Regulation of Medical Devices in Australia and New Zealand. By Judy Bingham, MHSc, FSHP, GAICD and Philippe Robertson

Transcription

1 Regulation of Medical s in Australia and New Zealand By Judy Bingham, MHSc, FSHP, GAICD and Philippe Robertson 24

2 Introduction The Therapeutic Goods Administration (TGA) regulates the supply of medical devices in Australia according to criteria prescribed by the Therapeutic Goods Act of 1989 and related regulations. 1,2 Since October 2002, the fundamental principles underlying medical device testing and assessment in Australia have been based on principles similar to those developed for the European Union that are part of a global harmonization approach through the Global Harmonization Task Force. However, the regulation of devices in Australia is unique in that an approval process resulting in the device s entry in the Australian Register of Therapeutic Goods (ARTG) must be followed. New Zealand currently does not have extensive regulations covering medical devices. In 2004, the New Zealand Regulatory Authority, MEDSAFE, introduced Web Assisted Notification of s (WAND), which provides notification by the sponsor to the authority about devices currently marketed in New Zealand. 3 WAND was established in anticipation of harmonization of the regulatory framework between Australia and New Zealand under the TransTasman Harmonization Agreement. While harmonization has not proceeded, the WAND system for medical devices has remained in effect. Australia Australia s regulatory system for medical devices has the following features: a device classification scheme based on different levels of risk for each class of device essential principles detailed in Schedule 1 of the Therapeutic Goods (Medical s) Regulations 2002, 4 for the quality, safety and performance of the medical device that must be adhered to before the product can be supplied the use of recognized standards to satisfy the requirements of the essential principles options for satisfying and assessing compliance with the essential principles manufacturer quality systems, device testing and design evaluation a comprehensive postmarket surveillance and adverse incident reporting program appropriate regulatory controls over medical device manufacturing a statutory committee, the Medical s Evaluation Committee (MDEC), which provides advice to the minister of health on issues relating to the safety, quality, performance and timely availability of medical devices and on the policies, procedures and priorities that should be applied to the administration of the medical devices legislation Definition of a Medical A medical device is defined in the Therapeutic Goods Act as any instrument, apparatus, appliance, material or other article (whether used alone or in combination, and including the software necessary for its proper application) intended, by the person under whose name it is or is to be supplied, to be used for human beings for one or more of the following: (i) diagnosis, prevention, monitoring, treatment or alleviation of disease; (ii) diagnosis, monitoring, treatment, alleviation of or compensation for an injury or disability; (iii) investigation, replacement or modification of the anatomy or of a physiological process; (iv) control of conception A device does not achieve its principal intended action in or on the human body by pharmacological, immunological or metabolic means, but may be assisted in its function by such means; or an accessory to such an instrument, apparatus, appliance, material or other article. It should be noted that a key part of this definition is the intended purpose specified by the manufacturer of the medical device. Classification Schedule 2 of the Therapeutic Goods (Medical s) Regulations describes the classification rules for medical devices and is based on: the manufacturer s intended use the level of risk the degree of invasiveness in the human body There are five classes of medical devices: Class I Class IIa Class IIb Class III Active Implantable Medical s (AIMD) It is the manufacturer s responsibility to correctly classify its medical device based on the classification rules described in the regulations. Suitable justification however is required in cases where TGA s opinion differs from that of the manufacturer. Manufacturers must ensure that their products comply with the essential principles of safety and performance, including clinical performance, and must document a comprehensive risk assessment for every product. For devices above Class I, the manufacturer is required to have an independent certification of compliance. TGA performs random audits to ensure compliance, including correct product classification. Regulatory Focus 25

