presentation: session 4b: medical devices (ivds) - application … · 2015-10-15 · paul cohen...

Medical devices (IVDs) - application audits (technical file reviews)

Session Chair ― Wendy-Jane Morrow Chief Executive Officer, IVD Australia Speakers / Panelists ― Chris Harwood Assistant Director, Therapeutic Goods Administration Euan Miller Assistant Director, Therapeutic Goods Administration Paul Cohen Regulatory Affairs & Quality Manager, Roche Diagnostics Australia

Medical Devices (IVDs) Application audits (technical file review)

Chris Harwood Devices Application and Verification Section Medical Devices Branch Devices Sponsor Information Day 2015

15 October 2015

Purpose

Facilitate better understanding of the regulatory requirements for IVD medical devices

ARTG inclusion – explain the process of auditing including examples

Application audits (technical file review) 2

Process for ARTG inclusion

Application audits (technical file review) 3

Audits – ‘To be, or not to be…’

• the devices prescribed under paragraph (i) to (viii) of subregulation 5.3(1)(j) • does not apply if TGA issued conformity

assessment certificate

TGA must select application for audit - s.41FH(1)(a) …

• issues with the application or concerns about the device

The TGA may select an application for audit - s.41FH(1)(b)…

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What will happen? The TGA will give a written selection notice within 20 working days after receiving effective application • informing about the audit • requiring information relevant to the audit • advising of an audit fee (where applicable)

The sponsor has • 20 working days to provide information • 28 calendar days to pay the audit fee (where applicable)

• The application will lapse if information and/or audit assessment fee is not received.

• The sponsor can apply for reduction of the audit assessment fees if audit assessment can be abridged (when submitting the application)

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More questions about what will happen…

No other fees after audit will commence

No legislative timeframe for audits

The TGA may require additional information

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IVD medical devices, applications for which must be selected for audit i. Non assay specific quality control material monitoring a Class 4 IVD ii. IVD intended for self-testing iii. IVD intended for point of care testing iv. Class 3 IVD intended to detect a sexually transmitted agent v. IVD for managing and monitoring the treatment of infections diagnosed

using a Class 4 IVD medical device vi. IVD supplied under the pharmaceutical benefits scheme vii. IVD used in a national screening program viii.Where the TGA is not satisfied that the body issuing certification has the

appropriate expertise in relation to the assessment of conformity assessment procedures implemented by the manufacturer

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Where TGA is not satisfied that the body issuing the certification has the appropriate expertise • Class 3 IVD – moderate public health risk or high personal risk • Certificate ISO 13485 – quality management system compliance

only • No evidence of product review or compliance with the essential

principles • Audit is required to ensure conformity assessment procedures

have been applied to the devices of the kind to confirm safety and performance

Therapeutic Goods (Medical Devices) Regulations 2002, Regulation 5.3(1)(j)(viii)

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Audit – what does it mean? In auditing the application, TGA may consider all or some aspects of the following: • The application is effective

− made for a kind of device and in accordance with the form and manner approved

− information is not false or misleading • Matters certified by the sponsor under s.41FD are

correct Therapeutic Goods Act 1989, section 41FI

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Matters certified • Evidence of the appropriate conformity

assessment procedures − including the declaration of conformity

• Essential principles • Advertising • Excluded Purposes • Is information in the application correct

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Essential Principles EP 1: Use of a medical device not to compromise health and safety

EP 3: Medical device to be suitable for intended purpose

EP 5: Medical devices not to be adversely affected by transport or storage

EP 6: Benefits to outweigh any undesirable effects

EP 9.2: Minimisation of risks associated with use of medical devices EP 10: Measuring function accurate and measurements expressed in Australian

legal units of measurement

EP 13: Information to be provided with medical devices

EP 14: Clinical evidence – appropriate for the use and classification

EP 15: Principles applying to IVD medical devices only Application audits (technical file review) 11

Essential Principle 15 IVD medical devices only

EP 15.1 The analytical and clinical characteristics support intended use

EP 15.2 Accuracy, precision, sensitivity, specificity, stability, control of interference and measurement of uncertainty as appropriate

EP 15.3 Traceability of calibrators and controls must be assured

EP 15.4 Verification the IVD has performed as intended at the time of use

EP 15.5 Particular requirements for self-testing by a lay person

EP 15.6 Instructions for self-testing must be easy to understand and apply

EP 15.7 The reduction of risk for self-testing Application audits (technical file review) 12

