TORs

2 December 2008

VACCINE PRESENTATION AND PACKAGING ADVISORY GROUP (VPPAG)

REVISED TERMS OF REFERENCE, 2008

Background

Vaccines are developed and manufactured by industry and used according to public health need.  A vaccine’s presentation and packaging (termed ‘image’ by industry) should meet developing country needs, to the extent feasible, to facilitate rapid uptake.   Therefore, the public sector should articulate in advance and with specificity these packaging and presentation needs and work with industry to meet those needs.  As we look to the future, it is essential to understand and analyze the trade-offs between product characteristics using a mix of field experience, industry capabilities and economic considerations, and technical data.

It will be critical to give guidance to manufacturers for them to have a better basis for investment decisions. The public sector has not routinely defined the preferred profiles of future vaccine products.  Hence, as the time lag for the introduction of new vaccines has narrowed considerably between industrialized and developing countries over the past few years, the public sector has too often been left adjusting systems to accommodate vaccine presentations and packaging developed for industrialized countries, such as the packaging of recent new products of global importance, for example, rotavirus, pneumococcal and HPV vaccines, and, according to early indications, a candidate malaria vaccine. 

The Vaccine Presentation and Packaging Advisory Group (VPPAG) was established by the GAVI Alliance in 2007 to respond to specific requests for technical advice regarding rotavirus and pneumococcal vaccines.  For the latter, this fed into the WHO target product profile (TPP) for pneumococcal vaccines to be eligible for the Advance Market Commitment (AMC) financing.  VPPAG also responded to a request from industry to provide guidance on rotavirus vaccines, primarily around reducing the package volume of existing products to ease cold chain burden for resource-poor countries. Following a successful dialogue with one company, it was possible to fruitfully engage another in a similar exercise.

One of the main lessons learned by the VPPAG was the need to embark upon the process very early as it is difficult to make substantial changes in vaccine formulation and presentation once the product is beyond preclinical development and has entered phase 1 clinical trials.  For example, the inclusion of a vaccine preservative which may enable a multidose vial of a vaccine to be kept beyond a single session under certain conditions or additives that would create improved vaccine thermostability or to prevent freeze-damage to a vaccine currently commercialized or in late-stage development would require repeating clinical trials, licensure and WHO pre-qualification steps, all of which are time-consuming and can be extremely costly. 

Therefore, it is hoped to sensitize vaccine manufacturers progressively to developing-country programmatic preferences and operational realities and sensitize the public sector to industry constraints and economic realities. 

New governance

In 2008, responsibility for convening the VPPAG was transitioned to WHO, and an extended purpose proposed.  VPPAG is currently being supported by several partners including UNICEF and the PATH-WHO “Optimize: Immunization Systems and Technologies for Tomorrow” project whose mandate includes working with stakeholders to ensure that future vaccine products and delivery technologies have characteristics that are consistent with developing-country needs. Members that had initially been selected by GAVI to advise them were requested to continue their work on the VPPAG for the time being.   

As stated in the introduction, VPPAG is intended to mainly advise the vaccine manufacturing industry. It has no WHO policy-making or directive power, but can contribute to the WHO processes for setting policy, norms, and standards. It is intended to combine and translate its members field and research experience, as well as WHO policy guidelines and vaccine manufacturing knowledge into useful and practical guidance to vaccine manufacturers to ensure rapid and effective uptake of the vaccines in the public sector market of developing countries.

Also, as a body that creates a unique forum for diverse partners and stakeholder (including the countries that ultimately will benefit from this work) in the vaccine development and presentation world, it presents an important external input to the policy-making bodies in WHO, such as TLAC, where appropriate. Similarly it may provide insights to other bodies such as UNICEF SD, GAVI Secretariat and the like.

Purpose of VPPAG

1.      To provide a forum for industry and the public sector dialogue on presentation and packaging of vaccine products and  responding to industry requests for guidance as well as proactively engaging industry where appropriate.

2.      To continue to facilitate improvements in presentation and packaging of vaccine products that are available or near market readiness, to maximize their appropriateness for public sector use in developing country markets, through specification of preferred product profiles.

3.      To continue generic work to establish optimal vaccine presentation and packaging guidelines in conjunction with different vaccination strategies in order to maximize the appropriateness of vaccine packaging and presentations for the settings in which the products will be employed.

Process

·         Hold periodic group meetings to advance the workplan, discuss proposals, provide an advocacy forum with industry, share technical and programmatic information on developing country preferences and manufacturing processes within industry, etc.

 ·         Consult Regional Working Groups and developing countries through other fora and mechanisms (e.g. Technet consultation).

 ·         Support additional direct consultations with countries and other activities, as needed.

