International Coordinating Group meningitis annual meeting report 2015

18-19 June 2015 – WHO Headquarters, Switzerland

Contents

Abbreviations and acronyms ................................................................................. 1

Executive summary ............................................................................................... 2

Epidemic season 2015: epidemiological overview .................................................. 3

Update on the Men A conjugate introduction ....................................................................................... 3

ICG response and performance ............................................................................. 4

Procurement of the 2015 stockpile: chronology and challenges ............................. 5

Nm C outbreaks in Niger and Nigeria, 2015 ........................................................... 7

Discussion of ICG forecast stockpile 2016 .............................................................. 7

Ceftriaxone stockpile and management ................................................................ 8

Financial updates .................................................................................................. 9

Use of GAVI funds 2009-2015 WHO/UNICEF (operational costs) ............................................... 9

Revolving fund balance ............................................................................................................................... 10

Sustainability of the vaccine stockpile beyond 2015 ............................................ 10

2015 procurement and challenges UNICEF-SD ............................................. 11

Epidemic season 2015: epidemiological overview ................................................ 12

Outcome of ICG members decisions regarding ICG vaccine stockpile composition

(quantities and type of vaccine) .......................................................................... 12

ICG achievements during the meningitis investment case, 2009-2015 .................. 12

Manufacturers presentation on supplies: forecast 2016-2017 .............................. 13

Bio-Manguinhos/Finlay Institute............................................................................................................ 13

GlaxoSmithKline ............................................................................................................................................. 13

Sanofi Pasteur ................................................................................................................................................. 13

Serum Institute of India .............................................................................................................................. 14

Action points of the 2015 ICG meeting ................................................................ 15

Annex 1. Meeting agenda ................................................................................... 18

Annex 2. List of participants ................................................................................ 20

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Abbreviations and acronyms

Bio-M Bio-Manguinhos

EVS Emergency Vaccination and Stockpiles

GSK GlaxoSmithKline

ICG International Coordinating Group (on Vaccine Provision for Epidemic Meningitis Control)

IFRC International Federation of the Red Cross and Red Crescent Societies

LTA Long-Term Agreement

MoH Ministry of Health

MSF Médecins Sans Frontières

Nm A Neisseria meningitidis type A

Nm C Neisseria meningitidis type C

NRA National Regulatory Authority

PS Polysaccharide

RF Revolving fund

SII Serum Institute of India

Spn Streptococcus pneumoniae

UNICEF United Nations Children's Fund

UNICEF-PD UNICEF Programme Division

UNICEF-SD UNICEF Supply Division

WHO World Health Organization

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Executive summary

The 2015 meningitis 'epidemic season' in Africa's 'Meningitis Belt' brought a spike in meningitis cases not seen since 2012 with 18 700 suspected cases reported up to 31 May 2015. The fact that the epidemics were the result primarily of meningitis serogroup C, until now not seen to be the cause of extensive outbreaks in Africa, took the affected countries and ICG by surprise. While it is uncertain whether this emergent serogroup will continue to cause extensive epidemics next year, the ICG members considered that a high risk exists. The ICG mandate is to plan and be prepared for potential outbreaks and have a sufficient supply of vaccine (and antibiotics) available for shipment at short notice.

That mandate was severely hampered at the start of the 2015 season – the stockpile of vaccines the ICG manages was insufficient to meet the need in 2015. Despite the request made by ICG to UNICEF-SD, only 300 000 doses of the 1.5 million doses of CW-containing polysaccharide vaccine needed were offered by a vaccine manufacturer with prequalified vaccine, Sanofi Pasteur. On 25 November 2014, UNICEF-SD informed the ICG that despite the important shortfall of polysaccharide vaccine for emergency response, they could not procure the vaccine offered in the tender process by Finlay Institute/Bio-Manguinhos because it was not prequalified by WHO. With the severe shortage of vaccine the ICG tapped into the revolving fund it had established to procure this vaccine directly from the manufacturer. The vaccine offered by Sanofi Pasteur could not be made available due to quality problems with the diluent, and so instead expensive conjugate vaccine was made available. The ICG Secretariat was also able to obtain additional doses of CW-containing vaccine from GSK, made available in response to the emergency. This experience highlights the importance of working with several manufacturers to maintain production of polysaccharide CW-containing vaccine, in the face of dwindling commercial interest.

While the introduction of Men A conjugate vaccine has been quite successful in dramatically reducing Nm A outbreaks, a risk of Nm C and Nm W outbreaks remains and the ICG and partners responsible for procurement must ensure that sufficient vaccine stocks are available to respond to them.

Concerning Ceftriaxone, the stockpile was also insufficient in meeting country requests and the ICG recommended maintaining a stock of 7 000 treatments of a five-day course of ceftriaxone from multiple manufacturers.

The annual ICG meeting on 18 and 19 June 2015 reviewed the last epidemic season, and sought to find solutions to the issues raised to be better prepared for the 2016 epidemic season.

Stakeholders attending the closed session on day 1 were ICG members (IFRC, MSF, WHO, UNICEF-PD), the ICG Secretariat, and WHO colleagues working on meningitis; a short portion of day 1 was also opened to representatives of the GAVI Alliance and UNICEF-SD. Day 2 was an open session, to which vaccine manufacturers were invited in addition to the stakeholders already mentioned.

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Session 1. Meningitis outbreak response (closed

session between ICG members)

Chairperson: Olivier Ronveaux, WHO

See Annex 1 for the agenda of the meeting, and Annex 2 for the list of participants.

