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  • Vaccines Assessment: Quality and Clinical Requirement

    Joint UNICEF, UNFPA and WHO meeting with manufacturers

    Copenhagen 2 – 4 December 2019

    Godwin Enwere VAX Team | PQT/RPQ/MHP Cluster | HQ WHO, Geneva

  • Quality requirements for prequalification

    Godwin Enwere PQ Vaccines Assessment Team WHO HQ

  • Specific aspects for Vaccines Prequalification  General understanding of production process and quality control

    methods – Quality

     Production consistency at commercial scale (assessed by testing of samples of final product) – Quality

     Compliance with GMP – Quality

     Programmatically suitable presentation – Quality

     Compliance with WHO recommendations and UN tender specifications including labels and package inserts - Quality

    Godwin Enwere PQ Vaccines Assessment Team WHO HQ

  • Guidance documents

    Process as per a set of WHO Recommendations

     Procedure for assessing the acceptability in principle, of vaccines for purchase by United Nations agencies TRS 978 Annex 6 2013. https://www.who.int/immunization_standards/vaccine_quality/

     Assessing the programmatic suitability of vaccine candidates for WHO prequalification. https://www.who.int/immunization_standards/vaccine_quality/ps_pq/en/

     List of WHO Good Manufacturing Practice (GMP) Guidelines. https://www.who.int/medicines/areas/quality_safety/quality_assurance/production/en/

     Guidance on reporting variations to a prequalified vaccine (Post PQ requirements). https://www.who.int/immunization_standards/vaccine_quality/variations_pq_vaccine/en/

     WHO Vaccine-specific standardization. https://www.who.int/biologicals/vaccines/en/

    Godwin Enwere PQ Vaccines Assessment Team WHO HQ

  • Format of submission

    Godwin Enwere PQ Vaccines Assessment Team WHO HQ

    Common Technical Document (CTD) [ICH M4]

    Vaccine Prequalification Dossier (VPQD)

    We shall continue to receive Product Summary File till the end of 2021

  • PQ Vaccines Assessment Team

    WHO HQ

    ICH M4

    S.1 P.1 S.2 P.2 S.3 P.3 S.4 P.4 S.5 P.5 S.6 P.6 S.7 P.7


  • Module 1: • Specific module pertaining to

    administrative and prescribing information  It contains information not included in the other modules

    but required to assess the product for prequalification purposes

    PQ Vaccines Assessment Team

    WHO HQ

  • Module 1 General Information Required to assess Vaccines for PQ purposes

    Godwin Enwere PQ Vaccines Assessment Team WHO HQ


    1.2 CORRESPONDENCE 1.2.1 Copy of the letter from the manufacturer 1.2.2 Agreed minutes of pre-submission meetings.

    1.3 SITE MASTER FILE (SMF) as per WHO TRS No 961, Annex 14, 2011

    1.4 COMPLIANCE INFORMATION 1.4.1 Certificate for establishment licensure by the NRA of the country of manufacture. 1.4.2 Copy of GMP certificate or other evidence of GMP compliance. 1.4.3 Copy of MAs for all formulations and presentations in the country of manufacture or country of reference for the vaccine submitted for PQ, or the EMA under Article 58. 1.4.4. Policy for assignment of date of manufacture of intermediates as well as final product, including diluents, as appropriate. 1.4.5 If the vaccine contains or consists of GMO, a copy of the Environmental Risk Assessment is needed.


    1.5.1 Description of presentations available to UN agencies, including diluent, dosage forms, doses, sizes and type of containers and VVM type and location. 1.5.2 Vaccine temperature stability profile: as required to support the assignment of VVM type. Extended Controlled Temperature Conditions (ECTC WHO TRS No. 999 Annex 5, 2016), it is critical studies properly designed and appropriate statistical analysis to justified the use after ECTC exposure. 1.5.3 Description of immunization /administration devices, if any. Any devices provided with the vaccine must be prequalified, as applicable. 1.5.4 Recommended schedule and route of administration. 1.5.5 Artworks or mockups of labels (in English). 1.5.6 Samples of package inserts (in English) to be used for supply through UN agencies. Translation to French, Portuguese, Russian and Spanish, as required.

