Quality System Information for Certain Premarket Application Reviews; Guidance for Industry and FDA Staff
This document supersedes the draft Guidance on Quality System
Regulation Information for Various PreMarket Submissions
released for comment on August 3, 1999
U.S. Department Of Health and Human Services
Comments and suggestions may be submitted at any time for Agency consideration to Dockets Management Branch, Division of Management Systems and Policy, Office of Human Resources and Management Services, Food and Drug Administration, 5630 Fishers Lane, Room 1061, (HFA-305), Rockville, MD, 20852.
When submitting comments, please refer to Docket No. 99D-2212. Comments may not be acted upon by the Agency until the document is next revised or updated.
For questions regarding the use or interpretation of this guidance contact Kimberly A. Trautman at 301-796-5515 or by email firstname.lastname@example.org.
Additional copies are available from the Internet. You may also send an e-mail request to email@example.com to receive an electronic copy of the guidance or send a fax request to 301-847-8149 to receive a hard copy. Please use the document number (1410) to identify the guidance you are requesting.
Quality System Information for Certain Premarket Application
Scope: Use this guidance for PMA; PMA Supplement;
PDP; HDE; and Modular Review Submissions.
|This document is intended to provide guidance. It represents the Agency’s current thinking on this topic. It does not create or confer any rights for or on any person and does not operate to bind the Food and Drug Administration (FDA) or the public. An alternative approach may be used if such approach satisfies the requirements of the applicable statute and regulations.|
Medical device premarket applications submitted under section 515(c)(1)(C) of the Federal Food, Drug, and Cosmetic Act (the Act) [21 U.S.C. 360(e)(c)(1)(C)], are required to include a number of information components, as set forth in 21 Code of Federal Regulations (CFR) Sec. 814.20. One component covers the current good manufacturing practice requirements included in the Quality System (QS) regulation. A Premarket Approval Application (PMA) is required to include a complete description of the methods, facilities, and controls, in sufficient detail so that FDA can make a knowledgeable assessment of the quality control used in producing the medical device (21 U.S.C. 515(c)(1)(C)).
This guidance has been prepared by the Center for Devices and Radiological Health (CDRH), in coordination with the Center for Biologics Evaluation and Research (CBER), to assist medical device manufacturers in preparing and maintaining the QS information required in premarket submissions.1
This guidance replaces "Guidance for Preparation of PMA Manufacturing Information," found in FDA 91-4245 and FDA 92-4165. This updated guidance includes information that is consistent with the QS regulation that became final on October 7, 1996. ("Medical Devices; Current Good Manufacturing Practice (CGMP) Final Rule; Quality System Regulation" (61 FR 52602--52662).2
CDRH's Office of Compliance (OC) will review the QS information submitted in your premarket submission at the same time the Office of Device Evaluation (ODE) reviews the other portions of your application. The appropriate Offices in CBER will review the QS information submitted in CBER regulated premarket submissions. This QS information guidance is meant to help applicants in providing the necessary information in a clear format for efficient review and timely decisions.
This guidance document requests that you provide copies of written procedures or lists of items related to the QS regulation. In most cases, these procedures or lists are explicitly required under provisions of the QS regulation. In the case where the information is not explicitly required under statute or regulation (e.g., production flow diagram, list of any standards used, process validation master plan), we believe the information is the type you are likely to create and maintain as part of your Quality System. Your submission of such information as part of the application process may reduce or eliminate the need for us to request additional information to determine your compliance with the QS regulation under 21 CFR 820. In addition, we believe your submission of this information can help us focus the preapproval inspection process and limit the amount of time our field staff will need to spend in your facility.
A manufacturer who chooses to meet application requirements for the QS information in an alternative way may wish to consult with the appropriate office within the Center prior to the submission. The FDA staff can help identify areas that might raise particular concerns for Center reviewers or investigators.
Note: During a pre-approval inspection, FDA may assess any of the requirements of the Quality System regulation, not just the ones referenced below. ______________
1 PMA amendments or supplements should include design and/or manufacturing information that differs from what has already been submitted in the original PMA or in a prior amendment or supplement for the device.
2 The Quality System regulation (Title 21 Code of Federal Regulations Part 820) text and preamble.
The Least Burdensome Approach
In developing the guidance, we carefully considered the relevant statutory criteria for Agency decision-making. We also considered the burden that may be incurred in your attempt to comply with the guidance and address the issues we have identified. We believe that we have considered the least burdensome approach to resolving the issues presented in the guidance document. If, however, you believe that there is a less burdensome way to address the issues, you should follow the procedures outlined in the "A Suggested Approach to Resolving Least Burdensome Issues" document.
A. General Information
If you are participating in a modular review, FDA suggests, for simplicity, that the design control information and manufacturing information be submitted in module(s) that are separate from other information. (This may be one or two modules). Any manufacturing process information needed by FDA for ODE’s safety and effectiveness review should be submitted in those modules to be reviewed by ODE.
Each copy of a premarket submission should include a separate volume or volumes that cover QS information. The volume(s) should have numbered pages, to facilitate our review and any discussions with you.
When multiple facilities are involved in the design, assembly, or processing of the device, you should submit applicable QS information for each facility in separate volumes that clearly identify the facility to which it applies.
2. Cover Letter
With each submission of QS information, you should include a cover letter that has the following information to help FDA manage your premarket application and related documents more efficiently:
3. What to Send
The initial volume for each facility should include the following information:
Note: If you are resubmitting information, you should verify that the information does not include any changes that would require a PMA amendment. (See 21 CFR §814.37.)
You can facilitate our review by formatting your submission in the order presented below. Provide the most up to date information as it applies to the device under review and to each facility identified in the application. Address all items for each original application. Address all pertinent items for each supplement.