3 Class I devices have been deemed low risk; they include hospital beds, wheelchairs, stethoscopes and crepe bandages. They can be registered in Australia using an online application. Within Class I, devices that are provided sterile or have a measuring function are classified Class I sterile and Class I measuring, respectively. The marketing application for a Class I sterile or Class I measuring device must be supported by evidence of conformity assessment (such as a CE certification), which indicates that the device has been fully examined by TGA or under another regulatory system that is accepted by TGA. Class IIa and Class IIb devices include monitoring equipment, surgical instruments, stents and catheters. As for Class I sterile and Class I measuring devices, the marketing application for Class II devices imported into Australia must be supported by a conformity assessment by TGA or evidence of a conformity assessment completed under another regulatory system that is accepted by TGA. Class III and AIMD devices require not only evidence of conformity assessment but also a detailed and certified assessment of their design dossier. Class III devices include heart valves; AIMD classification includes cardiac defibrillators and pacemakers. The marketing application for a Class III device imported into Australia must be supported by evidence of conformity assessment by the TGA or evidence of conformity assessment completed under another regulatory system that is accepted by TGA, except that TGA undertakes full conformity assessment on Class III devices that contain a medicine, human blood or plasma, or material of animal, microbial or recombinant origin. TGA assesses the manufacturer s quality management system which may include an onsite audit in addition to reviewing the technical documentation. Assessment by TGA is also required for Australian manufacturers of all medical devices above Class I intended for marketing in Australia. The purpose of a TGA assessment of a medical device is to confirm safety and efficacy in accordance with the intended use as declared by the manufacturer. This assessment is done on an application-by-application basis. No comparisons of clinical effectiveness or cost benefit within product groups or for like products are undertaken by TGA or are required to be undertaken under the legislation. The application process via Electronic Application Lodgement (DEAL) is summarized in Figure 1 and conformity assessment requirements are shown in Figure 2. 6,7 Assessment The classification of a medical device determines the conformity assessment procedure. A manufacturer can choose the conformity assessment procedure to ensure that the device is adequately assessed to conform to the particular requirements for the class of device. s in higher classifications are required to undergo a more stringent form of conformity assessment than those in lower classes. The responsibility for conformity assessment rests with the medical device manufacturer. For Class I devices imported into Australia, the manufacturer self-certifies and signs a declaration of conformity (see Figure 2, Part 6). For all higher classes of devices and Class I devices manufactured in Australia, TGA s role is to issue certification after confirming that the conformity assessment procedures are appropriate and have been applied. Alternatively, an overseas NB may issue certification for higher class devices imported into Australia, except Class III devices containing a medicine, human blood or plasma, or material of animal, microbial or recombinant origin. Essential Principles The essential principles of safety and performance detailed in Schedule 1 of the Therapeutic Goods (Medical s) Regulations apply to all medical devices. The general principles apply to all devices, however some principles dealing with design and construction may not be applicable to all devices. The manufacturer needs to determine which principles are applicable and must suitably justify those that they believe are not applicable. General Principles 1. use of a medical devices not to compromise health and safety 2. design and construction of medical devices to conform with safety principles 3. medical devices to be suitable for intended purpose 4. long-term safety 5. medical devices not to be adversely affected by transport or storage 6. benefits of medical devices to outweigh any side effects Principles of Design and Construction 1. Materials used in a medical device must have appropriate chemical, physical and biological properties. 2. A medical device must be designed and produced in a way that minimizes the risk of infection and microbial contamination. 3. A medical device must be designed and produced in a way that minimizes the risk of injury associated with its construction and environmental properties. 4. A medical device that has a measuring function must be designed and produced in a way that ensures that the device provides accurate, precise and stable measurements. 26

4 Table 1 CASO and MASO Standards Standard Title Biological Evaluation of Medical s ISO Standard Number and Issue Clinical Investigation of Medical s for Human Subjects AS ISO Medical s Application of Risk to Medical s EN ISO Medical s s Requirements for Regulatory Purposes ISO A medical device must be designed and produced in a way that ensures that the exposure of a patient, or other person, to radiation is minimized. 6. A medical device that incorporates an electronic programmable system must be designed and produced in a way that ensures the system s performance, reliability and repeatability. 7. Information provided with a medical device must explain how to use the device safely. 8. Every medical device requires clinical evidence demonstrating that the device complies with the applicable provisions of the essential principles. Standards The essential principles set out the requirements for medical device safety and performance. Compliance with applicable medical device standards is not mandatory, but is one way to establish compliance with the essential principles. A manufacturer s compliance with one or a number of medical device standards allows a presumption of conformity with the relevant essential principles. Table 1 lists the Assessment Standard Orders (CASO) and Medical Standard Orders (MDSO) that TGA highly recommends the manufacturer follow for all devices. Other standards should also be used by the manufacturer to demonstrate compliance with the applicable essential principles, as applicable to their particular device. The Role of Clinical Evidence The essential principles define the results to be attained or the risks and hazards to be addressed during product development, but do not specify the technical solutions for doing so. Manufacturers can choose how they meet these requirements. The mechanics for demonstrating compliance defined for each class of medical device are described in the guidance document on conformity assessment procedures. 9 The essential principles relevant to the device must be considered. For example, essential principles 1, 3, 4 and 6 require that the medical device achieve its intended performance during normal conditions of use, and that any undesirable side effects are minimized and acceptable when weighed against the benefits of the intended performance. Once a design specification that inherently minimizes the identified risks has been defined, the manufacturer must decide how to demonstrate conformity of the design specification with the relevant essential principles. In many instances, this will be achieved through implementation, maintenance and regular inspection of a quality management system. Clinical Evidence Requirements The medical device regulations require a medical device to: have clinical evidence that it is appropriate for its use and classification; demonstrate compliance with essential principles of performance and safety; and have undergone a clinical evaluation by the manufacturer as part of the conformity assessment procedure. A case-by-case approach matches clinical data requirements with the device s intended purpose. As a general rule, data requirements will vary according to the nature and clinical application of the technology used in or by the device. s based on new or unproven technology and those that extend the intended purpose of an existing technology through a new clinical use must be supported with clinical investigation data. s based on an existing technology and intended for an established and accepted use may rely on literature review. Furthermore, there may not be clinical trial data of a contemporary standard available for some long-established technologies. In such cases, the role of the literature review is to draw together all available trial data, reports of clinical experience, postmarket reports, adverse event data and expert opinion to establish the device s performance and safety. The clinical evaluation may also draw on other information such as the risk analysis, preclinical testing and the history of use of the technology to reduce the reliance on clinical data. Application s Selected Class IIb medical devices, all Class III medical devices and AIMDs on the ARTG undergo a mandatory TGA application audit. Other classes of medical devices on the ARTG may also be randomly selected for an application audit. These audits are carried out once TGA receives the application and prior to the device s inclusion on the ARTG. If an application Regulatory Focus 27

