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Regulation impact statement: Changes to premarket assessment requirements for medical devices
Attachment B: Regulation of medical devices in Australia
Under the Therapeutic Goods Act 1989, medical devices must be included on the Australian Register of Therapeutic Goods (ARTG) prior to supply in Australia unless exempt from that requirement. In order to be included on the ARTG, devices must have the necessary conformity assessment certification to ensure they are of acceptable safety and quality, and perform as intended. An application must be made to the TGA to include the device on the ARTG, supported by the appropriate conformity assessment certification. The level of assessment conducted by the TGA at the point of application for ARTG inclusion depends on the following:
- the risk classification of the device, against the following range:
- Class I: low risk
- Class I - supplied sterile and/or incorporating a measuring function: low–medium risk
- Class IIa: low–medium risk
- Class IIb: medium–high risk
- Class III: high risk
- AIMD (Active Implantable Medical Devices): high risk
- whether the TGA or an overseas body issued the conformity assessment certificate
- whether the certificate was issued under the provisions of trade facilitation agreements in place with European countries55
- whether there are any concerns with the application that would require the TGA to request further information for review prior to inclusion.
Conformity assessment is the systematic examination of evidence generated, and procedures undertaken, by the manufacturer to determine that a medical device is safe and performs as intended and therefore conforms to the Essential Principles.
The Essential Principles set out the requirements relating to the safety and performance characteristics of medical devices. There are six general Essential Principles that apply to all devices and a further nine Essential Principles about design and construction that apply to devices on a case-by-case basis:
- use of medical devices not to compromise health and safety
- design and construction of medical devices to conform to safety principles;
- medical devices to be suitable for intended purpose;
- long-term safety;
- medical devices not to be adversely affected by transport or storage; and
- benefits of medical devices to outweigh any side effects.
- chemical, physical and biological properties;
- infection and microbial contamination;
- construction and environmental properties;
- medical devices with a measuring function;
- protection against radiation;
- medical devices connected to or equipped with an energy source;
- information to be provided with medical devices;
- clinical evidence; and
- principles applying to IVD medical devices only.
The regulatory framework provides flexibility for manufacturers and caters for technological advances and changes in the development of new medical devices. It does not mandate the means by which a manufacturer must prove that they have met the Essential Principles.
It is the responsibility of the manufacturer to gather the evidence required to demonstrate compliance with the Essential Principles. In order to do that, manufacturers must comply with a minimum set of conformity assessment procedures defined in legislation which are based on the level of risk of the device:
- Class I: Conformity assessment for Class I (low risk) medical devices is self assessed by the manufacturer. They must apply a conformity assessment procedure and prepare an Australian Declaration of Conformity, however, it does not need to be submitted to the TGA prior to submitting a device application. Once included on the ARTG, the sponsor must provide the evidence to the TGA upon request.
- Class IIa and Class IIb: Conformity assessment for Class IIa (medium risk) and Class IIb (medium – high risk) medical devices provides for an initial and ongoing review of the manufacturer's quality management system (QMS) by a Conformity Assessment Body (CAB).
- Class III: Conformity assessment for Class III (high risk) medical devices has two elements:
- initial and ongoing review of the manufacturer's quality management system by a CAB
- a review of the design of the device by a CAB.
For review of the manufacturer's quality management system by a CAB (required for Class IIa, IIb and III medicinal devices) the manufacturer has two options:
- A full quality assurance procedure, where all clauses of the applicable QMS standard must be applied, including design and development activities
- A production quality assurance procedure, where all clauses of the QMS standard are applicable, but clauses relating to design and development activities can be excluded.
There are two methods of review of the design of the device required for Class III medical devices, which depend on the type of quality assurance procedure applied by the manufacturer:
- Design Examination: where the manufacturer has applied a full quality assurance procedure, the CAB conducts an examination of the design dossier (consisting of technical documentation, design files, risk analysis etc.) to assess compliance with the Essential Principles; or
- Type Examination: where the manufacturer has applied a production quality assurance procedure, the CAB conducts an examination of a representative sample of each Class III medical device. Testing can be conducted by the CAB, or the CAB can conduct tests on the device at the manufacturer's site and supervise or review the testing, or the CAB can subcontract the testing to an accredited test laboratory.