Essential Principle 13 Information provided with medical device

EP 13.1 General

EP 13.2 Location – unless impracticable or inappropriate – must be provided on the device itself

- Including information about the sponsor (Regulation 10.2)

EP 13.3 Particular requirements

EP 13.4 Instructions for use

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What information is required? • Refer to the s.41FH selection notice for detailed list

and description • Information format

− Global Harmonisation Task Force (GHTF) Summary Technical Documentation (STED): Guide/template

− International Medical Device Regulators Forum (IMDRF): Table Of Contents – pilot study

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Technical file

• Represents information held by the manufacturer generated by QMS, design, development and production

• Depth and detail of information primarily dependant on the classification and type of device

• For applications containing multiple IVD devices of the same kind, information generally assessed in detail for one device (if it is representative of the kind)

• Time of the audit depends on a number of factors

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Essential Principles – what is assessed? • Clinical evidence

− Clinical Evidence Report EP 14 and Part 8 of Schedule 3

− Clinical Utility − Clinical Performance − Correlating the use of the IVD with a specific clinical

condition − A measure of the IVDs ability to correctly identify

patients as either having or not having a particular condition

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Essential Principles – what is assessed? • Analytical Performance

− Accuracy, sensitivity, specificity, traceability, measurement range

• Intended User – laboratory, point of care, self-testing • Assay principle and components • Device history, design and manufacturing information • Stability Studies

− Shelf life, in use, transport • Risk Analysis • Labelling and IFU Application audits (technical file review) 17

Example: Happy Home Urine Screen

• Class 2 IVD – Self-Testing – screening test for urinary tract infection

• Low public health risk or moderate personal risk

• Demonstrates compliance with the EPs

• Demonstrates the IVD is safe and efficacious

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Happy Home Urine Screen • Clinical Evaluation (A) − 2000 random urine samples − Results compared to culture (gold standard)

and cell count (microscopy) − Sensitivity 90% Specificity 90%

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Happy Home Urine Screen • Clinical Evaluation (B)

− 100 lay people following the IFU only − Test - their own urine − Test - blinded positive and negative specimens − Completed questionnaire on IFU suitability − Results were confirmed by culture/comparator

devices/trained individuals − Sensitivity and Specificity 100%

Application audits (technical file review) 20

Happy Home Urine Screen • Clinical Evaluation (C)

− 150 specimens from 3 clinical sites from symptomatic individuals

− Tested by trained individuals and confirmed by culture

− Sensitivity 96% Specificity 80%

Application audits (technical file review) 21

Example: Genetic Mutation XYZ Assay • Class 3 IVD – Genetic Alteration IVD detection of

circulating cancer cells • The information provided is acceptable • Demonstrates compliance with the EPs in relation

to analytical performance

Application audits (technical file review) 22

XYZ Assay • Clinical Evaluation

− Clinical samples evaluated covering the assay range − Clinical sample number low (<100) − Samples were evaluated and compared to the gold

standard − Assay is linear, sensitive and specific over the assay

range • Treatment of the condition is very effective • The function of the assay is to detect a patient relapse • Untreated relapses can be aggressive

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XYZ Assay

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XYZ Assay • Clinical Evaluation • Limited clinical data is available around the decision

point • Results at this low level show increased variation • Missing a relapse could have serious consequences for

the patient • Further clinical data is required

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What will happen after TGA assess all the information provided?

Recommendation on whether to

include the kind of device in ARTG

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Audit assessment is complete Audit

assessment complete

Decision to include device in ARTG May include decision to impose additional conditions

Decision not to include device in ARTG Provide reasons for the decision

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Where do we go from here?

Ensure all information provided is correct

Ensure sufficient information available to substantiate the application of conformity

assessment procedures and compliance with the essential principles

ARTG Inclusion

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Further information TGA website • Application Audit (Technical File Review) of IVD Medical Device

Applications • News, consultations, guidance, subscribe to updates

ComLaw: Database of Commonwealth law • Therapeutic Goods Act 1989, Chapter 4 • Therapeutic Goods (Medical Devices) Regulations 2002

Essential principles; Classification rules; Conformity assessment procedures

International Medical Device Regulators Forum website • Table Of Contents pilot study • GHTF Standard Technical Document

Contact the TGA Medical Devices Branch • devices@tga.gov.au 1800 141 144

Application audits (technical file review)

The Application-eBS

Important!

Be specific and clear!

Step 1

Step 2

Selection for Application Audit –Section 41 FH

Sponsor Documents required for the Technical File Review

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