Epidemic season 2015: epidemiological overview

Following the introduction of MenAfriVac™, meningitis cases have been decreasing in the 'meningitis belt' of Africa since 2010. The past two years have been particularly 'quiet'—the epidemic threshold1 was reached in small areas of Benin, Burkina Faso, Guinea, Nigeria and South Sudan in 2013; and Ethiopia, Guinea and Nigeria in 2014. The main pathogen identified during these years in the belt was Streptococcus pneumonia (Spn), while Neisseria

meningitidis (Nm) W135 serogroup was the predominant pathogen in most epidemic areas, except for South Sudan in 2013 and Guinea in 2014, where Nm A was predominant. In Nigeria, Nm C was predominant in 2013 and 2014.

The meningitis disease burden for 20152 is approximately 18 700 suspected cases and 1 400 deaths. In comparison those numbers were 11 650 suspected cases and 1 126 deaths in 2014. This indicates there has indeed been an increase in the number of cases over last year.

Two relatively large epidemics this year were due to the Nm C serogroup – in Niger and Nigeria causing 10 700 cases, 620 deaths, and involving a total of close to 20 districts: Nm C had not been the cause of extensive outbreaks before. Increased meningitis activity was also reported in Guinea and in the Democratic Republic of the Congo in 2015. Nm A was confirmed in the former and only Streptococcus pneumoniae (Spn) was confirmed in the latter.

What is clear from the experience of this year's meningitis season is that countries were ill prepared for an outbreak of Nm C, and the International Coordinating Group's (ICG) stockpile of CW-containing vaccine was insufficient at the time it was needed despite the clear ICG request during the 2014 meeting, both of which contributed to the growth of the epidemics in Niger. Given the high risk of extension of Nm C outbreaks during the next meningitis season it is imperative the stockpile contains a sufficient quantity of CW-containing vaccine prior to January 2016.

Update on the Men A conjugate introduction

The MenAfriVac™ (Men A conjugate vaccine) campaign in the 'meningitis belt'3 of Africa began in 2010. Since then the vaccine has been administered to over 200 million of people across the belt through the support of the World Health Organization (WHO) and partners with the GAVI Alliance (financial support). The programme will continue through 2017. The result has been a dramatic reduction in number of cases of meningitis from the Nm A serogroup, with no Nm A outbreaks in vaccinated areas.

1 New guidelines for the alert and epidemic thresholds have been in place since January 2015, but this discussion and the data

discussed have relied on the previous guidelines. 2 Burden based on data gathered through week 22.

3 This includes 22 countries or 26 countries in the 'extended meningitis belt'.

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ICG response and performance

During the 2015 meningitis season, the ICG received 10 requests for vaccine from two different countries (Niger and Nigeria), seven of which were approved (see Table 1). Nigeria made two requests, which were fulfilled with polysaccharide ACWY vaccines (from Sanofi Pasteur) in both instances. Concerning Niger, Request #10 replaces requests #7, #8 and #9. The delays between the ICG decision and the reception of vaccine in Niger were particularly long for requests #3 and #4 because of the unavailability of vaccine – caused by the fact that the United Nations Children's Fund Supply Division (UNICEF-SD) did not manage to procure the vaccines on time – and the time it took for Finlay Institute and GlaxoSmithKline (GSK) to make vaccine available for shipment once plan B (purchase via the revolving fund or direct contact between the ICG Secretariat and GSK) was activated.

The time between receipt of an ICG request and shipment of vaccine to a country should take no longer than 10 days.

• ICG Secretariat receives request and distributes it to ICG members (if no information is missing): 1 day

• ICG members review the request: 2 working days

• (If request approved) packing of vaccine and shipment to country: 7 days.

In practice however, delays can creep into the process, particularly when requests arrive incomplete and require additional clarification (a number of action points aim to address this issue including a change to Table 1).

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Table 1. ICG requests received in 2015

Countries No. doses

requested No.

doses

approved

Reception to

circulation (working

days)

Additional

info

submitted

Decision (working

days)

Decision

to

reception

Vaccination

starts (after

reception)

Observations

Nigeria

#1/2015 203 647 204 850

+ 47 500

donated

0 days 2 days 1 day 8 days 9 days 204 850

doses

approved

(+47 500

doses

donated)

Nigeria

#2/2015 127 451 104 390 1 day 1 day 1 day 8 days 20 days

Niger

#3/2015 37 920 37 920 1 day NA 1 day

(from the

circulation)

21 days 2 days

Niger

#4/2015 388 062 179 446 1 day 1 day 2 days 13 days 4 days

Niger

#5/2015 291 878 265 344 0 days NA 3 days 4/10 days 2/8 days 2 shipments

Niger

#6/2015 249 206 200 000 3 days 5 days

(submitted

after the

decision)

3 days (From the

circulation)

9 days 8 days

Niger

#7/2015 205 424 0 1 day NA NA NA NA Cancelled

Niger

#8/2015 213 416 0 1 day NA NA NA NA Cancelled

Niger

#9/2015 - - NA NA NA NA NA Request not

circulated.

Cancelled

Niger

#10/2015 533 400 415 415 0 days NA 2 days 5 days 4 days

Procurement of the 2015 stockpile: chronology and challenges

At their annual meeting in July 2014, the ICG requested 1.5 million doses of CW-containing vaccine and 1.5 million doses of Men A conjugate vaccine for the 2015 stockpile. Procurement of this stockpile was hampered by myriad problems, linked principally to the unavailability of vaccine from manufacturers (a gap of 1.5 million doses) prior to the meningitis season in January 2015 and UNICEF-SD's lack of flexibility to adapt to the situation and find solutions. All of the problems with respect to procurement have solutions associated with them as action points, which can be found at the end of report.

Replaced by request #10/2015

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During the 2015 meeting the ICG highlighted the lack of problem-solving from UNICEF-SD as a serious concern. The main issue occurred when UNICEF-SD did not propose any solutions to fill the gap of 1.5 million doses in the stockpile, considering that Sanofi Pasteur could not supply the vaccine. Since WHO could not rely on UNICEF-SD, it intervened on behalf of the ICG to find a solution and fill the gap. This resulted in the ICG procuring vaccine directly from Finlay Institute/Bio-Manguinhos (Bio-M)4.