The most common conformity assessment procedure applied by manufacturers of Class III medical devices is a full quality assurance procedure including design examination. The production quality assurance procedure, including type examination, is used less often due to inherently higher costs associated with conducting tests on individual medical devices each time the design of the device is changed. This system of review is consistent with the framework recommended by the GHTF.56
In Australia the TGA is the only CAB allowed to perform conformity assessments. However, certification issued by European CABs (also known as Notified Bodies) may be accepted by the TGA under the Therapeutic Goods Act 1989 and regulations for most medical devices, except for:
- a subset of high risk devices (such as those containing tissues of animal origin or medicines)
- medical devices made by Australian manufacturers.
In those instances, a conformity assessment certificate issued by the TGA is required which involves a conformity assessment review of the manufacturer and devices.
A TGA-issued Conformity Assessment Certificate can be used to support inclusion in the ARTG of the medical devices covered by that certificate and may also support market authorisation by other overseas regulators.
Conformity assessment reviews of the technical and QMS elements involve desk-top assessments of the evidence provided. This is the internationally recognised review methodology and does not specifically provide for testing of individual medical devices before marketing approval (although such testing may be conducted during a Type Examination described above). The conformity assessment methodology allows for the safety, performance and quality of a device to be determined for all products manufactured. Testing of individual devices only provides information in relation to the particular device, or batch of devices, tested.
Under the full quality assurance procedures, manufacturers of Class III devices are required to implement a quality management system (QMS) that ensures appropriate control over the design, production, packaging, labelling and final inspection of the device, and implementation of an appropriate ongoing monitoring system.
In certain circumstances, following a desktop review of the manufacturer's QMS documentation, a CAB (including the TGA) may elect to undertake an on-site audit to satisfy itself that the elements required in the QMS are in place and operational. The TGA may also elect to do its own on-site audit for products with overseas certification if, following a desk top assessment, the evidence presented does not adequately cover the areas in which the TGA has an interest.
The term 'audit' (termed an inspection by other agencies) means an on-site examination of the systems, documents, processes, equipment and premises used in order to determine compliance with the requirements of the relevant manufacturing standard. A successful audit is one component of the process leading to the manufacturer of a Class III device being issued a TGA Conformity Assessment Certificate (the other component being a Design Examination).
The technical aspect of the audit is a focussed and well documented sampling exercise that includes assessment of receipt and storage of raw materials and components; verification of their compliance with specifications; control of production processes and finished product verification; and storage and release procedures. This is combined with in situ observations of the suitability of the premises and the company's routine manufacturing practices. Auditors assess the company's production systems against the relevant standards. Nontechnical factors that may influence company directions (e.g. financial position or management attitude) fall outside the scope of a conformity assessment audit.
By necessity, the actual date of an audit of an overseas manufacturing facility is arranged with the auditee; this can be months in advance of on-site attendance. The TGA cannot exercise any of its regulatory powers outside Australia. TGA officers visiting overseas manufacturing sites are invitees who have no power to remain on site without the permission of the auditee. If TGA officers were to detect serious failings of the quality system (with significant risk of producing harmful product), or observe fraud or falsification of products or data at an overseas manufacturing site, this would be reported to the regulatory authority operating in that country. Any further inspections or investigations would then rest with that authority.
During any audit (either of an Australian or overseas manufacturer), it is common to find deviations from the prescribed standards. Deviations from these standards are so called 'nonconformities' that are classified as Major or Minor according to the risk they might represent to the end-user of the devices being manufactured. Major non-conformities are those that may produce a product that is unsafe or of substandard quality. Minor non-conformities are minor deviations from the requirements of the standard that may lead to the production of sub-optimal products if not corrected.
The discouragement, detection and prosecution for unlawful manufacturing activities must involve the regulatory authority operating in that country. The TGA can conduct a short notice or unannounced audit of an Australian manufacturer if alerted by overseas intelligence (or any other source) to potential irregularities.
