Contents of a Dossier
WHO reviews the product dossier to:
- assessing the product and how it performs
- assess product manufacture
- determine whether the manufacturer's quality management system is of an adequate standard to warrant a site inspection.
It must therefore contain:
- product information
- design and manufacturing information
- product performance specification, and information about associated validationa and verification studies
- labelling information
- commercial history
- regulatory history
- information about the quality management system.
Details of the information provided for each of the above categories is given in the drop-down sections below.
Please refer to the relevant WHO guidance documents (prequalification guidance, technical guidance series, technical specifications series and sample product dossiers) for additional detailed information when compiling the product dossier.
ESSENTIAL PRINCIPLES CHECKLIST
An essential principles checklist can be used by manufacturers to readily understand how the manufacturer demonstrates compliance with the essential principles for a particular IVD. The checklist also facilitates easy identification of relevant documents and data for conformity assessment purposes. The contents of the checklist vary depending on the type of IVD in question. More complex IVDs are more likely to reference a larger number of standards, test reports and documents. In those cases the checklist might be many pages long.
As a top-line guide only, the following criteria constitute a simple overview of essential principles relating to an IVD:
- its use must not compromise health and safet
- its design and construction must conform with safety principles
- it must be suitable for intended purpose
- it must not to be adversely affected by defined transport or storage
- it must achieve its intended purpose
- its risk versus benefits must be acceptable to user, patient and any other applicable individual
- it must have easy-to-use instructions / protocol for use, with reduced risk of error in use and interpretation
- it must meet acceptable performance specifications such as sensitivity, specificity, trueness, repeatability, reproducibility, control of interference and limits of detection
- its design must allow for verification by user (positive and negative controls)
- it must have traceability of controls and calibrators.
The following is a recommended template for the contents of a checklist.
Identity of the IVD
The manufacturer should identify the IVD, and when applicable the various configurations/variants covered by the checklist.
Applicable to device?
Is the listed essential principle applicable to the IVD? Here the answer is either "Yes" or "No". If the answer is "No", this should be briefly explained.
Method used to demonstrate conformity
In this column, the manufacturer should state the type(s) of method(s) that it has chosen to demonstrate conformity, e.g. the recognized standard(s), industry or in-house test method(s), comparison study(ies) or other method used.
The method used to demonstrate conformity may include one or more of the following:
- conformity with recognized or other standards
- conformity with a commonly accepted industry test method (reference method)
- conformity with appropriate in-house test methods that have been validated and verified
- comparison to a diagnostic already available on the market.
After having stated the method in the previous column, here the manufacturer should name the title and reference the recognized standard(s), industry or in-house test method(s), comparison study(ies) or other method used to demonstrate conformity. For standards, this should include the date of the standard and where appropriate, the clause(s) that demonstrates conformity with the relevant essential principle.
Reference to supporting controlled documents
This column should contain the reference to the actual technical documentation that demonstrates conformity to the essential principle, i.e. the certificates, test reports, study reports or other documents derived from the method used to demonstrate conformity and its location within the product dossier.
Table for illustrative purposes. When creating such a table the essential principles listed in the first column should be extracted from GHTF’s guidance document Essential principles of Safety and Performance of Medical Devices (GHTF/SG1/N68:2012).
Examples of a completed checklist can be found in the WHO sample product dossiers:
Instructions for compilation of a product dossier ‒ IMDRF ToC (PQDx_018, Version 5, November 2022)
Table of Content (ToC) - Product Dossier Checklist (PQDx 049, version 4, 15 November 2022)
WHO sample product dossiers for WHO prequalification
Global Harmonization Task Force* guidance
GHTF/SG1/N68:2012 Essential Principles of Safety and Performance of Medical Devices
GHTF/SG1/N70:2011 Label and Instruction Use for Medical Devices
GHTF/SG2/N54R8:2006 Medical Devices Post Market Surveillance: Global Guidance for Adverse Event Reporting for Medical Devices
GHTF/SG2/N57R8:2006 Medical Devices Post Market Surveillance: Content of Field Safety Notices
* A voluntary group of representatives from regulatory authorities (United States, Canada, European Union, Japan, and Australia), as well as representatives from the medical device industry. In 2012 GHTF was replaced by a regulators-only group, the International Medical Device Regulators Forum (IMDRF), which has adopted the GHTF classification rules and other GHTF regulatory guidelines. IMDRF continues to maintain GHTF guidelines and develop more guidance that will encourage international regulatory convergence and support innovation and timely access to safe and effective medical devices globally.
International Medical Device Regulators Forum guidance
Essential Principles of Safety and Performance of Medical Devices and IVD Medical Devices (IMDRF/GRRP WG/N47 FINAL:2018)
International Organization for Standardization guidance
ISO 13485:2003 Medical devices – Quality management systems – Requirements for regulatory purposes
For guidance on implementation of ISO 13485:2016 see ISO 13485:2016 Medical devices – A practical guide
ISO/TR 10013:2001 Guidelines for quality management system documentation
ISO 18113-1 Clinical laboratory testing and in vitro diagnostic test systems
ISO 18113-2 Clinical laboratory testing and in vitro diagnostic test systems
ISO 18113-3 Clinical laboratory testing and in vitro diagnostic test systems
ISO 18113-4 Clinical laboratory testing and in vitro diagnostic test systems
ISO-18113-5 Clinical laboratory testing and in vitro diagnostic test systems
ISO/TR 18112:2006 Clinical laboratory testing and in vitro diagnostic test systems – In vitro diagnostic medical devices for professional use – Summary of regulatory requirements for information supplied by the manufacturer
ISO15198:2004 Clinical laboratory medicine – In vitro diagnostic medical devices – Validation of user quality control procedures by the manufacturer
ISO/FDIS 17511 In vitro diagnostic medical devices – requirements for establishing metrological traceability of values assigned to calibrators, trueness control materials and human samples
ISO 15194:2009 In vitro diagnostic medical devices – Measurement of quantities in samples of biological origin – Requirements for certified reference materials and the content of supporting documentation
ISO 14971:2019 Medical devices – Application of risk management to medical devices
Clinical and Laboratory Standards Institute guidance
CLSI EP25-A Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline (2009)