Jul 13, 2022 | Medical Device, Regulatory
Planning a biological evaluation of your medical device? Then you need to be familiar with ISO 10993-1. This primer covers the fundamentals.
The International Organization for Standardization (ISO) develops and publishes a wide range of proprietary, industrial and commercial standards – including standards for the biological evaluation of medical devices. As a medical device manufacturer, you’re probably aware of ISO 10993 and its twenty-some parts. However, these parts are highly detailed and ever-changing – and up for regulatory interpretation.
What do you – the manufacturer – really need to know?
Let’s start at the beginning with ISO 10993-1: “Biological evaluation of medical devices – Part 1: Evaluation and testing within a risk management process.”
What is ISO 10993-1?
ISO 10993-1 is the first part of a series of standards to evaluate the biocompatibility of medical devices. Biocompatibility, as defined by the FDA, is the ability of a device material to perform with an appropriate host response in a specific situation. In other words, manufacturers need to ensure that the various materials and manufacturing processes used in a device or a device delivery system support safety or do not pose risks to patients or clinicians.
The overall purpose of ISO 10993-1 is to provide a framework in which to plan a biological evaluation – as a part of the overall evaluation and development of each medical device. It sets the stage to thoroughly identify potential risks resulting from the product’s materials as well as manufacturing processes. Generally, this starts with a complete chemical characterization.
Why is ISO 10993-1 Important?
While ISO 10993-1 sets the stage and the remaining parts of ISO 10993 dig into the details, Part 1 should by no means be overlooked. This is because the 2018 update of ISO 10993-1 indicated a significant shift in the approach to supporting preclinical medical device safety. Instead of a checklist-based approach, the standard moved towards a risk-based approach that starts with understanding the materials and the chemical constituents in those materials.
With increased emphasis on chemical characterization, biocompatibility testing alone cannot always be relied on to support medical device safety. A thorough understanding of the materials and manufacturing process (as mentioned, most often addressed with chemical characterization) should precede any biological testing. This will also help to refine the biological test plan.
How Do Regulatory Authorities Approach ISO 10993-1?
Every region has different interpretations and preferences for what they want to see in the application process. Not to mention, while the EU for the most part accepts ISO standards without exceptions, the U.S. FDA does not recognize all ISO 10993 standards. So, simply following ISO standards may not result in the acceptance of your biocompatibility evaluation.
The good news is that ISO 10993-1 is recognized by both the FDA and EU Medical Device Regulation (MDR). However, both regulatory bodies differ in their approach to assessing quality and overall risk profile, device classifications and clinical testing procedures.
In 2020, the FDA published their own guidance to provide further clarification regarding the use of ISO 10993-1. While the standard has not been harmonized across all EU countries, the MDR considers it “state of the art,” as it is the most recent published version of an accepted standard.
When Should Medical Device Manufacturers Consider ISO 10993-1?
ISO 10993-1 is applicable fairly early in the medical device testing and risk management process. This is because it actually helps medical device manufacturers understand their product testing requirements by classifying medical devices according to the nature and duration of contact with human tissues when in use.
So, once a manufacturer identifies this information, they can use it as a guide to identify the biological endpoints that need to be addressed to support safety for your device according to the standard. This will also help fill in some of the gaps with their timeline for regulatory submission.
ISO 10993-1 should also be considered when there is a change in the medical device’s manufacturing process, material or supplier. These changes can have unintended consequences for safety and may require testing to demonstrate equivalence to the initially approved or cleared product.
What Do Medical Device Manufacturers Need to Do to Comply?
There are generally three phases involved in evaluating biological risk as part of a biological evaluation under ISO 10993-1: complete chemical characterization, toxicological risk assessment, and biocompatibility testing, ideally in that order.
- Complete Chemical Characterization: Identifies the chemicals and the quantity of those chemicals per device. Additional data often needs to be generated through extractables/leachables (E/L) testing. E/L testing can provide sufficient data to support some biological endpoints, including genotoxicity and systemic toxicity, helping you avoid costly and time-consuming biological testing.
- Toxicological Risk Assessment: Considers each chemical and the quantity, and derives a margin of safety based on patient population and intended use.
