Leading Practices on Compliance Series: Design History File (DHF): Tips for Creating a Successful DHF Tuesday, November 27, :00 1:00 pm Eastern

Transcription

1 Leading Practices on Compliance Series: (DHF): Tips for Creating a Successful DHF Tuesday, November 27, :00 1:00 pm Eastern Jack Ward, Senior Director Myraqa, Inc.

2 Leading Practices on Compliance Series: Jack Ward Senior Director Myraqa, Inc. 11/27/ Association for the Advancement of Medical Instrumentation 1 FDA Requirements The (DHF) is a requirement of the FDA cgmp/quality System Regulation medical device regulations, 21 CFR Part 820. Definition of DHF from a compilation of records which describes the design history of a finished device. The Design Controls section (21 CFR Part ) of the Quality System Regulation includes specific DHF requirements. 11/27/ Association for the Advancement of Medical Instrumentation 2

3 FDA Requirements 21 CFR Part (j) Establish and maintain a DHF for each type of device The DHF shall contain or reference records necessary to demonstrate that the design was developed in accordance with: The approved design plan The requirements of this part (the regulation) 11/27/ Association for the Advancement of Medical Instrumentation 3 Background FDA comments on the importance of the DHF, excerpted from the cgmp/quality System Regulation preamble (comment 90): The DHF, in contrast (to the DMR), contains or references all the records necessary to establish compliance with the design plan and the regulation, including the design control procedures. The DHF illustrates the history of the design, and is necessary so that manufacturers can exercise control over and be accountable for the design process, thereby maximizing the probability that the finished design conforms to the design specifications. 11/27/ Association for the Advancement of Medical Instrumentation 4

4 Key Points 1. There are no specific requirements for the format or organization of the DHF. 2. It is important to remember that the DHF contents are quality records, and are therefore subject to the requirements for records as defined by 21 CFR : Maintained at the manufacturing establishment, or other location reasonably accessible Legible and stored to minimize deterioration and prevent loss 11/27/ Association for the Advancement of Medical Instrumentation 5 Key Points 2. DHF quality record requirements (continued): Backed up if stored electronically Retained for a period of time equivalent to the design and expected life of the device (in no case less than two years from the date of release for commercial distribution) 3. If your company uses a phased-based approach to design, it is important to ensure that the DHF is completed correctly during each phase, according to your DHF SOP. 11/27/ Association for the Advancement of Medical Instrumentation 6

5 Key Points 4. If your company uses outsourcing to contract all or part of the design process to partners or suppliers, remember that regulatory and compliance responsibilities remain with the manufacturer and cannot be delegated. 5. When the FDA inspects the design control subsystem, the DHF will be used as the basis for the inspection. All DHF records must therefore be available for the inspection, including records for design activities that have been outsourced. 11/27/ Association for the Advancement of Medical Instrumentation 7 Key Points 6. In addition to compliance, an accessible and wellorganized DHF can be an indispensable technical asset for other project teams, including teams at different company locations or those teams that might initiate a similar product design at a later date or with different project members. 11/27/ Association for the Advancement of Medical Instrumentation 8

6 Key Points 7. All revisions of design documents must be included in the DHF once design control is initiated for a project. This approach captures the history of the design. For example, the Device Master Record (DMR) is developed during the design and development process, and transferred to production as part of design transfer. The DHF should therefore contain preliminary revisions of the DMR to accurately reflect the history of the design. 11/27/ Association for the Advancement of Medical Instrumentation Design Control 483 Observations (g) Validation 154/527 = 28% (i) Changes 87/527 = 16% (a) General 59/527 = 13% (f) Verification 56/527 = 10% (j) DHF 31/527 = 8% (e) Review 31/527 = 7% (c) Inputs 18/527 = 6% (b) Planning 33/527 = 5% (h) Transfer 26/527 = 4% (d) Outputs 20/527 = 3% 11/27/ Association for the Advancement of Medical Instrumentation 10

