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
Informal Consultative Meeting for Diagnostic Manufacturing Associations, UN Procurement Agencies and WHO , 4 February 2009
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
Informal Consultative Meeting for Diagnostic Manufacturing Associations, UN Procurement Agencies and WHO , 4 February 2009
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
Informal Consultative Meeting for Diagnostic Manufacturing Associations, UN Procurement Agencies and WHO , 4 February 2009
Quality Management System
Informal Consultative Meeting for Diagnostic Manufacturing Associations, UN Procurement Agencies and WHO , 4 February 2009
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.
Informal Consultative Meeting for Diagnostic Manufacturing Associations, UN Procurement Agencies and WHO , 4 February 2009
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
Informal Consultative Meeting for Diagnostic Manufacturing Associations, UN Procurement Agencies and WHO , 4 February 2009
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
Informal Consultative Meeting for Diagnostic Manufacturing Associations, UN Procurement Agencies and WHO , 4 February 2009
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
Informal Consultative Meeting for Diagnostic Manufacturing Associations, UN Procurement Agencies and WHO , 4 February 2009
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
Informal Consultative Meeting for Diagnostic Manufacturing Associations, UN Procurement Agencies and WHO , 4 February 2009
Purpose of the Inspection
• Verify the QMS claims
• Strengthen national regulatorycapacity (NRA staff)
• Beneficial for the manufacturer
Informal Consultative Meeting for Diagnostic Manufacturing Associations, UN Procurement Agencies and WHO , 4 February 2009
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
Informal Consultative Meeting for Diagnostic Manufacturing Associations, UN Procurement Agencies and WHO , 4 February 2009
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
Informal Consultative Meeting for Diagnostic Manufacturing Associations, UN Procurement Agencies and WHO , 4 February 2009
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
Informal Consultative Meeting for Diagnostic Manufacturing Associations, UN Procurement Agencies and WHO , 4 February 2009
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)
Informal Consultative Meeting for Diagnostic Manufacturing Associations, UN Procurement Agencies and WHO , 4 February 2009
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
Informal Consultative Meeting for Diagnostic Manufacturing Associations, UN Procurement Agencies and WHO , 4 February 2009
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.
Informal Consultative Meeting for Diagnostic Manufacturing Associations, UN Procurement Agencies and WHO , 4 February 2009
Often done fairly well
• Document control
• SOPs
• Training records
• Audit reports and scheduling
• Corrective actions linked to audits
• Equipment records
Informal Consultative Meeting for Diagnostic Manufacturing Associations, UN Procurement Agencies and WHO , 4 February 2009
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
Informal Consultative Meeting for Diagnostic Manufacturing Associations, UN Procurement Agencies and WHO , 4 February 2009
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
Informal Consultative Meeting for Diagnostic Manufacturing Associations, UN Procurement Agencies and WHO , 4 February 2009
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
Informal Consultative Meeting for Diagnostic Manufacturing Associations, UN Procurement Agencies and WHO , 4 February 2009
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
Informal Consultative Meeting for Diagnostic Manufacturing Associations, UN Procurement Agencies and WHO , 4 February 2009
Questions?
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