- Biocompatibility Testing: Covers local effects (e.g., irritation) and any systemic effects specific to the device that could not be addressed in the toxicological risk assessment (e.g., pyrogenicity), or need to be conducted to mitigate potential concerns identified in the toxicological risk assessment (e.g., genotoxicity or subacute/subchronic toxicity).
Once all of the data have been gathered, ISO 10993-1 requires a qualified individual, usually a toxicologist, to review the data and develop a weight of evidence argument called a biological evaluation.
Historically, device manufacturers have been able to reach successful submission with biocompatibility testing alone. However, more often than not, this is no longer the case. Beginning with biocompatibility testing is no longer a best practice because complete chemical characterization followed by a favorable toxicological risk assessment can often address several biocompatibility endpoints.
Key Takeaways for Compliance
- Use a risk-based approach to support the safety of your product.
- Use chemistry data and risk assessment to develop a biocompatibility test plan. This can often save unnecessary use of animals in testing and costly test articles.
- Outsource testing to an experienced laboratory partner that offers a full range of preclinical device testing services. This can be instrumental in accelerating the process and getting your device to market before others.
- Work with qualified scientists, chemists and toxicologists. ISO 10993-1 also includes ensuring that qualified individuals carry out the biological evaluation, so it matters whom you choose to work with. Many regulators request credentials of the medical device evaluation staff to determine credibility and gauge the quality of resulting data.
Can Device Manufacturers Manage 10993-1 Testing In-House?
The above best practices for ISO 10993-1 compliance beg the question: Can medical device manufacturers actually conduct medical device testing themselves?
To answer this, you have to ask another question: Do you have the capability, qualifications and experience to conduct complete chemical characterization and the corresponding data analysis, toxicological risk assessments and GLP compliant in vitro and in vivo biocompatibility testing?
If the answer is no to any or all parts of that question, you may have to resort to piecemeal testing. This may result in a number of challenges, including:
- Longer timelines
- Higher costs
- Miscommunications between parties
- Loss of information altogether
- Insufficient information to support your submission (often by way of incomplete chemical characterization due to unidentified compounds)
While all of these problems are serious, the last one poses the most risk to your submission success. Reporting unknowns may cause regulators to reject your submission or issue requests for additional information (AIs). Unknowns are expensive. On average, repeat testing can cost more than $75,000 and 27 weeks of time.
So, what other options are available to a device manufacturer?
Working with a Medical Device Testing Partner
Reading through and understanding ISO 10993-1 is one thing. Following it according to regulatory guidance – including the necessary vertical guidances for specific product groupings – is another. This is true for a few reasons:
- Language used in regulatory standards can be vague and subject to interpretation
- A common practice in one region may not be recognized in another
- Interpretations evolve as regulators receive additional data when reviewing submissions
Because of these evolving interpretations, it’s critical to stay informed and current to ensure medical device submissions are aligned accordingly with guidance. This in and of itself is a challenging and time-consuming endeavor.
However, these challenges inherent to global submissions should not dissuade medical device manufacturers from the financial and healthcare opportunities available. Those who prioritize patient safety – in lockstep with the priorities of the regulatory landscape – and take special care when setting project expectations and timelines will better navigate global submissions. Especially if they don’t do it alone.
Manufactures that turn to experienced laboratory patterns to develop a regulatory submission strategy (and have the infrastructure and experience to support testing) will help achieve regional compliance and get their medical devices everywhere they need to be.
WuXi AppTec has a state-of-the-art analytical chemistry laboratory and experienced scientists, chemists and toxicologists – focused on ensuring the biological evaluation strategies and testing you require meet the latest regulatory standards. Our chemistry experts understand that unknowns are unacceptable™. We guide our clients’ test plans based on our industry knowledge, regulatory collaboration and the extensive number of products we have assisted through product clearance.
Our technical and regulatory experts serve as active participants and hold leadership positions with international regulatory standards committees. This allows us to track regulatory trends and even anticipate regulatory changes ahead of the published standards and guidances.
Talk to an expert about your upcoming project to see how we can help.