During the discussion ICG members considered withdrawing ICG procurement activities from UNICEF-SD (and therefore the GAVI Alliance, as the latter will only work with UNICEF-SD). UNICEF's Programme Division (UNICEF-PD) offered to play a role in facilitating communication between the ICG and the UNICEF-SD in the future. The main problems with respect to the 2015 vaccine stockpile are discussed below.

Only at the end of November 2014 did ICG members become informed that the ICG request for the 2015 stockpile would not be met, leaving the ICG little time to prepare a plan B. The tender process resulted in Bio-M offering 1.5 million doses of CW-containing polysaccharide and Sanofi Pasteur offering 300 000 doses of CW-containing polysaccharide vaccine, however because the vaccine from Finlay Institute/Bio-M was not WHO prequalified, UNICEF-SD could not consider it (even though Bio-M had other prequalified vaccines and had procured from them in the past). This meant that UNICEF-SD would only be able to secure 300 000 of the 1.5 million doses of CW-containing vaccine that the ICG had estimated would be needed for the season, creating a significant vaccine gap.

The ICG therefore requested WHO to procure (using funds from the revolving fund) vaccine directly from Bio-M/Finlay Institute: 300 000 doses of polysaccharide ACW (at US$ 2.5/dose), agreeing to buy an additional 500 000 doses after prequalification (with a shelf life 24 months).

The ICG also requested UNICEF-SD to procure 1.5 million doses of Men A conjugate from the Serum Institute of India (SII); and 200 000 doses of polysaccharide ACWY vaccines from Sanofi Pasteur (Menomune®, price US$ 5.8/dose; shelf life of 24 months). Signature of the contract between Sanofi Pasteur and UNICEF-SD was delayed and in January the contract had still not been signed. In February 2015, Sanofi Pasteur informed the ICG that there was a problem with the quality of the diluent of Menomune® and it could not commit to supplying the doses offered in the tender, at least not in time for the epidemic season.

Given the Nm C outbreak situation in Nigeria, and the vaccine shortage, Sanofi Pasteur offered to supply 138 570 doses of Menomune® that had a short shelf life (expiration between April and December 2015). Sanofi would not donate doses close to expiry and WHO negotiated a price of US$ 3.85 per dose. The ICG agreed to procure 104 000 doses of this vaccine (all the doses Sanofi Pasteur offered except those expiring within less than one month), at the negotiated price of US$ 3.85/dose to respond to the request for Nigeria. This procurement was outside of the 2015 stockpile procurement process.

The ICG also approved the procurement by UNICEF-SD of 200 000 doses of Menactra® (conjugate vaccines from Sanofi Pasteur) at US$ 25/dose (total cost US$ 5 million), under two assumptions: that no other vaccine was available on the market and that GAVI would finance those 200 000 doses (based on an email received from UNICEF-SD). It was later learned, however, that GSK had 1 million doses of polysaccharide vaccines in stock, which it offered to the ICG at US$ 4/dose – and the ICG purchased 500 000 doses (see Table 2).

GSK had not responded to the procurement tender for the 2015 stockpile and UNICEF-SD failed to convince them later to do so. However thanks to direct contact initiated by one ICG Secretariat member and in the face of the emergency situation in Niger, GSK supplied

4 Finlay Institute and Bio-Manguinhos are partners.

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500 000 doses of Men ACWY polysaccharide vaccine (Mencevax®) to the ICG, which were deployed to Niger (note that the ICG only approved 415 415 doses, but UNICEF-SD sent all 500 000 doses to Niger).

The administrative procedures pertaining to the WHO procurement process were also discussed; delays occurred in procurement, as these procedures are not adapted to responding to emergencies. WHO will be looking at establishing a new mechanism for 2016 that allows for emergency/expedited procurement.

Nm C outbreaks in Niger and Nigeria, 2015

The number of cases of meningitis in Nigeria passed the epidemic threshold during week 7 of 2015 in the northwest districts of Kebbi (86 cases) and Sokoto (20 cases); these districts are considered the 'epicentre' of the outbreak. Meningitis then spread to the southwest of Niger (affecting the regions of Niamey, Dosso and Tillaberi), which is unusual for meningitis outbreaks. The predominant pathogen was confirmed to be Nm C.

Data from the Nm C outbreaks in Nigeria differ substantially between organizations (e.g. Médecins Sans Frontières (MSF) suggested about 5 500 cases from one state in Nigeria, while WHO/ministry of health (MoH) stated about 3 000 cases from five states). The reasons for this are likely due to lack of adequate surveillance and reporting.

The vaccination response in Nigeria relied on the remaining quadrivalent Men ACWY vaccine (Menomune®) stockpile from 2014. Approximately 310 000 people were vaccinated. In Niger, two different polysaccharide (PS) vaccines and a conjugate vaccine were used. The target age group was 2–15 years, and the target group was schools, with a catch-up in the community. Approximately 800 000 people were vaccinated.