I. Design Control Information____________________________
|Design Controls, General, 820.30(a) |
|1.||You should provide an explanation of where in your design and development process the device became subject to your design control program. |
|Design and Development Planning, 820.30(b) |
|2.||You should provide the design and development plan(s), or a summary of the plan(s), for the device under review. |
|Design Input, 820.30(c) |
|3.||You should provide a copy of the procedure(s) used for the identification and control of design input for the device under review. |
Examples of potentially relevant aspects for design input consideration:
Design Output, 820.30(d)
|4.||You should provide a copy of the procedure(s) used to define and document design output in terms that allow an adequate and measurable evaluation of conformance to design input requirements for the device under review. Provide a list of the design outputs you consider essential for the proper functioning of the device for the device under review. |
Your identification of essential design outputs will help us determine the adequacy of your design verification and design validation.
|Design Review, 820.30(e) |
|5.||You should provide a copy of the procedure(s) that define and control the design reviews for the device. |
|Design Verification, 820.30(f) |
|6.||You should provide a copy of the procedure(s) used to verify the device design for the device under review. |
|Design Validation, 820.30(g) |
|7.||You should provide a copy of the procedure(s) used to validate the device design for the device under review. |
|Design Transfer, 820.30(h) |
|8.||You should provide a copy of the procedure(s) used to transfer the design output to manufacturing for the device under review. |
|Design Changes, 820.30(i) |
|9.||You should provide a copy of the procedure(s) for controlling design change. |
|Design History File, 820.30(j) |
You should provide a copy of the procedure(s) for maintaining the contents of the Design History File (DHF) for the device under review.
If more than one device shares a common design history file, explain how you identify each device within the group having common design elements.
II. Manufacturing Information __________________________
Quality System Procedures, 820.20(e)
You should provide a copy of your basic quality system procedure(s).
|Production Flow |
|2.||You should provide a production flow diagram that identifies the steps involved in the manufacture of the device under review. This information helps to show the important aspects of your production process. |
|Use of Standards |
|3.||You should provide a list of any standard(s) used in the manufacturing process or for the device itself. |
|Purchasing Controls, 820.50 |
|4.||You should provide a copy of the procedure(s) for purchasing controls. This is especially important if you use a contract design service or contract manufacturer(s) for the device under review. The controls applicable to these suppliers should be specified. |
For additional guidance on the relationship between purchasing controls and receiving acceptance activities, see the QS regulation preamble comment #99. [61 FR 52624; see footnote 2.]
|Production and Process Controls, 820.70 |
|5.||You should provide a copy of the procedure(s) for environmental and contamination controls, if such conditions could adversely affect your device. (Note: if this involves a large number of procedures, a sample of the most relevant procedures would be sufficient.) |
|Inspection, Measuring, and Test Equipment, 820.72 |
|6.||You should provide a copy of the procedure(s) that explain how inspection, measuring, and test equipment is routinely calibrated, inspected, checked, and maintained. (Note: if this involves a large number of procedures, a sample of the most relevant procedures would be sufficient.) |
|Process Validation, 820.75 |
|7.||You should provide a copy of your process validation master plan, or a description of which manufacturing processes you will validate, for the device under review. Provide a list of processes for the device under review that you do not plan to validate but will verify by inspection and test. |
The QS regulation requires you to validate processes whenever the results of a process cannot be fully verified by subsequent inspection and test methods. If you choose to validate a process that can be fully verified by subsequent inspection and test, these processes are also subject to the validation requirements of 21 CFR § 820.75. For additional guidance, see the Global Harmonization Task Force's Process Validation Guidance http://www.ghtf.org/documents/sg3/sg3_fd_n99-10_edition2.pdf (Note the QS regulation does not permit option E in Figure 1 of the Global Harmonization Task Force's Process Validation Guidance.)
|Process Validation, 820.75(a) |
|8.||You should provide a copy of the validation procedure(s) or individual validation plan(s) for each process that will be validated for the device under review. When available, you should provide a copy of any completed validation reports. |
Your validation plan and procedures(s) should be in place at the time of submission of the manufacturing information. Process validations do not have to be completed at the time of submission. However, process validations must be completed prior to the preapproval inspection and prior to distribution of any finished devices. [820.75(a)].
|Receiving Acceptance Activities, 820.80(b) |
|9.||You should provide a copy of the procedure(s) for receiving or incoming acceptance activities. (Note: if this involves a large number of procedures, a sample of the most relevant procedures would be sufficient.) |
|Final Acceptance Activities, 820.80(d) |
|10.||You should provide a copy of the procedure(s) for final acceptance activities. (Note: if this involves a large number of procedures, a sample of the most relevant procedures would be sufficient.) |
|Nonconforming Products, 820.90 |
|11.||You should provide a copy of the procedure(s) for handling nonconforming product. If your Corrective and Preventive Action (CAPA) procedure(s) includes provisions for handling nonconforming product, then please specify where that information is located in your CAPA procedure(s). |
|Corrective and Preventive Action (CAPA), 820.100 |
|12.||You should provide a copy of the procedure(s) for your corrective and preventive action (CAPA) system. |
|Complaint Files, 820.198 |
|13.||You should provide a copy of the procedure(s) for handling complaints and Medical Device Reporting (MDR) (21 CFR § 803). If your CAPA procedure(s) includes provisions for handling complaints and MDRs, then please specify where that information is located in your CAPA procedure(s). |
For a general discussion on the intent of the complaint handling requirements, see the QS regulation preamble comment #190. [61 FR 52638-52639]
|Servicing, 820.200 |
|14.||You should provide a copy of the procedure(s) for servicing, if appropriate, for the device under review. |
For a discussion on servicing reports with respect to complaint handling and CAPA, see the QS regulation preamble comment #201. [61 FR 52640]