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Regulation impact statement: Proposed regulatory scheme for personalised medical devices, including 3D-printed devices

Version 1.0, December 2019 - OBPR reference: 24680

21 February 2020

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Technology changes have the potential to deliver significant benefits and opportunities to Australians. Recent advances are both disrupting and changing the health sector, where there is rapid change in the availability and type of medical devices intended to be personalised for individuals.

Sometimes, the treatment requirements of a particular patient cannot be met with commercially available mass-produced medical devices. In these cases, healthcare providers make, or provide specifications to a manufacturer to make, personalised devices to meet the patients' needs.

However, medical devices are not without risk, and there is increasing recognition globally of the patient safety issues that can arise with medical devices. Recent high-profile cases have brought into question the effectiveness of the existing medical device regulatory frameworks; as a consequence, regulators around the world are increasing their scrutiny of the manufacture of medical devices.

In Australia, there has recently been a review of the medicines and medical device regulation,[1] as well as a number of Senate inquiries on medical device regulation in recent years. In order to continue to provide a high level of stringent oversight, the regulation of personalised medical devices is one such area that requires increased focus.

This Regulatory Impact Statement is intended to support the decision on whether or not to introduce regulatory reforms for medical devices that are manufactured for particular patients (personalised medical devices). These are devices that are captured in the current regulatory framework under:

  • the custom-made medical device definition, and its corresponding exemption (explained in more detail below);
  • medical devices that are referred to in the definition of manufacturer under Section 41BG of the Therapeutic Goods Act 1989 (the Act) as devices already supplied but intended to be assembled or adapted to suit an individual; and
  • medical devices incorporating human-origin materials that are currently regulated as biologicals under the Act.

Current regulation of custom-made medical devices

The Therapeutic Goods (Medical Devices) Regulations 2002 (MD Regulation) define a custom-made medical device as:

  • made specifically in accordance with a request by a health professional specifying the design characteristics or construction of the medical device; and
  • intended to be used only in relation to a particular individual, or to be used by the health professional to meet special needs arising in the course of his or her practice.

To import, export or supply a medical device in Australia, it must be included on the Australian Register of Therapeutic Goods (ARTG), unless an exemption applies. This is the approval required to market medical devices in Australia.

The safety, quality and performance of medical devices is established through conformity assessment. Conformity assessment is the systematic and ongoing examination by the manufacturer of evidence and procedures to determine that the safety of a medical device is acceptable and that the device performs as intended and, therefore, conforms to the essential principles (which set out the fundamental design and performance requirements for medical devices[2]).

An applicant must be able to demonstrate that the appropriate conformity assessment procedure has been applied to their device in order to apply for inclusion of the medical device in the ARTG. This is generally demonstrated by providing certification or documentation issued to the manufacturer by an appropriate assessment body (e.g., the TGA or a comparable overseas regulator). This follows third-party (independent) assessment of the manufacturer's facilities and processes and, for higher-classed medical devices, an additional in-depth design examination (evaluation) of the medial device.

There are four significant differences in the way custom-made medical devices are regulated in comparison to other medical devices: the conformity assessment procedure for custom-made medical devices, compliance with the essential principles, exemption from inclusion in the ARTG, and record keeping and reporting.

Conformity assessment procedure

In Australia, medical devices are stratified in a regulatory classification ruleset from Class I at the low end of the spectrum, to Class III at the highest. Regulatory oversight is commensurate with this classification. Manufacturers of medical devices higher than Class I, that have a measuring function, or that are supplied sterile, must be certified by the regulator (or a specified third-party representing the regulator) to ensure the manufacturer's systems provide sufficient assurance of the devices' safety and performance prior to their supply on the Australian market.