Table 2. Vaccine procurement in 2015, by vaccine type, quantity, and cost

Vaccine type Quantity Unit cost (US$) Total cost (US$) Procurement

Nigeria

PS ACYW (Menomune®) 204 850* 5.0 1 024 250 UNICEF-SD (GAVI)

PS ACWY (Menomune®) 48 000* 5.0 240 000 UNICEF-SD (GAVI)

PS ACWY (Menomune®) 104 390 3.8 396 682 UNICEF-SD (GAVI)

Niger

PS ACW (Finlay Institute) 38 000 2.5 95 000 WHO (RF)

PS ACW (Finlay Institute) 180 000 2.5 450 000 WHO (RF)

PS ACW (Finlay Institute) 82 500 2.5 206 250 WHO (RF)

Tetravalent (Menomune®) 200 000 - - Loan from Mali

PS ACW (Finlay Institute) 160 000 2.5 400 000 WHO (RF)

Conj. ACWY (Menactra®) 200 000 25.0 5 000 000 UNICEF-SD (GAVI)

PS ACWY (Mencevax®) 500 000 4.0 2 000 000 UNICEF-SD (GAVI)

Total doses

1 717

740 9 812 182

* From the 2014 stockpile. PS, polysaccharide; RF, revolving fund; Menomune® and Menactra® are products of Sanofi Pasteur; Mencevax® is a product of GSK.

Discussion of ICG forecast stockpile 2016

Based on (a) the dynamics of meningitis epidemics, the ICG considers there is a high risk that the meningitis C epidemic could extend to other countries in 2016 and 2017, given the

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emergence of a new strain of Nm C in Africa, with has proven its epidemic potential and extension to several countries and (b) almost 20 years of the ICG dealing with epidemics of NmA and the use of between 3 to 5 million doses of vaccine to respond to epidemics of NmA during epidemic seasons, the ICG recommended having 5 million doses of CW-containing vaccine in the stockpile for 2016, with a preference for multivalent conjugate vaccine and 1.5 million doses of Men A conjugate vaccine, of which there is sufficient supply. The ICG requested that the full quantity be available in early January 2016.

The ICG Secretariat will make the initial contact with the manufacturers concerning the 5 million doses. This tender will need to be worded in such a way as to ensure manufacturers offer all CW-containing vaccines available (e.g. manufacturers of polysaccharide vaccines may not provide an estimate for a request for only conjugate vaccines). To that end, it was planned to share the number of doses sought but not their composition on day 2 when the manufacturers were present – and in so doing, determine what the manufacturers could provide (i.e. breakdown of planned production of polysaccharide and conjugate vaccines).

Other options for vaccine formulation were also discussed, in case the ICG could not negotiate a more affordable price than US$ 25/dose, but ultimately the ICG decided to request availability of every possible formulation from each manufacturer, and build the best stockpile from what was offered. During the discussion, it was noted that the price of multivalent conjugate vaccines was too high, and the ICG members sought ways to get manufacturers to lower the price. As a way to do that, it was suggested that the ICG appeal to the manufacturers' corporate social responsibility in addition to initiating a communications campaign directed towards the public, so as to highlight the need for affordable multivalent conjugate vaccines. It was agreed that the comprehensive communications campaign strategy should be initiated as soon as possible, in tandem with identifying and contacting other potential donors of financial support. The ICG decided to conduct a media campaign to raise awareness on the 2016-2017 Nm C epidemic risk and the need for increased vaccine supply. The issue of vaccine cost, particularly of the conjugate vaccines, will be one of the targets of the campaign. A consultation between the Secretariat and manufacturers began shortly after the meeting adjourned, so that manufacturers had the maximum amount of time to present their options and the ICG to decide its stockpile, in order to ensure the vaccines would be ready by 1 January 2016. The tender for the 5 million doses including all possible combinations of conjugate and polysaccharides CW-containing vaccine was to be issued by UNICEF-SD by September 2015 and bids will be sought from all manufacturers (including GSK). The exact 2016 stockpile composition will be decided by the ICG after the tender process, which took place in September 2015.

Ceftriaxone stockpile and management

During the 2015 season, manufacturers did not have a supply of ceftriaxone ready for immediate delivery. There were delays in the provision of diluent for injection as well. The ICG stockpile of ceftriaxone at the beginning of 2015 was 1 491 vials. This quantity was not sufficient to meet the 2015 needs and 26 500 doses were procured – 5 000 doses constituted ICG request #1; 3 000 doses ICG request #2; 18 500 doses ICG request #4). After delivery of the supplementary antibiotics, the ICG stockpile contained just 991 vials (as of 17 June 2015). It took on average 27 days to deliver the antibiotic after ICG approval – far too long for emergency response.

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Discussion focused on increasing the stockpile and the feasibility of implementation of the currently recommended five-day protocol (versus the previous single-dose protocol) with the antibiotic. It was decided based on the available data to keep a stockpile according to the five-day protocol. At US$ 1.05 per dose, cost would not be a factor.

It was agreed to establish and maintain sufficient stockpiles of ceftriaxone from manufacturers certified as having Good Manufacturing Practices (in at least two locations, Cyprus and Turkey were proposed), which can be shipped quickly in tandem with vaccine for meningitis treatment. (This includes the supplies needed for use like diluents, etc.) It was also decided to ask manufacturers to replenish the quantities used and sell the oldest antibiotic first (i.e. rotate stock) while maintaining a stock that has at least a two-year shelf life.

The ICG agree to ensure a sufficient supply of antibiotic to provide 7 000 treatments of a five-day protocol.

Financial updates

Use of GAVI funds 2009-2015 WHO/UNICEF (operational costs) The emergency stockpile for the period 2009-2015 was financed by the GAVI Alliance – US$ 55 million, of which US$ 14 million was for operational costs and technical support (10.4 million to WHO; 3.6 million to UNICEF-PD for social mobilization) and US$ 41 million for vaccine procurement. A revolving fund mechanism was created in 2010 to ensure sustainability beyond GAVI support, and has also provided more autonomy for decisions. The total expenditure on operational costs for the period 2009-2015 has been US$ 2 819 033. Considering the total income received or due (excluding the 1.9 million unspent funds – conditional payment), this leaves a balance of US$ 5 691 217 available (see Table 3).