5 Figure 1. Medical s: A Sponsor s Roadmap to Market Sponsor obtains device classification and GMND code from manufacturer Class I Class Is, Im, IIa, IIb, III, AIMD manufactured in Australia OR contains material of human, animal or microbial origin, or a medicine YES NO Manufacturer s evidence is not required to be submitted. An Australian Declaration of must be submitted if requested. Sponsor obtains a copy of the manufacturer s evidence. An Australian Declaration of must be submitted if requested. Sponsor obtains conformity assessment (CA) certificate(s) issued by TGA or MRA certificates issued by notified body. Sponsor submits manufacturer s evidence Sponsor submits the CA or MRA Manufacturer s evidence accepted? NO Manufacturer s evidence accepted? NO Suitable manufacturer s evidence must be accepted to proceed Sponsor submits application (no application fees) Sponsor submits application (application fee) Sponsor submits application (application fee) TGA reviews application Selected by TGA for a nonmandatory application audit? YES Mandatory level-2 audit YES Colour Key Sponsor Activity TGA requests documents Sponsor submits requested information within 20 working days Manufacturer Activity TGA Activity Information Box TGA reviews response TGA includes the medical device on the Australian Register of Therapeutic Goods (ARTG) has been identified for an audit, the sponsor is required to provide further documentation to support the application. Postmarket Monitoring and Vigilance A manufacturer must implement and maintain a postmarket monitoring system to seek and assess information concerning the performance of its devices. Postmarket surveillance of medical devices by TGA includes compliance testing and audit of technical files and certification. The Vigilance is based upon GHTF recommendations. Sponsors are required to report any problems to the device manufacturer. Manufacturers are required to report the problem to TGA. 28