As a global company with operations across Asia, Europe, and North America, WuXi AppTec provides a broad portfolio of R&D and manufacturing services that enable global pharmaceutical and healthcare industry to advance discoveries and deliver groundbreaking treatments to patients. Through its unique business models, WuXi AppTec’s integrated, end-to-end services include chemistry drug CRDMO (Contract Research, Development and Manufacturing Organization), biology discovery, preclinical testing and clinical research services, cell and gene therapies CTDMO (Contract Testing, Development and Manufacturing Organization), helping customers improve the productivity of advancing healthcare products through cost-effective and efficient solutions. WuXi AppTec received AA ESG rating from MSCI in 2021 and its open-access platform is enabling more than 5,800 collaborators from over 30 countries to improve the health of those in need – and to realize the vision that “every drug can be made and every disease can be treated.”
Nov 13, 2021 | General, Medical Device, Medical Device Testing, Microbiology, Package Testing, Regulatory, Technical Expertise
Understanding Medical Device Verification and Validation
When it comes to ensuring the safety and efficacy of medical devices, rigorous processes are in place to verify and validate their performance. This blog will delve into the world of Class II medical devices, shedding light on the critical aspects of verification and validation.
Definition of Class II Medical Devices
Class II medical devices are a pivotal category in the world of healthcare products. They include a wide range of items, from infusion pumps to diagnostic equipment, and more. Because these devices pose a moderate to high-risk to patients and users, their verification and validation processes are vital to ensure their safety.
Verification vs. Validation
Before we dive into the specifics of Class II medical device verification and validation, it’s crucial to understand the difference between these two terms. The verification process confirms that the device has been created correctly according to predefined specifications and requirements. Validation, on the other hand, ensures that the device’s design meets user needs and intended uses as specified.
Steps to Class II Medical Device Verification
1. Establish Verification Objectives and Plan Verification Activities
The verification process begins with defining clear objectives. These objectives outline what you aim to achieve through verification, such as ensuring that the medical device meets specific performance and safety requirements. Once you’ve established the objectives, you’ll create a comprehensive plan that outlines how it will be conducted. This includes determining the scope of the verification, identifying resources required, and defining the verification strategy.
2. Create Test Protocols
Test protocols are detailed documents that specify how each verification test will be conducted. They include step-by-step instructions, acceptance criteria, and the equipment and resources needed for testing. Test protocols ensure that verification activities are standardized and repeatable.
3. Execute Verification Tests and Collect Data
With protocols in hand, you’ll proceed to execute the tests. This involves physically or digitally testing the device to verify its performance and safety. Different types of tests may include functional testing, durability testing, electrical testing, and more, depending on the device’s nature and intended use.
4. Data Analysis
After data collection, thorough analysis is conducted to determine whether the device passes or fails each verification test. The analysis compares the collected data to the acceptance criteria established in the test protocols.
5. Review and Approval
The verification results and the verification report are reviewed by a cross-functional team, which may include quality assurance, engineering, and regulatory experts. This team evaluates whether the device has successfully met the verification objectives and if it complies with the specifications and regulatory requirements.
6. Corrective Actions (if Necessary)
If any issues, discrepancies, or failures are identified during the review, corrective actions must be taken. This might include retesting, design modifications, or process improvements to ensure compliance and safety.
Steps to Class II Medical Device Validation
1. Define Validation Requirements and Create a Validation Plan
The first step in the process is to clearly define the scope and objectives of the validation process, including what needs to be validated and the acceptance rate. From there, you’ll develop a comprehensive validation plan that outlines the entire process, including roles and responsibilities, validation activities, and a timeline. The plan should act as a roadmap for the validation process, specifying what will be tested, how it will be tested, and what success criteria must be met.
2. Validation Testing
This step involves the execution of the tests and procedures outlined in the validation plan. It may include functional testing, performance testing, environmental testing, and more, depending on the device’s intended use and regulatory requirements.
3. Data Analysis
Once the validation tests are completed, the collected data will be thoroughly analyzed. This analysis involves comparing the test results to the predetermined acceptance criteria specified in the validation protocol.
4. Review and Approval
The validation results, along with the validation report, are reviewed by a cross-functional team that may include quality assurance, engineering, and regulatory experts. The team evaluates whether the device has successfully met the defined validation objectives and if it complies with regulatory requirements.