Table 3. Operational cost expenditure by year

Income

2008-2009 US$ 1 500 000

2010-2011 US$ 1 500 000

2012-2013 US$ 4 132 700

Outstanding amount from donor 2015 US$ 1 377 550

Conditional payment US$ 1 900 000

Total revenue US$ 10 410 250

Expenditures (Award 58865)

2008-2009 US$ 567 860

2010-2011 US$ 998 328

2012-2013 US$ 640 809

2014 US$ 401 722

2015* US$ 210 314

Total expenditures US$ 2 819 033

* Through 15 June 2015.

Of the US$ 41 million received from GAVI for vaccine procurement, US$ 25 711 872 has been spent. Table 4 shows vaccine procurement by year.

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Table 4. UNICEF-SD vaccine procurement 2009-2015*

* All figures in US$.

The overall balance is US$ 13 288 128: US$ 4 100 000 is available at UNICEF-SD considering the expenditures (vaccine procurement of US$ 25 711 872 and a reimbursement of US$ 2 million to MSF and WHO), plus US$ 9 188 128 at GAVI (outstanding payment for UNICEF-SD). Funding is due to expire at the end of 2015. In order for the ICG to continue the collaboration, the Secretariat must file a 'no-cost extension' with the Alliance, which will allow the ICG to continue to use the remaining investment case funds from the 2014/2015 biennium beyond 31 December 2015 for vaccine (including antibiotics and equipment such as needles, water, etc.) and operational costs.

Since those funds will be insufficient for the next biennium, the ICG decided to request additional financial support from GAVI. Securing that funding is a process: requests must be put into a form called the 'Vaccine Investment Strategy' that goes to GAVI's Policy Committee for review, which after deliberation will give it to GAVI's Management Board for approval.

ICG members decided to request the no-cost extension and additional financial support from the Alliance based on the nature of the 2015 epidemic season, particularly the possibility of a more severe Men C epidemic in 2016.

The revolving fund mechanism was created in 2010 to ensure financial sustainability of the emergency vaccine stockpile beyond GAVI support and ensure the ICG remained independent. The status of the revolving fund is discussed below.

Revolving fund balance The revolving fund is used solely to purchase vaccines and pay for their shipment. While it is housed within WHO, it is an autonomous budget line that can only be accessed by the ICG and its Secretariat. As of 18 June 2015, the revolving fund had a balance of US$ 5 074 940 (Table 5).

Table 5. Revolving fund 2010-2015

Award Reimbursements Total Expenditure Balance

2010-11 2012 2013 2014 2015

56669 2 122 050 3 224 779 283 525 1 130 698 6 761 052 1 686 112 5 074 940

62423 178 458 178 458 178 458 0

Sustainability of the vaccine stockpile beyond 2015

Meningococcal vaccine 2009 2010 2011 2012 2013 2014 2015

A Conj $127,694 $383,026

AC PS $7,736,413 $2,819,509 $197,436 $108,360

ACW PS $1,856,534 $75,936 $153,711

ACYW PS $3,375,402 $3,810,451

ACYW Conj $5,067,400

Total $7,736,413 $4,676,043 $273,372 $3,483,762 $281,405 $383,026 $8,877,851

$25,711,872

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It was noted that steps to secure long-term funding for the meningitis stockpile should begin. As mentioned above, it was suggested to initiate a comprehensive communications campaign strategy as soon as possible, in tandem with identifying and contacting other potential donors. The communications strategy should include media projects and press releases about the need for meningitis vaccines, the need for their costs to be lower and highlighting the success of the ICG and partners in rolling back the number of meningitis cases and fatalities. To that end MSF is planning a press release about the meningitis outbreak in Niger.

Session 2. Procurement issues (ICG, GAVI, UNICEF-SD)

2015 procurement and challenges UNICEF-SD

Discussion during this session touched on issues that have been raised in previous ICG meetings. The representative from the GAVI Alliance raised the following points:

• The partnership between ICG and the GAVI Alliance is to end 31 December 2015; ICG members agreed the partnership should continue for another two years, and the Secretariat would be filing a no-cost extension by end of June 2015. In addition, the ICG would be requesting financial support for the next biennium to fund the costs of the vaccine stockpile (vaccines, antibiotics and equipment) and operational costs as well (the precise amount will be dependent upon the types of vaccine offered during the tender process and their costs.

• The Alliance would appreciate outbreak response progress and financial reports being sent at the same time and consolidated into one report (joint UNICEF-SD and WHO/UNICEF-PD report or meningitis outbreak response activities and vaccine procurement joint report).

It was noted that UNICEF-SD wanted the forms separate, so the issue was left to UNICEF-SD and the Alliance to resolve.

• The Alliance wanted an update on how the revolving fund is progressing, and stressed the Alliance's desire that GAVI-eligible countries be exempt from vaccine reimbursement.

Given the revolving fund's relative sustainability and success in quickly purchasing and shipping vaccines to countries in need when doses in the stockpile were lacking (e.g. in 2015), ICG members were adamant the revolving fund remain functional. What followed was a discussion of UNICEF-SD's failure to obtain the doses of vaccine requested by the ICG for the 2015 epidemic season (see the section Procurement of the 2015 stockpile for details).

• GAVI has no mechanism to respond to unexpected fund requests for emergencies.

ICG members and partners made a recommendation to the GAVI Secretariat to work on this option.

• GAVI's commitment was for Men A. The Alliance has not considered further investments in meningitis prevention.

It was discussed that the epidemiological situation has changed and GAVI needs to reconsider its position.

The representative from UNICEF-SD noted many of the problems discussed in the section Procurement of the 2015 stockpile and presented similar ways to address them (many of which are addressed in the action points).

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The discussion that followed dealt with improving communication between the ICG Secretariat and UNICEF-SD to improve joint problem-solving, as well as the challenges facing the partnership to ensure that 5 million doses of CW-containing meningitis vaccine are available on 1 January 2016.

