WHO PROCEDURE FOR CHANGES TO A WHO …

1 PQDx_121 v1 27 June 2014 WHO PROCEDURE FOR CHANGES TO A WHO PREQUALIFIED IN VITRO DIAGNOSTIC WHO Prequalification of In Vitro Diagnostics Programme P r e q u a l i f i c a t i o n T e a m - D i a g n o s t i c s PQDx_121 v1 27 June 2014 Page 2 of 16 Table of Contents 1. Introduction .. 3 2. Intended Audience .. 3 3. Definitions .. 3 4. Abbreviations .. 3 5. Scope .. 4 6. Determining the significance of a change to a prequalified product .. 4 7. Change notification categories .. 5 Minor CHANGES .. 6 Substantial CHANGES to manufacturing processes, facility or equipment .. 7 CHANGES to the manufacturing quality control procedures .. 8 CHANGES in 8 CHANGES in product s software .. 9 CHANGES in materials/components .. 10 CHANGES to labelling .. 10 CHANGES leading to a new product .. 11 8. Other CHANGES requiring the submission of a Change Notification .. 11 CHANGES in product name, product code(s) and/or manufacturer name only.

2 11 CHANGES in the regulatory or certification status of the product .. 11 9. Notification of CHANGES to WHO .. 12 10. Change assessment fee .. 12 11. Attachments to the Change Notification form .. 12 12. Assessment of submitted Change Notification .. 13 13. Failure to comply with requirements to notify CHANGES .. 14 14. Annual reporting of CHANGES .. 15 15. Relevant documents .. 15 16. Contact information .. 16 PQDx_121 v1 27 June 2014 Page 3 of 16 1. Introduction The World Health Organization (WHO) Prequalification of In Vitro Diagnostics (IVDs) Programme is coordinated through the department of Essential Medicines and Health Products (EMP). The aim of the WHO Prequalification of IVDs Programme is to promote and facilitate access to safe, appropriate and affordable IVDs of good quality in an equitable manner. Focus is placed on IVDs for priority diseases and their suitability for use in resource-limited settings.

3 The WHO Prequalification of IVDs Programme undertakes a comprehensive assessment of individual IVDs through a standardized PROCEDURE aimed at determining if the product meets WHO prequalification requirements. The prequalification assessment process includes three components: Review of a product dossier; laboratory evaluation of performance and operational characteristics; and manufacturing site(s) inspection. Post-market surveillance is a WHO post-qualification activity which includes reactive and proactive measures, through complaint reporting and post-shipment/pre-distribution lot testing. Post-qualification also includes mandatory manufacturer notification of CHANGES to the product or the quality management system. 2. Intended Audience This document aims to provide manufacturers with information on CHANGES to the product, to its regulatory or certification status and/or to the Quality Management System (QMS) that must be notified to WHO.

4 It is recommended that manufacturers with WHO prequalified product(s) read this document. 3. Definitions In vitro diagnostic1 A medical device, whether used alone or in combination, intended by the manufacturer for the in vitro examination of specimens derived from the human body solely or principally to provide information for IVD, monitoring or compatibility purposes. Manufacturer2 Any natural or legal person with responsibility for design and/or manufacture of a IVD product with the intention of making the IVD product available for use, under his/her name; whether or not such a IVD product is designed and/or manufactured by that person himself/herself or on his/her behalf by another person(s). 4. Abbreviations IVD In vitro diagnostic WHO World Health Organization QMS Quality management system 1 From Glossary and Definitions of Terms Used in GHTF Documents, GHTF/SC/N4:2012 (Edition 2) PQDx_121 v1 27 June 2014 Page 4 of 16 5.

5 Scope As part of the life cycle of a prequalified IVD, CHANGES to it, its regulatory or certification status and/or the QMS under which it is produced may become necessary. Such CHANGES (sometimes referred to as variations ) to prequalified products may be minor, administrative or substantial. As part of theirits QMS, the manufacturer should have a system in place to design, validate and implement CHANGES and to determine their significance. This document describes the conditions under which WHO should be notified about CHANGES to a prequalified product, its regulatory or certification status and/or to the QMS under which it is manufactured. Because it is not possible to describe all potential CHANGES , this document provides guidance and a non-exhaustive list of generic examples. If in doubt or where the guidance does not sufficiently clarify a specific scenario, it is the manufacturer s responsibility to seek advice from WHO and to properly document the reason why a change was not reported to WHO.

