WHO Medicines Prequalification Guidance

Many of the guidance documents approved by the WHO Expert Committee on Specifications for Pharmaceutical Preparations (ECSPP) are of significant interest and value for manufacturers. But the ECSPP approval process can be lengthy. To be able to respond promptly to demands for new products or for new formulations of existing products, or to incorporate recent pharmaceutical technology developments in their manufacturing processes, manufacturers often require guidance within a much shorter timeframe.

The WHO Prequalification Team therefore works closely and intensively with pharmaceutical experts to develop guidance, as needed, and promptly. In so doing it both facilitates and eases the technical burden associated with quality medicines manufacturer, and expands the range of appropriate products for meeting treatment needs. Moreover, much of the guidance so developed ― together with feedback from manufacturers and regulators ― forms the basis of guidance documents submitted to ECSPP, thereby also facilitating ECSPP processes.

WHO prequalification guidance documents, application forms and templates are listed below. (Date of issue is given in brackets.) Applicants are also advised to consult these and the guidance documents approved by ECSPP.

 

General guidance

General notes on Biopharmaceutics Classification System (BCS)-based biowaiver applications (1 November 2014)


Comparator products

Guidance on selection of comparator pharmaceutical products for equivalence assessment of interchangeable multisource (generic) products (2015)

Recommended comparator products: antimalarial medicines (9 February 2017)

Recommended comparator products: anti-tuberculosis medicines (9 February 2017)

Recommended comparator products: influenza-specific antiviral medicines (9 February 2017)

Recommended comparator products: medicines for hepatitis B and C (9 February 2017)

Recommended comparator products: medicines for HIV/AIDS and related diseases (9 February 2017)

Recommended comparator products: neglected tropical disease medicines (9 February 2017)

Recommended comparator products: reproductive health medicines (9 February 2017)


Study design

Guidelines for good clinical practice for trials on pharmaceutical products (1995)

Guidance on bioequivalence studies for reproductive health medicines (7 July 2014)

Notes on the design of bioequivalence study: albendazole (13 September 2015)

Notes on the design of bioequivalence study: artemether + lumefantrine (1 April 2008)

Notes on the design of bioequivalence study: atazanavir + ritonavir (1 April 2008)

Notes of the design of bioequivalence study: clofazimine (18 November 2016)

Notes on the design of bioequivalence study: cycloserine (13 October 2015)

Notes of the design of bioequivalence study: daclatasvir (18 November 2016)

Notes on the design of bioequivalence study: darunavir (13 October 2015)

Notes on the design of bioequivalence study: darunavir + ritonavir (13 October 2015)

Notes on the design of bioequivalence study: diethylcarbamazine (13 October 2015)

Notes on the design of bioequivalence study: dihydroartemisinin + piperaquine (13 October 2015)

Notes of the design of bioequivalence study: dolutegravir (18 November 2016)

Notes on the design of bioequivalence study: efavirenz (13 October 2015)

Notes of the design of bioequivalence study: emtricitabine/tenofovir/dolutegravir (18 November 2016)

Notes on the design of bioequivalence study: entecavir (13 October 2015)

Notes on the design of bioequivalence study: ivermectin (13 October 2015)

Notes on the design of bioequivalence study: lamivudine/tenofovir/dolutegravir (18 November 2016)

Notes on the design of bioequivalence study: mebendazole (1 September 2015)

Notes on the design of bioequivalence study: praziquantel (13 October 2015)

Notes on the design of bioequivalence study: simeprevir (13 October 2015)

Notes on the design of bioequivalence study: sofosbuvir (13 October 2015)

Notes on the design of bioequivalence study: sofosbuvir/ledipasvir (18 November 2016)

Notes on the design of bioequivalence study: tenofovir (13 October 2015)

Notes on the design of bioequivalence study: terizidone (13 October 2015)


Application forms & templates

Application for a biowaiver: additional strength (1 May 2012)

Application for a biowaiver: Biopharmaceutics Classification System (BCS) (1 November 2014)

Application for a biowaiver for zinc products (10 November 2016)

Presentation of bioequivalence trial information form (27 January 2017)

Guidance documents

Collaboration in verification of good manufacturing practices (GMP) compliance between WHO-PQT and medicines manufacturers interested in submitting an application for WHO prequalification (16 June 2016)

Collaborative procedure between World Health Organization (WHO) and selected national medicines regulatory authorities (NMRAs) in inspection activities (16 January 2010)

Points to consider for inspections of biowaiver data (10 October September 2016)

Q&A: Heating, ventilation and air-conditioning systems  (1 November 2016)


Application forms & templates

Collaborative procedure between World Health Organization (WHO) and selected national medicines regulatory authorities (NMRAs) in inspection activities (Annex A): Expression of interest (18 January 2010)

Collaborative procedure between World Health Organization (WHO) and selected national medicines regulatory authorities (NMRAs) in inspection activities (Annex B): Expression of interest (18 January 2010)

Collaborative procedure between World Health Organization (WHO) and selected national medicines regulatory authorities (NMRAs) in inspection activities (Annex C): Shared inspection schedule (18 January 2010)

Collaborative procedure between World Health Organization (WHO) and selected national medicines regulatory authorities (NMRAs) in inspection activities (Annex D): Form for nomination of an observer or co-inspector (18 January 2010)