It was agreed that in the future, UNICEF-SD would provide timely feedback throughout the tender process, in order to find solutions together with the ICG Secretariat to meet the vaccine supply needs estimated by the ICG and help prevent a situation like in 2015.

Session 3. Update of partners regarding ICG decisions

(ICG, GAVI, UNICEF-SD)

Chairperson: Imran Mirza, UNICEF Programme Division

Epidemic season 2015: epidemiological overview

Refer to the presentation bearing the same name in Session 1.

Outcome of ICG members decisions regarding ICG vaccine stockpile

composition (quantities and type of vaccine)

The ICG recommended having 5 million doses of CW-containing vaccine in the stockpile for 2016, with a preference for conjugate vaccine (and 1.5 million doses of Men A conjugate vaccine, of which there is sufficient supply). See Session 1 Discussion of ICG forecast

stockpile 2016 for details.

ICG achievements during the meningitis investment case, 2009-2015

An overview of the WHO/UNICEF investment case between 2009 and 2015 was given before discussing the ICG's achievements. In planning for the progressive introduction of Men A conjugate vaccine in 2010, it was decided that there was still a need to maintain a stockpile of polysaccharide vaccines to cover CW serogroups.

The ICG has effectively responded to outbreaks with a stock of vaccine (Men AC + ACW + ACWY + Men A conjugate) of 67 million doses of vaccine from 2009 to 2015 (see Table 6).

Table 6. Vaccine in ICG stockpile each year, 2009-2015

Vaccine (million doses) 2009 2010 2011 2012 2013 2014 2015 Total

Men AC polysaccharide 14.0 6.2 6.8 5.5 3.5 0 0 36.0

Men ACW/ACWY

polysaccharide 4.8 2.76 1.5 1.475 2.0 1.5 1.2* 15.235

Men A conjugate 0 0 3.0 3.0 4.0 4.0 1.5 15.5

Men ACWY conjugate 0.2* 0.2

Total 18.8 8.96 11.3 9.975 9.5 5.5 2.9 66.935

* Doses not available on 1 January 2015, but procured throughout the epidemic.

The financial update presented on day 1 was also shared. Refer to the Financial updates section from day 1 for details.

Other achievements included the following: ICG/WHO spurred the development of two new polysaccharide vaccines, Men AC and Men ACW, produced by Bio-M/Finlay Institute. It

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stimulated demand for production of polysaccharide vaccines (that represent less profit for manufacturers) during the transition to conjugate vaccines (more profit for manufacturers), which are more efficacious than polysaccharide vaccines, conferring longer lasting immunity (10 years versus 2 to 3 years with polysaccharide vaccines), as well as reducing carriage.

Manufacturers presentation on supplies: forecast 2016-2017

Bio-Manguinhos/Finlay Institute Two representatives from Bio-M joined the meeting by telephone.

At full capacity, Finlay Institute could produce 1 million doses of ACW polysaccharide vaccine in two months (with their current bulk stock, 800 000 doses could be produced within one month) but this vaccine is currently not prequalified. The representatives from Bio-M stressed that there is no other demand nor market for polysaccharide vaccines, so given the production is for the ICG, the ICG procurement agency must be clear in its need and include a firm and timely offer for purchase, in order to cover expenses arising from the prequalification process.

The issue of WHO prequalification was further discussed. In order for UNICEF-SD (the ICG procurement agency mandated by GAVI for the use of funds from the investment case) to purchase non-prequalified vaccines, three conditions must be met:

1. The manufacturer has other vaccines that are prequalified

2. National regulatory authority (NRA) is considered functional for the country of production

3. The product must be registered for sale in two other countries which both have functional NRAs.

Bio-M/Finlay Institute cannot meet the final point. However, this had not prevented UNICEF-SD purchasing vaccine from them in the past (in 2013 for Guinea, on behalf of the ICG, and for Ethiopia, outside of the ICG). The ICG has also purchased ACW polysaccharide vaccine from Bio-M in the past, via the revolving fund (e.g. 600 000 doses5 sent to Niger during the 2015 epidemic, as well as 500 000 doses in 2014, part of which were deployed to Uganda) to cover stockpile shortages.

GlaxoSmithKline Representatives from GSK were invited to the meeting but could not attend. The current stock of Mencevax® Men ACYW polysaccharide vaccine held by GSK was stated as 500 000 doses.

Sanofi Pasteur At full capacity, Sanofi Pasteur stated it could produce:

• 7 million doses of ACWY conjugate vaccine (Menactra®)

• 2.5-3 million doses of ACWY polysaccharide vaccine (Menomune®).

Menomune®, the first quadrivalent meningococcal polysaccharide vaccine prequalified by WHO, has been on the market since 2013. Because of problems with the diluent, this vaccine is currently unavailable and Sanofi Pasteur was unable to confirm availability for the first quarter of 2016. This is a problem for the ICG as the stockpile needs to be available by January of every year, before the epidemic season starts.

5 As of June 2015.

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In order to secure 2.5-3 million doses of ACWY polysaccharide vaccine (Menomune®), Sanofi Pasteur indicated that a bid would be required two years beforehand (assuming full production capacity), as they normally plan their supply one year in advance.

The pricing of Menomune® was not discussed for the 2016 stock. Sanofi Pasteur could not commit any quantity for the 2016 epidemic season beyond 300 000 (the same number offered for the 2015 stockpile, but which they could not supply due to the diluent quality problems mentioned above) – and this number was contingent on a firm commitment on the part of UNICEF-SD (equivalent to prepayment). This issue will need to be solved.

The representative from Sanofi Pasteur brought up that it was complex for Sanofi Pasteur to maintain the stockpile of doses purchased by the ICG on their premises. This was an issue that caused problems in the tender process for the 2015 stockpile as well.