5. Corrective Actions (if Necessary)
If any issues, discrepancies, or deviations from the validation protocol are identified during the review, corrective actions are taken. This might involve retesting, design modifications, or process improvements to ensure compliance and safety.
6. Regulatory Submissions
For medical devices subject to regulatory approval, this step involves preparing and submitting the validation documentation, amongst other required documentation, to the relevant regulatory authorities. This documentation is essential for gaining approval or clearance to market the device.
Partner with WuXi AppTec for Your Class II Medical Device Needs
Have an idea for a Class II medical device? WuXi AppTec leads the way in the field of medical device manufacturing, providing an extensive array of services to bring your innovative concept to market. Whether you’re envisioning a groundbreaking device or require assistance navigating the manufacturing process, our dedicated team stands ready to offer our expertise.
While we don’t offer in-house design capabilities, we excel at connecting you with the ideal resources to kickstart your device project. When you reach the manufacturing stage, we can assume the responsibility, alleviating the burdens associated with production. Our commitment to adhering to stringent quality manufacturing practices is unwavering, and our impressive list of certifications attests to our dedication to maintaining the highest standards in Class II medical device manufacturing. Moreover, our facility in St. Paul, Minnesota proudly holds an ISO 13485 certification, complies with ISO 14644-1 class 7 cleanroom standards, and boasts an accreditation from the American Association of Tissue Banks. We’re also fully aligned with FDA regulatory requirements, ensuring we can take on almost any device manufacturing project.
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Want to learn more about how we can support you? Reach out to our team today.
Nov 13, 2021 | General, Medical Device, Medical Device Testing, Microbiology, Package Testing, Regulatory, Technical Expertise
Medical Device Industry Trends for 2024 and Beyond
The medical device industry is constantly evolving, driven by advancements in technology, changing healthcare needs, and a growing focus on patient-centric care. As we look ahead to 2024 and beyond, several key trends are poised to shape the future of the medical device industry. In this article, we’ll explore these trends and how they are set to revolutionize the healthcare landscape.
Minimally Invasive Devices
One of the most significant trends in the medical device industry is the continued development of minimally invasive devices. These innovations are designed to minimize the risk of infection, reduce large scars, and accelerate patient recovery rates. The key breakthrough here is the ability of new devices to enable surgeons to make smaller incisions, drastically changing how surgery is performed.
Minimally invasive procedures have become increasingly popular due to their many benefits. Patients experience less pain, shorter hospital stays, and quicker returns to their daily lives. Surgeons can perform complex procedures with great precision, all while minimizing trauma to the patient’s body. As technology continues to advance, we can expect further refinements in minimally invasive devices, expanding their application to a wider range of medical procedures.
Wearables
Wearable devices have been making waves in the consumer market for years, and their influence is extending into the medical sector. In 2018, the Apple Watch was classified as a Class II medical device, marking a significant milestone in the convergence of technology and healthcare. However, what’s truly exciting is the growing interest among medical device creators in incorporating technology into wearable medical devices.
These medical wearables go beyond counting steps or monitoring heart rate. They include advanced ECG monitors, bio patches that track vital signs, and more. Wearable medical devices offer continuous monitoring and real-time data collection, enabling healthcare professionals to gain deeper insights into patient health. As these devices become more sophisticated and accessible, they have the potential to revolutionize remote patient monitoring, chronic disease management, and early disease detection.
Have an Idea for a Class II Medical Device? Work with WuXi AppTec
As these exciting trends unfold in the medical device industry, it’s essential for innovators and healthcare professionals to stay informed and collaborate with leading companies in the field. WuXi AppTec is at the forefront of medical device manufacturing, offering a wide range of capabilities to bring your ideas to life. Whether you have a concept for a novel Class II medical device or need support in navigating the process, our team is here to assist you.
While we don’t have in-house design expertise, we can match you with the right resources to get your device off the ground. Then, when you’re ready for manufacturing, we’ll take the stress off your plate with our robust capabilities. We adhere to high-quality manufacturing practices and have a range of certifications to hold us to the highest standards in Class II medical device manufacturing. Additionally, our St. Paul, Minnesota facility is ISO 13485 certified, meets ISO 14644-1 class 7 cleanroom standards, and maintains accreditations with the American Association of Tissue Banks. We also maintain global regulatory compliance with the FDA and ISO governing bodies.