For Class III (high risk) devices, and where the manufacturer has applied a full quality assurance procedure, technical documentation relating to the design of the specific device (design dossier) is reviewed to demonstrate compliance with the Essential Principles.
The documentation reviewed during a design examination includes, but is not limited to, the following:
- details of the processes, systems and measures used for controlling, monitoring and verifying that at each stage of the design process, the device complies with the applicable provisions of the essential principles
- details of the design specifications for the kind of device, including:
- compliance with any standards that have been applied
- the results of the risk analysis carried out
- a copy of the clinical evidence
- a copy of the information provided with the device (e.g. labels, instructions for use etc)
- unlike the QMS audit, the design examination conducted by the CAB is conducted solely as a desk top review of the documentation and does not involve an on-site audit component.
The risk management approach is linked to the classification system for medical devices. Manufacturers or sponsors classify the medical device according to its intended purpose and the degree of risk involved for the patient, the user and the environment. The device classifications are determined using a set of rules contained in the Regulations that take into account the degree of invasiveness in the human body, the duration and location of use and whether the device relies on a source of energy other than the body or gravity. There are two sets of classification rules; one based on the above and the other is for In-Vitro Diagnostic devices (IVDs). The risk classification table relevant to hip, knee and shoulder joint implants is shown below, with the IVD table shown in the Glossary.
|Class I||Low||Surgical retractors, tongue depressors|
Class I – supplied sterile
Class I – incorporating a measuring function
|Low-medium||Sterile bandages, drainage bags|
|Class Iia||Hypodermic needles, suction unit|
|Class Iib||Medium-high||Lung ventilator, hip, knee and shoulder joint implants|
|Class III||High||Heart valves|
|AIMD (Active Implantable Medical Devices)||Implantable defibrillator|
The level of regulation incrementally increases as the level of risk increases. Based on the medical device classification system (other than IVD medical devices) the levels of premarket assessment of medical devices can be summarised as follows:
Class I medical devices
Most Class I medical devices validly lodged under the TGA's electronic lodgement system will result in an automatic entry to the ARTG. There is no assessment of the application. However, applicants must certify as to a range of matters in relation to the device. The automatic entry process is monitored by a random selection process, with 10 per cent of applications selected for review at the postmarket stage. There is also provision for targeted review, where the TGA considers there is reason for such a review.
Class I measuring, Class I sterile, Class IIa and Class IIb medical devices
Before making an application to include a Class I measuring, Class I sterile, Class IIa or IIb medical device on the ARTG, the Manufacturer's Evidence (see Glossary) must have been accepted by the TGA. The details of the device application will be compared with the details on the Manufacturer's Evidence, to ensure that the device is appropriately covered by conformity assessment certification and an administrative review of details of the application will be conducted, such as appropriate classification and intended purpose. No further assessment is conducted unless it is an application that is required to be audited under the Regulations or the application is selected for a non-mandatory application audit.
Class III and active implantable medical devices (AIMD)
Applications for Class III and AIMD devices are subject to acceptance of Manufacturer's Evidence. They will generally undergo a Level 2 application audit assessment (see Glossary).
The Australian-based sponsor of a medical device is responsible for making an application for inclusion of a medical device in the ARTG, not the manufacturer of the device (although the manufacturer may be the sponsor if they are Australian-based).
In Australia, acceptable conformity assessment certification is required before an application can be made to include a medical device in the ARTG – that is, a Conformity Assessment Certificate must be from an appropriate EC notified body, or must have been issued by the TGA. Under the devices regulatory framework, no certification from other countries outside Europe, including the USA, can be accepted.
Medical devices can be included in the ARTG once a proper application is made, and the product has undergone the required conformity assessment certification. Some applications must be subject to an audit (which involves checking some or all aspects of the application and certification) and other applications may be selected for audit at the TGA's discretion.
The nature of the audit and the documentation required for assessment will depend on the level of risk associated with the medical device.
