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Pre-submission

Pre-submission

A manufacturer who wishes to apply for evaluation for prequalification of an in vitro diagnostic (IVD) must first complete and submit a pre-submission form, to provide summary information about the product, its regulatory version and the manufacturer. This information will enable WHO to determine whether the product is eligible for prequalification assessment and, if so, the type of assessment (full or abridged) that will be applied. It is also used to determine the regulatory version intended for prequalification and to plan for each of the components of the prequalification assessment process. 

Applications for WHO prequalification of IVDs are only accepted for products that are commercially available at the time of submission for prequalification assessment. Any exemptions must be agreed upon by WHO prior to the submission of the application for prequalification.

Each pre-submission form can refer to only one IVD and manufacturers may make no more than two attempts to submit a pre-submission form for a specific product. If, after two attempts to submit a pre-submission form a manufacturer has not provided the necessary information, the application for prequalification for that product will be rejected.

Manufacturers must not submit a product dossier together with the pre-submission form. Dossiers that are submitted in the absence of a formal request from WHO will be destroyed without prior notice.

1.1 Legal manufacturer

For the purpose of prequalification, WHO uses the following definition of "manufacturer": "any natural or legal person with responsibility for design and/or manufacture of an in vitro diagnostic (IVD) with the intention of making the IVD available for use, under his or her name, whether or not such an IVD is designed and/or manufactured by that person him- or herself or on his or her behalf by (an)other person(s)". Applications for WHO prequalification of IVDs are accepted only from the legal manufacturer of the product.

1.2 Authorized contacts for the manufacturer

The "authorized contacts for the manufacturer" are two people explicitly designated by the manufacturer to represent that manufacturer for the purposes of the WHO prequalification. These two authorized representatives will be the primary contact points for WHO in relation to the prequalification application submitted by the manufacturer. Therefore, the manufacturer is requested to ensure that all contact details provided in the pre-submission form are current. WHO suggests that the manufacturer ensures that the product manager/marketing and the technical/manufacturing functions of the manufacturer are covered by the two selected authorized contacts. A signed letter from the manufacturer stating that these two people are authorized to represent the manufacturer for the purposes of prequalification must be attached to the pre-submission form. The manufacturer should notify WHO of any changes to the authorized contacts.

Section 2

2.1. Product name and product code/catalogue number for WHO prequalification assessment

2.1.1 Only one IVD is permitted per pre-submission form. The name for one product only should be provided.

2.1.2 Provide the product code/catalogue number and the product kit size:

  • For products available in multiple kit sizes the kit size and product code for each individual kit size should be given.
  • For products with multiple kit configurations the contents, the quantity or volume of each component and product code (if applicable), should be listed.
  • Photographs of all kit components (packaged and individually) must be attached to the pre-submission form.

2.1.3 If reagents are provided in multiple boxes, the name and product code/catalogue number for each size of reagent box should be provided; e.g. if controls are provided separately to the test reagents, the catalogue number for the controls should be given.

  • For each different box size of reagent, the number of tests and product code for each box size should be listed.

2.1.4 A "dedicated instrumentation" defines a situation where the assay must be run on a specific instrument as part of the testing protocol. The instrument and assay reagents are only ever used in combination to perform the assay. If dedicated instrumentation is required to perform the assay please provide the name of the instrument(s) or component(s) and possible combinations of these, as well as the relevant product code(s)/catalogue number(s) (e.g. for the nucleic acid extraction units, amplification units, etc.).

2.1.5 A "regulatory version" relates to the information associated with a submission for approval by a regulatory authority. The submitted version is defined by all of the documentation related to development, manufacture, and intended use, labelling and post market surveillance of the product, and all the documented evidence supporting the safety and performance claims associated with that submission. If any aspect of this documentation differs in any way from the submissions made to different regulatory authorities or assessment bodies (Health Canada, US Food and Drug Administration, a Notified Body for CE marking, etc.), it is considered to be a different regulatory version.

Please indicate the year related to the regulatory version of the product being submitted for prequalification only.

2.2. Current instructions for use and user manual

Provide document control details for the instructions for use documentation and the user manual(s) relevant to this product.

