Let’s say you are going to have a procedure for a medical implant. Of course, you are thinking about one overarching question: Is it safe? Will it work with my body? This is where biocompatibility testing for medical devices is particularly important as a protective factor.
Biocompatibility is a term that implies medical devices will not elicit any potentially harmful reaction when they come into contact with your body. Biocompatibility is extremely important in the development of medical devices to ensure the health and safety of users.
In the medical device safety space, there are two main relevant standards: ISO 10993 biocompatibility and USP Class VI. Maybe you have seen those terms before, and you were unsure of what they mean or how they each differ. Let’s get into the world of iso biocompatibility 10993 and USP Class VI.
ISO 10993: A Global System for Biological Evaluation
First, let’s examine iso biocompatibility 10993. The full name is ISO 10993 – “Biological Evaluation of Medical Devices.” ISO 10993 is managed and published by the International Organization for Standardization (ISO). ISO is an independent, non-governmental organization that develops and publishes international standards.
The primary intent of ISO 10993 biocompatibility is to evaluate the potential interaction of medical devices with your body. Specific considerations include the type of contact the device will have with your tissues and fluids, as well as the duration of that contact. This is a totality of circumstances approach that encompasses many potential risk-relevant factors in biocompatibility testing for medical devices.
The good thing about ISO 10993 is that it is a universal platform for biocompatibility testing for medical devices.. It comes with designation as an accepted standard and is often required to enter any open regulatory markets around the world, including ruling bodies such as the FDA in the USA, the EU Medical Device Regulation (EU MDR), and many others. If a manufacturer provides an iso biocompatibility 10993 assessment, that can aid in demonstrating the device’s safety in so many jurisdictions.
Within ISO 10993 biocompatibility, an entire suite of key biocompatibility tests for medical devices is included. The tests can be measured individually to assess certain things related to biocompatibility, and they are:
Cytotoxicity: The basic test examines if the potential materials used in your device release toxic substances to your cells. This is typically the first sign of possible cellular harm at the contact site.
Sensitization: This assesses the risk of your device materials causing an allergic response. It is important to define those materials that can generate discussion concerning hypersensitivity issues in some individuals.
Irritation and Skin Sensitization: This is a branch of general sensitization and reviews the risk of localized irritation on contact with skin or mucous membranes.
Systemic Toxicity: These tests look at the overall impact of your device materials on your body when the exposure is over time. It considers the possibility of leachable materials adversely affecting organs or systems that are not directly involved at the exposure site.
Genotoxicity, Carcinogenicity, or Reproductive Toxicity: The critical genetic evaluations investigate the potential for your device materials to damage DNA, cause cancer, or negatively affect reproductive health. These are long-term safety considerations of paramount importance within iso biocompatibility 10993.
Implantation: For devices designed for implantation, these studies examine the long-term interaction between the device and the surrounding tissues. They assess tissue response, degradation of the material, and overall biocompatibility over extended periods.
USP Class VI: Focus on Plastics for the U.S. Market
Now, let’s focus on USP Class VI biocompatibility. The full name is United States Pharmacopeia (USP) Class VI Plastics Testing. It is an activity of the U.S. Pharmacopeial Convention, which is a scientific not-for-profit organization that publishes and establishes standards for medicine quality and other healthcare technologies.
The main focus of the USP Class VI biocompatibility standards is on the plastics that are used in medical devices and pharmaceutical packaging. It is specifically important to relate to materials that have short-term contact with your body. Think of components of a disposable syringe, or the plastic of a vial of medicine that you could inject, and these may be assessed under USP Class VI biocompatibility.
You’ll also note, USP Class VI biocompatibility is primarily focused on the U.S. market. So you are going to see it used with drug containers and medical devices that have limited or short-term contact with patients. Providing valuable insights, its scope is more focused when compared to the larger examination ISO 10993 biocompatibility provides. This is particularly relevant when considering FDA USP Class VI requirements.
When we examine the USP Class VI biocompatibility standards, they also contain a key assessment list of biocompatibility tests for medical devices, which are designed to measure the biocompatibility of those plastic materials. These include:
Systemic Injection Test: This assessment tests for the leachability of the plastic extract directly into animals (usually mice), which are observed over time for systemic toxicity. This would identify if a leachable from the plastic could cause an overall harmful reaction to the body.
Intracutaneous Test: In this test, extracts from the plastic material are injected intradermally in an animal (typically rabbits). The injection sites are observed for possible signs of local irritation, which may appear as redness, swelling, and inflammation. This testing represents the material’s potential to cause an unfavourable skin reaction upon contact, an important consideration under USP Class VI biocompatibility standards.
Implantation Test: In this test, polymer samples of the plastic material are implanted into the muscle of an animal (typically rabbits) for a specified duration (usually 72 hours and 7 days). The tissue surrounding the implant was examined further microscopically. This offers an evaluation of the short-term biocompatibility of the plastic material when in direct contact with animal tissue.
