Quality Assessment. Updates. Lynda Paleshnuik Hua YIN. A list of products registered using this procedure is publicly available.

Transcription

1 Quality Assessment A list of products registered using this procedure is publicly available. Updates Lynda Paleshnuik Hua YIN 1

2 Overview Quality Guidelines Generics guideline The new SRA guideline Key published quality guidelines WHO publications and PQ guidelines Additional PQ guidance (published on website) Highlights of PQ Requirements Other Updates 2

3 Overview Assessment areas: Quality: API & FPP Efficacy/Safety: Bioequivalence, Biowaiver Product information (WHOPARs ) Products to be prequalified, have to meet the norms and standard as recommended by WHO 3

4 PQ Quality guidelines For multisource (generic) products the product dossiers have to meet the norms and standard as specified in the Generics Guidance For SRA approved products, please see Guidance on submission of FPPs approved by SRAs 4

5 PQ Generics Guideline Preparation of Prequalification Product Dossier in CTD Format: How to format the dossier The expected contents of modules including details of module 1 (regional information) Guideline on submission of documentation for a multisource FPP: Quality Part Comprehensive quality GL-detailed information on the technical requirements for the dossier to be submitted for quality assessment. 5

6 PQ Generics Guideline QIS/QOS-PD templates have been required as part of quality dossiers since March 2011: Quality Overall Summary-Product Dossier (QOS-PD) Quality Information Summary (QIS) should be submitted in Word format! Note: Current versions: QIS ( ), QOS-PD ( ) Revisions are in progress Access through the PQP website to ensure the current guideline/template is used. 6

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9 The new SRA guideline Guidelines on submission of documentation for prequalification of FPPs approved by stringent regulatory authorities (SRAs): TRS 986 Annex 5 (2014) This replaces both: Guidelines on submission of documentation for prequalification of innovator FPPs approved by SRAs: TRS 961 Annex 11 (2011), and Draft guidance for generic FPPs approved by SRAs. 9

10 The new SRA guideline Combines generic and innovator products in one guideline Introduce QIS-SRAtemplate to provide a condensed summary of key information of the FPP as approved by the reference SRA, and it should be submitted in Word format to be revised whenever any variations affect the QIS- SRA 10

11 Key published quality guidelines Guidelines on APIMF procedure: TRS 948, Annex 4 (2008) Guidelines for registration of fixed-dose combination medicinal products: TRS 929, Annex 5 (2005) maybe targeted for revision in the future WHO guidelines on variationsto a prequalified product TRS 981, Annex 3 (2013) Guidelines on the requalificationof prequalified dossiers: TRS 957, Annex 6 (2010) 11

12 PQ Variation guidance WHO guidelines on variations to a prequalified product Published and implemented in May 2013 More comprehensive and explanatory guidanceon the classification and technical requirements of the changes Requirements are aligned with the Quality Guideline New approaches to management of variations, such as "do and tell",i.e.implementing the change immediately upon notification 12

13 To improve the handling of variation applications with the increasing number of variations Timelines have been established for each variation category: 30 days for notifications; 60 days for minor changes; and 90 days for major changes. PQ Variation guidance During the past year (1 May April 2014), the median WHO time for review: 15 days for notifications; 20 days for minor changes; and 26 days for major changes. The PQ website has additional information on variations 13

14 PQ Variation guidance WHO guidelines on variations to a prequalified product: implemented on May 2013 the PQ website has additional information on variations including: a general introduction to variations, and a procedural guidance including WHO review application forms clarifications to the current GL timelines 14

15 WHO publications and PQP guidelines PQP guidelines are published in the Technical Report Series (TRS)of the WHO Expert Committee on Specifications for Pharmaceutical Preparations: available for download at: Along with PQP guidelines, other WHO guidelines and points to consider are published in the TRS, e.g. Development of paediatricmedicines: points to consider in pharmaceutical formulation (2013) 15