Serum Institute of India

Representatives from Serum Institute of India were invited to the meeting but could not attend.

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Action points of the 2015 ICG meeting

GAVI Alliance-ICG partnership

1. Continue the partnership between WHO/UNICEF and GAVI: request no-cost extension for an additional two years (2016/2017); request additional funding for the next biennium as well, to pay for vaccines, antibiotics, equipment and operational costs (the amount of these funds will be dependent on the outcome of the tender process); meningitis emergency funds to be initiated asap and needs to include financial certificate. ACTION: Emergency Vaccination and Stockpiles (EVS),

WHO

Partnerships between ICG and vaccine manufacturers

2. Get bids from all manufacturers (including GSK) based on the ICG's decision to have 5 million doses of CW-containing vaccine in the stockpile (while conjugate vaccine would be the best option, cost is a factor; and thus a tender based on what each company can produce and have ready to ship by 1 January 2016 will be considered as options for the stockpile). ACTION: UNICEF-SD

3. Motivate manufacturers (namely Finlay Institute) to submit dossier for WHO prequalification, so that UNICEF-SD can work with them without hindrance. Note: The issue barring prequalification appears to be cost. Finlay Institute/Bio-M want an assurance that ICG will purchase a specific number of doses if they seek prequalification (due to cost of conducting the appropriate trials prior to certification). ACTION: EVS, WHO

4. WHO should identify and foster relationships with key people within multinational vaccine manufacturing companies to help facilitate the process of vaccine stockpiling and disbursal on the part of manufacturers (e.g. re-establish relations with GSK). ACTION: EVS, WHO

5. WHO will organize with UNICEF-SD individual meetings with manufacturers by the end of July 2015 to discuss:

- with Sanofi: Options for increasing the stock of 300 000 Menomune® doses offered by Sanofi for 2016, and for making them available by January 2016.

- with Finlay Institute/Bio-M: Whether the firm commitment they require will be on an annual basis and to determine the issues that need to be addressed to request WHO prequalification (including whether the data from vaccination in those aged <8 years old is still required). Encourage Finlay Institute/Bio-M to submit their dossier for WHO prequalification, so that UNICEF-SD can work with them without hindrance.

- with manufacturers: Options for making the Men CW-containing conjugate or polysaccharide vaccine affordable and available (e.g. through appeal to manufacturers).

- with manufacturers: Find ways to facilitate the process of vaccine stockpiling and disbursal on the part of manufacturers. Manufacturers increasingly are asking for prepayment of vaccines (so-called 'firm commitments') and are resistant to stockpiling vaccines, to share the risk because these vaccines have a limited market outside of the ICG.

Communications campaign strategy

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Undertake a communications and media campaign to raise awareness on the need for increased vaccine supply and the need for diverse sources of funds for their procurement (note: MSF is planning a press release on the outbreak in Niger as part of this action). ACTION: ICG Secretariat

Internal processes

6. Review and resolve internal delays within WHO (i.e. to speed up the approval process), with respect to the purchase and shipment of vaccine in response to outbreaks. ACTION: ICG SECRETARIAT

7. Add a column to the ICG request table (see Table 1), which would explain any salient details of problems and methodologies to address them (e.g. for request #3 there was a 21-day lag for the vaccination campaign in Niger, but no details of what held it up). ACTION: ICG SECRETARIAT

8. Explore the possibility of having the ICG acquire the leftover stocks of mono conjugate C vaccine from the United Kingdom. ACTION: EVS, WHO

9. Enhance the capacity of those filling out the ICG request forms so the forms are accurate and contain 'clean' data on which the ICG can base their decisions (this will save time). ACTION: WHO Meningitis team/ICG Secretariat unless otherwise noted below. Solutions discussed include:

- Provide a sample form on the WHO website showing potential answers;

- Create and publish a guidance document on how to fill out the request form (and show common 'pitfalls');

- Include a training module on completing the request form at the meeting to be held in Ethiopia in November 2015;

- Document the sections where the problems with the request forms usually occur so they can be addressed by WHO/ICG. (It was noted by representative from the International Federation of the Red Cross and Red Crescent Societies (IFRC) that maps are often neglected in the request form. If mapping is an issue identified as needing support, the representative from IFRC stated she could ask the IFRC mapping department if they could assist country officers in this area [depending on need, this could be offered for both meningitis and OCV request forms]). ACTION: IFRC

- Instructions on the request form should be amended to state clearly that no question should be left blank, but rather the country officer should always write something (e.g. "Not available" or "No data") instead.

Communication/UNICEF-SD partnership

10. Enhance communication and clarify roles with UNICEF-SD, to prevent reoccurrence of the incomplete tender request based on UNICEF’s unilateral decision prior to this year's meningitis season. All parties need to be more flexible, and where an issue arises, it was recommended to "pick up the phone" to sort out the problem rather than relying on email, protocol or "unilateral decisions". The ICG Secretariat may need to assume some of the burden of negotiations with manufacturers, as UNICEF-SD cannot be expected to play this role). ACTION: ICG SECRETARIAT/UNICEF-

SD

11. Involve UNICEF-PD in discussions with UNICEF-SD for technical input and to facilitate communication. ACTION: ICG SECRETARIAT/UNICEF-SD

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12. The ICG should consider other mechanisms for vaccine procurement to use in the event the procurement processes with UNICEF-SD cannot be improved. The representative from IFRC suggested that the IFRC Supply Division could assist with meningitis vaccine procurement for the ICG should the ICG desire to stop the relationship with GAVI/UNICEF-SD. (This was stated particularly to note that there are other actors for vaccine procurement than just UNICEF-SD.) ACTION: ICG

13. Start tender process earlier than in previous years—this was stressed by the ICG and UNICEF-SD. That is, action needs to be taken imminently to start this process, including the long-term agreements (LTAs) – that is, signing LTAs in December is too late. ACTION: UNICEF-SD

ICG stockpile

14. Create a mechanism to clearly account for all vaccines disbursed from the ICG stockpile (to prevent missing doses and counterfeiting of vaccines), which also encompasses returning unused doses of vaccines.