Let’s Get Started
Want to learn more about how we can help you? Reach out to our team today.
Oct 19, 2021 | General, Medical Device, Medical Device Testing, Microbiology, Package Testing, Regulatory, Technical Expertise
Quality Medical Devices Start with a Quality Manufacturer
Medical device component manufacturers are the backbone of your Class II medical device operation. Whether it’s a life-saving implant, a diagnostic instrument, or a sophisticated monitoring device, the quality of each component directly impacts patient outcomes. You already know that medical device component manufacturers must meet stringent standards in order to help your Class II medical device succeed. But, how do you know that they will meet your expectations?
When you’re interviewing potential medical device component manufacturers, there are a few questions you can ask to see if they’ll be the right fit for you. In this blog, we’ll go over what you should look for in a manufacturer to help you find the best partner for your operation.
Keep These Items in Mind When Looking for Medical Device Component Manufacturers
Experience
Your medical device needs to be of the highest quality to ensure patient safety. That means you must partner with an experienced medical device component manufacturer. Collaborating with an experienced manufacturer means tapping into their wealth of knowledge, allowing you to avoid potential problems and risks.
Regulatory Compliance and Certifications
The medical industry is heavily regulated by various authorities. Experienced manufacturers have a thorough understanding of these regulations and can effectively navigate the complex compliance landscape. They help ensure the components they produce meet the necessary regulatory requirements, streamlining the approval process for your medical device.
When interviewing potential partners, ask the following questions. Do they have the appropriate facilities and quality systems to produce the type of product you need? Do they have the appropriate certifications for the class product you’re manufacturing? Is their risk management process robust? Are they experienced in method transfer? You might also look for certain certifications, like ISO 13485 and ISO 14644-1 accreditations.
Quality Control and Assurance
Quality control and assurance processes are essential to ensure patient safety and regulatory compliance. Quality control processes will usually include risk assessments, pre-manufacturing inspections, in-process testing, and final product inspection.
Innovation and Technology
Your potential partner should invest in research and development, apply cutting-edge technologies, and adapt to industry trends and advancements. By pursuing these innovations, they can create better-quality devices at a much faster rate. They may even be able to lower your production costs.
Scalability and Production Capacity
When interviewing potential companies, ask about their capacity to meet volume requirements. They must be able to scale production up and down in order to match your needs. If not, you could fail to meet demand or end up with too much product.
Supply Chain Resilience and Risk Management
The COVID-19 pandemic demonstrated that supply chains can be disrupted at any moment. A potential partner should have supplier diversity and a sourcing strategy to help avoid disruptions. If disruptions do occur, they should have a contingency plan to combat them.
Cost Transparency
A great partner will always be up front about their pricing structure. This should include all factors that affect cost — including material, labor, and other considerations. Your partner should also avoid unnecessarily low-cost options to preserve the integrity of your product.
High-Quality Customer Service
The last thing you want is to partner with a company that’s unpleasant to work with. Your potential partner should make an effort to build a close working relationship and in-depth understanding of your medical device and your business. This will help them provide better support throughout the process.
Start Working with an Experienced Medical Device Component Manufacturer
When you’re ready to work with an experienced Class II medical device manufacturer, turn to WuXi AppTec. For over 20 years, we’ve partnered with small teams and large corporations to create medical devices that positively impact patients. We’re ready to do the same for you.
Our experts provide end-to-end, integrated services, enabling clients to transform ideas into life-changing healthcare solutions for patients and caregivers. We’ve supported numerous devices with the strategies and testing needed to gain market access, avoid costly delays, and support changing requirements throughout a product’s life cycle.
From materials characterization to custom studies, reprocessing validations to lot release, our team has you covered. We can create customized solutions for each customer and project. This includes advising you on ongoing regulatory changes, supporting interaction with regulatory bodies, leading scientific discovery, guiding study design, and applying our expertise across medical devices and combination devices.
Let’s Make Something Great Together
Ready to learn more about what we can do for you? Contact us for a no-strings-attached consultation.