Standard conditions apply to all medical devices included on the ARTG. One of these is for a sponsor of a device to keep distribution records of all their medical devices which will include records of distribution centres, hospitals and export countries to which the device has been supplied. This does not extend to records of the individual users of medical devices (individual doctors or patients). For Class III (high risk) devices, these distribution records must be kept for 10 years and must be provided when requested by the TGA.
It is a requirement that the sponsor keep an up-to-date log of information about the performance of the device which includes any information of which the sponsor is aware relating to:
- any malfunction or deterioration in the characteristics or performance of the device
- any inadequacy in the design, manufacture, labelling, instructions for use or advertising materials of the device
- any use in accordance with, or contrary to, the use intended by the manufacturer of the kind of device that has led to any complaint or problem in relation to the device, no matter how minor
- information that indicates that the device does not comply with the essential principles
- information that indicates that an overseas issued conformity assessment certificate has been restricted, suspended, revoked or is no longer in effect.
A condition that is routinely applied to Class III devices is that the sponsor must provide three consecutive annual reports to the TGA following inclusion of the device in the ARTG. The annual report must include all complaints relating to the device and problems with the use of the device that have been received by the sponsor over the year.
Irrespective of any conditions that are imposed on the inclusion of a medical device in the ARTG, it is an offence under the Therapeutic Goods Act 1989 for a sponsor of a medical device that is included on the ARTG not to report to the TGA:
- specified information relating to a problem with the device that might lead, or might have led, to the death or to a serious deterioration in the health of a patient or a user of the device
- any information relating to any technical or medical reason for a malfunction or deterioration of a device that has led the manufacturer to take steps to recall the device
- information that indicates that the device of that kind does not comply with the essential principles
- information that indicates that an overseas-issued conformity assessment certificate has been restricted, suspended, revoked or is no longer in effect.57
The Australian regulatory framework for medical devices includes provision for postmarket monitoring by the TGA, including: checking evidence of conformity; conducting periodic inspections of manufacturers' quality management systems and technical documentation; and imposing specific requirements for manufacturers and sponsors to report, within specified timeframes, adverse incidents involving their medical devices. Postmarket monitoring by the TGA is carried out to ensure the ongoing regulatory compliance and safety of medical devices supplied to the Australian market.
In support of the TGA's postmarket monitoring activities, the sponsor of a medical device has ongoing responsibilities once a device has been included in the ARTG. These statutory responsibilities include that the sponsor must report to the TGA adverse incidents; overseas regulatory actions; and the results of investigations undertaken by the manufacturer. The sponsor must also maintain distribution records.
Sponsors are required to report certain individual adverse incidents involving their medical devices to the TGA within statutory timeframes that depend on the seriousness of the incident. Adverse incidents involving serious public health risks are to be reported within 48 hours. Serious adverse incidents that resulted, or may have resulted in death or serious injury are to be reported within 10 working days. Other adverse events that resulted in injury or may have resulted in injury are to be reported within 30 working days. The TGA reviews all individual adverse incident reports and undertakes its own investigation if required. Sponsors of Class III medical devices must also keep an up to date log of information about the performance of the device and provide annual reports to the TGA as described in the 'market authorisation' section above.
Manufacturers also have ongoing obligations in respect of their devices which will vary depending on the conformity assessment procedures that apply to the particular device. The manufacturer also has specific obligations which include cooperation with the TGA in any review to determine whether conformity assessment procedures have been properly applied to the devices covered by a conformity assessment certificate. Manufacturers are also required to notify the TGA of any plan for substantial changes to the quality management systems, the product range covered by those systems or the design of the devices covered by a conformity assessment certificate. Failure to comply with these requirements may result in revocation of a Conformity Assessment Certificate by the TGA and the consequent cancellation of the devices from the ARTG.
The manufacturer is required to have, as part of its quality management system, a procedure for gathering information on the performance and safety of the device in the postmarket phase and to ensure any information gathered continues to demonstrate compliance of the device with the Essential Principles throughout the product's life. This procedure includes the requirement for the manufacturer to maintain a system for receiving and investigating problem reports and complaints and for undertaking corrective action for a device.
