Biocompatibility and Performance of Medical Devices

Jean-Pierre Boutrand

• Verlag: Woodhead Publishing
• Jahr: 2019
• ISBN:
  9780081026441
• Auflage: 2
• Thema: Technology & Engineering
• Thema: Materials Science

Biocompatibility and Performance of Medical Devices, Second Edition, provides an understanding of the biocompatibility and performance tests for ensuring that biomaterials and medical devices are safe and will perform as expected in the biological environment. Sections cover key concepts and challenges faced in relation to biocompatibility in medical devices, discuss the evaluation and characterization of biocompatibility in medical devices, describe preclinical performance studies for bone, dental and soft tissue implants, and provide information on the regulation of medical devices in the European Union, Japan and China. The book concludes with a review of histopathology principles for biocompatibility and performance studies.

• Presents diverse insights from experts in government, industry and academia
• Delivers a comprehensive overview of testing and interpreting medical device performance
• Expanded to include new information, including sections on managing extractables, accelerating and simplifying medical device development through screening and alternative biocompatibility methods, and quality strategies which fasten device access to market

Part One

Introduction to biocompatibility in medical devices

1

Strategies to accelerate medical market access and manage risks of biocompatibility

R. Eloy ^a ; S.J. Goldenberg ^{b a} NAMSA, Lyon, France
^b Veeva Systems, Pleasanton, CA, United States

Abstract

The extensive use of medical devices for the treatment and prevention of acquired, inherited, traumatic or degenerative lesions in the body generated a tremendous need for technologies and materials under the control of regulations, using standards as tools. However, there are significant challenges to execute all the biocompatibility testing needed, largely described in other chapters, while also taking into consideration the need to bring products to market in a time and cost-effective manner. It is important to understand the overall market access approach as well as common points of failures for medical devices when looking to decrease time and cost to market.

Keywords

Biocompatibility; Market access; Medical devices

1.1 Introduction

Medical devices (MDs) and biomaterials have been employed empirically for more than 2000 years but their use has dramatically increased during the last century, essentially over the last 40 years. In response to an ever-increasing demand for improved quality of life in a steadily aging population, improved technologies in metal, ceramic and polymer science have opened up new areas for MD applications in orthopedy, cardiovascular assistance/repair, general surgery, and wound healing. It has been acknowledged that in this rapidly evolving domain, the mean “industrial life” of a MD is about five years.

Therefore, it is crucial that all stakeholders in the MD development process think about how to bringing a product to market. Successful medical devices must speak to all involved stakeholders. This simple yet vital concept is critically important when considering medical device development and assessing the feasibility of device technology. Stakeholders in medical device innovation include the customer, marketing specialists, the engineering and manufacturing team, safety/regulatory bodies, the payer, and investors. Only through integrated development can truly safe and effective MD be brought to market in a time and cost effective manner.

These stakeholders whom are jointly developing new concepts and products and their challenge and that for the Regulatory Authorities is to ensure the safety and the appropriate performance of MDs. Despite considerable progress in the development of test standards for the evaluation of biological responses and notwithstanding a general consensus about the efficacy of existing procedures, the predictive value of these tests and their objectivity is still challenged. It is the aim of this chapter to report and discuss how to think across the MD development process and offer critical examples of the complex biocompatibility concepts.

1.2 Medical device development process and significance of material selection

Today, up to 88% of medical technology companies fail to deliver significant return to their investors (Ref). To improve upon this a Core Team must be an integrated, collaborative, flexible, cross-functional team that incorporates core strategic functions (Clinical, Regulatory, Legal, R&D, Reimbursement, Engineering, Sales and Marketing), but also has the ability to execute the tactical plans. Increasingly, as companies try to differentiate unique de novo materials or modifications/additives to common materials are used in the medical device development process. Biocompatibility of these novel materials is a crucial component in the development process for these products, but they can lead to challenges that can increase the time and cost to market. The integrated Core Team should be a part of all key decisions so the appropriate business and clinical decision can be made and not an engineering decision alone.

