Identifying Hurdles to Gaining Medtech Market Approval

There is no single path to market approval success, so failure to launch is a very real risk—approximately three-quarters of medtech innovations fail to make it to market.¹ Developing a medical device and then getting it approved by regulators is a costly and complicated process that involves research and development, manufacturing, regulatory compliance, and, eventually, marketing. Even small delays can stall momentum and add delays of weeks or months to a product’s launch. Encountering too many unplanned challenges can not only stall a project but also do real harm to a medtech company’s bottom line.

While challenges are a natural part of any innovation process, anticipating and planning for them is essential. This can only be achieved with a sound knowledge of the obstacles to market approval—both well-known and less commonplace—that await the developers of medical devices throughout the innovation process.

Common Challenges in the Approval Process

Some challenges to medical device approval are more commonly encountered, usually governed by high-level standards such as the EU MDR, U.S. FDA, ISO, ASTM, and MEDDEV, as well as those for risk management and biocompatibility. They are generally anticipated early in development, and there are well-known and well-traveled paths to overcome them. 

Regulatory Compliance—Mandatory for market approval of any medical device, compliance with regulatory requirements such as FDA QMSR and ISO 13485 necessitates clear documentation, testing, and quality control measures to ensure devices meet all safety and efficacy standards. Medical device manufacturers should be aware of the need to adhere to these regulations, and it is best to address them from the outset.

User-Centered Design—Every device must account for its intended users, including healthcare professionals, patients, caregivers, or service technicians. This requires a thorough understanding of the device’s use journey and the integration of human factors engineering to ensure usability (ISO 62366), minimize user errors and decision points, and enhance patient and user safety.

Device Integration—When developing a medical device, it is important to consider integration with existing systems and devices in the environment where it will be used. For instance, does the device interfere with the intended operation of another device? The more complex the device, the more interactions and combinations that must be considered (e.g., electromagnetic, size/shape, sounds, visual information, etc.).

Materials, Biocompatibility, and Toxicology—Choosing the right material is of utmost importance. The material must be durable, safe, and biocompatible (ISO 10993). The material must also be able to withstand the necessary sterilization processes and not degrade over time. Careful consideration of material selection is obviously critical; a device utilizing well-known materials with relevant standards will be much easier to obtain approval for than a more exotic material.

Software and Cybersecurity—The use of connected devices is increasing rapidly, but it poses a potential threat to the safety of patient data and device functionality from cyber attacks. For Software as a Medical Device (SaMD), the IEC series of standards (81001, 82304, and 62304) are in place to address many of these concerns.

With the emergence of AI-powered medical devices, additional risks have arisen. To train an AI/ML model, it is crucial to have access to relevant clinical data. However, the demand for patient records data will lead to challenging discussions about the balance between patient confidentiality versus the value of creating better medical devices.

Verification and Validation—Extensive preclinical testing is always conducted to verify and validate the safety and effectiveness of a device, but designing studies that adequately demonstrate clinical efficacy while meeting regulatory requirements can be a complex and costly process.

Manufacturability—Achieving cost-effective, high-quality production while adhering to regulatory requirements can be a challenging task. However, with proper planning and expert engineering knowledge, it is possible to ensure the manufacturability of complex devices while maintaining their design integrity. If using contract manufacturing, try to engage a supplier that has already been certified to ISO 13485.

These issues represent some of the more obvious challenges to market approval. However, other potential problems can be encountered during the medical device innovation process, and they often go unrecognized until it is too late. Being mindful of these can help maximize the likelihood of successfully launching a product. 

The following outlines some of the “hidden” pitfalls that can force a potentially life-changing medical product to fail to make it through the approval process and suggests how they might be avoided.

Specification Complexity—Know Your Requirements

The design requirements or engineering specifications established in the early stages of creating a new product help guide design and development efforts. Engineering standards are a key input to the design requirements, and the number of standards that apply can vary depending on the complexity of the device.

For example, ISO 14630:2012 specifies the general requirements for non-active surgical implants, and it contains requirements such as intended performance, design attributes, materials, design evaluation, manufacture, sterilization, packaging, and information supplied by the manufacturer. This top-level standard can be broken down into 29 separate design requirements.

Similarly, ISO 16061:2021 specifies requirements for instruments used in conjunction with non-active surgical implants. Depending on the type of instrument, there may be up to 96 design requirements here. 