    Godwin Enwere PQ Vaccines Assessment Team WHO HQ

  • 1.5.7 Template of lot summary protocol (LSP). 1.5.8 Self-assessment against programmatic suitability for prequalification (PSPQ). Mandatory characteristics will determine whether the application is accepted for review or rejected. Compliance with critical characteristics needs to be assessed. 1.6 SUPPLEMENTAL PRE-CLINICAL & CLINICAL INFORMATION (PRE AND POST MA) 1.7 REGULATORY ACTIONS

    1.7.1 Information on refusals, withdrawals, suspensions, even including those initiated by the manufacturer. 1.7.2 List of lots rejected by the NRA, if applicable. 1.7.3 Restrictions on distributions and recalls, including those initiated by the manufacturer 1.7.4 Clinical trial suspensions. 1.7.5 Dosage or schedule changes since the initial marketing authorization in the country of manufacture and/or the country of reference. 1.7.6 Changes in target populations since the initial marketing authorization in the country of manufacture and/or the country of reference.

    Godwin Enwere PQ Vaccines Assessment Team WHO HQ

    Module 1 (cont.)


    1.8.1 Quantity of finished product distributed in vials/doses whether domestic or export.

    1.8.2 List of countries where the product has received a MA and whether supplied.

    1.8.3 Lot release process by the NRA/NCL and recording system for distribution.

    1.8.4 Summary of the international packaging and shipping procedures and the validation – (including box sizes, packing volumes, etc.).

    WHO requirements WHO/IVB/05.23 Guidelines on the international packaging and shipping of vaccines should be followed.

    Godwin Enwere PQ Vaccines Assessment Team WHO HQ

    Module 1 (cont.)

  • Module 2

    Godwin Enwere PQ Vaccines Assessment Team WHO HQ

    As per ICH guidelines M4Q, M4S, M4E):

    2.1 Table of Contents (Modules 2-5) 2.2 VPQD introduction 2.3 Quality Overall Summary 2.4 Nonclinical Overview 2.5 Clinical Overview 2.6 Nonclinical Written and Tabulated Summaries Pharmacology Pharmacokinetics Toxicology 2.7 Clinical Summary. Studies Clinical Efficacy, Clinical Safety, Literature References. Synopses of Individual Studies.


  • Module 3: Quality Aspects


    Godwin Enwere PQ Vaccines Assessment Team WHO HQ

  • DRUG SUBSTANCE (DS)  The DS is the unformulated active (immunogenic) substance

    which may be subsequently formulated with excipients to produce the drug product.

     The DS may be: whole bacterial cells, viruses, or parasites (live or killed); crude or purified antigens isolated from killed or living cells; crude or purified antigens secreted from living cells; recombinant or synthetic carbohydrate, protein or peptide antigens; polynucleotides (as in plasmid DNA vaccines); or conjugates.

    Godwin Enwere PQ Vaccines Assessment Team WHO HQ

    Module 3: Drug Substance (S)

  • Godwin Enwere PQ Vaccines Assessment Team WHO HQ

    Module 3: Drug Substance


    3.2.S.1 General Information (name, manufacturer)

    3.2.S.2 Manufacture (name, manufacturer)

    3.2.S.3 Characterization

    3.2.S.4 Control of Drug Substance

    3.2.S.5 Reference Standards or Materials

    3.2.S.6 Container Closure System

    3.2.S.7 Stability

  • 3.1 Table of content Drug substance 1.General information (Information on the nomenclature of the DS; recommended INN, Biological/chemical/compendial/national names, Strain/structure details) 2. Manufacture

    1.Information on the manufacturer (Identification, address, activities) 2. Description of Manufacturing Process and Process Controls (Flow diagram) 3.Control of Materials (Source of starting & raw materials biological/chemicals/ SPF eggs/Cell and Seed Bank System, Full characterization and manufacturing processes including test methods and results) 4.Controls of Critical Steps and Intermediates (selection and justification of critical manufacturing steps, process controls, and acceptance criteria – CQA & CPP) 5.Process Validation and/or Evaluation (Full description of studies for critical manufacturing steps i.e. starting from Cell/Seed culture, Harvesting, Purification, Detoxification & modification and inactivation. Procedures for container closure, filling, transport & storage. Details of PV 3 Lots, lot sizes and all IPC & QC test results) – VMP

    Godwin Enwere PQ Vaccines Assessment Team WHO HQ

  • 3.2.S.2.6 Manufacturing Process Development (any major changes & optimization made throughout the development. Conclusions from the assessment used to evaluate product consistency. Cross-reference to the non-clinical and clinical & PV studies used batches)

    3. Characterization 1.Elucidation of Structure and other Characteristics (Physicochemical, Immunological and Genetic Characterization and test results) 2.Impurities (Process related from manufacturing DS i.e. BSA, Trypsin, antibiotic, HCP, DNA. Product related impurities i.e. due to alteration of antigen. The impurities should be ident