1. Vaccine Presentations and Programmatic Implications WHO / IVB / EPI

2. TITLE from VIEW and SLIDE MASTER | September 19, 2015 2 |2 | New Vaccine supply Supply situation for new vaccines (PCV, RV, Penta) is challenging Imbalance of preferred vs. alternative products Delays of introduction foreseen through 2015 Hib –Improved since mid-2011, but two products temporarily suspended and one product with delayed shipments –Supply tight and needs to be closely managed –Countries requesting switches to 10-dose vial presentation need planning to ensure wastage is reduced Pneumococcal –Supply and demand situation is dynamic –PCV supply tight for countries planning to introduce from 2013 onwards (mainly PCV13) –New AMC tender closed –New manufacturers not expected on market before 2015/16

3. TITLE from VIEW and SLIDE MASTER | September 19, 2015 3 |3 | New Vaccine supply Rotavirus –Supply is limited with delays expected until 2015 –Product preference for RV1 (2-dose) – manufacturer increasing production capacity Yellow Fever –Fragile market (manufacturer suspended, continuous production challenges) –Supply meets requirements for emergencies and routine immunizations –Limited number of campaigns conducted due to insufficient supply MenA –Monopoly supply market with increasing, high demand levels

4. TITLE from VIEW and SLIDE MASTER | September 19, 2015 4 |4 | GAVI supply allocation criteria SourceMetricObjective Allocation criteria used in situations where total demand exceeds total supply available for new introductions (equal weighting) WHO Burden of disease as mortality per 100,000 vaccinated Maximize health impact GAVIDate of Board/EC approval (Month/Year)Minimize delay of introduction WHO Existence of functioning country AEFI reporting system (Y/N) Provide safe delivery WHO/UNICEF% DTP3 CoverageProvide successful delivery WHO % of the total required cold chain capacity for new vaccine at central and sub national levels Introduction preparedness

5. TITLE from VIEW and SLIDE MASTER | September 19, 2015 5 |5 | PNEUMOCOCCAL VACCINES

6. TITLE from VIEW and SLIDE MASTER | September 19, 2015 6 |6 | PCV10 and PCV13 Summary of product characteristics PCV13 Prevenar - Single dosePCV10 Synflorix - Two doseVaccine 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F1, 4, 5, 6B, 7F, 9V, 14, 18CV, 19F, 23FSerotypes 3 dosesNumber of doses Infants (under 12 months of age)Target Age Group 3 doses, with DTPEPI Schedule 4 weeks Min interval between doses 24 months at 2 - 8 degrees celcius36 months at 2 - 8 degrees celciusShelf Life No data - WHO recommends completing a course with the product started. If product unavailable, alternative product may be used to conclude the course. Interchangeability Intramuscular Method administration Liquid - Single dose vialLiquid - Two dose vial - preservative freePresentation 12 cm34.8 cm3 Per dose cold chain requirement $3.50 per dosePrice (through AMC) VVM30VVM7VVM type 5%10%Wastage rate N/A Two dose preservative free presentation: All opened vials must be discarded 6 hours from first opening or at the end of each session, whichever comes first. Special Precautions

7. TITLE from VIEW and SLIDE MASTER | September 19, 2015 7 |7 | Two-dose presentation of preservative-free 10-valent pneumococcal conjugate vaccine (Synflorix™) Two dose preservative free presentation: All opened vials must be discarded 6 hours from first opening or at the end of each session, whichever comes first. Vaccine WHO prequalified with following considerations: Pre-introduction –Enhanced HCW training on proper use of two-dose presentation –Ensure training materials in place in immunization centers –Place stickers on refrigerators at all levels indicating that opened vials must be discarded six hours after opening Vaccine will only be shipped once training has taken place – countries need to state readiness, endorsed by WHO, for shipment to take place Post-introduction evaluations based on random sampling procedures specifically looking at HCW behavior and knowledge to be undertaken six months after introduction. If PIE shows need for re-training, additional intensified training to be undertaken to assure appropriate continued use of this presentation.

8. TITLE from VIEW and SLIDE MASTER | September 19, 2015 8 |8 | Synflorix™ fridge sticker To be placed on all refrigerators prior to vaccine arrival in country Manufacturer to make it available before vaccine introduction Countries to distribute to all health facilities and certify that stickers are in place

9. TITLE from VIEW and SLIDE MASTER | September 19, 2015 9 |9 | ROTAVIRUS VACCINES

10. TITLE from VIEW and SLIDE MASTER | September 19, 2015 10 | Rotavirus vaccines SAGE review of evidence on rotavirus disease burden, timeliness of vaccination and safety and effectiveness of different immunization schedules. WHO continues to recommend that first dose of rotavirus vaccine be administered as soon as possible after 6 weeks of age, along with DTP doses. Current age restrictions of rotavirus vaccines may prevent vaccination of many vulnerable children in settings where DTP doses are given late (i.e. after 15 weeks for DTP1 or after 32 weeks for DTP2 or DTP3). By allowing children to be immunized with RV at any time, able to immunize children who are currently excluded from the benefits of rotavirus vaccines. Models developed by PAHO to detect AEFI associated with RV to be disseminated to all introducing countries. Important to establish baseline incidence of intussusception at sentinel sites and to use epidemiological studies to assess safety of RVs.

