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Prequalification Team ─ Diagnostics

Prequalification of In Vitro Diagnostics Programme- Internal Document

INTERNAL REPORT ON THE PRODUCT DOSSIER SCREENING

Purpose of the document

The Prequalification of In Vitro Diagnostics Programme utilizes internal procedures to ensure the efficient review and assessment of all applications to the Programme. One such process is the screening for completeness of the manufacturer’s submitted product dossier before it undergoes substantive technical review. The purpose of this document is to identify if a dossier meets a minimum threshold of acceptability and whether to progress towards prequalification assessment.

Prequalification of In Vitro Diagnostics Programme- Internal Document

INTERNAL REPORT ON THE PRODUCT DOSSIER SCREENING

Application Number: / PQDx
Product Name:
Manufacturer Name:
Product code(s)/catalogue number(s) and regulatory version:
Product kit size(s) (number of tests per kit): / T/kit
Date product dossier received by WHO: / DD/MM/YYYY
Date dossier screened: / DD/MM/YYYY
Name of PQDx screening reviewer:
PQDx clearance: Name and signature
Date: / DD/MM/YYYY

Table of Contents

Table of Contents 2

Scope 5

Legend of Codes Used 5

1. Comparison with the Letter of Agreement 5

2. Product Dossier Screening Overview 6

3. The Product Dossier 6

4. Dossier Format 6

5. Product Information 6

5.1. Regulatory versions of this product 6

5.2. Product description including variants (configurations) and accessories 8

5.3. Essential principles (EP) checklist 9

5.4. Risk analysis and control summary 9

6. Design and Manufacturing Information 9

6.1. Product design 9

6.1.1. Design overview 9

6.1.2. Formulation and composition 9

6.1.3. Biological safety 10

6.1.4. Documentation of design changes 10

6.2. Manufacturing process 10

6.2.1. Overview of manufacture 10

6.2.2. Sites of manufacture 11

6.2.3. Key suppliers 11

7. Product performance specifications, and associated validation and verification studies 11

7.1. Analytical Studies 11

7.1.1. Specimen type 12

7.1.2. Analytical performance characteristics 12

7.1.2.1. Accuracy of measurement 12

7.1.2.1.1. Trueness of measurement 12

7.1.2.1.2. Precision of measurement 12

7.1.2.1.2.1. Repeatability 12

7.1.2.1.2.2. Reproducibility 13

7.1.2.2. Analytical sensitivity 13

7.1.2.3. Analytical specificity 13

7.1.2.4. Traceability of calibrators and control material values 14

7.1.2.5. Measuring range of the assay 14

7.1.2.6. Validation of assay cut-off 14

7.1.2.7. Validation of assay procedure – reading time 14

7.2. Stability (excluding specimen stability) 15

7.2.1. Claimed shelf life 15

7.2.2. In-use stability 15

7.2.3. Shipping stability 16

7.3. Robustness Studies 16

7.4. Clinical evidence (clinical or diagnostic sensitivity and specificity) 17

7.4.1. Clinical evaluation - Manufacturer 17

7.4.2. Clinical evaluation - Independent study/ies 17

8. Labelling 18

8.1. Labels 18

8.2. Instructions for use 18

8.3. Instrument manual 18

9. Commercial history 19

9.1. Countries of supply 19

9.2. Adverse events and field safety corrective actions 19

10. Regulatory history 20

11. Quality management system 21

11.1. Quality manual 21

11.2. Quality management system certification 21

4. Dossier Format 22

4.1. Dossier submission format 22

4.2. Layout and order 22

4.3. Language 23

12. Product Dossier Screening Report 23

Scope

This internal report on the screening of the submitted product dossier has been prepared to provide summary information on the product dossier screening and a recommendation, such that the PQ Team can make a decision on whether to progress the dossier towards a prequalification assessment.

Legend of Codes Used

The below listed codes should be used in the column on the right side of the checklist in this document.

Y / Yes
N / No
N/A / Not applicable (comments required)

1. Comparison with the Letter of Agreement

Question / Y / N / NA / Comments/Explanation
Has the original signed Letter of Agreement been submitted as the cover letter of the dossier?
Does the application number on the Product dossier checklist match with the PQ number stated on the Letter of Agreement?
Does the product name match with the name provided in the Letter of Agreement?
Does the product code(s) match with the code(s) provided in the Letter of Agreement?
Does the manufacturer name match with the name provided in the Letter of agreement?

2. Product Dossier Screening Overview

Question / Y / N / NA / Comments/Explanation
Was the dossier submitted with the Product dossier checklist?[1]
For each requirement, were the volumes/pages clearly labelled in the checklist?

3. The Product Dossier

Question / Y / N / NA / Comments/Explanation
Has the authorized contact person for the manufacturer signed and dated the manufacturer declaration on the checklist?
Is the authorized contact person for the manufacturer that signed the declaration the same person as detailed on the pre-submission form[2] and named in the authorization letter from the manufacturer?

