Steps for Getting a Custom-made Medical Device (CMD) into the Market

# Introduction

Promoting personalized medical equipment presents a formidable task, entailing adherence to numerous regulatory requirements and stringent quality assurance standards. This blog will elaborate on the fundamental steps involved in launching a uniquely designed medical device, encompassing design and conception, rigorous testing and validation, regulatory adherence, and strategic marketing and distribution approaches. Acquiring an understanding of these procedures ensures that your tailor-made medical device meets all necessary benchmarks and reaches its intended audience securely and effectively.

# Definition

A Custom-made Medical Device pertains to a medical product meticulously crafted and manufactured for a singular patient. Examples encompass auricular splints, dentures, orthodontic tools, orthotics, and prosthetics. The intent behind a custom-made medical device is to cater to the distinctive medical requisites of an individual patient, which cannot be addressed adequately by standard off-the-shelf medical devices.

These specialized medical devices have the potential to augment a patient's mobility and functionality, aid in the treatment of medical conditions or injuries where other effective treatments might be lacking, and enhance the patient's overall quality of life by engineering and fabricating a device precisely tailored to their unique anatomical or physiological attributes. Customized medical devices can also be employed during surgical procedures or as a part of ongoing care to optimize patient outcomes.

A custom-made device differs from standard products in that it necessitates a prescription from a licensed professional. Understanding this crucial aspect is essential. It entails a thorough comprehension of the specific needs and prerequisites upon which the fabrication of the actual device will be based.

# Relation between production technology and classification

Mass-produced medical devices are manufactured in significant quantities and intended for use by a wide range of patients. They follow a standard specification and aren't personalized for individual patients, aiming to meet general medical needs.

If a piece of equipment is crafted through 3D printing to suit a specific patient's unique anatomical or physiological characteristics, then it qualifies as custom-made. Medical 3D printing involves creating tangible replicas of anatomical structures to directly or indirectly fashion medical equipment. Utilizing techniques like MRI, X-Ray CT, and other 3D imaging methods, digital models of structures are generated for 3D printing. This approach has gained significant traction in both clinical and research-oriented healthcare endeavors. Notably, 3D printing facilitates rapid and cost-effective production of small batch sizes, presenting a notable advantage.

In the coming years, it is predicted that with the diminishing costs and increased accessibility of the technology, its integration in medicine will expand. This anticipated trend is expected to drive higher adoption of 3D printing in clinical and educational settings, improved regulatory guidelines, and heightened competition among medical device manufacturers.

# Registration directions

There are two distinct categories of specialized equipment:

• General Custom-made Devices,

• Class III Implantable Custom-made Devices,

It's imperative to strictly comply with the standards outlined in Annex XIII for generic devices. As part of compliance and regulatory adherence, ensure the following:

• Issue a comprehensive statement validating the custom-made nature of the device.

• Safeguard all documentation demonstrating conformity in the Competent Authority Archive for 10 years, extending to 15 years for implanted devices.

• Implement Post-Market Clinical Follow-up (PMCF) processes to vigilantly monitor and assess the performance of the devices, ensuring they meet the required standards and pose no risks to patients.

# MDCG 2021-3

The MDCG group has released an instructive guide on custom-made devices, structured in a question-and-answer format. In this guide, the following types of devices are classified under the custom-made device definition:

• Mass-Produced Items Requiring Modification: These are products produced in large quantities that need adjustments to meet the unique requirements of a professional user. They are referred to as adaptable gadgets.

• Devices Manufactured Through Industrial Methods with Patient Customization: This includes products mass-produced using industrial manufacturing processes, potentially following a written prescription from a qualified individual. These are termed patient match devices.

It is crucial to ensure that your product doesn't fit into either of these categories, as it may then not be considered a custom-made item.

# General custom-made vs. class III implantable device

​Category	General Custom-Made Medical Devices	Class III Implantable Medical Devices
​Definition	​Devices designed and manufactured for a specific patient based on their unique anatomical or physiological characteristics, intended for exclusive use.	High-risk medical devices that are surgically implanted into the body and intended to stay there for an extended period of time.
Examples	​Prosthetics, orthotics, hearing aids, dental implants.	Heart valves, pacemakers, artificial joints, spinal cord stimulators.
​Regulatory Classification	Class I (low-risk) or Class II (moderate-risk) medical devices.	​Class III (high-risk) medical devices.
Regulatory Requirements	Must meet relevant regulatory requirements, including design control and quality system requirements.	​Must undergo rigorous premarket review, including clinical trials, to demonstrate safety and effectiveness.
​Manufacturing Standards	​Must adhere to relevant manufacturing standards, such as ISO 13485.	​Must adhere to relevant manufacturing standards, such as ISO 13485, and have a validated manufacturing process.
​Patient Impact	Improves patient quality of life, functionality, and addresses medical conditions or injuries that may not have other treatment options.	Can significantly improve patient outcomes and quality of life, but also have potential for serious adverse events or complications.

