Design Controls for the Medical Device Industry, Third Edition

Marie B. Teixeira

• Publisher: CRC Press
• Year: 2019
• Print ISBN: 9780815365525
• eBook ISBN: 9781351261463
• Topic: Medicine
• Subtopic: Biotechnology in Medicine

This third edition provides a substantial comprehensive review of the latest design control requirements, as well as proven tools and techniques to ensure a company's design control program evolves in accordance with current industry practice. It assists in the development of an effective design control program that not only satisfies the US FDA Quality Systems Regulation (QSR) and 13485:2016 standards, but also meets today's Notified Body Auditors' and FDA Investigators' expectations.

The book includes a review of the design control elements such as design planning, input, output, review, verification, validation, change, transfer, and history, as well as risk management inclusive of human factors and usability, biocompatibility, the FDA Quality System Inspection Technique (QSIT) for design controls, and medical device regulations and classes in the US, Canada, and Europe. Practical advice, methods and appendixes are provided to assist with implementation of a compliant design control program and extensive references are provided for further study.

This third edition:

1. Examines new coverage of ISO 13485-2016 design control requirements
2. Explores proven techniques and methods for compliance
3. Contributes fresh templates for practical implementation
4. Provides updated chapters with additional details for greater understanding and compliance
5. Offers an easy to understand breakdown of design control requirements
6. Reference to MDSAP design control requirements

Chapter one

Introduction

Quality system requirements apply to all organizations providing medical devices regardless of the type or size of the organization. Medical device manufacturers are required to establish and maintain quality systems to help ensure that their products consistently meet applicable requirements and specifications.

In the United States, the quality system requirements for FDA-regulated devices are codified under 21 CFR Part 820—Quality System Regulation (QSR). Likewise, ISO 13485 is an international quality management system standard applicable to medical devices. ISO 13485 is considered compatible with the QSR. The QSR and ISO 13485 Standard include the requirements related to the methods used in, and the facilities and controls used for, designing, manufacturing, packaging, labeling, storing, installing, and servicing finished medical devices. Manufacturers are expected to adopt current and effective methods and procedures to control the design and development of medical devices.

What is “design control”? Design control may be thought of as a system of checks and balances that ensure that the product being developed will meet the performance requirements for the product; the applicable statutory and regulatory requirements for marketing and distributing the product; the needs of the end user (i.e., customer); and is safe and effective for its intended use. Simply put, design controls are a documented method of ensuring that what you think you are developing is what you wanted to develop in the first place and that what finally comes off the production line is what the customer needs and wants and you can legally market and distribute.

Why design controls? The Safe Medical Devices Act of 1990 (the SMDA), enacted on November 28, 1990, amended Section 520(f) of the Food Drug and Cosmetic Act, providing the Food and Drug Administration (FDA) with the authority to add preproduction design controls to the current Good Manufacturing Practice (cGMP) regulation. This change in law was based on findings that a significant proportion (44%) of device recalls were attributed to faulty design of product believed to be due to an inadequate allocation of resources to product development.¹ FDA published the revised cGMP requirements in the final rule entitled “Quality System Regulation” in the Federal Register of October 7, 1996. This regulation became effective on June 1, 1997, and remains in effect today.

When the FDA first began inspecting medical device manufacturers for compliance with the design control requirements, they kept track of the areas where manufacturers were most deficient. The results of 157 inspections from June 1, 1998, through September 30, 1999, showed that inadequate design and development planning was the most significant problem area.² Now, almost 20 years later, compliance with design control requirements still remains a problem for medical device manufacturers with the majority of inspectional observations and warning letter citations under the design element having to do with design validation, the design change control process, and a lack of, or inadequate design control procedures.

From 2011 to 2016, the FDA issued 3,884 warning letters to medical device firms for quality system (QS)/GMP deficiencies. Of the warning letters issued, 647 (17%) included design control citations.³ If we look at the most recent available data from CY2016, warning letter citations for design controls continue to hold steady at 18%. The breakdown of the design control subsystem citations for CY2016 is shown in Table 1.1.⁴ Inspectional 483 observations from CY2016 are consistent with warning letter citation areas of noncompliance.

If during an FDA inspection of your facility any major deficiencies exist, the FDA will classify the Establishment Inspection Report (EIR) as Official Action Indicated (OAI) and, based on the significance (risk) of the device and the findings, will determine which administrative and/or regulatory action to initiate. Such actions include, but are not limited to, issuance of a Warning Letter, injunction, detention, seizure, civil penalty, and/or prosecution.