11. TITLE from VIEW and SLIDE MASTER | September 19, 2015 11 | Rotarix™ and Rotateq™ Summary of product characteristics Human-bovine, pentavalent (RotaTeq  )Human monovalent (Rotarix  ) Vaccine 32 Number of doses in schedule 3 doses with DTP2 doses - with DTPEPI Schedule 4 weeksMin interval between doses OralMethod administration Liquid Presentation 46.3 CM317.1 CM3 Per dose cold chain requirement 24 months at 2 - 8 degrees celcius36 months at 2 - 8 degrees celciusShelf Life No VVMVVM 14VVM type 5% Wastage rate No VVM technology has been validated for use with this vaccine as those currently available do not match the stability profile of vaccine components. It is very important for potency of this vaccine that the cold chain storage conditions are maintained from delivery to administration. Additional training need of health care workers to alert them to the Rotarix™ safety attention point (proper opening of twist-cap tube to avoid programmatic errors). Special Precautions

12. TITLE from VIEW and SLIDE MASTER | September 19, 2015 12 | Rotavirus vaccines: Key program elements for introduction Key issues related to rotavirus vaccine safety: 1)AEFI monitoring Should ideally have AEFI surveillance that can detect intussusception cases Assess the baseline intussusception rate in the country Have a well-trained AEFI committee capable of monitoring and assessing AEFIs Report whether country has an Institutional Development plan 2)Training Ensure that health workers know that on-time vaccination is important 1)Preparation for risk communication Need to have in-country personnel who are well-informed about all aspects of the vaccine and are able to discuss the vaccine benefits, risks and how risk is being monitored.

13. TITLE from VIEW and SLIDE MASTER | September 19, 2015 13 | Intussusception Intussusception (IS) occurs when one section of the intestine becomes infolded or telescoped within another section of the intestine It is the most common cause of bowel obstruction in infants and young children, with a peak incidence at 4- 10 months of age Signs and symptoms are those of bowel obstruction: –Abdominal pain, vomiting, bloody stools –Abdominal distension, abnormal bowel sounds, occasional abdominal mass If untreated, it can be fatal due to vascular compromise and bowel ischemia Diagnosis is made by radiology or surgery Treatment is by 1) reduction enema guided by ultrasound or X-ray, or 2) by surgery Intestine with intussusception

14. TITLE from VIEW and SLIDE MASTER | September 19, 2015 14 | Intussusception and rotavirus vaccines The causes of acute intussusception (IS) in the majority of cases are not known. It is thought that the following may play a role: –Anatomy, e.g. lead point of the infolding due to a polyp or Meckel's diverticulum –Mesenteric lymphadenitis due to respiratory or gastrointestinal infections (viruses, bacteria, parasites) –Nutrition An association between IS and RotaShield vaccine was identified in the months after this rotavirus vaccine was introduced in the United States in 1998 and resulted in discontinuation of RotaShield use in 1999 –Increased numbers of IS cases were shown to occur in infants 9-14 days following administration of the first dose of RotaShield vaccine –Risk of IS was estimated at ~1 excess case of IS per 5,000 - 10,000 infants during the immediate post-vaccination period –This association of IS and RotaShield was identified through passive AEFI surveillance

15. TITLE from VIEW and SLIDE MASTER | September 19, 2015 15 | Intussusception and rotavirus vaccines RotaTeq and Rotarix were recommended for use by WHO with the advice that vaccine introduction be done in association with post-marketing safety surveillance. (2007 WHO Rotavirus vaccine position paper) In August 2010 and in December 2010, the Global Advisory Committee on Vaccine Safety (GACVS) reviewed data collected through active sentinel post-marketing safety surveillance in Mexico and Australia which revealed a small increased risk of IS shortly after the first dose of RotaTeq and Rotarix vaccination. –Risk of IS was estimated at 1-2 excess case of IS per 100,000 infants during the immediate post-vaccination period; this is substantially smaller than the risk of 1 excess case per 5,000 – 10,000 infants seen with RotaShield –GACVS review of rotavirus vaccine safety is on the WHO website at http://www.who.int/vaccine_safety/topics/rotavirus/en/index.html http://www.who.int/vaccine_safety/topics/rotavirus/en/index.html –GACVS will continue to review new safety data as data become available GACVS noted that the benefits documented with rotavirus vaccine greatly outweigh the risk of vaccine-associated IS