# Documentation

The essential document to be generated, known as the statement, holds significant importance for items produced on a made-to-order basis. While there is no specific standardized format, it must encompass the following critical details:

a. Manufacturer's Information:

- Name and address of the manufacturer,

- Locations of all manufacturing facilities,

b. Authorized Representative:

- Name and address, if applicable,

c. Device Identification:

- Information facilitating the unique identification of the device,

d. Intended User Declaration:

- A clear declaration that the device is intended for use by a specific patient or user, identified by name, abbreviation, or numerical code,

e. Prescribing Professional Details:

- Name of the prescribing individual, authorized by national law based on professional credentials,

- Name of the healthcare facility, if applicable,

f. Prescribed Attributes:

- Precise attributes of the product as specified by the prescription,

g. Compliance and Safety Declaration:

- A declaration confirming the device's compliance with the general safety and performance standards outlined in Annex I,

- If applicable, a list of requirements not fully met, accompanied by an explanatory rationale,

h. Medical Ingredient Statement:

- A statement indicating if the device contains or incorporates a medical ingredient, such as derivatives of human blood or plasma, human or animal tissues, or cells, as defined by Regulation (EU) No 722/2012, where appropriate.

# PRRC - Person Responsible for Regulatory Compliance

The Person Responsible for Regulatory Compliance (PRRC) holds the responsibility for ensuring adherence to regulatory requirements. As per the Medical Device Regulation (MDR), it is mandatory for your company to designate a PRRC, and in the case of selling customized products, this PRRC must be adequately informed about these specific goods. If needed, external consulting firms may be engaged; however, meeting several key prerequisites is essential.

# Documents archiving

If your products are implantable, it's imperative to maintain documentation for a minimum of 15 years, and at least 10 years for other medical devices. Effective archival is crucial. Additionally, you must be prepared to provide copies of promotional paperwork related to custom items to the appropriate authorities upon request.

Hence, establishing a comprehensive record retention policy is paramount. This policy should clearly outline the duration for which these documents should be retained, ensuring alignment with the stipulated retention requirements. Recognizing the importance of this aspect is vital. Accessibility to these records is equally crucial, especially when the competent authority may contact you a decade after product distribution.

# PMCF: Post-production Information

A manufacturer of specialized equipment should continue learning even after the post-production stage. As outlined in Annex XIV Part B, one effective approach for this ongoing learning is through Post-Market Clinical Follow-up (PMCF). Additionally, in line with Article 87(1) of the MDR 2017/745, the manufacturer remains obligated to inform the authorities about any challenges uncovered. Consequently, it is unwise to presume that a custom-made device automatically complies with the standards set for generic devices.

# QMS

If your focus is solely on custom-made devices, and they fall below the classification of class III implantables, there's no explicit mandate for a certified Quality Management System (QMS). However, for class III implantables, it's important to opt for a route where a certified QMS is a requirement. We strongly recommend choosing an alternative route for other devices as it can lead to more effective fulfillment of certain requirements.

For instance (though not an exhaustive list):

- Providing a suitable format for the assertion,

- Offering a how-to guide for form completion,

- Establishing guidelines for document archiving,

- Conducting a thorough review of custom devices as part of the post-marketing process,

In cases where your business is relatively small, one could argue that there might not be a significant number of individuals handling this. However, it's crucial to recognize that in the event of these employees leaving, a substantial amount of expertise could be lost. Therefore, it's advisable to incorporate this expertise into a documented procedure to ensure consistent adherence to regulations and uniformity in actions across the organization.

# Activities flow

To determine the process steps for developing a medical device, a systematic approach is vital:

1. Identify the Need: Recognize the necessity for the medical device, addressing a specific requirement or problem.

2. Assess Feasibility: Evaluate the practicality and viability of creating the device to meet the identified need.

3. Evaluate Risks: Conduct a thorough risk assessment to identify potential challenges and hazards associated with device development.

4. Evaluate Benefits: Assess the potential advantages and positive impacts the device could have on patients or the healthcare system.

5. Consider Regulatory Requirements: Take into account the applicable regulatory standards and requirements that the device must comply with.

6. Determine Design Specifications: Define precise design specifications based on the identified need and regulatory guidelines.

7. Develop and Test Prototype: Create a prototype of the device, allowing for testing and refinement to ensure it meets design specifications.