All MDs today are being looked at in context of their value to the healthcare eco-system. Companies that plan for the components of a value-oriented product from the very beginning of the product cycle can be rewarded with an offering that: (1) is attractive across multiple value-differentiated stakeholders, (2) has faster-to-market cycle times, (3) can deliver faster and more profitable growth, and (4) decrease costs to develop clinical data that go beyond regulatory claims.

The patient perspective, while seeming obviously important, as frequently not be included in the MD development process. Today, regulatory bodies and payors are looking more favorably upon companies that take the patient perspective into account. This perspective includes materials that are friendly to the patient and their experience during a procedure (hot cold sensitivity, pressure, irritation, etc.) and are a way to use materials to you a company's advantage in differentiation.

1.3 Accelerating time to market

Creative thinking about potential stakeholders and getting detailed stakeholder input at the beginning of the new product development process will help avoid the costly re-work of capturing missed data. A few expensive examples for a cardiac product could include:

• ● Tracking down patients after a pivotal clinical trial has completed its follow-up phase because several large payers for reimbursement approval require data on a particular patient subgroup in the clinical effectiveness model. The additional expense may double what was already invested because once a patient has left a study, they are often hard to track down. Given that the cost for clinical investigation trials for high-risk device approval is estimated at $40 million (USD),² this data requirement could quickly escalate costs. In addition to the financial cost, there is the cost of lost time to market as data would need to be captured through a survey or some other form of clinical data gathering, which may take several months to compile and analyze.
• ● Funding a costly postapproval time and motion study with several managing clinics because the use of the medical device frustrates established clinical protocols. Adoption and referrals for the product have slowed because clinicians believe it is a bottleneck to handling or expanding their patient load.

Thus, early planning can save time and money by adding a few secondary data endpoints to a clinical study rather than funding numerous post market studies. By anticipating the needs of a diverse potential stakeholder population for a given device, companies can avoid developing products with limited value (or “low-value” products) and may avoid costly downstream data collection activities.

Biocompatibility is a key part of that. Increasingly raw material suppliers are keeping their testing data on file with the FDA in a “Masterfile” that can include up to permanent implant testing. While these materials won't be differentiating the time and cost savings could be significant and reduce the need for biocompatibility testing from 6 mos to an 8 week chemical characterization and toxicology assessment.

1.4 Concept of biocompatibility and impact on market access

The concept of biocompatibility is analyzed and completed by examples of harmful effects related to medical devices that illustrate by contrast the concept of “bio-incompatibility”. It is also important to consider what materials you select carefully from the beginning as a simple material change could have significant negative impacts on time to market if bridging studies cannot be completed and a product needs to be completely retested for biocompatibility.

Recently, the FDA has undertaken new efforts on how to evaluate materials for potential safety issues (Ref). The FDA is taking a broad effort to engage the public and stakeholders to gather information to help inform their regulatory decisions. The FDA's focus in March 2019 was on several products that had produced problematic trends. Silicone breast implants were noted as having issues with implant rupture and implant-associated anaplastic large cell lymphoma. Metal in devices was also called out and is particularly interesting due the length of time metal has been used in permanent implant devices. A particular focus for metal devices was put on metal debris (from articulating metal-on-metal surfaces). Lastly, the FDA focused on animal derived materials and the need for continued work on infectious disease transmission through proper processing. The FDA stated their interest in improving the regulatory framework to support new data and research about these materials and all materials used in medical devices.

While the medical device industry is constantly making strides forward for both safety and efficacy, one can look at recent US recalls (Ref) to see instance of device failures that may have been detectible during biocompatibility studies. For example, the CyPass Micro-Stent was recalled in August 2018 due to a loss of corneal endothelial cells relative to c...

Inhaltsverzeichnis

• Cover image
• Title page
• Table of Contents
• Copyright
• Dedication
• Contributors
• Foreword
• Introduction
• Part One: Introduction to biocompatibility in medical devices
• Part Two: Evaluation and characterization of biocompatibility in medical devices
• Part Three: Testing and interpreting the performance of medical devices
• Part Four: International regulation of medical devices
• Part Five: Histopathology principles for biocompatibility and performance studies
• Index