WHO-UNICEF-UNFPA Meeting Copenhagen November 2015

Transcription

1 WHO-UNICEF-UNFPA Meeting Copenhagen November 2015 Quality Assessment: Updates Lynda Paleshnuik Lead Quality Assessor 1

2 Overview Submitting your dossier Before you submit WHO publications and PQ quality guidelines Using the principle quality guidelines Guideline revisions planned or in progress Additional guidance documents (published on website) 2

3 Prequalification of Medicines - Assessment A manufacturer wishing their medicinal product to be prequalified must submit extensive information on the product to allow qualified teams of assessors to comprehensively evaluate its quality, safety and efficacy. Assessment areas: Quality Bioequivalence APIMF/Prequalification of APIs Clinicians/WHOPARs and product information 3

4 Before submitting your dossier The advancement of a dossier through the assessment process depends on a number of factors in the control of the manufacturers, including: communication we are responsive to questions out your response time after PQ questions are sent preparation before submitting the dossier 4 especially important if you are new to PQ

5 Before submitting your dossier Make use of available tools to help advance your dossier: Prequalification website Screening checklist newly published Prequalification guidelines 5

6 apps.who.int/prequal/ 6

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8 Screening checklist Now published under the above pathway, i.e.: Information for applicants Prequalification guidelines Provides the criteria used to accept a dossier into the assessment stream. Ensuring the elements in the checklist are covered is an excellent first step in preparing to submit your dossier. 8

9 Screening checklist example sections 9

10 WHO PQ Published Guidelines PQ guidelines are published in the Technical Report Series (TRS) of the WHO Expert Committee on Specifications for Pharmaceutical Preparations. Complete list available for download at: who.int/medicines/publications/pharmprep/en/ 10

11 WHO TRS other useful guidances Along with PQ quality guidelines, other WHO guidelines and points to consider are published in the TRS. Some non-pq guidelines that provide supportive guidance: Pharmaceutical development of multisource (generic) pharmaceutical products - point to consider (2013 Annex 3 TRS 970) Development of paediatric medicines: points to consider in pharmaceutical formulation (2013 Annex 5 to TRS 970) 11

12 Principle PQ quality guidelines Note that the two main PQ quality guidelines (quality and variations) refer to PQ in the title, and are not to be confused with more general guidelines published by WHO TRS 970 Annex 4 Guidelines on submission of documentation for a multisource (generic) finished pharmaceutical product for the WHO Prequalification of Medicines Programme: quality part TRS 981 Annex 3 WHO guidelines on variations to a prequalified product 12

13 General quality guidelines NOTE: a general WHO quality guideline is published in TRS 986 (2014). This GL is based on the PQ quality guidelines (TRS 970, Annex 4). this Use the PQ Q GL to submit a dossier to PQ GL includes many PQ-specific requirements, i.e. gives more specific instruction to enable applicants to meet requirements 13

14 General quality guidelines TRS volumes are indicated for your information, however, to avoid possible confusion: always obtain PQ guidelines through the PQ website 14

15 Using the principle PQ quality guidelines General preparation GL: Guidelines on submission of documentation for a generic FPP: preparation of product dossiers: TRS 961 Annex 15 (2011) - provides detailed information on preparation of the dossier in CTD format: How to format the dossier The expected contents of modules including details of module 1 (regional information) i.e. PQ in this case 15

16 Progress since this publication (2011) Section 5 on Module 3 (quality) describes the three options for submission of API information to PQ: Use of CEP, use of APIMF, or full data in the dossier. Since publication, the process for prequalification of APIs has been established. Therefore the quality guideline (published 2012) describes four options for submission of API information: Prequalified API, CEP, APIMF, or full data in the dossier. API issues will be discussed in Antony s presentation 16

17 Using the principle PQ quality guidelines TRS 970 Annex 4: quality GL the quality GL gives detailed information on submitting the Q data what data should be included the expectations for each section of the dossier in CTD format, including for example: how impurity limits may be qualified, expectations for method validation, and requirements for stability studies 17

