WHO Public Assessment Reports (WHOPARs) are a key prequalification output: providing insight and transparency about the process followed to prequalify a specific finished pharmaceutical product (FPP).

The value of the WHOPAR for regulators and procurers lies in the fact that it summarizes WHO‘s assessment of the data and information provided by the manufacturer and describes the quality, safety and efficacy of the prequalified product. The product information, which is an essential component of a prequalified FPP, forms an important part of the WHOPAR.

Parts 3 and 4 of a WHOPAR – product information for the user and product information for the health care provider – have been quality assured by WHO. In effect they form a component of the prequalified medicinal product. Therefore they may be altered only after this has been accepted by WHO. The final product information for an authorized product may differ from that published in the WHOPAR where changes are requested by an authorizing national medicines regulatory authority.

If a product (including its information) is altered outside these procedures it can no longer be considered to be prequalified. (But see also the section on deviations below.)

Parts of a WHOPAR

A WHOPAR consists of eight parts:

Part 1: Abstract

Part 2: All accepted presentations (including photo)

Part 3: Product information for the user

Part 4: Information for the health care provider

Part 5: Labelling

Part 6: Scientific discussion

Part 7: Steps taken for prequalification

Part 8: Steps taken following prequalification.

Information for development of a WHOPAR

The structure and format of the WHOPAR are adapted from the European Public Assessment Report, as published by the European Medicines Agency (EMA), to serve the requirements of WHO medicines prequalification.

In submitting a product for evaluation for prequalification an applicant must contribute the information and/or documents that will be needed – in the event of prequalification – for development of or inclusion in the WHOPAR. The information and/or documents to be submitted will depend upon whether the product has been approved by the national medicines regulatory authority (NMRA) of an ICH member or associated member country or is a multisource generic product submitted for full assessment. (ICH is the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use . See http://www.ich.org/)  Further details are given in the WHO Public Assessment Reports table. It outlines the information required for inclusion in and indicates who (the applicant or WHO) is responsible for development of each part of a WHOPAR.

Failure to submit the required documentation to be included in a WHOPAR may result in rejection of the application.

Steps in developing a WHOPAR

The sequence for developing a WHOPAR following prequalification of an FPP is as follows:

Step 1:  The applicant submits documents required for the WHOPAR as part of the initial submission for evaluation for prequalification to WHO.

Step 2:  WHO compiles the draft WHOPAR when the assessment and inspections have been completed successfully.

Step 3:  WHO forwards the draft WHOPAR to the applicant for review. (Documents are exchanged in electronic format by the applicant and WHO, generally  by email.)

Step 4:  The applicant reviews and comments on (annotates) the draft WHOPAR, in particular to ensure that the WHOPAR does not contain any proprietary or confidential information.

Step 5:  The applicant returns the annotated draft WHOPAR to WHO.

Step 6:  WHO reviews the annotated text – Steps 3 to 6 may need to be repeated if an item requires further clarification – and finalizes the WHOPAR.

Step 7:  If the FPP, as produced at the specified manufacturing site(s), meets the prequalification requirements, WHO accepts the FPP for inclusion in the WHO List of Prequalified Medicinal Products (i.e. prequalifies it) publishes the WHOPAR and informs the applicant accordingly.

Step 8:  Within three months after acceptance/publication of the WHOPAR, the applicant provides a mock-up of the final patient information leaflet (PIL), taking into consideration the recommendations as described in the European Commission's guideline on the readability of the labelling and the package leaflet of medicinal products for human use.

Guidance relating to development of contents of WHOPAR

WHO prequalification guidance documents should be consulted before preparing the PIL, the summary of product characteristics (SmPC) and the labelling document that will form the basis of Parts 3, 4 and 5, respectively of the WHOPAR for a prequalified product.

These documents include templates and annotated templates:

• PIL template (for part 3 of a WHOPAR)
• Annotated PIL template (for part 3 of a WHOPAR)
• SmPC template (for part 4 of a WHOPAR)
• Annotated SmPC template (for part 4 of a WHOPAR)
• Labelling template (for part 5 of a WHOPAR)
• Annotated Labelling template (for part 5 of a WHOPAR).

