inspections of sites of manufacture of diagnosticsiso 13485:2003 ( standard ) – medical devices...

Informal Consultative Meeting for Diagnostic Manufacturing Associations, UN Procurement Agencies and WHO , 4 February 2009

Inspections of Sites of Manufacture of Diagnostics

PREQUALIFICATION OF DIAGNOSTICS

Jeanette Twell


PQ process- Inspections

Manufacturer submits

application

Accepted

RejectedApplication is

screenedManufacturer pays fee and

submits dossier

Dossier is reviewed

Accepted

Rejected

Manufacturing Site Inspection

Meets WHO

requirements

Does not meet

WHO

requirements

Meets WHO

requirements

Does not meet

WHO

requirements

Product is prequalified

Product Laboratory Evaluation


Quality Management System

� The system should ensure consistency and

improvement of working practices, which in turn should provide products and services that meet customer's

requirements.

� Provides confidence to the organization and its customers that it is able to provide products that

consistently fulfill requirements


Quality Management System


Quality Management System - Resources

� International Organization for Standardization

(ISO) provides commonly used international standards that provide a framework for an effective

quality management system and manufacturing

processes.

� The Global Harmonization Task Force (GHTF)

also provides guidance documents for use by manufacturers and for assessment.

� Technical and QMS experts are essential to the process.


The ISO Standard for QMS and Quality of Product for Medical Devices

� ISO 13485:2003 (Standard) – Medical devices – Quality

management systems – Requirements for regulatory purposes

� ISO 14969:2004 (Technical Report) Medical devices –

Quality management systems – Guidance on the application of ISO 13485:2003

The QMS and the quality of product are addressed in ISO 13485


International Organization for Standardization (ISO)

Who uses ISO 13485?

� US FDA Quality System (FDA 21 CFR Part

820) regulation now 'harmonized' with

ISO 9001 and ISO 13485 (minor variations)

� European Union

� Health Care Canada

� TGA Australia

� GHTF – Japan, Canada, Australia, US & EU

AHWP – aligned with GHTF


The ISO Standard for QMS and Quality of Product for Medical Devices (continued)

� ISO 14971:2007 Medical devices

- Application of risk management to medical devices

� ISO 2859-1: Sampling procedures for inspection by attributes – Part 1: Sampling schemes indexed by

acceptance quality limit (AQL) for lot-by-lot inspection

� ISO 17025: 2005 General requirements for the competence of testing and calibration laboratories

Other ISO standards and technical reports and GHTF documents are utilized


The ISO Standard for QMS and Quality of Product for Medical Devices (continued)

� ISO 14644:series - Cleanrooms and associated

controlled environments.

(includes classification of air cleanliness and test

methods)

� GHTF/SG3/N99-10:2004: Quality Management Systems – Process Validation Guidance.

(includes Installation Qualification (IQ), Operational Qualification (OQ) and Performance Qualification (PQ))

Other ISO standards and technical reports and GHTF documents are utilized


Purpose of the Inspection

• Verify the QMS claims

• Strengthen national regulatorycapacity (NRA staff)

• Beneficial for the manufacturer


Inspections site visits – what is inspected?

Inspect

• QMS – quality manual, SOPs, training records,

audit records, corrective actions, complaints handling, equipment maintenance records

• Manufacturing process – cleanliness, labelling,

QC check points

• QC – laboratory QMS

• Batch release records


What is inspected?

ISO13485:2003

1 Scope2 Normative references3 Terms and definitions

4 Quality management system including documentation requirements

5 Management responsibilityincluding customer focus, quality policy

6 Resource management

including human resources, work environment

7 Product realization

including production and service provision, control of monitoring and measuring devices

8 Measurement, analysis and improvement

including control of nonconforming product, improvement


Inspections site visits - overview

• Total mission - 6 days per site, 10 days per two sites

• 4 days on site of manufacture• 2 days travelling time per mission

Inspections consist of

• One WHO DLT staff member• 2 externally sourced inspectors (expertise in

manufacturing processes, quality control and QMS)

• Inspector/s from the National Regulatory Authority

Inspection team consists of


Inspections site visits

� First, lead inspector (WHO staff member)

• reviews report on dossier

• selects and briefs other inspector/s

• arranges site visit logistics (agenda, travel, etc)� Then, the site visit

• 4-5 days for initial inspection; may be fewer days for subsequent visits (risk managed approach)

• 3 inspections (includes 2 surveillance) in a 5 year period if no major issues; product variations reviewed

• includes inspection of all aspects of product with immediate feedback to manufacturer on site

(preliminary draft report)


Inspections site visits (continued)

� Finally, lead inspector (WHO staff

member)

• sends draft report that describes

non conformances, then follows

up on non conformances and issues final inspection report

• summary report for website

• prepares internal DLT post

inspection report as part of DLT quality management system


Pilot Inspection

Resulted in

• Minor changes required for DLT inspection

process documentation.

• Need for additional time for an initial inspection –anticipate less for follow up inspections.

• Required repeated requests to address the non compliances satisfactorily thus extending the

time to inspection close out.


Often done fairly well

• Document control

• SOPs

• Training records

• Audit reports and scheduling

• Corrective actions linked to audits

• Equipment records


Often need improvement

• Risk analysis of processes

• Analysis of QC for trends

• Management review – scant evidence,

not done frequently

• Audit content – often not challenging

the system

• Batch release records – not reviewed

critically


Often need improvement

• Cleaning instructions inadequate

• Follow through of 'opportunities for

quality improvement' superficial – need

to consider lateral implications and risk

• Assessment of suppliers, particularly critical components, by manufacturer

not done or not documented adequately


Certification already?

• ISO 13485

• Notified Body (provide report to WHO)

• NRA capacity building opportunity

• WHO - aspects of particular interest

� PMS, customer complaints follow up/recalls

� Stability testing

� Transportation monitoring

� Batch release - specific QC issues


Activities 2009-10

� Perform PQ inspections following prioritization of applicants and review of dossiers

� Capacity building of local government entities to develop/strengthen national regulation, QMS

policies and accreditation/inspection processes

� Increase awareness and capability of

manufacturers to meet quality standards

� Post market surveillance of diagnostics

including review and capacity building of testing

laboratories and EQAS programmes


Questions?

inspections of sites of manufacture of diagnosticsiso 13485:2003 ( standard ) – medical devices...

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