For custom-made medical devices, third-party assessment is not required. Manufacturers of custom-made medical devices may instead make use of an exemption pathway, which largely only requires the manufacturer to:

  • advise the TGA that they are supplying particular kinds of custom-made medical device[3]; and
  • keep written records for each custom-made device supplied and notify the TGA of any adverse events or recalls related to the custom-made medical device (retained for at least 5 years)[4]

There is little or no monitoring of compliance with these requirements. At the time the regulations came into place in 2002, custom-made medical devices were generally bespoke devices or devices modified for a specific patient. Typical examples were dentures and dental crowns, or prescription spectacles. At that time, it was considered that as custom-made devices were generally quite low risk products produced as 'one-off' items, third-party review of the manufacturer's facilities and processes, and in-depth examination of the devices design, for each custom–made device supplied would have been too onerous and would have affected supply of custom made devices given that most were low risk products.

Essential principles

The essential principles set out the fundamental safety and performance principles for medical devices. There are six general essential principles that apply to all devices (relating to health and safety, including long-term safety, with benefits outweighing the risks), a principle that covers information that must be provided with a medical device, another principle that covers clinical evidence requirements, and a further seven essential principles about design and construction that apply to devices on a case-by-case basis. This principles-based regulatory framework caters for technological advances and changes in the development of new medical devices, and provides flexibility for manufacturers. It does not mandate the means by which a manufacturer must prove that they have met the essential principles.

Custom-made medical devices, unlike other medical devices, are not required to fully comply with all of the essential principles. The written records required for custom-made medical devices must include a statement that the device complies with the applicable provisions of the essential principles or, if the device does not comply with all applicable provisions of the essential principles, an explanation of which essential principles the device does not comply with and the reasons for the non-compliance.

This relates to the 'one-off' nature of custom-made medical devices. For example, requirements for information supplied with a non-custom-made device are quite extensive, but this may be less extensive for a one-off' custom-made medical device.[5] Normal requirements for clinical evidence can also be impossible to meet for 'one-off' custom-made medical devices, as approaches such as clinical trials and tracking of devices in use are not always possible with one-off custom-made medical devices.[6]

Exemption from inclusion

Custom-made medical devices are exempt from the requirement for medical devices to be included on the ARTG and, as a result, are also not subject to third-party assessment and approval of the medical device prior to supply.

Inclusion on the ARTG brings with it a range of obligations and responsibilities, which do not apply for custom-made medical devices. For example, manufacturers of implantable medical devices are required to report to the TGA annually for the first three years they are included on the ARTG, and this does not apply for custom-made implantable medical devices.

There is also a range of enforcement mechanisms and sanctions linked to ARTG inclusion that cannot be applied to custom-made medical devices. For example, suspension or cancellation of an ARTG entry, such as where there are safety or compliance concerns, effectively removes a kind of medical device from the Australian market; this does not apply to custom-made medical devices not included on the ARTG. Further, most criminal and civil sanctions available under the Act relate to inclusion in the ARTG or other approvals by TGA, and thus cannot be applied to custom-made medical devices or their manufacturers or suppliers.

Record keeping and reporting

As noted above, the manufacturer of a custom-made medical device is required to advise the TGA that they are supplying a kind of custom-made medical device, and keep written records for each custom-made device supplied (to be retained for at least 5 years).

Record-keeping and reporting requirements applying to devices other than custom-made medical devices are considerably more extensive. These requirements are conditions on the inclusion of a medical device on the ARTG, and non-compliance can result in the loss of marketing approval for the device (which is not applicable for custom-made medical devices, as these are not approved for supply, so the approval cannot be withdrawn). Further, records for high class and implantable (non-custom-made) medical devices are required to be kept for longer than 5 years, reflecting the long expected lifetime for these devices. Manufacturers of higher class devices are additionally required to make annual reports to the TGA during the first few years they are supplied.

Current regulation of diagnostic imaging and anatomical models

The accuracy of images and anatomical models is very important in ensuring correct diagnosis, or effective investigation, of anatomy, physiology, or pathology (disease) of a person.

Classification rule 5.4[1] specifies that non-active (non-energy using) medical devices used to record X-ray diagnostic images (such as X-ray film) are classified as Class IIa medical devices. Under another classification rule, 4.3, diagnostic scanning equipment-the X-ray machine, MRI, PET or CT scanner are also Class IIa (or higher). The Class IIa classification means that manufacturers must implement a formal system of quality control (termed a quality management system) and they must also be certified and inspected by a suitable third party (such as the TGA or a European Union notified body).