16 WHO publications and PQP guidelines NOTE:Ageneral WHO quality guidelineis published in the newest TRS, i.e. TRS 986 (2014): Guidelines on submission of documentation for a multisource (generic) finished pharmaceutical product: quality part This GL is based on the PQ quality guidelines (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 Use the PQ Q GLto submit a dossier to PQ this GL includes many PQ-specific requirements, i.e. gives more specific instruction to enable applicants to meet requirements 16

17 WHO publications and PQP guidelines All current guidelines and templates for PQP should be assessed through the PQP website Non-PQP guidelines may provide supportive guidance Wherever there is conflict between PQP guidelinesand other GLs, PQP guidelines prevail in PQP 17

18 Additional PQ guidance published on PQP website Guidance on preparation of product information (PIL, SmPC, labels) and compilation of the WHOPAR Q and A for submission of zinc sulfate dossiers. Additional guidance for submission of the Acceptability Study ( 28 July 2014 ) Q and A for submission of magnesium sulfate injections (19 September 2013) Clarification on the process for introducing a supplier of nonplant-derived-artemisinin(may 2013) 18

19 Highlights of PQ Requirements Reduced requirements (since 2010): 1. Reduced the number of FPP batchesrequired to establish the shelf-life, The number of FPP batches required to establish the shelflife has been reduced from 3 pilot to>= two batches of at least pilot scale, or in the case of an uncomplicated FPP [e.g. immediate release solid FPPs (with noted exceptions) and non-sterile solutions], at minimum one batch of at least pilot scale, and a second batch which may be smaller (e.g. for solid oral dosage forms, or tablets or capsules). 19

20 Highlights of PQ Requirements A complicated FPP includes sterile products, inhalation and transdermal products, and FDCs including ritonavir/lopinavir, rifampicin or an artemisinin. When the applicant is unclear about a product category, PQ should be consulted, Dr.Matthias Stahl at stahlm@who.int 20

21 Highlights of PQ Requirements 2. Established genericsare have been marketed for at least5 years, and they have manufactured either 10 batches in the past year, or 25 batches in the past 3 years. Instead of process validation and some pharmaceutical development data, the applicant may provide a product quality review (PQR). The PQR replaces the developmental pharmaceutics data on 1)formulation development (P a)) and 2) manufacturing process development (P.2.3 a)), and the section on process validation, P.3.5 of the CTD. 21

22 Highlights of PQ Requirements 3. Reduced requirements at time of submission for 2nd-line TB products (2010) RH products (2012) NTD products (under consideration) 22

23 Highlights of PQ Requirements September 2011: required stability conditions for PQ are: API:30 C ±2 C / 65% ±5% RHor 30 C ±2 C / 75% ±5% RH FPP:30 C ±2 C / 75% ±5% RH API related updates to be covered by Ms. Isabel Ortega 23

24 PQ Time is improving Days Median WHO time Median Applicant time Median time to PQ 24

25 Deficiencies in generic product dossiers Journal of Generic Medicines 9(2)

26 Combined list of all APIs and FPPs invited for prequalification 1. Antiretroviralsas single-ingredient formulations for use in adults and adolescents 1.1. Nucleoside/nucleotide reverse transcriptase inhibitors Number of individual FPPs prequalified Number of individual FPPs under assessment Abacavir, tablet 300 mg 5 1 Abacavir, tablet 600 mg Lamivudine, tablet 150 mg 8 Lamivudine, tablet 300 mg 3 Tenofovir disoproxil fumarate, tablet 300 mg 7 1 Zidovudine, tablet 300 mg 7 Zidovudine, capsule 250 mg 2 26

27 Summary In order to meet current requirements, be aware of: the current guidelines found through the PQP website the PQ Generic guidelines (published in 2012) prevail where there is any noted difference compared to other guidelines Variation and SRA guideline newly published Pay attention to PQ specific requirements (reduced requirements and stability requirements) 27

28 QUESTIONS? Questions? Thank you!

29 Acronyms! API: active pharmaceutical ingredient 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 FPP: finished pharmaceutical product

30 Acronyms! MRA: mutual recognition agreement PQP: Prequalification of Medicines Programme QIS: quality information summary (required quality template) QOS-PD: quality overall summary product dossier (required quality template)