Joshita Majumdar, freelance medical writer at Kolabtree05.29.20
The Poly Implant Prosthesis (PIP) scandal back in 2010 contributed to the European Commission reviewing its regulations to keep pace with innovation and ensure patient safety—passing the new Medical Device Regulation (MDR) in 2017. As notified bodies become more stringent during the approval process, manufacturers must consider how to meet new requirements without significantly delaying the journey to market. Considering verification and validation earlier in medical device development could be the key to faster and more efficient approval.
Before launching a product, medical device manufacturers must prove their device is safe and effective for its intended use. How they prove this depends on what type of approval they need — here we’ll look at US Food and Drug Administration (FDA) approval and European CE marking.
U.S. Approval
The FDA categorizes medical devices into three classes based on the level of control necessary to assure the safety of the device based on invasiveness and potential risk to the patient. The device’s class determines the type of the application required for FDA clearance.
Class I is a gentle device and may be exempt from premarket notification submissions, since it has the least associated risk to patients. Class II devices typically require a 510(k) premarket notification as the risks increase. Finally, Class III devices often require premarket approval before launch because they are the most invasive and therefore pose the highest risk to patients.
CE Marking
Manufacturers that want to launch a product in Europe must complete a clinical evaluation report (CER). The CER, which is part of the technical file, should provide information including product description, manufacturing information, risk management, design verification and validation and labelling information.
The introduction of the new European Medical Device Regulations in May 2021 (MDR) will impose stricter requirements for CERs. They will no longer be a static document; European bodies will require manufacturers to regularly update CERs using post-market surveillance (PMS) data to show that the product continues to meet the clinical standards defined in the original report across its entire lifespan.
Good clinical evaluation practice when applying for approval in any territory provides patients with safe products and helps manufacturers develop a repeatable and more efficient production process. Considering the factors of verification and validation earlier in the product’s lifecycle can also optimize approval. If manufacturers do not include these practices earlier on, they may discover an issue post launch that can put patients at risk and bring their reputation into question.
Verifying and Validating
For any application of device approval, medical manufacturers must prove that their product has been developed, manufactured and evaluated accurately. Medical manufacturers must document different types of accuracy, such as clinical, design, and process, with verification and validation processes.
Design validation proves to the clinical community that a product meets its intended uses and user needs. Process validation shows that the manufacturer and any third parties have used ISO 13485 compliant materials and manufacturing processes so that the product is fit for use.
Clinical evaluation requires both validation and verification. Clinical verification should be proven across the entire lifecycle of the product and provide evidence that each process has been completed so that the product meets specified requirements. Manufacturers should conduct end level user testing and ask a third party to test the product using a set of given instructions to validate that the product works.
Making Comparisons
When submitting a 510(k) for a Class I or II device, manufacturers prove that the device is as safe and effective as a predicate. Once the new MDR comes into force, manufacturers must also establish equivalence in a clinical evaluation report.
Selecting the correct predicate device is vital to proving substantial equivalence. The FDA recommends choosing a device that is most similar to the new device, technically, biologically and clinically. Choosing a predicate device with a similar design and specifications, similar materials and a similar clinical purpose can speed up the approval process, because companies have already tested the predicate and performed risk analysis for a similar intended use or application.
Choosing a device that is too dissimilar, especially in application, means that the manufacturer cannot prove efficacy. For example, comparing a new device that inspects an area of the body with an existing device that treats that same area will not prove substantial equivalence and the FDA will not approve the product.
Testing
Clinical evaluation also requires manufacturers to prove that the medical device is safe and effective for use with different types of performance testing. Bench testing should simulate how the product would work in a daily setting. For example, when developing a portable breast cancer screening device for patients to use at home, we simulated a test using a silicone breast with 3D printed tumors — the device finding the tumors validates that it works.
More invasive devices, for example class III devices for the FDA, require clinical trials to prove efficacy. Seeking support from healthcare professionals or hospitals can help manufacturers to design a trial that will be approved by an ethics committee.
Risk Management
Both FDA and CE approval requires medical device manufacturers to create a risk management report about the new device. This report calls out all the potential failures of the device and discusses how to mitigate these failures.
