Contents and Structure of a WHOPAR

WHO Public Assessment Reports (WHOPARs) are a key output of the WHO Prequalification Team: medicines, providing insight and transparency as to the process followed to prequalify the finished pharmaceutical products (FPPs) concerned.

A WHOPAR is of great value for regulators and procurers. As well as summarizing the assessment of the data and information provided by the manufacturer, it describes the quality, safety and efficacy of the prequalified product. Indeed, the product information is an essential component of a prequalified FPP.

Parts 3 and 4 of a PAR — 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 an application for variation has been accepted by PQTm. If a product (including its information) is altered outside this procedure 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 2a: All accepted presentations

Part 2b: Appearance of Product

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 Harmonisation 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 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 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 the European Medicines Agency.

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 an SRA
  • 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)
  • aligning the product information with the corresponding texts in a more recently published WHOPAR of a comparable product (e.g. same API, comparable pharmaceutical formulation, same dosage strength) is possible.

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

Following posting of the WHOPAR on the PQTm website updating of the PIL and SmPC may be necessary. For example:

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

In these cases the applicant should submit the new texts to PQTm with a tabular overview of the changes (pre-change/post-change) together with the reasons for any changes, a short expert statement, and any references. A statement from WHO PQTm as to the acceptability of the new texts must be received before either the PIL and or the SmPC can be changed.

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 PQTm.

Procedural guidance

Guidelines for registration of fixed-dose combination medicinal products (2005)

Procedure for prequalification of pharmaceutical products (2011)


WHOPAR section guidance

Section guidance for part 3 — patient information leaflet (PIL) — of a WHO Public Assessment Report (WHOPAR) (24 October 2016)

Section guidance for part 4 — summary of product characteristics (SmPC) — of a WHO Public Assessment Report (WHOPAR) (25 October 2016)

Section guidance for part 5 — labelling of a WHO Public Assessment Report (WHOPAR)

Section guidance or part 6 —  scientific discussion — of a WHO Public Assessment Report (WHOPAR) (25 October 2016)


Templates

Annotated labelling template (25 October 2016)

Labelling template (25 October 2016)

Annotated patient information leaflet (PIL) template (24 October 2016)

Patient information leaflet (PIL) template (24 October 2016)

Annotated summary of product characteristics (SmPC) template (24 October 2016)

Summary of product characteristics (SmPC) template (24 October 2016)

 


Links to non-WHO guidance documents that can be consulted when preparing product information

European Commission (EC) guidance concerning the Braille requirements for labelling and the package leaflet (2005) 

EC guideline on summary of product characteristics (SmPC) (2009)

EC guideline on the readability of the labelling and the package leaflet of medicinal products for human use (2009)

European Directorate for the Quality of Medicines standard terms database

European Medicines Agency (EMA) guidance on excipients labelling (2003)

EMA guidance on maximum shelf-life for sterile products for human use after first opening or following reconstitition (1998)

EMA guideline on excipients in the dossier for application for marketing authorisation of a medicinal product of the Committee for Medicinal Products for Human Use (2007)

EMA guideline on risk assessment of medicinal products on human reproduction and lactation: from data to labelling (2008)

EMA Working Group on Quality Review of Documents compilation of use of terms in product information (2011)

EMA Working Group on Quality Review of Documents compilation of stylistic matters in product information (2009)

Marketing authorization of pharmaceutical products with special reference to multisource (generic) products: WHO manual for national medicines regulatory authorities (NMRAs) (2011)

MedDRA (version 12.0) terminology to be used in Section 4.8 “Undesirable effects” of SmPC (2010)

EMA tables of non-standard abbreviations to be used in the summary of product characteristics (2012)