4. Dossier Format

See page 21 of this document.

5. Product Information

5.1. Regulatory versions of this product

Question / Y / N / NA / Comments/Explanation
Was Section 5.1 submitted?
Did the manufacturer identify if there are multiple regulatory versions of this product? / Choose name of type of regulatory approval.
RoW: specify country
(CE-mark) Directive 98/79/EC:
Self-declared CE-mark, Annex III
Full quality assurance certificate, Annex IV.3/ Product design examination certificate, Annex IV.4
Type examination certificate, Annex V/ Production quality assurance certificate, Annex VII
USFDA:
Premarket Approval (PMA) or 510(k) clearance
Health Canada:
Medical device license and summary report for a Class III IVD or Medical device license and summary report for a Class IV IVD
TGA Australia:
License for manufacture/ AUST R Number
Full quality assurance certificate/ Application audit report/ Production quality assurance certificate
JMHLW Japan:
License for manufacturer/ Recognized foreign/ manufacturer/ Minister’s approval
If the product has multiple regulatory versions, did the manufacturer clearly indicate which regulatory version of the product is submitted for prequalification assessment? / Choose name of type of regulatory approval.
RoW: specify country
(CE-mark) Directive 98/79/EC:
Self-declared CE-mark, Annex III
Full quality assurance certificate, Annex IV.3/ Product design examination certificate, Annex IV.4
Type examination certificate, Annex V/ Production quality assurance certificate, Annex VII
USFDA:
Premarket Approval (PMA) or 510(k) clearance
Health Canada:
Medical device license and summary report for a Class III IVD or Medical device license and summary report for a Class IV IVD
TGA Australia:
License for manufacture/ AUST R Number
Full quality assurance certificate/ Application audit report/ Production quality assurance certificate
JMHLW Japan:
License for manufacturer/ Recognized foreign/ manufacturer/ Minister’s approval
For all of the documents submitted in the product dossier, is the regulatory version to which they relate identified?
If there are documents that do not relate to the regulatory version submitted for prequalification, is a justification provided for their inclusion in the product dossier?

5.2. Product description including variants (configurations) and accessories

Question / Y / N / NA / Comments/Explanation
Was Section 5.2 submitted?
Is the intended use of the diagnostic identified?

5.3. Essential principles (EP) checklist

Question / Y / N / NA / Comments/Explanation
Was an EP checklist submitted in the form of a table?
Is the product name and product code the same as that for the product submitted for PQ?

5.4. Risk analysis and control summary

Question / Y / N / NA / Comments/Explanation
Was Section 5.4 submitted?
Has a risk analysis been submitted?
Has a summary report of risks identified during the risk analysis process and conclusion/statement been submitted?
Is the product name and product code the same as that for the product submitted for PQ?

6. Design and Manufacturing Information

6.1. Product design

6.1.1. Design overview

Question / Y / N / NA / Comments/Explanation
Did the manufacturer provide information on the design overview of the product?
Did the manufacturer provide a flowchart of the design process, including design inputs and outputs for the product for prequalification?

6.1.2. Formulation and composition

Question / Y / N / NA / Comments/Explanation
Did the manufacturer provide for each of the ingredients formulation/composition information (e.g. information such as nucleic acid sequences for primers, ingredient lists for buffers, amino acid sequence details for recombinant proteins)
Did the manufacturer identify the sources of the materials from which the IVD components are constructed?

6.1.3. Biological safety

Question / Y / N / NA / Comments/Explanation
Is there a list of all biological components included in the product under assessment?
Bacterial origin
Viral origin
Parasitic origin
Animal origin (such as plasma, cells, tissues, or their derivatives)
Human origin (such as plasma, cells, tissues, or their derivatives)

6.1.4. Documentation of design changes

Question / Y / N / NA / Comments/Explanation
Did the manufacturer provide records of design changes for the product submitted for prequalification?
If the manufacturer claims no changes, is there a statement that no changes have been made to the product since design lock down?

6.2. Manufacturing process

6.2.1. Overview of manufacture

Question / Y / N / NA / Comments/Explanation
Has an overview of the entire manufacturing process been submitted?
Has a manufacturing flow chart of the entire manufacturing process been submitted?

6.2.2. Sites of manufacture

Question / Y / N/ NA / Comments/Explanation
Was a list of all critical manufacturing sites that are involved in the manufacture of this product provided?
For each site, are the following included:
The name of the site
The physical address of the site
A description of the component manufacture/stage of the manufacturing process carried out at the site
A description of the manufacturing site
A simple site plan highlighting production areas
The number of employees at the site
A description of any other manufacturing that occurs at this site

6.2.3. Key suppliers

Question / Y / N / NA / Comments/Explanation
Did the manufacturer provide a list of all key suppliers of ingredients/products/services for the manufacture of this product?