Table 1.1 Design control subsystem warning letter cites 2016

Total Citations = 37
21 CFR 820.30(g) = 9	21 CFR 820.30(e) = 2
21 CFR 820.30(i) = 8	21 CFR 820.30(h) = 2
21 CFR 820.30(f) = 4	21 CFR 820.30(a)(1) = 1
21 CFR 820.30 = 3	21 CFR 820.30(b) = 1
21 CFR 820.30(j) = 3	21 CFR 820.30(c) = 1
21 CFR 820.30(a) = 2	21 CFR 820.30(d) = 1

If any of these deficiencies exist for foreign manufacturers, based on the significance (risk) of the device and the findings, a Warning Letter and/or Warning Letter with Detention without Physical Examination will be considered by the Center for Devices and Radiological Health (CDRH)/Office of Compliance (OC).

¹  Preproduction design controls were added to the Safe Medical Devices Act in 1990. This Act provided FDA the authority to add preproduction design controls to the cGMP regulation. This was felt necessary due to findings that showed a significant proportion, 44%, of device recalls were attributed to faulty product design. The proportion was even greater for software-related recalls at 90%.

²  FDA QSIT Workshop, Orlando, FL, October 1999.

³  FDA—Medical Devices. WL Citations by QS Citations (CY2011–CY2016).

⁴  FDA—Medical Devices. CY2016 Design Control QS Subsystem WL Citations.

Chapter two

Device classification

Before we talk about who is required to comply with design control requirements and what those requirements are, let’s talk a little about medical device classification. Medical devices are typically assigned a device class. In the United States, medical devices fall into three device classes. In Europe, Canada, Australia, Brazil, and Japan there are currently four medical device classes. Additionally, the European and Australian classification system includes a Class I sterile and Class I measuring function category (See Table 2.1).

The amount of control needed for a medical device to ensure its safety and effectiveness is dependent upon its medical device class. A Class I device represents the lowest risk of harm to the user and requires the least amount of regulatory control, whereas a Class III or IV device represents the greatest amount of risk of harm to the user and requires the most regulatory control.

The class to which a medical device is assigned is based upon its safety and effectiveness or “risk.” In the United States, the FDA determines and assigns the device class by considering the following factors:

• Intended use—who is the device intended for?

• Indications for use—what are the conditions for use of the device including the conditions of use prescribed, recommended, or suggested in the labeling or advertising of the device, and other intended conditions of use?

• Safety/risk—what is the probable benefit to health from use of the device when weighed against any probable injury or illness from such use—risk/benefit?

• Effectiveness—what is the reliability of the device?

In Europe, Canada, Australia, and Brazil, medical devices are also classified using a risk-based classification scheme; however, it is the manufacturer’s responsibility to determine device class. In determining the device classification, manufacturers must consider the following:

• Device intended use—what part of the body is affected?

• Device duration of contact—how long the device is in continuous use?

• Device degree of invasiveness—the degree in which the device contacts the patient?

Table 2.1 Medical device classes

Country

Class

Class...

Table of contents

• Cover
• Half Title
• Title Page
• Copyright Page
• Table of Contents
• Preface
• Author
• Chapter 1 Introduction
• Chapter 2 Device classification
• Chapter 3 Overview of design controls
• Chapter 4 Design and development planning
• Chapter 5 Design inputs: Part I
• Chapter 6 Design inputs: Part II
• Chapter 7 Design outputs
• Chapter 8 Design review
• Chapter 9 Design verification
• Chapter 10 Risk management
• Chapter 11 Design validation
• Chapter 12 Biocompatibility
• Chapter 13 Design transfer
• Chapter 14 Design change
• Chapter 15 Design history file
• Chapter 16 The FDA inspection technique
• Appendix A: Design controls procedure
• Appendix B: Design input document
• Appendix C: Product claims sheet
• Appendix D: Input/Output design traceability matrix
• Appendix E: Project approval form
• Appendix F: Design phase review meeting record
• Appendix G: Risk analysis
• Appendix H: Clinical evaluation report
• Appendix I: Design transfer checklist
• Appendix J: Design change form
• Appendix K: Approval for sale form
• Appendix L: Engineering change order form
• References
• Index