However, the diagnostic and interpretative image-recording software for use with X-ray, magnetic resonance imaging (MRI), positron emission tomography (PET), and computed tomography (CT) scans is usually classified at the lowest regulatory classification-Class I-rather than Class IIa like X-ray film and diagnostic image-scanning equipment, despite such software having the same importance when it comes to required diagnostic accuracy.

This is largely a product of the time the regulations were developed rather than the risk profile of these image-recording technologies.

Similarly, anatomical models used for diagnosis or investigation of the anatomy, or used to plan surgical procedures, are also usually Class I even though their accuracy is critical in planning surgery.

The rationale for classifying X-ray film at Class IIa also holds for other diagnostic image-recording and anatomical modelling technologies that perform a similar function to that of the X-ray film.

Current regulation of medical devices with human-origin components

At present, a subset of combination products (medical devices that include materials of non-viable animal, microbial, or recombinant origin) are regulated as Class III medical devices (the highest regulatory class), and are included on the ARTG as a medical device. These devices undergo a high level of regulatory assessment by the TGA. Both the medical device components and the other therapeutic materials are assessed together as part of a design examination assessment prior to inclusion on the ARTG.

However, medical devices that include human-origin materials (for example, an artificial mechanical kidney that uses another person's stem cells) are not regulated as medical devices but instead are regulated as Biologicals under the Biologicals regulatory framework under the Act and the Therapeutic Goods Regulations 1990; this is at odds with how comparable overseas regulators regulate these products.

The growth of 'personalised medical devices'

Personalised medical device is a broad term used to describe all of the various types of medical devices that are intended to address the particular needs of an individual. As outlined above, these may be currently regulated as custom-made medical devices, medical devices assembled or adapted to suit an individual, and/or medical devices incorporating human-origin materials. Personalised medical devices range dramatically in type and form - from prosthetics and implants to devices made using emerging technologies and advanced manufacturing methods, for example, bones, ears, exoskeletons, windpipes, jaw bones, tissues, and organs, many of which have been described in a number of recent publications.[7]

Over the past two decades, advances in technology and materials science have delivered significant benefits to the health sector, including the application of emerging technologies to medical devices.

These technologies mean that it is now possible to manufacture medical devices personalised to the individual, using modern manufacturing systems, including design software, and additive manufacturing such as 3D printing, etc. This contrasts to the traditional bespoke production methods for custom-made medical devices, such as a dental laboratory technician or dentist individually fashioning a tooth crown by hand. The advanced technologies have (or will) enable an expansion in the types of custom-made medical devices available and accessibility of custom-made medical devices, a reduction in the cost of custom-made medical devices, and an increase in the percentage number of custom-made medical devices which can be supplied to the market.

Rapid advances made in technology and materials science in the last two decades have delivered great benefits to the health sector but medical device regulatory frameworks have not kept pace.

Two areas that have had a particular impact on personalised devices are medical-imaging technology and manufacturing technology. One example is 3-Dimensional (3D) printing, where it is now possible for a healthcare professional to custom-make implantable medical devices (such as a replacement hip), designed exactly to a patient's specifications, using 3D-printing technology. Such a custom-made medical device, when produced by more traditional methods, would previously have been difficult to make, very expensive, and a rarely used option.

International response

The regulators of ten global medical device jurisdictions, including Australia, together form the International Medical Device Regulators Forum (IMDRF)[8] - an organisation established as the successor to the Global Harmonisation Taskforce (GHTF). This group's goal is to develop a harmonised regulatory model that will be adopted by all member jurisdictions to ensure that patients have access to medical devices that meet appropriate safety and performance standards, and to facilitate global supply. The ten jurisdictions already have regulatory requirements which are similar to one another, and are based on the work of the GHTF, of which Australia was also a founding member.

In 2018, the IMDRF established a personalised medical devices working group to develop guidance that establishes definitions and regulatory pathways for regulatory authorities to consider in the regulation of medical devices that are intended for individuals. The goal was to promote global harmonisation in the terminology and premarket requirements for such devices. Australia chairs the working group, and has made significant contributions to the work in the space of the regulation of personalised medical devices.

