Vaccine Assessment for Prequalification and Programmatic Suitability for Prequalification

Transcription

1 Vaccine Assessment for Prequalification and Programmatic Suitability for Prequalification Dr Drew Meek Prequalification Team/Vaccines Assessment Regulation of Medicines and other Health Technologies World Health Organization Geneva, Switzerland

2 Prequalification process Scientific review of quality dossier Scientific review of clinical data Testing of samples Consultation with responsible NRA Inspection to manufacturing facilities

3 Pharmaceuticals Vs Vaccines Pharmaceuticals Produced and controlled using physicochemical methodologies Vaccines Production and testing using biological systems Raw materials Manufacturing processes Quality control methodologies Each vaccine is a unique product Slide 3

4 Complex release process QC lab. tests certificate of analysis vaccine lot QA GMP compliance batch records Manufacturer s release Mfr. Country Reg Authority UN supply PQ vaccines lab tests doc.review NRA release vaccine distribution on the market specific to vaccines specific to vaccines

5 Quality Relationships Quality Control GMP Sampling Specifications Testing Personnel Training Validation Self inspection Quality Objective Quality Manual Management Aspect Quality system Quality Policy Quality Assurance Quality Management

6 Quality aspects considered Manufacturing Process and Process Controls Controls of Critical Steps and Intermediates Manufacturing Process Development Process Validation Control of Drug Substance and Drug Product Specifications & their justification Analytical procedures including validation Batch analysis

7 Quality aspects considered Container Closure System Stability Real time and accelerated VVM selection ECTC indication? Consistency of Production at commercial scale

8 Quality aspects considered Programmatically suitable presentation Compliance with GMP Compliance with WHO recommendations and UN tender specifications including labels and inserts Capacity of Production

9 Number of Cases Common deficiencies Dossier Review- Quality A B C D E F G H I J K L Type of Deficiency A. Unclear specifications for biological raw materials, intermediates or finished product. B. Insufficient information on stability of intermediates or finished product or cumulative stability. Missing information on storage time for intermediates. C. Validation of in-house, new tests or in-house references. D. Insufficient information on trend analysis, rejected batches, retest policy and out of specification policy. E. Incomplete information for Master and/or Working Cell Bank, Master and/or Working Seed, seed lot system; primary cultures. F. Unclear production process for intermediates, insufficient information on validation of production process and consistency lots. G. Insufficient information on diluents, buffer, non-biological reagents and non-active ingredients. H. Lack of tests required by WHO or the tests or specifications are different from WHO. I. Unclear composition of finished product, formulation of the finished product or presentation. J. Lack of comparability data for new production method or new production facility. K. Lack of data to prove efficiency of proposed preservative or proposed concentration. L. No information or unclear information on lot numbering system or setting date of manufacture.

10 Dossier Review Clinical aspects Clinical development program Applicant s sponsored clinical t rial overview Clinical summary Independent Clinical ex pert report Pharmacovigilance plan

11 Common deficiencies as per categories

12 Outcome of the review of Dossier Scenario 1: Dossier review does not raise any outstanding issues Scenario 2: Dossier review raises outstanding issues for clarification/additional information (no major) Consistency testing and inspection are scheduled Outstanding issues may be followed up at site inspection &/or request for additional information Consistency testing and inspection are scheduled Scenario 3: Dossier review raises major technical and programmatic issues Ad Hoc committee is convened Request for additional information to give final recommendation Stopping the PQ Slide 12

13 Copenhagen, Denmark September Slide September 2018

14 Programmatic Suitability for Prequalification Programmatic Suitability for Prequalification Slide 14

15 Programmatic Suitability for Prequalification Programmatic Suitability for Prequalification Dossier screening by WHO/PQT for completeness of content Dossier also screened for PSPQ compliance non-compliance with a mandatory characteristics > rejection of dossier non-compliance with a critical characteristics > referral to Standing Committee unique/novel characteristic identified > referral to Standing Committee Slide 15

16 Can a review by the standing committee happen before submission? Yes Vaccine development an extended process Manufacturers can discuss with PQ Secretariat pre-submission A briefing package can be prepared with company input for the SC to consider.

17 Who makes the final decision?

18 Mandatory characteristics Antimicrobial preservative is required in ready to use injectable vaccines containing more than two-doses. Thermostability: The vaccine or any component presented for prequalification should not require storage at less than -20 C. Dose volume for injectable vaccines for children 5 years and under should be not more than 1 ml vaccine presented for prequalification should not require an intravenous route of administration Slide 18

19 Unique or innovative characteristic No guidance documents developed Examples: Nano-patches, micro-needle application Based on programme knowledge SC will judge the suitability of such vaccines for the developing market PQT/VXA responsible for evaluation of quality and clinical aspects of vaccine delivered with the technology Slide 19

20 Critical characteristics (1) The vaccine should fit into currently commonly used schedules of vaccination visits. Oral vaccines should be ready to use Thermostability: If the vaccine requires storage below +2 C during its shelf-life period, it should be stable at +2 C and +8 C for a minimum of 6 months Vaccine Vial Monitor (VVM): Proof of feasibility and intent to apply appropriate VVM if a tender requirement Slide 20

21 Critical characteristics (2) Antimicrobial preservative is required in ready to use injectable vaccines containing two-doses or in vaccines requiring reconstitution that are not live-attenuated Dose volume of injectable vaccines can be delivered using available PQed auto-disable syringes Vaccines in pre-filled injection devices should have an auto-disable feature Packaging material can be disposed of appropriately in the field using standard procedures Slide 21

22 Preferred characteristics (1) Slide 22

23 Preferred characteristics (2) Ready to use vaccines Multicomponent vaccine presentations minimise potential for error Antigenic stability following reconstitution Minimise number of doses that cannot be reused in subsequent sessions once the container is open 10 doses per vial in routine setting ; 10 doses per vial in campaign setting Doses per secondary container reflect logistical needs Small volume per dose in secondary container Small, standardised dose volumes for oral vaccines Slide 23

24 Preferred characteristics (3) Increased thermostability No freeze sensitivity Minimise environmental impact of packaging Compact pre-filled auto-disable injection system Labelling legibility Barcoding Slide 24

25 /pspq2_v pdf Slide 25

26 Thank you