session c2: ivds · 2014-10-16 · • clinical evidence report −ep 14 and part 8 of schedule 3...

Session C2: IVDs Application Audits (Technical File Reviews)

Chris Harwood

Sponsor Information & Training Day - 9 September 2014

Devices Application and Verification Section Office of Devices Authorisation

Legislative Background • Section 41 FH of the Act

− 41FH (1) (a) The Secretary must select…

− 41FH (1) (b) The Secretary may select…

• Regulation 5.3(1)(j)(i) to (viii) mandatory IVD audits

• Section 41 FI specifies two aspects requiring audit − The application is made in accordance with the requirements of the

Act

− Matters certified by the sponsor under s41FD are correct

Session C2: IVDs - Application audits (technical file reviews)

Legislative Background (continued) • s41FH (2) – Selection notice informing the sponsor that the

application is selected for audit and requesting information relevant to the audit

• s41FH (3) – Selection notice must be given within 20 working days after an effective application is made

• Regulation 5.2 – The period for providing information to the TGA is 20 working days

• s41FK(a) - Lapsing of the application • Regulation 9.2 – The audit fee is payable within 28 calendar days • Regulation 9.7 – Reduction of assessment fees – abridged

assessment


Regulation 5.3(1)(j)

(i) Non assay specific quality control material monitoring a Class 4 IVD (ii) An IVD intended for self-testing (iii) An IVD intended for point of care testing (iv) A Class 3 IVD intended to detect a sexually transmitted agent (v) An IVD for managing and monitoring the treatment of infections diagnosed

using a Class 4 IVD medical device (vi) An IVD supplied under the pharmaceutical benefits scheme (vii) An 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

IVD Medical Device applications that must be selected for audit


Where the 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 • Supported by ISO 13485 Certification only – quality management system

compliance • No evidence of product review or compliance with the Essential Principles • Audit is required to ensure conformity assessment procedures have been

applied to this kind of device to confirm IVD safety and efficacy

Regulation 5.3(1)(j)(viii)


Technical File • Represents information held by the manufacturer generated by

− Quality management system, design, development and production • GHTF STED - provides a guide • s41FH Initial request includes a detailed request for information • s41JA request if further information is required • Depth and detail of the information primarily dependant on risk

classification of the device • For an application containing multiple IVDs of the same kind,

generally detailed information about one IVD will be requested. • Processing time of the audit is dependant on a number of factors


Essential Principles 1 - Use of a medical device not to compromise health and safety 3 - Medical device to be suitable for intended purpose 5 - Medical devices not to be adversely affected by transport or storage 6 - Benefits to outweigh any undesirable effects 9.2 - Minimisation of risks associated with use of medical devices 10 - Measurements made must be expressed as Australian units 13 - Information to be provided with medical devices 14 - Clinical evidence – appropriate for the use and classification of the

device 15 - Principles applying to IVD medical devices only


Essential Principles (cont.)

13.1 - General 13.2 - Location – unless impracticable or inappropriate - must be

provided on the device itself 13.3 - Particular requirements 13.4 - Instructions for use

EP 13 : Information to be provided with medical devices


Essential Principles (cont.)

15.1 - The analytical and clinical characteristics support intended use 15.2 - Accuracy, precision, sensitivity, specificity, stability, control of

interference and measurement of uncertainty as appropriate 15.3 - Traceability of calibrators and controls must be assured 15.4 - Verification the IVD has performed as intended at the time of use 15.5 - Particular requirements for self-testing by a lay person 15.6 - Instructions for self-testing must be easy to understand and apply 15.7 - The reduction of risk for self-testing

EP15: Principles applying to IVD medical devices only


What is Assessed? • Is the application correct? • Evidence of appropriate conformity assessment procedures

including the manufacturer`s declaration of conformity • Check :

− EP compliance, Advertising, Excluded Purposes − Intended User – laboratory, point of care, self-testing − Assay principle and components − Device history, design and manufacturing information

• Risk Analysis (ISO 14971:2007) • Labelling and IFU • Stability Studies – shelf life, in use, transport


What is Assessed? (cont.) • Analytical Performance

− Accuracy, sensitivity, specificity, traceability, measurement range

• Clinical Utility • Clinical Evidence Report

− EP 14 and Part 8 of Schedule 3 • 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


Example 1 • Happy Home Urine Screen

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

• The information provided is acceptable

• Demonstrates compliance with the EPs

• Demonstrates the IVD is safe and efficacious


Example 1 (cont.)

• Clinical Evaluation (A) − 2000 random urine samples − Results compared to culture (gold standard) and cell

count (microscopy) − Sensitivity 90% Specificity 90%


Example 1 (cont.) • 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%


Example 1 (cont.)

• Clinical Evaluation (C) − 150 specimens from 3 clinical sites from symptomatic

individuals − Tested by trained individuals and confirmed by culture − Sensitivity 96% Specificity 80%


Example 2 • 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


Example 2 (cont.) • 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


Example 2 (cont.)


Example 2 (cont.) • 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


References • Therapeutic Goods Act 1989 (Chapter 3)

http://www.comlaw.gov.au/Series/C2004A03952 • Therapeutic Goods (Medical Device) Regulations 2002

http://www.comlaw.gov.au/Series/F2002B00237 − The Essential Principles (Schedule 1) − Classification Rules (Schedule 2A) − Conformity Assessment (Schedule 3)

• IVD Guidance Documents http://www.tga.gov.au/industry/ivd-guidance.htm

− Application Audit (Technical File Review) of IVD Medical Device Applications

http://www.tga.gov.au/industry/ivd-application-audit.htm • GHTF STED

http://www.ghtf.org/documents/sg1/pd_sg1_n063.pdf


http://www.comlaw.gov.au/Series/C2004A03952

http://www.comlaw.gov.au/Series/F2002B00237

http://www.tga.gov.au/industry/ivd-guidance.htm

http://www.tga.gov.au/industry/ivd-application-audit.htm

http://www.ghtf.org/documents/sg1/pd_sg1_n063.pdf

Questions?


SESSION C2: IVDs Application audits (Technical File Reviews)

George Koumantakis Manager, Scientific & Regulatory Affairs

Roche Diagnostics Australia

Important!

Be specific and clear!

Step 1

Step 2

Submission

Payment

41JA

41JA Information

1. Manufacturer’s Declaration of Conformity 2. Labelling & Packaging 3. Instructions for use/technical documentation 4. Stability studies

• Closed • In Use • Transport

5. Clinical evaluation report 6. Risk Management Report 7. Evidence (analytical)

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