The IMDRF describes personalised medical devices in one of three ways - custom-made, patient-matched, and adaptable. The IMDRF definitions and associated examples are provided in Appendix 1.

These different types of personalised medical devices are introduced below, together with some examples of each.

Comparison and examples of the different types of medical device proposed
Personalised medical devices
Custom-made Patient-matched Adaptable Non-adaptable mass-produced
Comment A type of mass-produced medical device.
Intended to be:

manufactured specifically to address one or more of the recipient's

anatomical features

physiological features

a pathological condition

manufactured specifically to match a particular individual's

anatomical features

physiological features

a pathological condition

adapted after supply to address a particular individual's

anatomical features

physiological features

a pathological condition

or adapted in order to be properly installed

used by individuals or healthcare institution where the standard sizes and designs are suitable for the individual or institution's needs.

Intended recipient An individual patient or a healthcare professional, such as a surgeon A particular individual A particular individual or a healthcare institution

An individual or a healthcare institution

(Note: not intended for any particular individual)

When manufactured On demand, following request from a healthcare provider On demand, following request of an individual (usually a healthcare provider but may also be a lay person depending on the device) When the manufacturer predicts/estimates there will be a market for the device. When the manufacturer predicts/estimates there will be a market for the device.
Overall responsibility for the device Authorising healthcare professional Manufacturer Manufacturer Manufacturer
Reason specific type of personalised device required The health professional has determined that there is no other suitable device on the market in Australia (i.e., on ARTG) that meets the needs of the intended recipient

There is no suitable adaptable medical device available for the individual's needs.

The individual's needs can be met with a device that can be manufactured within the design envelope of an existing design.

There are no non-adaptable mass-produced medical devices available that can meet the needs of the individual or healthcare institution.

The designed adaptability of the adaptable medical device is sufficient to meet the needs of the individual or healthcare institution.

Not applicable. Not a personalised medical device.
Specifications

Design characteristics specified and provided by an authorised professional to the manufacturer. Manufacturer takes into account the specified design characteristics when manufacturing the device.

Design and design envelope determined by the manufacturer.

Specifications relating to the individual (e.g., length of arm) provided to the manufacturer. Device manufactured according to those specifications so long as they are within the previously validated design envelope.

Dimensions and design determined by the manufacturer.

Intended to be adapted or assembled after supply (by a surgeon, for example) in accordance with the manufacturer's validated instructions.

Adaptations and modifications may be made to specifications determined by the intended recipient so long as they are within the allowable parameters specified by the manufacturer in its instructions for use.

Dimensions and design determined by the manufacturer.
Typical number produced One-off Small to large volumes Mass-produced Mass-produced
Production process

Intended to be a one-off. It may or may not be possible to validate or verify certain elements of the design and production.

Is not intended to be reproduced.

Capable of being validated, verified, and reproduced (within the constraints of the design envelope). Capable of being validated, verified, and reproduced.

Capable of being validated, verified, and reproduced.

Continuous production process or homogeneous batch.

Example

Example 1-Addressing the needs of a patient

Following a car accident, a patient requires a new neck (cervical) disc. The surgeon undertakes diagnosis and assessment of the size of disc required. On reviewing the options available, the surgeon finds that the required disc is not available so the surgeon contacts a manufacturer and requests that a disc be produced according to specifications that will accord with the patient's anatomy.

Example 2-Addressing the needs of a healthcare professional

A surgeon has unusually long fingers and finds that conventional surgical tools available on the market do not meet his/her needs. The surgeon designs the specifications and asks a manufacturer to make a set of surgical clamps

A hip joint that is manufactured to be the necessary length, thickness, and angle for an individual patient, where the manufacturer is using a template and has made sure that joints are made within the minimum and maximum dimensions that the manufacturer has previously validated as being safe and performing as intended.

Adjustable-length crutches.

A mass-produced plastic (polymer) surgical implant for skull (cranial) reconstruction that is supplied to surgeons who then shape the device during surgery specifically to suit the patient's anatomy. The manufacturer provides instructions on how to shape the device.

Portable infusion pump

Footnotes

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