 ·         Act as a resource for WHO (and its advisory bodies), UNICEF SD, GAVI and other vaccine partners providing inputs on vaccine presentations and packaging where appropriate

Membership

VPPAG was originally established by GAVI without a formal selection process but rather by bringing together interested parties and experts in their field. This membership provides broad representation of vaccine industry through IFPMA and DCVMN and the agencies involved in immunization.  To maintain its strength, the membership of VPPAG should be made up by one representative for each of the following constituencies:

- IFPMA

- DCVMN

- WHO: EPI

- WHO: QSS

- PATH

- UNICEF: Supply Division

- UNICEF: Programme Division

- ImmunizationBasics

- CDC

- GAVI Secretariat 

It may also be appropriate for VPPAG to select additional agencies to be represented, individual experts, and more than one member from any agency. The chair of VPPAG is selected by VPPAG members, and rotated every two years.

One clear benefit of VPPAG is its ability to engage with and receive inputs from the vaccine industry. At the same time however, in giving recommendations to industry, it may occasionally deal with information that is proprietary to the specific company. In this case it is necessary that the IFPMA and the DCVMN representatives are excluded from the discussion, and a person representing the specific company involved is included instead. The IFPMA and DCVMN representatives would thus only be present in the generic issues discussion.

Review

VPPAGs terms of reference, purpose, membership, modus operandi, secretariat and outputs should be reviewed periodically, at least every three years.

ADDENDUM of 15 June 2009
Processes and procedures related to industry meetings with VPPAG

(1) Participation at regular meetings/calls

To facilitate planning, active participation and communication, groups such as IFPMA and DCVMN are encouraged to nominate a representative that can attend VPPAG meetings and coordinate the dissemination of information, e.g. meeting minutes, documents, etc., and input from their constituency. This does not exclude the participation of constituents in meetings. It does guarantee that meetings are scheduled so that the group representative can attend. 

Constituents are asked to notify VPPAG in advance of their planned attendance at upcoming meetings. Interest in attending should be announced by e-mail to the VPPAG chair, convener, and secretary, and to the group representative {see below}.

(2) Industry seeking confidential discussions with VPPAG, but without other industry participation or knowledge.

If individual manufacturers wish to discuss any matters with VPPAG, in confidence and without alerting other industry participants, VPPAG will hold a special session without any other industry participants. These meetings and their content will be minuted by the industry member involved and not by VPPAG; the industry member will then be responsible for circulating the meeting record/minutes to the attending member(s) of VPPAG for their review/confirmation.

Manufacturers who request such a meeting should do so by making a request to the VPPAG convenor and secretary and include with the request: objectives, expected outcomes and a list of expected participants and non-participants.

VPPAG members will keep confidential all matters including having had any consultation/discussion, as requested by the industry. No record of the meeting will be posted on the VPPAG public or restricted access sites.

(3) VPPAG seeking discussions with an individual manufacturer

If VPPAG wishes to discuss any matters with individual manufacturers, in confidence and without alerting other industry participants, VPPAG will hold a special session with that industry participant. These meetings and their content will be documented by VPPAG and not by the industry participant involved, but circulated to the industry participant involved for confirmation.

When VPPAG requests such a meeting they should do so by making a request to the manufacturer and include with the request: objectives, expected outcomes and a list of expected participants and non-participants.

VPPAG members and manufacturer participants should keep confidential all matters including having had any consultation/discussion, as requested by the VPPAG. No record of the meeting will be posted on the VPPAG public or restricted access sites.

Chair:                                        Osman Mansoor: omansoor@unicef.org

Convenor:                                 Soulemane Kone:  kones@who.int

Secretary:                                 Simona Zipursky: szipursky@path.org



Addendum as of March 9th

Quorum


VPPAG requires a quorum to be in attendance at a meeting in order for minutes to be approved or decisions to be taken.


VPPAG has defined the requirements of a quorum as follows:


- The Chair or convenor must be present

- At least one of either the IFPMA or DCVMN representatives must be present

- At least 5 members in total must be in attendance, including the Secretary.


Current Membership (as of January 2011)

Current Members
Osman Mansoor: omansoor@unicef.org UNICEF PD, Chair
Soulemane Kone: kones@who.int, Convener
Simona Zipursky: szipursky@path.orgSecretariat
Sheila Cattell: sheila.cattell@gskbio.com,  IFPMA
   
Gisele Corrêa Miranda: Gisa@bio.fiocruz.br, DCVMN Alternate
    Steve Drucker: steve.drucker@merck.com, IFPMA Alternate
    
Debra Kristensen: dkristensen@path.org, PATH
   
Drew Meek: meekd@who.int,  WHO QSS
Yalda Momeni: ymomeni@unicef.org, UNICEF SD
    Ann Ottosen: aottosen@unicef.org, UNICEF SD
    Jon Pearman jpearman@gavialliance.org GAVI Alliance
    