Using data generated from such programs (such as safety reports, including adverse event reports, results from published literature, any further clinical investigations and formal postmarket surveillance studies), a manufacturer is required to periodically review performance, safety and the benefit-risk assessment for its device through a clinical evaluation, and update the clinical evidence accordingly. This ongoing clinical evaluation process should allow manufacturers to communicate with conformity assessment bodies and regulatory authorities any information that has an important bearing on the benefit-risk assessment of the device or that would indicate a need for labelling changes regarding contraindications, warnings, precautions or instructions for use, etc. These reviews by the manufacturer are expected to be assessed by notified bodies or those undertaking re certification processes.
Just as with medicines, medical devices are authorised with an understanding of the expected type and frequency of side-effects. Postmarket vigilance and monitoring systems do not require expected side-effects to be reported to the regulator as these are a normal part of the use of the medical device. The TGA provides guidance as to the definition of a reportable adverse event for medical devices. This guidance (at section 22 of the Australian Regulatory Guidelines for Medical Devices58) states that side effects that are clearly identified in the manufacturer's Instructions for Use or labelling, or are clinically well known as being foreseeable and having a certain functional or numerical predictability when the device was used as intended, need not be reported.
The TGA's powers in relation to the keeping of records and reporting of adverse events and other safety matters are those set out in the Therapeutic Goods Act 1989 and are limited to sponsors and manufacturers. There is mandatory reporting for sponsors and manufacturers of life-threatening or serious public health related adverse events and non-mandatory reporting for other events.
There is no requirement under the legislation or relevant guidelines to report expected adverse events. Since rupture of breast implants is an expected event, sponsors and manufacturers are not required nor expected to routinely report these events to the TGA.
The TGA's powers do not include the regulation of clinical practice, including surgical practice, or matters relating to doctor-patient consultations. The Medical Board of Australia is responsible for all matters relating to the regulation of medical practitioners in Australia.
Reporting of adverse events by users is voluntary. The relevant TGA guidelines make it clear that users are encouraged to report events associated with the use of a medical device to either the sponsor or to the TGA. The reporting by health professionals, patients and the public is facilitated by the availability of a Users' Medical Device Incident Report on the TGA website and information provided directly to health professionals through a range of mechanisms about how and when to report medical device adverse events.
Thus, under the current regulatory framework, the capacity of the sponsor and/or manufacturer to provide comprehensive information to the TGA about adverse events and for the TGA to collect such information depends, to some extent, on relevant information being provided by those who have direct experience of those events, that is, patients and health professionals.
As a result, the adverse events reported to the TGA by healthcare professionals and consumers are limited to those that are reported voluntarily.
All adverse event reports or complaints received by the TGA are entered into a database. All reports and complaints are risk-assessed for frequency, severity and detectability by the TGA. This risk assessment is undertaken by a panel of clinicians and scientists within the TGA to determine if investigation is required. All reports are reviewed by an independent panel of experts, the Advisory committee on the Safety of Medical Devices (ACSMD)59, which provides advice regarding whether the investigation was sufficiently thorough and whether reports should be investigated further. If MDIRC considers that there are issues that require further investigation, the TGA will reopen reports and re-investigate.
The outcomes of the TGA's investigations may result in product recovery (recalls); or hazard and safety alerts; or product modification/improvement by a manufacturer; or surveillance audits of manufacturing sites.
A safety alert is advice regarding a specific situation with respect to a medical device which, whilst performing to meet all specifications, might present an unreasonable risk of substantial harm if certain specified precautions in regard to its use are not observed. A hazard alert is specific to implantable medical devices and involves the distribution of precautionary information about an implanted device where there is no stock to be recalled and all affected devices are already implanted.
The TGA can take action60 to suspend a device from the ARTG where, for example, the outcomes of the TGA's investigations indicate that there is a potential risk of death, serious illness or serious injury if the device continued to be included in the Register and can cancel a device from the ARTG if satisfied, for instance, that the safety or performance of the device is "unacceptable".
The TGA coordinates approximately 500 recalls of medical devices each year. The vast majority of recalls are undertaken voluntarily by the sponsor in cooperation with the TGA.