Failures can occur from factors such as bad design, misreading of labels, component faults or user mistakes. The manufacturer must identify all the possible errors that could occur and how to solve them, the possibility and frequency of recurrence and the possible harm to users caused by errors or failure. For example, if a valve in a ventilator breaks, can the health professional quickly fix the machine with a replacement or will the machine fail, leading to a potential loss of life for the patient?
Clear Instructions
The importance of clear labelling information for devices means that it is an area that authorities will frequently query during the application process. The intended use will influence how to label the device — for example, is it an over the counter item for patients, or will medical professionals use the product?
The intended user will influence how to label the device about factors such as safety, calibration and usage — a patient will need different instructions than a doctor. Clinical validation can also demonstrate that labels and instructions are clear and keep users safe.
Early Consideration
Medical device approval can be a lengthy process, as notified bodies will often query research, evidence and practices in the period between submission and approval. By thinking about clinical evaluation earlier in the product’s development, manufacturers can clearly validate and verify the product’s design, the processes used, and clinical purpose, to answer any queries the notified body might pose. Considering evaluation earlier on also allows manufacturers to make products more modular. This enhances their ability to test a product and validate each stage of development, instead of getting to launch and finding the product does not meet specifications, saving the company time and money.
Some businesses, particularly smaller businesses, might find that they do not have the skills or resources to evaluate new devices in-house at such an early stage of development. Smaller businesses also commonly outsource some work, for example they use contract manufacturers or third-party components to build devices, so cannot guarantee that everything is validated — a common issue.
Hiring a consultant can help smaller businesses better evaluate products and prioritize validation and verification earlier in the process. However, an external consultant from a notified body to help can be very expensive, so businesses are often reluctant to hire one until the business applies for approval. Companies in this position should consider how using a freelancer could help get products to market faster, safely and cost-efficiently.
A medical device consultant with previous experience in the industry can offer advice at every point of a product’s lifecycle, from conception to post-market evaluation, to help verify and validate each stage. Businesses can also consider how to work with a freelancer when planning testing, evaluation and approval. A freelance consultant with experience in product trials could help design batch testing or clinical trials and analyze and present data from the tests in a comprehensive way. A freelance clinical evaluation report writer can ensure businesses have all the documentation needed for applications by writing the entire report or carrying out gap analysis to find any areas that might have been missed.
As stricter approval processes come into effect, manufacturers should consider how planning clinical evaluation and verification earlier in the product development process, will ensure a much smoother ride.
Joshita Majumdar is a freelance medical writer at Kolabtree.
Before launching a product, medical device manufacturers must prove their device is safe and effective for its intended use. How they prove this depends on what type of approval they need — here we’ll look at US Food and Drug Administration (FDA) approval and European CE marking.
U.S. Approval
The FDA categorizes medical devices into three classes based on the level of control necessary to assure the safety of the device based on invasiveness and potential risk to the patient. The device’s class determines the type of the application required for FDA clearance.
Class I is a gentle device and may be exempt from premarket notification submissions, since it has the least associated risk to patients. Class II devices typically require a 510(k) premarket notification as the risks increase. Finally, Class III devices often require premarket approval before launch because they are the most invasive and therefore pose the highest risk to patients.
CE Marking
Manufacturers that want to launch a product in Europe must complete a clinical evaluation report (CER). The CER, which is part of the technical file, should provide information including product description, manufacturing information, risk management, design verification and validation and labelling information.
The introduction of the new European Medical Device Regulations in May 2021 (MDR) will impose stricter requirements for CERs. They will no longer be a static document; European bodies will require manufacturers to regularly update CERs using post-market surveillance (PMS) data to show that the product continues to meet the clinical standards defined in the original report across its entire lifespan.
Good clinical evaluation practice when applying for approval in any territory provides patients with safe products and helps manufacturers develop a repeatable and more efficient production process. Considering the factors of verification and validation earlier in the product’s lifecycle can also optimize approval. If manufacturers do not include these practices earlier on, they may discover an issue post launch that can put patients at risk and bring their reputation into question.
Verifying and Validating
For any application of device approval, medical manufacturers must prove that their product has been developed, manufactured and evaluated accurately. Medical manufacturers must document different types of accuracy, such as clinical, design, and process, with verification and validation processes.
Design validation proves to the clinical community that a product meets its intended uses and user needs. Process validation shows that the manufacturer and any third parties have used ISO 13485 compliant materials and manufacturing processes so that the product is fit for use.