Attach to the pre-submission form a copy of the English language version of the instructions for use (package insert).

The version of the instructions for use submitted along with the pre-submission form will be considered the official version submitted for prequalification assessment. During prequalification assessment, manufacturers cannot make changes to this version of the instructions for use without prior notification to WHO. Any changes to such version must be agreed with WHO prior to their implementation or the application may be terminated.

2.3. Transport, storage and operating temperatures

2.3.1 The transport, storage and operating temperature ranges must be clearly specified by the manufacturer. The manufacturer's specified transport, storage and operating temperatures ranges and shelf-life period upon manufacture should be provided for the assembled product.

"Shelf-life upon manufacture" is the period of time from when the product is released for supply until the expiry date ‒ during which time product performance is assured by the manufacturer.

For products where reagents are provided in more than one box, provide the transport, storage and operating temperature ranges and shelf-life periods for each box of test reagents required to perform the assay.

2.3.2 If there are any other specified storage conditions applicable to this product, also provide details of these storage requirements.

Note: If this product is accepted for prequalification assessment, you will be required to provide evidence as part of your product dossier submission (such as data generated through stability studies) demonstrating that the product continues to perform within specifications, to support all claims.

Section 3

For questions 3.1‒3.7. tick/check the boxes that are relevant to your product.

4.1 Assay controls

A "specimen addition control" provides confirmation to the user of the assay that the specimen being tested has been added to the assay.

"Control samples" (also called "test-kit controls") refer to preparations that are specifically designed by the manufacturer for this particular assay. These control samples are usually a positive and a negative control specimen.

4.2 Product usage

"Single run" refers to the number of specimens that can be tested consecutively by one operator without interruption (unless the recommended operation requires such interruption).

4.3 Indicative cost

Please provide the indicative cost per test in US dollars and if applicable, the cost of the dedicated instrumentation required to perform the assay.

5.1 Performance characteristics for serology enzyme immunoassays and rapid diagnostic tests

"Sensitivity" refers to clinical or diagnostic sensitivity. Sensitivity is the ability of a test to give a positive result for individuals that have the disease or disorder for which they are being tested. The disease status of the individual must be predefined by criteria that are independent of the test under consideration.

"Specificity" refers to clinical or diagnostic specificity. Specificity is the ability of a test to give a negative result for individuals that do not have the disease or disorder for which they are being tested. The negative disease status of the individual must be predefined by criteria that are independent of the test under consideration.

The above definitions are based on terminology used in the publicly available Harmonized Terminology Database, compiled by the Clinical and Laboratory Standards Institute.)

5.2 Specifications for CD4 technologies

Section 5.2. applies only to CD4 Technologies and should be left blank for other types of products.

5.3 Specifications for virological technologies

Section 5.3. applies only to virological technologies and should be left blank for other types of products.

6. Regulatory and commercial status of the product

6.1 Regulatory status of the product

6.1.1 Please refer to the definition of regulatory version provided in section 2.1.5. and identify the regulatory version of the product submitted for prequalification.

6.1.2 Please tick/check the boxes that are relevant to your product and provide details of all current regulatory approvals for this product.

"National regulatory authority" (NRA) means a government body or other entity that exercises a legal right to control the use or sale of IVDs within its jurisdiction, and may take enforcement action to ensure that IVDs diagnostics marketed within its jurisdiction comply with legal requirements.

"Regulatory approval" means that the NRA officially permits supply of this IVD in the country/region under its authority.

"Type of regulatory approval" refers to the relevant sections of the legislation that have been applied to the product for regulatory approval. Generally the details of the legislation applied for regulatory approval should be included on the certificate that demonstrates that the product is approved for supply.

Note: Certification information relating to ISO 13485 Medical devices ‒ Quality management systems ‒ Requirements for regulatory purposes should not be included here since questions relating to ISO 13485 are addressed in Section 7 of the pre-submission form.

6.2 Commercial agreements and re-branding

WHO requires this commercial agreement information available in order to determine eligibility for prequalification assessment. Applications for WHO prequalification of IVDs are accepted only from the legal manufacturer of the product.