Below these top-level standards, each type of device has additional standards that specify even more design requirements. It is worth remembering that failure to comply with applicable standards may result in delays or rejection of the technical file during the notified body (NB) review process. So, it is essential to have a clear understanding of the standards that apply to the device being designed at the outset.

This complexity can be surmounted by creating a list of the standards and the design requirements to illuminate the initial constraints a device faces and enable solutions to be factored in throughout the innovation process. RegNav by Element is a valuable resource I have used to identify the relevant standards.

Risk Business

It is important to note design requirements and risks are closely related. Every feature and function of a medical device has an inherent risk of causing harm. Therefore, to create an effective top-level design risk assessment, each risk should be connected to its equivalent design requirement. This can be a “one to many” situation—one requirement to many risks.

For example, a basic design requirement from ISO 14630 states the shape and dimensions of a surgical implant should be equivalent to the reference implant to satisfy the design attributes of ISO 14630 (5.j). The connected risk to this design requirement may read as follows:

Hazard: “Implant shape and dimensions cause injury to the patient.” or “Implant shape and dimensions cause injury to the user.”
Hazardous situation: “Sharp edge unintentionally cuts patient’s soft tissue during insertion.”
Potential harm: “Damage to tissues and bodily fluids.” This would then have an associated potential severity.

This example is basic, but it provides a good idea of how to connect different hazardous situations and potential harms with design requirements. Approaching risk in this way helps to simplify the process and ensure the risks of the device are captured. 

Good design requirements equal good risk statements, so it also reduces the amount of effort required. However, do not be tempted to decompose the features and functions into too many detailed risks in the analysis. Remember, there are design, use, system, and clinical risks that can be dealt with separately in different FMEAs.

Unique Identifiers—Who Are You?

The Unique Device Identification (UDI) system assigns unique identifiers to medical devices. Its stated aim is to improve tracking, safety, and efficiency in recalls. It also facilitates identification, monitoring, and regulatory compliance. 

The UDI reference must be on the device labeling (e.g., label and IFU), so it is essential to do this as early as possible to avoid holding up the design and development file, tech file submission, or pre-production. 

The Global Medical Device Nomenclature (GMDN) is a standardized system for the UDI. The GMDN consists of generic descriptors grouped according to related technologies and intended uses. In the United States, the FDA has the Global Unique Device Identification Database (GUDID), while the EU has the European Database on Medical Devices (EUDAMED).

To register a new device, the FDA GUDID database contains a minimum of 24 required attributes, while EUDAMED has 59. Early identification and creation of these attributes are key.

Additionally, each country and jurisdiction has a separate database, so the UDI must be registered in each country where the device is to be marketed. Each database also has its own rules, requirements, and filing format, which should be understood to avoid rejection. There are experts who can assist with the UDI process.

The Nuances of Biocompatibility

While biocompatibility is a commonly understood challenge, there is a nuance of the standard that is not always recognized. The ISO 10993 series provides guidance and requirements for biological evaluation to assess how the materials used in medical devices interact with the human body. The standard focuses on three areas:

1. Toxicity: Ensuring the material used in the device does not release harmful substances that can be toxic to the body.
2. Immunological response: Minimizing any immune reaction, such as inflammation or allergic reactions.
3. Compatibility with blood: Ensuring the materials that come into contact with blood do not cause clotting or degrade in a way that could be harmful.

Part 1 of the standard is crucial as it provides a framework for assessing the potential risks associated with the device materials and determining the type and extent of testing.

It is important to note ISO 10993 does not mandate testing but requires a risk-based approach. If a device uses materials, processes, and processing materials that already have well-established biological safety, then a risk assessment may be adequate to meet the standard. With this route, a thorough risk assessment needs to be conducted and a “story” built to justify this risk-based outcome. However, each regulatory agency and notified body may have different interpretations of the standard and risk. Therefore, an analysis should be undertaken of the countries in which the device will be launched.

If testing is necessary, three considerations must be planned for:

• Testing samples are required to be produced at the same production facility as the production device (or equivalent with a justification). The quantity of samples should also be planned in the test protocol, as substantial time and setup costs could be necessary to produce them.
• The choice of biocompatibility test lab can cause issues. The lab’s capability for implant testing, such as chemical characterization and the level of sensitivity the lab can obtain, needs to be agreed upon in the protocol.
• The lab location should also be considered. If it is outside the country where the samples are made, customs and shipping can cause delays, which may lead to the lab’s testing window being missed.