8. Manufacturing and Quality Control: Establish the manufacturing process and quality control measures to guarantee consistent and high-quality production.

9. Post-market Surveillance: Implement a system to monitor and collect data on device performance and user experiences after it enters the market.

10. Re-evaluate: Continuously assess and re-evaluate the device's performance, safety, and efficacy to make necessary improvements and updates.

# CE logo on a Custom-made device

Regarding the application of CE marking on a custom-made medical device, the concise answer is 'no'. Delving into the specifics, Article 20 of the Medical Device Regulation (MDR) 2017/745, titled 'CE marking of conformity,' provides comprehensive insights. According to this article, devices anticipated to meet the standards stipulated in the Regulation, with the exception of custom-made or experimental devices, are obligated to bear the CE mark of conformity as outlined in Annex V. Therefore, if your product falls under the category of a custom-made or experimental device, inclusion of the CE mark logo is not mandatory.

# Custom-made device for the UK (MHRA)

The definition of a custom-made medical device for the UK market is elucidated in the guidance provided by the UK Medicines and Healthcare products Regulatory Agency (MHRA) concerning the registration of medical devices in the UK. It's important to exercise caution and stay updated, considering that the UK MHRA is presently adhering to the Medical Device Directive (MDD) 93/42/EC for the UK Conformity Assessment (UKCA). However, given the ongoing efforts to establish new laws, the information presented in this advisory is subject to potential changes.

For those residing outside the UK and necessitating the registration of a custom device in the UK, seeking assistance from a UK Responsible Person (also recognized as an Authorised Representative in the EU) is advisable for managing the registration process on their behalf.

# Common examples of devices utilizing CMD regulations

Listed below are common examples of custom-made medical devices:

1. Prosthetic Limbs: Custom-made prosthetic limbs designed to match each patient's unique anatomy and functional requirements.

2. Dental Implants: Tailor-made dental implants crafted to perfectly fit a patient's mouth, optimizing both function and appearance.

3. Hearing Aids: Personalized hearing aids created to match an individual's specific hearing needs and preferences.

4. Orthotics for Patients with Neurological Conditions: Specially tailored orthotics providing support and improved movement for patients with conditions like cerebral palsy or multiple sclerosis.

5. Custom Surgical Equipment: Surgical equipment designed to simplify complex surgical procedures, enhancing patient outcomes through customization.

6. Assistive Technology Devices: Devices designed for assistive technology tailored to an individual's disability, aiding in daily tasks and improving quality of life.

7. Custom Implants: Implants custom-made to replace or repair damaged bone or tissue in the body, such as in cases of spinal cord injury or joint replacement.

8. Customized Diagnostic Instruments: Diagnostic instruments created to offer more precise and individualized assessments of a patient's medical status.

# Summary

Selecting the Custom-made Medical Device (CMD) classification for a medical device presents both promising opportunities and regulatory risks.

In terms of opportunities, CMD classification allows for the creation of tailor-made solutions that precisely meet the unique needs of individual patients. This can significantly enhance patient satisfaction and lead to improved outcomes in their medical treatment. Moreover, CMD classification fosters an environment of innovation and flexibility in device design and development. The freedom to innovate can potentially lead to groundbreaking advancements in patient-specific treatments, pushing the boundaries of medical technology.

Additionally, CMD classification can establish a specialized market niche for the device. This niche may have reduced competition and a more loyal customer base, providing a strategic advantage in the market.

However, along with these opportunities, certain regulatory risks are associated with CMD classification. One major risk revolves around ensuring compliance with the evolving and intricate regulatory requirements specific to CMDs. The unique nature of custom-made devices makes it challenging to comply with these requirements, and non-compliance can result in approval delays, penalties, or even the withdrawal of the product from the market.

Furthermore, accurate and comprehensive documentation and reporting become complex for CMDs due to their individualized nature. Incomplete or inaccurate documentation may pose significant regulatory hurdles and approval delays, underscoring the critical need for thorough and precise documentation.

Another risk pertains to standardization challenges. The unique characteristics of CMDs make standardization difficult, leading to potential inconsistencies in evaluations by regulatory bodies. Achieving a balance between customization and adhering to regulatory standards is crucial.

Lastly, ensuring the safety and efficacy of CMDs for diverse patient populations is a considerable risk. Any adverse events or a lack of expected efficacy could have severe consequences on patient health and regulatory trust.

Effectively navigating the CMD classification involves striking the right balance between leveraging the opportunities it offers and mitigating the associated regulatory risks. This requires a steadfast commitment to compliance, transparency, and implementing robust risk mitigation strategies throughout the development and approval processes.