Hardeep Sandhu: hjs3@cdc.gov, Govt./Tech  
Inderjit Sharma: inderjit.sharma@seruminstitute.com, DCVMN
    R
obert Steinglass: Robert_Steinglass@jsi.com, NGO

  

Pneumococcal and rotavirus vaccine presentation and packaging advisory group

Terms of reference (final)

2007

(also at: http://www.gavialliance.org/resources/VPPAG_TORs_2007_Final.doc)

   

Background

 

In November 2006, the board of the GAVI Fund approved financial support for GAVI-eligible countries wishing to introduce pneumococcal vaccine against Streptococcus pneumoniae and/or rotavirus vaccine (Europe and Latin America only) during phase II. Presently available pneumococcal and rotavirus vaccines were developed for single dose presentation without preservative.  

 

The pneumococcal vaccine available until mid-2009 is the Wyeth 7-valent vaccine in a single 0.5 ml dose pre-filled disposable syringe provided in packages of ten (Prevenar®). This presentation requires 55.9 cm3 per dose of storage space for cold chain and transport. This vaccine will be replaced for use in developing countries by a single-dose vial by 2009, and by 2011 onwards, by a multi-dose vial presentation of 13-valent pneumococcal vaccine. Wyeth requests guidance on the recommended presentation of a multi-dose vial for developing countries to initiate preparations for its production. In addition, it is expected that several other producers will come on line in the next few years, the first one being a 10-valent vaccine from GSK, expected in 2010. Therefore, a general recommendation for a range of possible vaccine presentations and vial sizes should be made for consideration by existing and future pneumococcal vaccine manufacturers.

 

Initial presentations of the single-dose rotavirus vaccines occupy 80-112 cubic cm per dose (see Table).  For rotavirus, there are presently two oral, live, attenuated vaccines available. The lyophilised vaccine formulated for reconstitution with a diluent (Rotarix® from GSK) requires two doses for a full course, and the liquid vaccine (RotaTeq® from Merck) requires three doses for a full course. The three-dose vaccine, presented in a pre-packaged single-dose application, is available in packages of two or ten doses and requires approximately 80.9 to 85.2 cm3/dose of cold storage space (170.4 cm3 for the two dose package and 809.4 cm3 for the full ten dose package).  The two-dose rotavirus vaccine presentation requires 156.0 cubic centimetres per dose of cold storage space, packaged with diluent, connector and applicator.

 

EPI vaccines supplied in multi-dose presentations typically occupy less than 10 cubic cm per dose. Single dose vials of liquid vaccines typically occupy 10 to 33 cubic cm.  These new vaccines will thus require substantially more space for cold chain storage and vaccine transport and distribution than currently used EPI vaccines. Consequently, this had cost implications for national vaccination programmes, such as cold chain expansion and maintenance, and frequency of vaccine delivery to district level.

 

   

Mandate

 

To recommend acceptable and preferred pneumococcal and rotavirus vaccine presentations and packaging for developing country procurement through the GAVI Alliance funding mechanism. Parts of this work shall inform the design of the target product profile (TPP) of the Advance Market Commitment for pneumococcal vaccine.

 

This is a component of activity 2.3.3.1 in the GAVI Workplan (commence roll-out of rota and pneumo investment cases).

 

Deliverables

 

The group will make recommendations for possible presentations of pneumococcal and rotavirus vaccines for procurement by developing countries through the GAVI Fund. The recommendations will cover at least the following issues. Other considerations will be addressed and included as they arise.

 

1.      Vaccine formulation (liquid or other? Is this up for discussion?)

2.      Multi-dose vial size (discussion to include cost and wastage considerations)

3.      Single dose options including a UniJect presentation

4.      Issues surrounding introduction of a mix of presentations (single dose and multi dose)

5.      Matching vaccine profile to vaccination setting (clinic, schools, outreach…)

6.      Inclusion of preservatives (thimerosal, 2-phenoxy ethanol, others?)

7.      Applicability of multi-dose vial policy (MDVP)

8.      Thermostability of the vaccine (sensitivity to heat and freezing)

9.      Vaccine vial monitors

10.  Packaging and how to minimize it

11.  Wastage and how to minimize it

12.  Cold chain requirements (volume per dose, temp monitoring..)

13.  Management of vaccine waste (PFS, vials, syringes)

14.  Acceptability to health workers

15.  WHO pre-qualification and other regulatory issues.

 

As part of the context, the group will also be mindful of the implications of any recommendation for other health systems issues related to vaccine introduction, including cost and financing, training needs for health workers (trade-off between innovation and familiarity), monitoring systems required, acceptability to the public and social mobilisation, and the whole range of issues related to introduction of any additional or new vaccine.

 

As much as possible, discussions should be anchored in lessons learned from the field from introduction of Hib and other vaccines to maximize the feasibility of pneumococcal and rotavirus vaccine introduction and provide a range of options for both industry and countries.