Oct 19, 2021 | General, Medical Device, Medical Device Testing, Microbiology, Package Testing, Regulatory, Technical Expertise
Innovation plays a pivotal role in enhancing patient care, diagnostics, and treatment outcomes. One critical aspect of this innovation is the design and development of Class II medical devices. This process involves a variety of stages, ensuring the final product meets safety, efficacy, and regulatory standards. In this blog, we’re diving into the intricacies of the medical device design and development process, its key stages, and the challenges you might face along the way.
Key Stages of the Class II Medical Device Design and Development Process
Design
The design phase stands as the cornerstone of the medical device development process, setting the stage for all subsequent steps. At this stage, engineers, designers, and medical professionals collaborate to define the device’s purpose, functionality, and appearance.
This stage is all about creating a design that seamlessly integrates form and function. Materials will be chosen for their mechanical and biocompatibility properties. Moreover, the design will be created to make the device intuitive, which can reduce the learning curve for users.
Prototyping
Once the design is established, it’s time to put it to the test. Prototypes allow for testing and refinement of the design. This phase can help identify design flaws early on, reducing the risk of costly modifications later in the process.
The first step in the prototyping process is called conceptual prototyping. This allows stakeholders to visualize the device and offer feedback before investing significant resources. Then it will enter functional prototyping, where the device will aim to perform its intended tasks, giving insights into potential design flaws, technical challenges, and areas for improvement. Then, it will go into iterative refinement, where the device’s features, mechanics, and materials are fine-tuned.
Risk Management
Risk management is a paramount component of the medical device design and development process. It encompasses a systematic approach to identifying, assessing, mitigating, and monitoring potential risks associated with the device’s use, manufacturing, and overall life cycle. A proactive strategy ensures the final product meets safety and regulatory requirements while minimizing potential harm to patients and users.
This process will first start with risk identification. These risks can be anything from mechanical failures and design flaws to usability issues and non-regulatory compliance. Once these risks are identified, you’ll enter into the risk assessment phase. Here, the risks are assessed in terms of severity, likelihood, and potential impact. Then, your team will come up with strategies to mitigate, monitor, and document these risks.
Challenges to Consider in Medical Device Design and Development
Before beginning your medical device design journey, it’s important to know the challenges and risks you may face.
Stringent Regulatory Requirements
Medical devices are subject to rigorous regulations to ensure patient safety. It can be difficult and time-consuming to navigate through various regulatory frameworks. Complying with these requirements while innovating can pose significant challenges.
Balancing Innovation with Safety
It’s important to push the boundaries of innovation in order to come up with life-saving solutions for patients. However, striking the right balance between creating groundbreaking devices and ensuring their safety can be an ongoing challenge.
Managing Project Timelines and Budgets
It’s no secret that medical device design and development often require substantial time and financial investments. Delays and budget overruns can occur due to unforeseen challenges, potentially affecting the device’s time-to-market and profitability.
Intellectual Property Concerns
Protecting intellectual property is especially critical in the medical device industry. It takes robust strategies to safeguard innovative ideas and designs from unauthorized use.
Benefit from Partnering with an Experienced Medical Device Manufacturer
Overcoming the challenges posed by medical device design can be difficult. With an experienced manufacturer by your side, you bring another set of skills to the table. More skills can accelerate your project.. At WuXi AppTec, we have over 20 years of experience creating high-quality Class II medical devices. We’ve worked with small and large teams to help them navigate the confusing world of medical device manufacturing. While we don’t have in-house design capabilities, we can help you find reputable sources to complete this step. When you’re ready, we’ll be here to help you manufacture your product and quickly get it to market.
Why should you work with us? We maintain industry certifications that hold us to the highest standards in medical device manufacturing. Our manufacturing facility in St. Paul, Minnesota is ISO 13485 certified, meets ISO 14644-1 class 7 cleanroom standards, and maintains accreditation with the American Association of Tissue Banks (AATB). We also go above and beyond to be helpful, ensuring you can navigate the medical device manufacturing process with ease.
Let’s Get Started
Want to learn more about how we can help you? Reach out for a no-strings-attached consultation.