Balancing the Benefits

Risk and the reduction of risk are crucial aspects of designing and developing medical devices. However, it should be acknowledged that it is impossible to eliminate all risks. Eliminating one risk may create new risks, resulting in an infinite timeline and cost loop, so the best approach is to try to eliminate certain risks and mitigate others to a level that is as low as reasonably possible.

This means medical devices will always contain a level of residual risk, which must be weighed against their clinical benefits. For example, a tongue depressor has low risk and relatively low benefit compared to a heart valve, which has high residual risk and even higher patient benefit. 

To complete this risk/benefit loop, a risk management report (RMR) should be prepared, which reports on the overall residual risk. The overall risk from the RMR is then compared to the clinical benefits and determines whether the benefits outweigh the risks (the Clinical Evaluation Report in EU Medical Devices Regulations). If the benefits do not outweigh the risks, the product will probably be rejected by the regulatory agency.

Therefore, this assessment should be conducted during the design inputs phase and rerun often throughout the development process—informally at first with the clinical director and innovation team, then more formally toward the end, as the detailed design and process development are established.

Test Your Risks

Preclinical testing (design verification and design validation) is a critical step in the development process to ensure product quality and reduce risk. However, testing can be time-consuming and expensive, so it should only be conducted when it is necessary to reduce risk.

Again, it is essential to start risk assessments early to determine what needs to be tested and how it should be tested. Also, note that, in some conditions, testing is mandated regardless of the level of risk; you must plan for these conditions.

Since testing samples need to be at the production level (or a justified equivalent), testing can be time-consuming and costly. If the testing needs to be repeated on future design iterations as the device design matures, the costs of remaking the samples can also add up quickly.

Understanding the level of risk, the necessity of testing, and the design’s maturity can significantly impact the length and costs of the innovation process. Allow the risk evaluation to guide testing.

Go Vegan

In the past few years, understanding the use of animal tissues and their derivatives (ISO 22442-1) in medical device design and production has become a requirement. Where possible, devices containing materials of animal origin (MOAO) should be replaced with other materials. This requirement also applies to any materials or process consumables used by the manufacturing facility.

As a result of the MDR requirement, the large medical device companies have been working with their manufacturers and suppliers to address most of the MOAO-related issues in the production process. This presents an opportunity for newer, smaller companies to leverage these efforts. This is another reason to partner with a contract manufacturer who is already certified to ISO 13485.

If MOAO must be used in the device’s design and production, it needs to be included in the risk management file and justified with a risk and benefit assessment. Nevertheless, their inclusion may still preclude the device’s approval in certain countries.

A Final Note

One final word on contract manufacturing: If you are planning to launch in the EU and certify the product to MDR (i.e., get a CE mark), the contract manufacturers you are using for any critical process need to be certified to ISO 13485. The kicker here is the certification needs to have been performed by the EU notified body; if not, the incoming inspection from that supplier is significant to reduce the risk.

Conclusion

Navigating the landscape of medical device approval necessitates an understanding of regulatory hurdles, design requirements, risks, and user needs. Hidden challenges like unforeseen design iterations or material biocompatibility concerns can derail projects if not considered proactively.

By addressing these critical aspects from the outset, innovators can streamline the approval process, reduce potential delays, and optimize the path to market approval. Establishing robust preclinical testing protocols and engaging in continuous risk evaluation throughout the development lifecycle are critical to mitigating these risks and guiding the testing program.

Ultimately, navigating the medical device approval process is complicated but entirely achievable using a strategic, informed approach that leverages both innovation theories and practices. Through close collaboration, careful planning, and adherence to regulatory standards, manufacturers can enhance the efficacy, safety, and marketability of their medical devices. The result: patients’ lives might be transformed and a significant contribution made to advancing state-of-the-art medtech solutions.

Reference

¹ tinyurl.com/mpo250351

Dr. Stuart Grant had a 25-year career with Johnson & Johnson MedTech and DePuy Synthes and is the named inventor on numerous patents for market-leading medical devices. He has extensive experience in the areas of customer needs and insights, front-end innovation, and product innovation management, including risk management (ISO 14971), design control, and technical file submission. Dr. Grant now works to guide innovators through every stage of the complex process of securing market approval for their medical innovations through his consultancy Archetype. He is also a lecturer in innovation at a number of UK universities.