Unraveling the Key Distinctions: ISO 10993 Versus USP Class VI in Detail
Having examined each standard separately, we want to emphasize the important differences between ISO 10993 biocompatibility and USP Class VI biocompatibility:
Scope and Focus:
ISO 10993 is a global standard for many types of medical devices. It considers many materials outside of plastics and different contact types and durations, hence a more global biological evaluation approach. In contrast, USP Class VI biocompatibility standard is a US market standard that has a focus on plastic materials for medical devices and pharmaceutical packaging, typically only for those with very limited patient contact. USP Class VI has a more restricted scope around materials and applications.
Testing Methodology and Breadth:
ISO 10993 involves a comprehensive approach to biocompatibility with over 20 standards with defined testing to determine, including cytotoxicity, sensitization, systemic toxicity, genotoxicity, implantation, blood compatibility, and chemical characterization. This allows for a detailed and nuanced risk evaluation. In contrast, USP Class VI biocompatibility uses three main biological reactivity tests, including systemic injection, intracutaneous, and implantation. While valuable for assessing adverse reactions, its testing regime is less extensive than the broad scope of ISO 10993.
Regulatory Compliance and Market Recognition:
ISO 10993 is widely accepted internationally and is often a requirement to gain access to many of the world’s largest markets. Proof of compliance with the appropriate parts of iso biocompatibility 10993 is important for all regulatory submissions throughout the world. USP Class VI compliance is critical for regulatory approval in the United States since it is closely tied to fda USP Class VI requirements for all the materials used in medical device and pharmaceutical packaging in that market, including considerations for USP Class VI single use silicone and USP Class VI medical silicones.
Certification and Demonstration of Compliance:
Although there is no formal “certification” with ISO 10993 biocompatibility, manufacturers show compliance by completing the relevant testing described in the various parts and through supporting documentation of the test results. This documentation is the required documentation for regulatory submissions. On the other hand, USP Class VI biocompatibility has certification for plastic materials that pass the testing, which provides certification that they conform to those specific biocompatibility requirements.
To further differentiate between these two examples of requirements, below is a useful table:
| Aspect | ISO 10993 | USP Class VI |
| Scope of Application | Global, diverse medical devices and materials | U.S., primarily plastic materials for medical/pharma |
| Range of Materials Evaluated | Broad, includes various materials beyond plastics | Primarily focused on plastic materials |
| Consideration of Contact Type | Comprehensive, various contact types and durations | Often focused on short-term or limited contact |
| Number of Testing Standards | Over 20 individual parts/standards | Three main biological reactivity tests |
| Depth of Biological Evaluation | Extensive and nuanced across multiple endpoints | More focused on specific systemic and local reactions |
| International Recognition | Widely recognized and often mandatory globally | Primarily relevant for the U.S. market |
| Link to Regulatory Bodies | Key for FDA, EU MDR, and other global authorities | Closely tied to fda USP Class VI requirements |
| Formal Certification | No direct certification, demonstration of compliance | Certification available for compliant materials |
Navigating the Choice: Which Standard Should You Use?
So, which standard should you be paying attention to for your biocompatibility testing for medical devices? The answer often depends on the specific context of your medical device or pharmaceutical packaging.
For Medical Devices:
Depending on the application, in most circumstances, especially if you are seeking global market access (i,e, FDA and EU), ISO 10993 is generally required for comprehensive biocompatibility. It provides a comprehensive process for thoroughly evaluating the biocompatibility of your healthcare products through a variety of testing.
For Pharmaceutical Packaging:
If you are interested in applying for FDA submissions for pharmaceutical packaging only, then USP Class VI may be sufficient based on fda USP Class VI requirements. The regulatory bodies have increasingly begun to stipulate chemical characterization data. Such part of iso biocompatibility 10993 suite goes into the chemical nature of the materials and potential leachables, representing a more comprehensive analysis of the makeup of the materials. This is also relevant for ensuring the biocompatibility of materials like USP Class VI single use silicone.
Considering Combined Testing:
Some manufacturers test their products to both standards so that they can take advantage of a wider clearance. This is a reasonable approach, as it confirms that the devices were developed and manufactured to meet augmented requirements for both the international and U.S. markets. As long as they were following iso biocompatibility 10993 and USP Class VI biocompatibility standards as applicable, there is a good amount of access in different regions, as well as reasonable assurance that their medical device is safe and effective for patient use.
Concluding Remarks: Confirming Safety with Rigorous Testing, Using a Trusted Partner
In conclusion, biocompatibility testing is a fundamental means of validating safety for medical devices and pharmaceutical packaging. ISO 10993 and USP Class VI are both important facets, but differ in testing, scope, and geographical intent. The choice will be based on the type of medical device, intended market, and supporting regulations.
Given this important stature, it is crucial to work with a knowledgeable and trustworthy source for manufacturing your medical-grade components. Enter Fecision as a top-tier injection molding service specializing in the manufacture of medical components:
- State-of-the-art facilities with the strictest Quality Control processes to ensure product integrity and biocompatibility for your medical devices.
- A staff full of professional engineers and technicians who are consistently producing medical devices compliant with industry standards and regulatory requirements.
- A culture of safety, innovation, and customer service within the medical metrology industry.
When you choose Fecision, you have a partner that is dedicated to your medical device’s safety and efficacy, and will help you with the challenges of biocompatibility testing and ultimately make a product that can provide peace of mind.