The TGA relies on the Uniform Recall Procedure for Therapeutic Goods (URPTG)61 in the management of recalls. The URPTG is the result of an agreement between the therapeutic goods industry and Commonwealth and state/territory health authorities. Its purpose is to define the action to be taken by health authorities and sponsors when therapeutic goods are to be removed from supply or use, or subject to corrective action for reasons relating to their quality, safety, efficacy or performance.
In voluntary recalls, the TGA expects that sponsors will act in accordance with the URPTG. In mandatory recalls (that is where the powers under the Therapeutic Goods Act 1989 are used), the TGA will usually require sponsors to comply with particular parts of the URPTG. No recall should be undertaken without consultation with the TGA and without the agreement of the TGA on the recall strategy. The text of recall letters needs to be approved by the TGA and must be despatched by the sponsor within 48 hours of receiving such approval.
In practice the TGA decides on a case by case basis whether to allow a sponsor to recall medical devices voluntarily or whether the TGA should exercise its statutory recall powers. As noted above, the vast majority of recalls are voluntary. This is for both practical and legal reasons. The TGA cannot exercise its statutory recall powers unless certain criteria are met, for instance that it appears to the TGA that the quality, safety or performance of the device is "unacceptable".62 Moreover, any decision to mandate a recall would be subject to internal and Administrative Appeals Tribunal review if the sponsor chose to challenge the basis for the recall.
A voluntary recall at the instigation of a sponsor of a device in relation to which a potential safety issue has been identified can be implemented very quickly and effectively. The TGA would only be likely to exercise its statutory powers where it appeared that the sponsor was not prepared to initiate a recall or that a sponsor-initiated recall was not being managed appropriately and the criteria for exercising those powers were met.
Whether the recall is voluntary, or the result of the TGA exercising its statutory powers, the sponsor cannot as a matter of law be required (for obvious reasons) to recall any devices that have actually been implanted. In the case of implantable medical devices, the obligations of the sponsor are limited to recalling devices that have been supplied to hospitals and surgeons and others to whom they have been distributed.
Only in the case of a statutory recall can the TGA direct the sponsor to inform the public or particular persons about the circumstances giving rise to the recall. Because the sponsor will not normally deal directly with those implanted with the device, or have access to the relevant personal information, this power could not be used to require the sponsor to contact those with implanted devices.
The TGA has no power (even in the case of a statutory recall) to require surgeons to contact their patients with implanted devices of the kind recalled to either advise them of the recall or to ensure that all patients consult the surgeon if they have any concerns about the implanted device. However, in appropriate cases, the TGA will directly contact relevant professional societies and provide public information on the TGA website directed to those who have the implanted device, to encourage appropriate clinical review.
The TGA has no regulatory authority to conduct or commission clinical research involving individual patients to investigate the impact on health outcomes from the use of a device included on the ARTG. The TGA may conduct its own tests, generally in accordance with accepted international standards, on a particular device in order to evaluate any specific concerns about the manufacturing quality or performance of the device itself.
- Agreement on Mutual Recognition in relation to Conformity Assessment, Certificates and Markings between Australia and the European Community or the European Free Trade Association, as in force from time to time.
- GHTF was a partnership between regulatory authorities and the regulated industry and is comprised of five Founding Members: European Union, United States, Canada, Australia and Japan. The International Medical Device Regulators Forum (IMDRF) commenced from February 2011 to build on the previous work of the GHTF, and to accelerate international medical device regulatory harmonization and convergence.
- See section 41MP of the Therapeutic Goods Act 1989.
- ACSMD consists of experts in consumer issues and numerous medical specialties including nuclear science and biomedical physics, oral and maxillofacial surgery, nursing, biomedical engineering, anaesthesia, orthopaedic surgery, cardio-thoracic and transplant surgery, cardiology and epidemiology and biostatistics.
- Under the Therapeutic Goods Act 1989 powers to take regulatory action are conferred on the Secretary of the Department of Health and Ageing. Those powers are exercised by officers of the TGA occupying positions to which relevant regulatory powers have been delegated by the Secretary.
- This would be grounds for cancelling the device from the ARTG.