18 Using the main PQ Guidelines TRS 981 Annex 3: variations GL the variation GL gives detailed information on how changes (API and FPP) are assessed changes are assessed by the same principles whether pre- or post- PQ changes e.g. change in API or FPP manufacturing site 18

19 Using the main PQ Guidelines - Variation Example: change in API supplier = variations 8d and 8e The GL outlines some of the general cases for this change an the level of risk associated with these cases, and the requirements to support the change. Note that in situations where you don t want to repeat a biostudy, it is critical to have the batch used in the biostudy fully characterized (for comparative purposes). 19

20 Using the main PQ guidelines - variations Note that in addition to the variation GL, the PQ website has additional information on variations including: a general introduction to variations, and a procedural guidance including WHO review timelines application forms clarifications to the current GL 20

21 apps.who.int/prequal/ 21

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24 Current PQ quality guidelines All current guidelines, guidances and templates for PQ should be assessed through the PQ website to ensure the current guideline/template is used; Note: QIS/QOS-PD templates have been required as part of quality dossiers since March 2011: Current versions: QIS ( ), QOS-PD (( ) it is important to use the current versions All relevant and related PQ guidelines can be found through this website 24

25 Supporting quality guidelines Procedure for prequalification of pharmaceutical products: TRS 961 Annex 10 (2011) Guidelines on the requalification of prequalified dossiers: TRS 957, Annex 6 (2010) 25

26 Supporting quality guidelines Guidelines for registration of fixed-dose combination medicinal products: TRS 929, Annex 5 (2005) Stability testing of APIs and FPPs: TRS 953, Annex 2 (2009) to be used in conjunction with the 2012 quality guideline - the 2012 PQ quality guideline prevails where there are differences 26

27 Supporting quality guidelines Guidelines on submission of documentation for prequalification of FPPs approved by SRAs: TRS 986 Annex 5 (2014) Applies to both generic and innovator FPPs. There is also a new document on stability data requirements for FPPs approved by SRAs (June 2015) 27

28 Revisions planned or in progress FDC guideline (current 2005) may be targeted for revision in the future Requalification guideline (current 2010) may be targeted for revision based on the experience obtained with the process 28

29 Additional guidance documents published on PQ website Information on submitting zinc sulfate dossiers: Q and A for submission of zinc sulfate dossiers (August 2013) Advice on zinc acceptability study (28 July 2014) Advice on selection of excipients for zinc products (October 2014) choosing excipients that don t affect absorption 29

30 Additional guidance documents published on PQ website Information on submitting other products: Magnesium sulfate injections Q&A (4 October 2014) Medroxyprogesterone acetate depot (DMPA) September 2015 FAQ for submission of reproductive health products (March 2012) - includes answers to some general questions such as batch size and established product requirements 30

31 Additional guidance documents published on PQ website Other documents include: Guidance on preparation of product information (PIL, SmPC, labels) and compilation of the WHOPAR 31

32 Summary points Preparation prior to submitting a dossier to PQ will expedite the dossier through the assessment process Get to know the PQ website Consult the screening checklist Be familiar with the comprehensive Q guidelines Be aware of supplementary guidance documents to help with your particular dossier 32

33 QUESTIONS? Questions? Thank you! 33

34 Acronyms! API: active pharmaceutical ingredient APIMF: API master file CEP: EDQM certificate of suitability CTD: common technical document EC: expert committee FPP: finished pharmaceutical product GL: guideline ICH: International Conference on Harmonization FDC: fixed-dose combination 34

35 Acronyms! PQ: Prequalification Team - Medicines PIL: patient information leaflet QIS: quality information summary (required quality template) QOS-PD: quality overall summary product dossier (required quality template) SmPC: summary of product characteristics WHOPARs: WHO public assessment reports 35