7 2011 Design Control Warning Letter Cites CFR (g) 34 CFR (i) 27 CFR (a) 17 CFR (f) 13 CFR (c) 11 CFR (e) 11 CFR (j) 10 CFR (b) 6 CFR (h) 4 CFR CFR (a)(1) 2 CFR (d) 2 TOTAL /27/ Association for the Advancement of Medical Instrumentation 11 Example of Warning Letter Text for DHF Observation You have failed to establish and maintain a design history file (DHF) for each type of device you manufacturer that contains software. Specifically, the self-contained XXX models, the Classic YYY models, and the ZZZ models. The DHF shall contain or reference the records necessary to demonstrate that the design was developed in accordance with the approved design plan and the requirements of 21 CFR 820, (21 CFR (j)). Above example is from an April 20, 2011 Warning Letter, available for review at FDA.gov 11/27/ Association for the Advancement of Medical Instrumentation 12

8 Common Compliance Issues 1. Poor DHF organization An example of poor organization would be if all necessary documentation is included in the DHF, but cannot be readily found. A table of contents that supports quick and accurate access to DHF contents is recommended. 11/27/ Association for the Advancement of Medical Instrumentation 13 Common Compliance Issues 2. Use of non-fda terminology The DHF regulation is intended to document compliance with the Design Control regulation. Many compliance issues can be traced to a company s misunderstanding of specific Design Control terminology. For example, a company might use terms such as MRD or PRD to identify required DHF contents for Design Inputs (21 CFR Part (c) these company specific terms and documents may not meet regulatory requirements. 11/27/ Association for the Advancement of Medical Instrumentation 14

9 Common Compliance Issues 3. DHF records do not demonstrate compliance to the approved design plan This is a common compliance problem. The DHF must document that the design was conducted according to the approved design plan. For example, if the design plan requires three design reviews, the DHF must contain the appropriate records to document that the three reviews were conducted as planned. 11/27/ Association for the Advancement of Medical Instrumentation 15 Common Compliance Issues 4. DHF records do not demonstrate compliance with 21 CFR Part Design Controls require specific activities and deliverables, such as a design plan, design inputs, design outputs, reviews, transfer, changes, risk analysis, verification and validation. The DHF must document that the design was conducted according to these requirements of Design Controls. 11/27/ Association for the Advancement of Medical Instrumentation 16

10 Common Compliance Issues 5. The DHF contains extraneous and inappropriate documents This is another common compliance issue. For example, records such as s, status meeting minutes, financial analysis, and employee performance or training records are not required or expected design records, and should be excluded from the DHF. These types of documents can make it difficult to locate and maintain the actual required design records. 11/27/ Association for the Advancement of Medical Instrumentation 17 Common Compliance Issues 6. Uncontrolled access to the DHF Once the required design records have been entered into the DHF, there should be control of access to these records in order to prevent removal, loss, or alteration. The Design Control or DHF procedures should define the required level of access control and expectations for records management of DHF records. 11/27/ Association for the Advancement of Medical Instrumentation 18

11 Sample Phase Chart - 1 Phase 1 Concept Phase 2 Feasibility Phase 3 Development Phase 4 Verification and Validation Phase 5 Commercialization Program Management Research and Development 1. Marketing Analysis and Business Assessme nt 1. Product Performan ce Qualificati on Report 1. Design and Development Plan 2. Clinical Plan 3. Phase Exit Design Review 1. Design Requirements Documents 2. Software Requirements Document 3. Technical Development Plans 1. Initial Traceability Matrix 2. Phase Exit Design Review 1. Preliminary DMR 2. Software Design Document 3. Verification and Validation Plans 1. Clinical Report 1. Program Readiness Report 2. Updated Traceability Matrix 3. Phase Exit Design Review 1. Verification Test Report 1. Final DMR 2. Validation Test Report 2. Phase Exit Design Review 1. Design Changes Finalized DHF Audit DHF Audit DHF Audit DHF Audit Initiate Design Controls 11/27/ Association for the Advancement of Medical Instrumentation 19 Sample Phase Chart - 2 Phase 1 Concept Phase 2 Feasibility Phase 3 Development Phase 4 Verification and Validation Phase 5 Commercialization Manufacturing Quality and Regulatory 1. Initial Process and Resource Assessment 1. Preliminary Regulatory and Clinical Strategy 1. Manufacturing Plan 2. Design Transfer Plan 1. Quality Plan 2. Regulatory Plan 3. Risk Management Plan 4. Initial Risk Assessment 5. Initial DHF 1. Process Validation Plan 1. In Process DHF - updated with all required Phase 3 deliverables, as defined in DHF SOP. 1. Approved Supplier List 1. In Process DHF - updated with all required Phase 4 deliverables, as defined in DHF SOP. 1. Design Transfer Report 2. Service and Support Plan 3. Process Validation Report 1. Regulatory Clearances 2. Risk Management Reports 3. Final DHF 4. QA DHF Audit Report 5. Register and List with FDA DHF Audit DHF Audit DHF Audit DHF Audit Initiate Design Controls 11/27/ Association for the Advancement of Medical Instrumentation 20

