Quality & Regulatory Environment in Medical Device Industry

I attended this ASQ presentation in Austin on Thursday, November 11th. I found the presentation very informative and quite illuminating. Some highlights are outlined in the next few bullets.

Description of Event:Speaker: Evangeline Loh, Ph.D., RAC (US, EU), Emergo Group

The medical device industry is estimated to be a $210 billon dollar industry, (1).  The definition of a medical device varies slightly around the world. The US is the largest market in both consumption and production (40% total market consumption). Japan is the next largest, and then Germany. This presentation will provide a brief overview of the global regulations for medical devices. In particular, the following countries/markets will be included: US, EU, Japan, Australia, China, and Canada. The quality system required for manufacturers will be discussed as well as medical device definitions and classifications. Harmonization has become a recent objective of the medical device industry and information on these endeavors will be provided.
(1) Acmite Market Intelligence, Study: World Medical Device Market

Key Takeaways:

Surprisingly, there is not a good, uniform definition of what exactly a medical device is. There is also an increasing overlap in technologies combining medical devices with biologics or drugs. Example: Stent coated with antibiotics. How the device is regulated depends upon the primary function of the product. In the example above, since the stent is performing the primary function of holding a blood vessel open, it is regulated in the US a a medical device. If the primary function was to deliver medication, it would be regulated as a drug. This is becoming an extremely complex area of regulation.

Worldwide, the two most commonly accepted medical device standards are ISO 13485 (EU) – Medical Devices, Quality Management Systems and FDA 21 CFR Part 820 (US) – Good Manufacturing Practices for Medical Devices. The ISO standard is the most widely accepted worldwide but is not currently recognized by the US. The two standards are ~ 95% equivalent.

There is a Global Harmonization Task Force (GHTF) currently issuing guidelines for a common worldwide structure for regulating medical devices.

Worldwide, there are two basic regulatory schemes for medical devices.

US Model:
Basic classes of devices identified
Specific letter codes to identify products very specifically
May hinder innovation since new/novel products require a longer process to have a letter code created for the device in addition to the other regulatory devices
Quality management system and registration required
Good Management Practices (GMR)
Ongoing compliance mandatory, FDA 21 CFR Part 820
Frequency of audits based on classification
CAPA feedback
Design controls

EU Model
CE marking is the ultimate goal
De facto expectation to annually certify to ISO 13845
Basic classes of devices identified
Broad letter codes that are more functional than specific in nature, generic rules not prescribed categories
Thought to allow more rapid approval of new/novel devices
Risk management required
Essential requirements identified
Labeling + Language requirements
Technical files
Design Controls
Clinical evaluation
Traditionally easier/faster to get certified in Europe than in the US

In the US, there are three broad classes of medical devices – Class I, Class II, and Class III. A class I device example is a toothbrush. Class II – stent, infusion pump. Class III – implantable heart pump

Compliance to the FDA standard is managed by:
Device submission material
FDA audits/inspections
Form 483 / warning letters
Adverse Event reporting system
Typical new approval process takes 1 year or more but is considered relatively efficient by worldwide standards.

Even the highest risk Class III device manufacturers only get audited by the FDA once every 2 years on average. The FDA can issue warning letters or non-compliance letters based on severity of issues found.

Device changes require FDA notification. There is an FDA flowchart detailing change requirements based on device type and significance of change made.
Reliability is never explicitly mentioned.

Design requirements are as follows:
Design Input, Design Output, Design review, Design verification, Design validation, design transfer, design changes, design history file. No specific testing recommendations or requirements are identified (types of tests, # of units tested, success rates, etc.).

Quality is handled via the Quality Management System requirements. Again. there are no hard and fast rules only general guidelines.

Statistics / sampling plans / CAPA feedback are required but no goals or requirements or set. The system seems to encourage setting a low bar on quality since the audits are keyed on attaining goals that were set.

Although there is some recognition of risk versus reward in the US, Europe gives greater consideration to this aspect. Example: All medical devices pose an inherent risk to the patient. Even relatively simple ones like catheters can cause death due to blood stream infection. For more complex cases like heart pumps, the device risk may be higher but the patient’s risk of non action is also higher. This is giver greater consideration in Europe than in the US.

Interestingly, ISO 13485 does not seem to require continuous improvement like ISO 9001. It does require implementation and maintenance of a quality management system.
The end result is a product CE marking followed by 4 digits with identify the notified body.

Classes I, II, and II with codes MDD (medical), VDD (in vitro), and AIMDD (active implantable, implantable)

EU makes a distinction between “cosmetic” and “medical” devices. Toothbrushes, wrinkle creams, etc are considered cosmetic and not regulated in the same manner.

ISO 13485 is specific to medical devices. It contains the elements of ISO 9001 plus:
Cleanliness requirements
Risk management
Post market surveillance requirements
Implantable requirements