The templates provide the structure for the relevant sections of a WHOPAR while the annotated templates provide guidance on the content and level of detail required in those sections.

In addition, guidance is available relating to a number of specific sections/sub-sections and to Part 6 (Scientific Discussion) of a WHOPAR:

• Section 5 (Storing X) of Part 3 (Patient Information Leaflet) of a WHOPAR
• Sub-sections 4.6 (Pregnancy and lactation), 4.8 (Undesirable effects) and 6.4 (Special precautions for storage) of Part 4 (SmPC) of a WHOPAR
• Section 9 (Special storage conditions of Part 5 (Labelling) of a WHOPAR
• Part 6 (Scientific Discussion of a WHOPAR).

Prequalification guidance is also available on:

• Ensuring consistency between product information documents for inclusion in WHOPARs.

Additionally, useful guidance on use of non-standard abbreviations, terms, terminology and stylistic matters is available from EMA.

Bibliographic submission

A bibliographic submission must be submitted in the case of a multisource generic product for which no (acceptable) comparator/reference product exists (such as products containing a new combination of active ingredients such as fixed-dose combinations (FDCs) or traditionally/used multisource products such as artemisinins) and should:

• contain information on safety and efficacy as would be requested by a stringent regulatory authority
• include a clinical overview written by a qualified person (the curriculum vitae of whom is included in the submission):
  • summarizing all relevant scientific literature, including, in the case of fixed-dose combination FPPs, including evidence relating to the safety and efficacy of the equivalent combination of the single active pharmaceutical ingredients
  • referencing original clinical research (if carried out)
  • referencing relevant treatment guidelines, particularly those issued by WHO
• other relevant documentation (listing all references and to be made available upon request by WHO) supporting the information that is or will be included in the PIL, SmPC and the summary of product safety and efficacy that will form part of the Scientific Discussion (i.e. Parts 3, 4 and 6, respectively, of a WHOPAR).

The format for presenting information and data should adhere to the recommendations found in Marketing Authorization of Pharmaceutical Products with Special Reference to Multisource (Generic) Products: a Manual for National Medicines Regulatory Authorities (NMRAs).

Further useful guidance is given in the WHO Guidelines for Registration of Fixed-dose Combination Medicinal Products (2005), particularly Appendix 2, which defines principles for determining whether data from the scientific literature are applicable.

Deviations from prequalified product information

Some deviations from the SmPC and PIL published with the WHOPAR are acceptable:

•    combining the PIL text with the SmPC text is acceptable if both texts are included in their entirety and any parts intended for professionals only are clearly marked
•    making available only the SmPC (and not also PIL) is acceptable for products that are administered in hospital/by a health care professional only
•    changing the order of items in the SmPC/PIL is acceptable if nothing is omitted (although the standard European format for a PIL and SmPC remains strongly recommended)
•    Where applicable the USAN may be used instead of the INN for the name of the active substance.

The reason for any deviation from the product’s prequalified texts must be clearly stated to WHO by the supplier whenever such a deviation applies.

Following the first posting of the WHOPAR on this website, updating of the PIL and SmPC may be necessary. For example, when:

•    WHO treatment recommendations change
•    the corresponding text for the innovator product has undergone significant updating
•    new and relevant scientific data have become available.

PQT/MED undertakes to account for this by ad hoc or periodic WHOPAR updates. However, suppliers are strongly encouraged to advise WHO of any potential need for updating the product information. In these cases, the supplier should submit the new texts to WHO with a tabular overview of the proposed changes (pre-change/post-change) together with the rationale and relevant references. 

Translations

All information related to prequalified products must be provided in English. The supplier should ensure that translations into other languages are of good quality. Translations should be made by qualified medical translators and should be double-checked by  the manufacturer or the translation office. A poor-quality translation may severely compromise the safety and efficacy of the medicinal product. Therefore, products not complying with this requirement cannot be marketed as prequalified.

Availability in other languages

For certain markets availability of the product information (PIL/SmPC/Labelling) in languages other than English may be necessary (as requested by the national medicines regulatory authority or procurement organizations). Ensuring the correctness of these translations is not within the remit of WHO.