Understanding CFDA Expectations Regarding Clinical Literature Evaluation for Medical Devices under Order 650: A Nerac Perspective

Transcription

1 Understanding CFDA Expectations Regarding Clinical Literature Evaluation for Medical Devices under Order 650: A Nerac Perspective Part I: The Predicate Device Problem By Richard Conforti, M.S., Nerac Analyst In 2014 the Chinese Food and Drug Administration, CFDA, updated their regulations on medical devices. These updates substantially changed the way in which a medical device company, particularly international companies not based or founded in China, registers their devices in China. The regulation updates ranged from minor changes, such as section titles and order, to major changes regarding which device(s) can be used to provide clinical evidence for proving safety and performance. According to the new regulations, when your device s registration expires, you are required to comply with the new regulations and register your device as though it is the first time you are filing for approval. These changes can seem daunting initially; however, after careful examination, the changes implemented by the CFDA can be addressed through the creation of a Clinical Evaluation Report, CER, which can be successfully written and submitted to the CFDA in compliance with CFDA Technical Guidance on Clinical Evaluation of Medical Devices. Class I medical devices are, the least demanding for CFDA approval as they present the lowest risk. Class I device approval essentially requires self certification and do not require a clinical evaluation or clinical trials. However, this is not the case for Class II or Class III medical devices. The CFDA does require clinical trials for all Class II and Class III devices. This creates quite a challenge because these clinical trials are required to be performed within China according to Order 650. The process of performing clinical trials is very cumbersome and expensive. However, the regulations provide an exception for performing clinical trials for Class II or III medical devices. According to Chapter 4, Clause 22 of Order 650: Clinical trials are not necessary in any of the following circumstances: (1) A predicate medical device with explicit operation mechanism, well established design, and mature production process has been marketed and used for years without any serious adverse event and without any change of typical intended use; (2) Safety and effectiveness of the device can be proven through non-clinical evaluation; (3) Safety and effectiveness of the device can be proven through analysis and assessment made with data from clinical trials or clinical use of predicate medical devices. The first exception refers to any devices on the CFDA s established list of medical devices exempted from clinical trials. This list is under constant adjustment and review. The second exception is extremely difficult when taken on its own as very few, if any, Class II or III devices could have safety and effectiveness proven non-clinically. The third and final exception is the focus of this article. The CFDA uses the term predicate device in Order 650. This is however, inaccurate, as by definition according to the US FDA a predicate device is one that is substantially equivalent to

2 for Medical Devices under Order 650: A Nerac Perspective 2 another device. The translation and definition the CFDA uses for predicate device in the regulations more accurately means same device. This is impossible to do, as even a minor update to your own device would change it and it is now no longer the same device. Fortunately, the CFDA recognizes this issue within the regulations and will in time update the regulations to more accurately reflect their view of a predicate device. In practice, the definition the CFDA uses in determining if a device can be a predicate device to your device is more in line with the US FDA s description of a predicate device. The US FDA requires a predicate device to be substantially equivalent to your device, which means that there can be differences between the two devices. Those differences however must not affect safety or effectiveness of your device. An important aspect of the Chinese regulation is that the differences between the predicate device and your device do not have to be supported in the clinical literature. Those differences do need to be supported; however the support and explanation for those differences can be shown using non-clinical means, such as bench testing, biocompatibility testing, etc. In order to establish that your device can be predicated upon another device already approved on the Chinese market, you must create a comparison table of your device and the predicate device. The CFDA places medical devices into one of two categories, passive or active medical devices. The table below defines passive vs. active medical devices: Table 1: Passive vs. Active Medical Device Predicate Comparison Specifics Device for transportation and storage of pharmaceutical liquid Device for alternation of blood and body fluid Device for medical dressing Surgical instrument (inserted) Passive Device Reusable surgical instrument Disposable aseptic surgical device Implantables Device for contraception and birth control Device for sterilization and cleaning Other contacting passive device Device for treatment through energy Device for diagnostic monitoring Active Device Device for body fluid transportation Device for ionized radiation Other general active device

