, Corrections and Removals, and Medical Device Tracking programs which relate to a firm's postmarket activities. In the case of the CAPA subsystem, if you are covering the satellite programs in your inspection, approximately half a day should be added to your subsystem inspection timeframe.
Rather than check every aspect of the firm's quality system, the subsystem approach focuses you on those elements that are most important in meeting the requirements of the quality system regulation and which are key quality indicators. Between 6-15 inspectional objectives are provided for the review of each subsystem. The review includes both a (broad) review of whether the firm has procedures in place, and appears to meet the requirements, and a closer (detailed) review of some records to verify that the requirements have been implemented in actual production, design and daily quality assurance situations.
One similarity between "top-down" and "bottom-up" inspectional approaches is record review. Both approaches involve review of raw data, or individual records. In the "top-down" approach, however, we are asking you to use a sampling approach to the record review. With the "top-down" approach, you will sample records in many of the subsystems to verify whether or not the firm is in compliance. In other words, you are doing the raw data review as you did in the past, but in a more controlled manner. We have provided sampling tables to assist you in determining how many records you need to review, and what confidence you can have in the potential prevalence of the observed conditions.
One new feature in the "top-down" inspection technique is the use of <<u>em>inspectional objectives and flow diagrams to guide you during the inspection. We have provided inspectional objectives and flow diagrams that are useful in inspecting the four major subsystems. The flow diagrams provide a quick overview of how the inspection of each subsystem should occur.
In addition to the inspectional objectives and flow diagrams, we have provided a narrative description describing how to perform the inspection of each subsystem. The narrative description includes a discussion on how to achieve each inspectional objective and reflects the questions contained within the flow diagrams. You are not bound to follow each and every sentence in the narrative. Rather, you should inspect the subsystem with the narrative guidance in mind.
The Quality System Regulation (21 CFR 820.3(k)) defines "Establish" as "define, document (in writing or electronically), and implement". The Quality System Inspection Technique uses the "establish" approach in conducting the inspection. For each subsystem, you will first determine if the firm has defined and documented the requirements (CAPA, Design, etc.) by looking at procedures and policies, and then you will bore down into records, using the sampling tables, where appropriate, looking at raw data to determine if the firm is meeting their own procedures and policies, and if their program for executing the requirement is adequate.
The duration of inspection is related to the depth of the inspection. Keep in mind that the subsystem approach provides you with the key inspectional objectives that can help determine a firm's state of compliance. At the same time, the guidance was designed to accomplish a complete review of all four subsystems in approximately one week. While the length of your inspections will vary, using key inspectional objectives will help assure that you look at the most important elements of the firm's quality system during the inspection.
Most device firms are inspected more than once. By probing different subsystems, different devices or different processes each time, FDA will eventually have covered most of the firm's quality system. You are not expected to cover everything in the firm and in the narrative each time. You are expected to evaluate the firm's quality system, but also to do it in an efficient and focused manner. Thus, you should limit the depth of coverage when necessary to meet the time frame suggested. As a general rule of thumb, one day should be sufficient to cover each subsystem when using the "top-down" approach described within this document. In practice, you may find that the inspection of a certain subsystem may take half a day, while another may take one and a half days. This situation would still reflect an overall one day per subsystem time frame.
By directing your attention to the major areas in a firm's quality system, you should be better able to determine if the firm's quality system is in control. Using the subsystem approach, you may find less opportunity to cite minor deviations from the quality system regulation than in the past. However, you will be citing more serious (systemic) deviations from the regulation.