7. Product performance specifications, and associated validation and verification studies

7.1. Analytical Studies

Question / Y / N / NA / Comments/Explanation
For each study submitted under section 7.1., are the study description, study identifier, product identifier (for example, lot numbers), IFU version used, identification of both PI and scientist conducting the study, date of study initiation, and the date of completion included?

7.1.1. Specimen type

Question / Y / N / NA / Comments/Explanation
Are the different specimen types that can be used with the product identified, including anticoagulants used to collect plasma?
Were studies that address duration, temperature, number of allowable freeze/thaw cycles and specimen stability claims done to support:
Stability claims
Storage claims
Is there a summary of the study findings?
Is there a study protocol and full report?

7.1.2. Analytical performance characteristics

7.1.2.1. Accuracy of measurement

7.1.2.1.1. Trueness of measurement

Question / Y / N / NA / Comments/Explanation
Was Section 7.1.2.1.1. submitted, including a study protocol and study report? [3]
Is there a summary of the study findings?
Is there a study protocol and full report?

7.1.2.1.2. Precision of measurement

7.1.2.1.2.1. Repeatability

Question / Y / N / NA / Comments/Explanation
Was Section 7.1.2.1.2.1. submitted?
Is there a summary of the study findings?
Is there a study protocol and full report?

7.1.2.1.2.2. Reproducibility

Question / Y / N / NA / Comments/Explanation
Was Section 7.1.2.1.2.2. submitted?
Is there a summary of the study findings?
Is there a study protocol and full report?

7.1.2.2. Analytical sensitivity

Question / Y / N / NA / Comments/Explanation
Was Section 7.1.2.2. submitted?
Is there a summary of the study findings, including a conclusion?
Is there a study protocol and full report?
For a quantitative assays, were the following parameters identified and were details provided on how they were derived:
Limit of blank (LoB): the number of standard deviations above the mean value of the specimen without analyte (measurand)
Limit of detection (LoD): the lowest concentration distinguishable from zero, based on measurements of specimens containing analyte (measurand)
Limit of quantitation (LoQ): the lowest concentration at which precision and/or trueness are within specified criteria

7.1.2.3. Analytical specificity

Question / Y / N / NA / Comments/Explanation
Was Section 7.1.2.3. submitted?
Is there a summary of the study findings?
Is there a study protocol and full report?
Were interference and cross-reactivity evaluated?

7.1.2.4. Traceability of calibrators and control material values

Question / Y / N / NA / Comments/Explanation
If the product includes calibrators and/or controls: Was Section 7.1.2.4. submitted?

7.1.2.5. Measuring range of the assay

Question / Y / N / NA / Comments/Explanation
Was Section 7.1.2.5. submitted?
Is there a summary of the study findings?
Is there a study protocol and full report?
For a qualitative test: Has a hook effect been documented or is there an explanation for why it is not applicable?

7.1.2.6. Validation of assay cut-off

Question / Y / N / NA / Comments/Explanation
Was Section 7.1.2.6. submitted?
If not applicable, was a rationale provided?
Is there a summary of the study findings?
Is there a study protocol and full report?

7.1.2.7. Validation of assay procedure – reading time

Question / Y / N / NA / Comments/Explanation
Was Section 7.1.2.7. submitted?
Is there a summary of the study findings?
Is there a study protocol and full report?

7.2. Stability (excluding specimen stability)

Question / Y / N / NA / Comments/Explanation
For each study submitted under section 7.2., are a study description, study identifier, product identifier (for example, lot numbers), IFU version used, identification of both PI and scientist conducting the study, date of study initiation and the date of completion included?

7.2.1. Claimed shelf life

Question / Y / N / NA / Comments/Explanation
Was Section 7.2.1. submitted?
Is there a summary of the study findings?
Is there a study protocol and full report?

7.2.2. In-use stability

Question / Y / N / NA / Comments/Explanation
Was Section 7.2.2. submitted?
Was an in-use stability study done for each assay component?
Is there a summary of the study findings?
Is there a study protocol and full report?

7.2.3. Shipping stability

Question / Y / N / NA / Comments/Explanation
Was Section 7.2.3. submitted for studies on one lot of product?
Is there a summary of the study findings?
Is there a study protocol and full report?

7.3. Robustness Studies[4]

Question / Y / N / NA / Comments/Explanation
Was Section 7.3. submitted?
Are a study description, study identifier, product identifier (for example, lot numbers), IFU version used, identification of both PI and scientist conducting the study, date of study initiation and the date of completion included?
Were studies done to address operator/human factors?
Were studies done to address specimen integrity and handling issues?
Were studies done to address reagent integrity issues?
Were studies done to address hardware, software and electronics integrity issues?
Were studies done to address issues related to the stability of calibration and internal controls?
Were studies done to address issues related to environmental factors and their impact on reagents, specimens, and test results?
For each of the issues to be addressed below to address robustness, were a full study protocol, method of data analysis and study conclusion provided?

7.4. Clinical evidence (clinical or diagnostic sensitivity and specificity)