3 for Medical Devices under Order 650: A Nerac Perspective 3 This table has 16 individual bullet points: 1. Basic Principles Working Principles Mechanism of Action 2. Structural Composition Product Composition Core Components 3. Manufacturing Process 4. Manufacturing materials in contact with human body 5. Performance Requirements Performance Parameters Function Parameters 6. Safety Evaluation (biocompatibility, biological safety, electrical safety, radiation safety, etc.) 7. Core Function 8. Conformed National/Industry Standards 9. Scope of Application Target Treatment Group Site of Application to/in the Body Methods Contacting with Human Body Indications Stage and Severity of Disease Operational Environment 10. Method of Application 11. Contraindications 12. Precautions and Warnings 13. Sterilization/Disinfection Methods 14. Packaging 15. Label 16. Product Specification. This list is for an active device. For a passive device the additional bullet points in numbers 1, 2, and 5 are not required. Each of the items in the list must be filled out for your device and any predicate device you are utilizing. Additionally, if there are differences between your device and the predicate device those differences must be called out in the table and data demonstrating that those differences listed do not affect safety and/or performance of the device must also be included. An important observation to note is when using a predicate device for your CFDA CER submission is that you limit the number of predicate devices you use to as few as possible. The best approach would be to use one predicate device (that has clinical data) to compare to your device and demonstrate that the differences between the predicate and your device are not clinically significant. This will lead to the strongest report you can provide to the CFDA in support of your device. In rare circumstances using more than one predicate device might be acceptable; this would have to be examined on a case by case basis. The CFDA s Order 650 is not meant to be intimidating. The order was created to align China s standards for medical devices with other regulatory agencies around the world. Attempting to undertake the task of developing a CER for the CFDA alone can be daunting, however,

4 for Medical Devices under Order 650: A Nerac Perspective 4 partnering with Nerac will help you navigate the process and successfully submit a CER to the CFDA. Call us at or click here to learn more! Look for Part II of this series, which will address creating a strong search strategy protocol and focusing on the best published clinical evidence to support your submission, to be published in an upcoming issue of the Nerac Strategist. About the Analyst Richard Conforti, M.S. Richard Conforti has been with Nerac for 2 years during which time he completed his Master s Degree in Neuroscience at the University of Hartford where he wrote a thesis entitled, Effect of the Ketogenic Diet on the Testosterone to Androstanediol Pathway in an Alzheimer Mouse Model. During this time, Richard has assisted medical device clients with meeting any of the following regulations: MEDDEV Rev. 3 Guideline on Medical Device Clinical Evaluation: A Guide for Manufacturers and Notified Bodies GHTF SG5-N2:2007 Clinical Evaluation Regulations on the Supervision and Management of the Medical Devices, issued by the State Counsel, effective as of June 1, 2014 (Order 650) The Medical Device Registration Rules (MDRR), issued by the China FDA, effective as of October 1, 2014 Richard has worked with a variety of medical devices such as cardiovascular, medical imaging, medical monitoring and sensors, orthopedics, neurological, gastrointestinal, spinal and others. Richard s primary area of expertise is neurological systems and diseases. He also has experience with human and animal biology and the pharmaceutical industry. Academic Credentials M.S. Neuroscience, University of Hartford B.S. Biology, Central Connecticut State University Professional Memberships Regulatory Affairs Professional Society (RAPS) Sigma Xi-The Scientific Research Society

5 for Medical Devices under Order 650: A Nerac Perspective 5 About Nerac is a global research and advisory firm for companies developing innovative products and technologies. Nerac provides expert insights that equip clients with the knowledge to develop or refine a technology, explore market growth opportunities, evaluate intellectual property strategies and respond to regulatory changes. Nerac serves approximately 20,000 users worldwide and delivers over 75,000 research projects and custom alerts each year. Nerac has a long, successful consulting history in a wide-range of industries with a strong focus in the areas of pharmaceutical, food and nutraceuticals, medical device, engineering, energy and advanced materials..