Vaccine Assessment for Prequalification and …...Copenhagen, Denmark 24 – 27 September 2018...

Copenhagen, Denmark 24 – 27 September 2018

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

E-mail: [email protected]


Prequalification process

Scientific review of quality dossier

Scientific review of clinical data

Testing of samples

Consultation with responsible NRA

Inspection to manufacturing facilities

Copenhagen, Denmark 24 – 27 September 2018 Slide 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


Complex release process

vaccine

lot

QC QA

certificate of analysis batch records

Manufacturer’s release

Mfr. Country Reg Authority

lab tests doc.review

NRA release

vaccine distribution on the market

specific to

vaccines

lab. tests GMP compliance

specific to

vaccines

UN supply PQ vaccines


Quality Relationships

Quality Management

Quality Control

GMP

Quality Assurance

Management

Aspect

Quality system

Quality Policy

…

Personnel

Training

Validation

Self

inspection

Quality

Objective

Quality

Manual

Sampling

Specifications

Testing


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



Container Closure System

Stability

• Real time and accelerated

• VVM selection

• ECTC indication?

Consistency of Production at commercial scale



• Programmatically suitable presentation

• Compliance with GMP

• Compliance with WHO recommendations and UN tender specifications including labels and inserts

• Capacity of Production


Common deficiencies – Dossier Review- Quality

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.

59

68

41

22 26

45

15

33

12 6 6

11

0

10

20

30

40

50

60

70

80

A B C D E F G H I J K L

Nu

mb

er

of

Cases

Type of Deficiency


Dossier Review – Clinical aspects

• Clinical development program

• Applicant ’s sponsored clinical t r ial overview

• Clinical summary

• Independent Clinical expert report

• Pharmacovigilance plan


Common deficiencies as per categories


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)

•Scenario 3: Dossier review raises major technical and programmatic issues

•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

•Ad Hoc committee is convened • Request for additional information to give

final recommendation

• Stopping the PQ

Copenhagen, Denmark 24 – 27 September 2018 Slide 13 24 – 27 September 2018


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


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.


Who makes the final decision?


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


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


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


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


Preferred characteristics (1)



• 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



• Increased thermostability

• No freeze sensitivity

• Minimise environmental impact of packaging

• Compact pre-filled auto-disable injection system

• Labelling legibility

• Barcoding


http://www.who.int/immunization_standards/vaccine_quality

/pspq2_v140512.pdf

http://www.who.int/immunization_standards/vaccine_quality/pspq2_v140512.pdf







Thank you

Vaccine Assessment for Prequalification and …...Copenhagen, Denmark 24 – 27 September 2018...

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