12 Methods of DHF Structure DHF Chapter 1 DHF Chapter 2 Next DHF Chapters 3 thru 5? METHOD 1 ORGANIZE DHF CONTENTS BASED ON DEVELOPMENT PHASE DELIVERABLES Contains all required design records for initial phase of development Contains all required design records for next phase of development Establish as many DHF Chapters as required, one for each remaining phase of product development Typical Records: 1. Design Input Requirements 2. Design and Development Plan 3. Risk Management Plan 4. Other Records per DHF SOP Typical Records: 1. Updated Design Input Requirements 2. Updated Design and Development Plan 3. Updated Risk File 4. Other Design Records per DHF SOP Typical Records: 1. Updated Design Input Requirements 2. Updated Design and Development Plan 3. Updated Risk File 4. Initial and updated Design Outputs, Design Verifications and Validations, Design Transfer, Design Changes and Risk Management Files 5. Other Design Records for each phase as per DHF SOP DHF Chapter 1 DHF Chapter 2 Next DHF Chapters 3 thru 9? METHOD 2 ORGANIZE DHF CONTENTS BASED ON SIMILAR RECORD TYPES Contains all required design records of identified record type 1 Contains all required design records of identified record type 2 Establish as many DHF Chapters as required, one for each identified record type, as suggested at right Typical Records: 1. Initial Approved Design Input Requirements and all subsequent updated and approved revisions Typical Records: 2. Initial Approved Design and Development Plan and all subsequent updated and approved revisions Typical additional DHF Chapters: 3. Design Reviews 4. Design Outputs 5. Design Verification 6. Design Validation 7. Design Transfer 8. Design Changes 9. Risk Management File 11/27/ Association for the Advancement of Medical Instrumentation 21 Post Transfer DHF 11/27/ Association for the Advancement of Medical Instrumentation 22

13 Summary 1. The cgmp/quality System Regulation (21 CFR Part 820) defines the (DHF) as a compilation of records which describes the design history of a finished device. 2. The Design Controls section (21 CFR Part ) includes specific DHF requirements: a. Establish and maintain a DHF for each type of device b. The DHF shall contain or reference records necessary to demonstrate that the design was developed in accordance with the approved design plan and requirements of the regulation 11/27/ Association for the Advancement of Medical Instrumentation 23 Summary 3. There are no specific requirements for the format or organization of the DHF, but remember that the DHF contents are quality records and must meet the requirements of 21 CFR Part Outsourcing of all or part of design activities does not relieve the manufacturer of regulatory and compliance responsibilities related to the DHF. 11/27/ Association for the Advancement of Medical Instrumentation 24

14 Summary 5. When the FDA inspects the design control subsystem, the DHF will be used as the basis for the inspection. All DHF records, including records for design activities that have been outsourced, must be available for the inspection. 6. A well organized and accessible DHF can be a very useful technical asset for other project teams, including teams at different company locations or those teams that might initiate a similar product design at a later date or with different team members. 11/27/ Association for the Advancement of Medical Instrumentation 25 Summary 7. All revisions of design documents must be included in the DHF once design control is initiated for a project. Examples of revisions of design records that must be contained in the DHF include design plans, design inputs, design outputs/dmr, design reviews, design verification, design validation, risk management files and design changes. 11/27/ Association for the Advancement of Medical Instrumentation 26

15 Questions? Type your question in the Q&A box on the left side of your screen and press Enter Or press *1 on your telephone keypad 11/27/ Association for the Advancement of Medical Instrumentation 27 Closing Reminders Please be sure to fill out the evaluation form at: AAMI offers the following educational programs that may be of interest to you: November 29, 2012: Leading Practices on Compliance Series: Corrective and Preventive Action (CAPA) webinar December 3-5, 2012: Design Control Requirements and Industry Practice course Arlington, VA December 4, 2012: Leading Practices on Compliance Series: Controlling Nonconforming Products webinar December 6, 2012: Design of Experiments for Design Control webinar 11/27/ Association for the Advancement of Medical Instrumentation 28