Clinical evaluation requires both validation and verification. Clinical verification should be proven across the entire lifecycle of the product and provide evidence that each process has been completed so that the product meets specified requirements. Manufacturers should conduct end level user testing and ask a third party to test the product using a set of given instructions to validate that the product works.
Making Comparisons
When submitting a 510(k) for a Class I or II device, manufacturers prove that the device is as safe and effective as a predicate. Once the new MDR comes into force, manufacturers must also establish equivalence in a clinical evaluation report.
Selecting the correct predicate device is vital to proving substantial equivalence. The FDA recommends choosing a device that is most similar to the new device, technically, biologically and clinically. Choosing a predicate device with a similar design and specifications, similar materials and a similar clinical purpose can speed up the approval process, because companies have already tested the predicate and performed risk analysis for a similar intended use or application.
Choosing a device that is too dissimilar, especially in application, means that the manufacturer cannot prove efficacy. For example, comparing a new device that inspects an area of the body with an existing device that treats that same area will not prove substantial equivalence and the FDA will not approve the product.
Testing
Clinical evaluation also requires manufacturers to prove that the medical device is safe and effective for use with different types of performance testing. Bench testing should simulate how the product would work in a daily setting. For example, when developing a portable breast cancer screening device for patients to use at home, we simulated a test using a silicone breast with 3D printed tumors — the device finding the tumors validates that it works.
More invasive devices, for example class III devices for the FDA, require clinical trials to prove efficacy. Seeking support from healthcare professionals or hospitals can help manufacturers to design a trial that will be approved by an ethics committee.
Risk Management
Both FDA and CE approval requires medical device manufacturers to create a risk management report about the new device. This report calls out all the potential failures of the device and discusses how to mitigate these failures.
Failures can occur from factors such as bad design, misreading of labels, component faults or user mistakes. The manufacturer must identify all the possible errors that could occur and how to solve them, the possibility and frequency of recurrence and the possible harm to users caused by errors or failure. For example, if a valve in a ventilator breaks, can the health professional quickly fix the machine with a replacement or will the machine fail, leading to a potential loss of life for the patient?
Clear Instructions
The importance of clear labelling information for devices means that it is an area that authorities will frequently query during the application process. The intended use will influence how to label the device — for example, is it an over the counter item for patients, or will medical professionals use the product?
The intended user will influence how to label the device about factors such as safety, calibration and usage — a patient will need different instructions than a doctor. Clinical validation can also demonstrate that labels and instructions are clear and keep users safe.
Early Consideration
Medical device approval can be a lengthy process, as notified bodies will often query research, evidence and practices in the period between submission and approval. By thinking about clinical evaluation earlier in the product’s development, manufacturers can clearly validate and verify the product’s design, the processes used, and clinical purpose, to answer any queries the notified body might pose. Considering evaluation earlier on also allows manufacturers to make products more modular. This enhances their ability to test a product and validate each stage of development, instead of getting to launch and finding the product does not meet specifications, saving the company time and money.
Some businesses, particularly smaller businesses, might find that they do not have the skills or resources to evaluate new devices in-house at such an early stage of development. Smaller businesses also commonly outsource some work, for example they use contract manufacturers or third-party components to build devices, so cannot guarantee that everything is validated — a common issue.
Hiring a consultant can help smaller businesses better evaluate products and prioritize validation and verification earlier in the process. However, an external consultant from a notified body to help can be very expensive, so businesses are often reluctant to hire one until the business applies for approval. Companies in this position should consider how using a freelancer could help get products to market faster, safely and cost-efficiently.
A medical device consultant with previous experience in the industry can offer advice at every point of a product’s lifecycle, from conception to post-market evaluation, to help verify and validate each stage. Businesses can also consider how to work with a freelancer when planning testing, evaluation and approval. A freelance consultant with experience in product trials could help design batch testing or clinical trials and analyze and present data from the tests in a comprehensive way. A freelance clinical evaluation report writer can ensure businesses have all the documentation needed for applications by writing the entire report or carrying out gap analysis to find any areas that might have been missed.
As stricter approval processes come into effect, manufacturers should consider how planning clinical evaluation and verification earlier in the product development process, will ensure a much smoother ride.
Joshita Majumdar is a freelance medical writer at Kolabtree.