   

Timeline

 

The work will be approached in two stages. The first  stage  will provide general recommendations as needed in establishing the Target Product Profile for the AMC by 1 August, 2007 and respond to a specific request from Wyeth and provide recommendations for their development process.  The second stage will address packaging issues with respect to rotavirus vaccines with a view to their eventual use in Asia and Africa as well as Latin America and European countries. The work of the group will continue until such recommendations are available. The need for continuing work will be assessed at the end of 2007

 

The specific work and deliverables of the stages can overlap in time and be undertaken simultaneously as appropriate.

 

Membership

 

The group will be composed of active members from

 

GAVI Secretariat: R. Lewis (Coordinator), I. Rizzo.

UNICEF: Osman Mansoor (Chair), Ann Ottosen

WHO: Patrick Zuber, Souleyman Kone, Radmila Mirzayeva

pneumoADIP: Angeline Nanni

rotaADIP and PATH: Robin Biellik, Alan Brooks, Carib Nelson

IFPMA: Yves Leurquin

DCVMN: Subhash Kapre

CDC: Vance Dietz

Immunization Basics: Robert Steinglass

 

Regional Working Groups or countries will be consulted through other meetings and mechanisms (e.g. Technet consultation)  

 

The group will be chaired by UNICEF with support from the GAVI Alliance Secretariat.

 

Modus operandi and reporting

 

The group will initiate discussions via email and pursue the work via teleconference and or video-conference as needed. A face-to-face meeting will be convened to review all the issues and finalise a draft recommendation if deemed necessary by the group.

 

The group will submit a draft recommendation to the Working Group for consideration followed by a final report to document the process.

     


 

Pneumococcal and rotavirus vaccine presentation and packaging working group

List of members

 

Agency

Name

Contacts

GAVI Secretariat (Coordinator)

R. Lewis

Technical and policy team

GAVI Alliance

Chemin des mines

c/o UNICEF

Palais de Nations

1211 Geneva 10, Switzerland

tel: +41 22 909 6515

fax: +41 22 909 6550

 

I. Rizzo

Country support team

GAVI Alliance

Chemin des mines

c/o UNICEF

Palais de Nations

1211 Geneva 10, Switzerland

tel: +41 22 909 6541

fax: +41 22 909 6550

UNICEF (Chair)

Osman Mansoor

Senior Adviser EPI (New Vaccines)

Program Division

United Nations Children's Fund

3 UN Plaza, New York, NY 10017 (room 840)

Phone: +1 212 326 7410

Fax: +1 212 8246460

Email: omansoor@unicef.org

 

Anne Ottosen

Contracts Officer

New Vaccine Unit

UNICEF Supply Division

 

phone +45 3527 3124

e-mail: aottosen@unicef.org.

 

WHO

Patrick Zuber

zuberp@who.int

 

Souleyman Kone

kones@who.int

 

Radmila Mirzayeva

Mirzayevar@who.int

pneumoADIP

Angeline Nanni, Director for Vaccine Finance & Supply

ananni@jhsph.edu

rotaADIP and PATH:

Robin Biellik

Rotavirus Vaccine Programme

PATH

Bâtiment Avant Centre; 13 chemin du Levant

01210 Ferney Voltaire, France

rbiellik@path.org;

Tel (33) 450 28 09 63

Fax (33) 450 28 04 07

 

 

Alan Brooks

Malaria Vaccine Initiative

PATH Malaria Vaccine Initiative

Bâtiment Avant Centre; 13 chemin du Levant

01210 Ferney Voltaire, France

abrooks@path.org;

Tel (33) 450 28 09 63

Fax (33) 450 28 04 07

 

Carib Nelson

PATH

1455 NW Leary Way

Seattle WA 98107 USA

cnelson@path.org

Tel 1-206-285-3500

Fax: 1-206-285-6619

 

IFPMA

Yves Leurquin

EVP International and Government Affairs
Crucell NV

Archimedesweg 4, NL-2333 CN Leiden, The Netherlands

Berna Biotech Ltd, Rehhagstrasse 79, CH-3018 Berne, Switzerland
Phone:  +41 (0)31 980 68 21          Fax.:  +41 (0)31 980 64 72
e-Mail: yves.leurquin@bernabiotech.com

 

DCVMN

Dr. Subhash Kapre
Serum Institute of India Ltd.,

212/2, Hadapsar,
Pune : 411 028, India

Tel. (Gen) : +91-20-2699.3900 Fax (Gen) : +91-20-2699.3921
Email : skapre@seruminstitute.com

Immunization BASICS

Dr. Robert Steinglass

robert_steinglass@jsi.com

 

 

 






 


 

ĉ
Oz Mansoor,
Jun 23, 2009, 1:09 PM
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