6 This document also describes when WHO considers a change to require a new application for prequalification. Manufacturers should read this document carefully and notify CHANGES to prequalified IVDs in accordance with the information provided in this document. NOTE: The examples provided in this document are only illustrative and are not intended to be exhaustive. 6. Determining the significance of a change to a prequalified product In order to meet the prequalification requirements, the manufacturer should establish, maintain and implement a PROCEDURE for categorizing and documenting any CHANGES to the IVD, its regulatory or certification status and/or the QMS. The manufacturer should then assess the significance of any change, according to the guidance provided in this document. To determine if a change requires notification to WHO, the manufacturer should evaluate the potential effect this change may have on the design, composition, safety, quality and/or performance of the IVD.

7 Consideration should be given as to whether or not the change has influenced the risk profile of the IVD in any manner (for example, if it has introduced new hazards, eliminated existing hazards, or had any influence on the level of risk associated with a hazard). Such CHANGES may require notification. CHANGES to the approved design, the construction, manufacturing site, raw material and/or composition of a prequalified IVD must be reported. WHO recommends that the manufacturer s decision on the type of change and the subsequent type of notification to WHO is based on the steps listed below: Identify the change and document the reasons for the change; conduct a risk analysis of the change and determine the potential impact of the change on the quality, safety and performance of the IVD ( When an IVD is part of a system, and any individual characteristic of the IVD or system CHANGES , the system as a whole should be evaluated); define the data needed to assess the impact of the change on the safety and performance of the IVD; review the risk assessment after necessary testing and before the introduction of hazard reduction steps ( labelling including instructions for use); and PQDx_121 v1 27 June 2014 Page 5 of 16 categorize the change at this point.

8 Aspects that should be considered include whether or not: Thethe change introduces new hazards that have not been previously addressed; the change adversely affects the risk associated with existing hazards; the change alters the details in the application submitted for prequalification (related to dossier, inspection, or laboratory evaluation), such as the intended use and/or compliance with the Essential Principles3 the change will introduce a different intended use (refer Section 5); the performance data (analytical and clinical) for the original prequalified IVD are sufficient to demonstrate conformity of the changed product with the required characteristics and performance of the original prequalified IVD; the change alters the manufacturing technologies or product range covered by the inspected QMS; the change affects the approved design; the change affects the continued compliance of the QMS with the relevant standards; and the change affects the continued compliance with WHO prequalification requirements.

9 If the safety and/or performance of the product has been or will be affected by the change, this constitutes at a minimum, a substantial change. If in doubt, the manufacturer should seek advice from WHO. NOTE: Where several, simultaneous CHANGES are being considered by the manufacturer, each change should be assessed separately, as well as the collective impact of the CHANGES . NOTE: CHANGES applied to an IVD must be undertaken in compliance with the requirements for control of design change as per ISO 13485:2003 Medical devices -- Quality management systems -- Requirements for regulatory purposes 7. Change notification categories After an IVD has been prequalified, the manufacturer must notify WHO regarding: any substantial CHANGES to the IVD prior to implementation of the CHANGES ; any CHANGES to the regulatory approval or certification status for the IVD, such as suspension or withdrawal of regulatory approval or certificate, in all countries of manufacture and supply; and/or any substantial CHANGES to the QMS.

10 NOTE: CHANGES may only be implemented by the manufacturer after WHO has approved the request for change. The requirement to notify a change is dependent on the significance of the change. Figure 1 provides an overview of actions required according to the classification of the change. 3 Please refer to the GHTF/SG1/N41R9:2005 Essential Principles of Safety and Performance of Medical Devices [Global Harmonization Task Force (GHTF) document; ] for further information. PQDx_121 v1 27 June 2014 Page 6 of 16 NOTE: The decision-making process to determine the type of change to the product (minor, substantial or leading to a new product) is the sole responsibility of the In the change notification, the manufacturer should provide a justification for having considered a change to be substantial. Minor CHANGES A manufacturer may make a minor change to a product and/or to the QMS after prequalification without submitting a new application for prequalification or a Change Notification, if the change does not affect the IVD's design, composition, safety and/or performance.