Collaborative procedure between World Health Organization (WHO) and selected national medicines regulatory authorities (NMRAs) in inspection activities (Annex E): Details of external expert (18 January 2010)

Collaborative procedure between World Health Organization (WHO) and selected national medicines regulatory authorities (NMRAs) in inspection activities (Annex F): Provisions for evaluators of product dossiers and for inspectors (18 January 2010)

Collaborative procedure between World Health Organization (WHO) and selected national medicines regulatory authorities (NMRAs) in inspection activities (Annex G): Appointment as an observer or co-inspector in a WHO inspection team: template letter (18 January 2010)

Collaborative procedure between World Health Organization and selected national medicines regulatory authorities in inspection activities (Annex H): Appointment of observer or co-inspector: template letter to supervisor (18 January 2010)

Example of a development plan to submit a medicinal product for prequalification (19 August 2016)

Request for pre-inspection (Annex 1) (19 August 2016)

ALL APPLICATION FORMS, EXAMPLES OF COMPLETED APPLICATION FORMS & TEMPLATES

Annotated labelling template (25 October 2016)

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

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

Application for a biowaiver: additional strength (1 May 2012)

Application for a biowaiver: Biopharmaceutics Classification System (BCS) (1 November 2014)

Application for a biowaiver for zinc products (12 December 2012)

Application for a variation to a prequalified finished pharmaceutical product (FPP) (4 December 2015)

Application for active pharmaceutical ingredient master file (APIMF) procedure (15 January 2016)

Application for active pharmaceutical ingredient (API) prequalification based upon stringent regulatory authority (SRA) assessment ― history of changes document (1 May 2013)

Application for an active pharmaceutical ingredient master file (APIMF) amendment (1 June 2016)

Application for new version of an active pharmaceutical ingredient master file (APIMF) (19 October 2015)

Application for prequalification of an active pharmaceutical ingredient (API) (15 January 2016)

Clinical trial protocol: zinc acceptability study in children with acute diarrhoea: a prospective, open-label (multicentre) interventional study (6 March 2016)

Collaborative procedure between World Health Organization (WHO) and selected national medicines regulatory authorities (NMRAs) in inspection activities (Annex A): Expression of interest (18 January 2010)

Collaborative procedure between World Health Organization (WHO) and selected national medicines regulatory authorities (NMRAs) in inspection activities (Annex B): Expression of interest (18 January 2010)

Collaborative procedure between World Health Organization (WHO) and selected national medicines regulatory authorities (NMRAs) in inspection activities (Annex C): Shared inspection schedule (18 January 2010)

Collaborative procedure between World Health Organization (WHO) and selected national medicines regulatory authorities (NMRAs) in inspection activities (Annex D): Form for nomination of an observer or co-inspector (18 January 2010)

Collaborative procedure between World Health Organization (WHO) and selected national medicines regulatory authorities (NMRAs) in inspection activities (Annex E): Details of external expert (18 January 2010)

Collaborative procedure between World Health Organization (WHO) and selected national medicines regulatory authorities (NMRAs) in inspection activities (Annex F): Provisions for evaluators of product dossiers and for inspectors (18 January 2010)

Collaborative procedure between World Health Organization (WHO) and selected national medicines regulatory authorities (NMRAs) in inspection activities (Annex G): Appointment as an observer or co-inspector in a WHO inspection team: template letter (18 January 2010)

Collaborative procedure between World Health Organization and selected national medicines regulatory authorities in inspection activities (Annex H): Appointment of observer or co-inspector: template letter to supervisor (18 January 2010)

Example of a completed application for a new version of an active pharmaceutical ingredient master file (APIMF) (4 April 2014)

Example of a completed application for an amendment to an active pharmaceutical ingredient master file (APIMF) (3 March 2016)

Example of a development plan for submission of a medicinal product for prequalification (19 August 2016)

Expression of interest to participate in the system of mutual audits within the network of quality control laboratories involved in WHO prequalification (1 October 2016)

Labelling template (25 October 2016)

Model  letter of access: active pharmaceutical ingredient master file (APIMF) (14 February 2014)

Model letter of agreement with recipient of technical assistance (13 February 2017)

Model letter of requalification (19 October 2016)

Notification of a change(s) to the key information of a product approved by a stringent regulatory authority (SRA) (4 December 2015)

Outline of content of an annual report on activities of a prequalified quality control laboratory (QCL) (4 June 2016)

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

Presentation of bioequivalence trial information form (8 January 2010)

Quality information summary (QIS) (23 September 2016)

Quality information summary (QIS) of the finished pharmaceutical product (FPP) approved by the reference SRA (QIS-SRA) (28 October 2013)

Quality overall summary: product dossier (QOS-PD) (4 January 2016)

Request for pre-inspection (19 August 2016)

Screening checklist  for generic products (1 June 2015)

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

Variation to a prequalified finished pharmaceutical product (FPP): annual notification (5 December 2015)

Variation to a prequalified finished pharmaceutical product (FPP): major, minor or immediate notification (5 December 2015)

WHO prequalified quality control laboratory (QCL) annual report on activities (1 October 2016)

Zinc product: acceptability study summary form (11 November 2016)