6.3 WHO history of product

Provide information on previous WHO assessment of the product.

Section 7  Quality management system

An effective quality management system (QMS) is a key consideration for all manufacturers of IVDs. Products submitted for prequalification assessment must be manufactured under an appropriate QMS. The quality management standard ISO 13485 Medical devices ‒ Quality management systems ‒ Requirements for regulatory purposes is considered to be a benchmark in quality management for the manufacturers of diagnostic products by regulatory agencies throughout the world. WHO prequalification assessment and inspection processes are based on the requirements of this internationally recognized quality management standard.

In this section provide information about the manufacturer's QMS and conformity to the referenced standards.

Section 8  Quality management system certification

If the manufacturer holds ISO 13485 certification for the manufacture of this product, details of this certification should be provided in this section. This certification must list all sites involved in the manufacture of the product.

The manufacturer will be required to provide evidence of all QMS claims as part of the product dossier submission.

9.1 Sites of manufacture

List all sites that are involved in the manufacture of this product. Include all stages of manufacture, e.g. design and development, assembly, labelling, packaging, lot release quality control, release for supply.

9.2 Contact person(s) for inspection

Provide contact information for the inspection authorized contact

9.3 Production

Provide information on the number of lots manufactured per year, their average size and the total number of products manufactured per year (including instruments).

9.4 Key suppliers

List all key suppliers which supply products/components/services for the manufacture of this product

Performance evaluation of IVDs submitted for prequalification is carried out by specified WHO Collaborating Centre(s) or a designated laboratory or laboratories (collectively referred to as “evaluating site(s)”), using the WHO prequalification evaluation protocol.

The manufacturer must choose one of two performance evaluation options:

  • Option 1: Performance evaluation commissioned by WHO and carried out at an evaluating site listed by WHO.
  • Option 2: Performance evaluation commissioned by the manufacturer and carried out at an evaluating site listed by WHO.

The manufacturer must tick/check the relevant box to indicate its choice of performance evaluation. Under Option 2, the manufacturer will bear the cost of the evaluation and be responsible for coordinating the evaluation directly with the evaluating site.

This declaration must be completed before the application will be considered for prequalification assessment. The declaration must be duly signed by the key authorized contact for the manufacturer designated under Section 1.2.

If a non-stringently assessed (rest of world) regulatory version of the product is submitted for prequalification assessment but a stringently assessed regulatory version also exists, WHO will review the differences between the two regulatory versions to determine eligibility for abbreviated assessment, based on the information provided in Annex 1.

In this section provide information on the product, its design and manufacturing, and labelling.

Submission procedure

Documentation to be submitted

The manufacturer must submit the following documentation

  • a completed pre-submission form
  • a signed letter stating that the two people referred to are authorized to represent the manufacturer for the purposes of prequalification of the product
  • photographs of all kit components (packaged and individually)
  • instructions for use
  • (if relevant) completed Annex 1: Eligibility for abridged prequalification assessment.

Where to submit the documentation

The pre-submission form and the respective attachments must be submitted electronically — as searchable PDF files — to: diagnostics@who.int.

Following submission

The completed pre-submission form and supporting documentation will be reviewed against the eligibility criteria for IVD prequalification to determine eligibility for prequalification assessment. If the product meets the criteria the manufacturer will be informed about the next steps to be followed, depending on the type of assessment (full or abridged) to be applied to the product. If necessary, WHO may request additional information and/or clarifications to assist it in the eligibility decision. The manufacturer must provide WHO with the information and/or clarifications so requested within the deadlines prescribed by WHO.

WHO will inform the manufacturer in writing of its decision as to whether or not the product is eligible for prequalification assessment. If a product is eligible for prequalification assessment, WHO will request the manufacturer to complete, sign and return to WHO a letter of agreement confirming that the product will undergo assessment by WHO, and the manufacturer's commitment to comply with the provisions of the prequalification assessment process. A prequalification dossier screening and assessment fee will also be due for payment by the manufacturer. Assessment cannot be initiated until the manufacturer has provided a signed and completed letter of agreement, and proof of payment the applicable prequalification fee.