- IFRC has asked CERN to come up with a simple way to dispose of used vials, such that they cannot be used again (e.g. with counterfeit vaccine) and can be safely discarded within the countries where they are used. CERN is interested in tackling the problem, but a timeline on when a design would be ready is unclear. ACTION: IFRC

15. Establish and maintain 7 000 treatments of a five-day course of ceftriaxone from multiple manufacturers, which can be shipped quickly in tandem with vaccine for meningitis prophylaxis. This includes the supplies needed for administration (diluents, equipment, etc.) ACTION: ICG SECRETARIAT

- Follow up with UNICEF-SD about use of its Copenhagen warehouse for storage [hold over from 2014 ICG meeting.] ACTION: ICG SECRETARIAT

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Annex 1. Meeting agenda

Day 1

Time Topic Presenter

Session 1. Meningitis outbreak response (ICG members only)

08:30 – 08:45 Arrival of participants

08:45 -09:00 Opening Remarks William Perea WHO

09:00-09:30 Epidemic season 2015:

Epidemiological Overview

ICG response and performance

Katya Fernandez

Alexandra Hill

09:30-09:50 Procurement of the 2015 stockpile: chronology and challenges

Alejandro Costa

09:50 - 10:30 Discussion

10:30 – 11:00 Coffee Break

11:00 –11:20 Outbreak response strategy and Men C outbreaks in Niger and Nigeria

Olivier Ronveaux

11:20 – 12:00 Discussion

12:00 – 12:45 Discussion on ICG forecast stockpile 2016 All

12:45 -14:00 Lunch

14:00 -14:30 Ceftriaxone use and order in 2015

Ceftriaxone stockpile management

Alejandro Costa, WHO

14:30 - 15:00 Financial updates

Use of GAVI funds 2009-2015 WHO/UNICEF (op. costs)

Revolving fund balance

Alejandro Costa

15:00 - 15:30 Coffee Break

15:30 - 16:15 Sustainability of the stockpile beyond 2015: options and way forward

All

Session 2. Procurement issues (ICG members, GAVI, UNICEF-SD)

16:15 - 16:40 2015 procurement and challenges UNICEF-SD (procurement)

Guillermo Gimeno, UNICEF-SD

16:40 - 17:05 Update from GAVI (future support stockpile) Patience Musanhu, GAVI Alliance

17:15 - 18:30 Reception All

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Day 2

Time Topic Presenter

Session 3. Update of partners regarding ICG decisions (ICG members, GAVI, UNICEF-SD,

manufacturers)

9:00 - 9.20 Epidemic season 2015 Katya Fernandez

9.20 - 09.45 Outcome of ICG members decisions Alejandro Costa

09.45 – 10.00 Discussion

10:00 - 10:30 Coffee Break

10:30 - 11:00

11:00 - 11:30

UNICEF-SD procurement forecast 3 years

ICG achievements during the meningitis investment case, 2009-2015

UNICEF-SD

Alejandro Costa (Marie-Pierre Preziozi)

11:30 - 12:30 Manufacturers presentation on supplies: forecast 2016-2017

Bio-Manguinhos/Finlay Institutea GSK*

Sanofi Pasteur

Serum Institute of India*

12:30 - 13:30 Lunch

13:30 - 14:30 Conclusions

a Participated by telephone. * Unable to attend.

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Annex 2. List of participants

ICG Executive Members

1 Myriam Henkens MSF myriam.henkens@msf.org

2 Florence Fermon* MSF florence.fermon@paris.msf.org

3 Robert Kezaala* UNICEF rkezaala@unicef.org

4 Imran Mirza UNICEF imirza@unicef.org

5 Amanda McClelland IFRC amanda.mcclelland@ifrc.org

6 Panu Saaristo* IFRC panu.saaristo@ifrc.org

7 Olivier Ronveaux WHO ronveauxo@who.int

8 Katya Fernandez WHO fernanadezk@who.int

ICG Secretariat 9 Alejandro Costa WHO costaa@who.int

10 Alexandra Hill WHO hilla@who.int

Amanda Gatto WHO gattoa@who.int

Associated Members

11 AFRO participant* WHO

12 EMRO participant* WHO

13 Tifenn Humbert* KL/Procurement representative

humbertt@who.int

14 Sylvie Briand* WHO briands@who.int

15 William Perea WHO pereaw@who.int

16 Marie Pierre Preziosi WHO preziosim@who.int

17 Jean Christophe Aze* WHO azej@who.int

Manufacturers ay 2 only) (d

18 Cíntia Nunes Cardoso Lopes Bio-Manguinhos Cnunes@bio.fiocruz.br

19 João Miguel Estephanio Bio-Manguinhos Joao.estephanio@bio.fiocruz.br

20 Françoise Griguer Sanofi Pasteur Francoise.Griguer@sanofipasteur.com

21 Marc La Force* Serum Institute of India fmarclaforce@gmail.com

22 Esthel Marie Van Brackel* GSK Esthel.m.van-brackel@gsk.com

Other associated members and representatives

23 Matthew Blakelyb GAVI Alliance mblakely@gavialliance.org

23 Melissa Malhame* GAVI Alliance mmalhame@gavialliance.org

24 Patience Musanhu GAVI Alliance pmusanhu@gavialliance.org

25 Isabelle Cantin* UNICEF icantin@unicef.org

26 Guillermo Gimeno UNICEF-SD ggimeno@unicef.org

* Unable to attend b Attended meeting on day 2 in place of Melissa Malhame.