6 Any reportable events must be tested against the reporting thresholds defined in the regulations and conveyed to TGA either directly or through the Australian sponsor within: 48 hours after becoming aware of a serious threat to public health 10 days after becoming aware of the death, or serious deterioration in the state of health, of a patient, a user of the medical device or another person 30 days after becoming aware of an event, if a recurrence of the event might lead to the death or a serious deterioration in the state of health of the individual. Fundamental Differences Between Australian and EU Regulatory s The EU has two directives that cover medical devices: the Medical s Directive (MDD) and the Active Implantable Medical Directive (AIMDD). Australia regulates both medical devices and AIMDs under the same legislation. Australia requires a manufacturer to sign a declaration that its products meet Australian requirements and the EU requires a manufacturer to sign a declaration that its products meet the EU requirements. The person responsible for placing the product on the market in Australia and certifying that the manufacturer has met Australia s requirements is the sponsor. In the EU, these tasks are performed by an Authorised Representative. ARTG is the register of information about therapeutic goods for human use that may be imported into, marketed in or exported from Australia. With few exceptions (exemptions by regulation or by application) all medical devices must be included in the ARTG before marketing in Australia. There are a few differences in classification. 10 Hip, knee and shoulder joint replacements are considered Class III in the EU and Class IIb in Australia. Medical devices intended for disinfecting, cleaning, etc. are Class IIa in the EU and IIb in Australia. Catgut sutures are no longer supplied in Europe, but are considered Class III in Australia. Assessment Procedures The Australian conformity assessment procedures have been modeled on those of the EU MDD. 11 The EU CE marking system is a declaration of conformity with the MDD. This declaration includes an obligation to report certain events to the Competent Authorities (government authorities) in the EU Member States. In Australia, events must be reported to TGA within the timeframes stipulated in the regulations. Certification to the annexes of the MDD by a European NB may be used in support of Australian conformity assessment procedures. Where differences exist, the Australian procedures have been developed so that assessable items may be supported by certification issued by EU NBs. Regulatory Reforms External Assessment Bodies One of the disadvantages for Australian manufacturers marketing their products in Australia is that while TGA accepts CE certification for medical devices manufactured overseas, inspections by the authority are required for Australian manufacturers of equivalent technology. This restriction in choice of conformity assessment bodies, coupled with long delays in TGA approval, has resulted in Australian manufacturers seeking CE certification from EU NBs in addition to the Australian TGA certification to ensure faster European approval and therefore market access. This inconsistency is currently under review by TGA, which is examining options for thirdparty conformity assessment. This would enable Australian manufacturers to use certification granted by bodies other than TGA. TGA is developing a consolidated reference document, Australian Regulatory Guidelines for Medical s (ARGMD), detailing the Australian regulatory requirements for medical devices. A number of draft sections have been released for consultation and the final guidelines are expected shortly. In Vitro Diagnostics New regulations covering in vitro diagnostics (IVDs) are planned for implementation in 2010 and are intended to set some boundaries in an industry that has been largely exempt from regulation in the past. TGA has sought guidance from GHTF, However, at the current time, no other country has adopted GHTF guidelines and the proposed regulatory model for IVDs is uniquely Australian and more complex than the current medical devices legislation. 12 New Zealand New Zealand currently does not have detailed regulations for medical devices. The responsibility for ensuring the supply of approved medical devices lies entirely with the customer. A company submitting a tender to supply devices for public health is required to demonstrate that the device is already approved for use in Australia or the US, or is CE marked. In 2003, MEDSAFE introduced the WAND, the system for notifying MEDSAFE about devices currently marketed in New Zealand. 13 WAND is a direct copy of Australia s DEAL system and initially allowed the New Zealand representative to clone an already approved device from the DEAL database. The functionality to clone an ARTG entry into WAND ceased in September Regulatory Focus 29

7 Figure 2. Assessment Procedures for Medical s Assessment Procedures Active Implants, III IIb, IIa Active Implants, III, IIb IIa I(sterile) Design Part 1 Declaration Delaration of + Product Design Examination Part 1 Declaration Delaration of Part 2 Type Examination Examination by Part 6 Declaration of Production Full (ISO 13485) Full (ISO 13485) Technical document Part 3 Active Implants, III, IIb, IIa, Part 3 III IIb IIa Part 4 Declaration of Active Implants, III, IIb, IIa I(sterile) Part 5 Declaration of IIb, IIa Class I sterile products and measuring devices Self Certification with Documentation available. Statistical Examination and Testing by 100% Examination and Testing by Production (ISO 13488) Product (ISO 9003) Evidence of = Assessment Branch of the TGA A small number of products such as contact lens solutions and bone cements containing a medicine that are classified as devices in the rest of the world are classified as medicines in New Zealand. References 1. Commonwealth of Australia. Therapeutic Goods Act Accessed 19 November Commonwealth of Australia. Therapeutic Goods (Medical s) Regulations ComLaw. Accessed 19 November New Zealand Government. Medicines (Database of Medical s) Regulations legislation.govt.nz. Accessed 19 November Ibid Ibid Therapeutic Goods Administration. Medical devices: a sponsor s roadmap to market. August tga.gov.au/devices/devroadmap/index.htm. Accessed 19 November Therapeutic Goods Administration. Australian medical devices guidelines: 3. assessment procedures Accessed 19 November Ibid Ibid Therapeutic Goods Administration. Differences between the Australian and European Union regulatory systems Fundamental differences and classification. Fact sheet no. 15. October Accessed 19 November Council Directive 93/42/EEC of 14 June 1993 concerning medical devices. site/en/consleg/1993/l/01993l en.pdf. Accessed 24 November Therapeutic Goods Administration. Overview of the regulatory framework for in-vitro diagnostic medical devices. February Accessed 19 November New Zealand Web Assisted Notification of s (NZ WAND) asp. Accessed 23 November Authors Judy Bingham, MHSc, FSHP, GAICD, is senior director, regulatory, Asia Pacific for Kendle, responsible for regulatory services in the Asia Pacific region, including clinical trial regulatory supporting global clinical trials and regulatory consulting and submissions services. She has more than 25 years experience in pharmaceutical research, development and commercialization, including business development. She can be reached at bingham.judy@kendle.com. Philippe Robertson is a senior consultant with Kendle. He has extensive experience in medical device regulation within Australia, New Zealand and Europe and has worked with several medical device start-up companies in the development of their preclinical and clinical plans and quality systems. He can be reached at robertson. phil@kendle.com. 30