16. TITLE from VIEW and SLIDE MASTER | September 19, 2015 16 | HUMAN PAPILLOMAVIRUS (HPV)

17. TITLE from VIEW and SLIDE MASTER | September 19, 2015 17 | WHO position paper on HPV vaccine WHO recommends that HPV vaccination should be introduced into national immunization programmes where prevention of cervical cancer and other HPV-related diseases is a public health priority and vaccine introduction is programmatically feasible and financially sustainable. Recommendation is to prioritize high coverage in primary target population of girls 9 through 13 years old. Other considerations: –Priority should be given to strategies that include populations who are likely to have less access to cervical cancer screening later in life. –HPV vaccine introduction should not divert resources from effective cervical cancer screening programmes. –HPV vaccination should be introduced as part of a coordinated strategy to prevent cervical cancer and other HPV-related disease. –Opportunities to link vaccine delivery to other health programmes targeting young people should be sought.

18. TITLE from VIEW and SLIDE MASTER | September 19, 2015 18 | HPV vaccines Two vaccines currently available, widely licensed, and WHO prequalified: –Cervarix® (bivalent): Prevents precancerous lesions from HPV types 16 and 18 –Gardasil®/Silgard® (quadrivalent): Prevents precancerous lesions from HPV types 16 and 18 and anogenital warts from HPV types 6 and 11 Up to 30% of all cervical cancer cases caused by HPV types other than 16 and 18, so these vaccines do not eliminate need for future cervical cancer screening. Neither vaccine will treat women with current HPV infection; both vaccines demonstrate best efficacy in individuals HPV-naïve to the vaccine types so best to vaccinate girls prior to initiation of sexual activity.

19. TITLE from VIEW and SLIDE MASTER | September 19, 2015 19 | HPV vaccine product characteristics CompositionBivalent Human Papilloma Virus (Types 16 & 18)Quadravalent Human Papilloma Virus (Types 6,11,16 & 18) Trade nameCervarix®Gardasil®/Silgard® Pharmaceutical FormLiquid Presentation1 & 2 dose vials1 dose vial Vaccine Vial MonitorType 14Type 30 Route of administrationintramuscular Shelf life 36 (2 dose vial) & 48 (1 dose vial) months at 2-8  C36 months at 2-8  C Schedule 3-dose schedule: a) baseline b) after 1 month c) after 6 months 3-dose schedule: a) baseline b) after 2 months c) after 6 months Minimum intervals between doses If flexibility in the schedule is necessary, the manufacturer recommends that the second dose is administered between 1 and 2.5 months after the first dose. A minimum interval of 4 weeks between first and second dose; and minimum interval of 12 weeks between second and third dose Target groups for immunization Females aged 9 years onwards Cold chain volume (per dose) 1 dose vial: 57.7 cm3 (carton of 1 vial) 11.5 cm3 (carton of 10 vials) 9.7 cm3 (carton of 100 vials) 2 dose vial: 28.8 cm3 (carton of 1 vial) 5.7 cm3 (carton of 10 vials) 4.8 cm3 (carton of 100 vials) 75cm3 (carton of 1 vial) 15 cm3 (carton of 15 vials) Special considerations Two dose preservative free presentation: All opened vials must be discarded 6 hours from first opening or at the end of each session, whichever comes first.

20. TITLE from VIEW and SLIDE MASTER | September 19, 2015 20 | National application for HPV vaccine support Special considerations (1) Countries must : Identify a single-year target vaccination cohort within the target population of 9-13 year old girls. Have demonstrated ability to deliver a complete multi-dose series of vaccines to at least 50% of the target vaccination cohort (i.e., 9-13 year old girls) in an average size district (preferably comprising urban and rural areas) using a strategy similar to the one proposed for national HPV vaccine delivery. Provide a report on the costing analysis of the proposed delivery strategy or strategies and evidence of non-GAVI resources to support delivery costs.

21. TITLE from VIEW and SLIDE MASTER | September 19, 2015 21 | National application for HPV vaccine support Special considerations (2) Countries are also requested to: Clarify how their plans for communication and social mobilization reflect the unique needs of the programme for reaching the priority audiences. Provide description of health services and/or health education currently provided to 9-13 year old girls. Provide cervical cancer burden (e.g. from Globocan database) Share national strategy for cervical cancer prevention and control with status of activities and next steps Finally, all technical elements common to any vaccine introduction need to be addressed as standard components of a GAVI application.

22. TITLE from VIEW and SLIDE MASTER | September 19, 2015 22 | National application for HPV vaccine support Special considerations (3) For all applications proposing to use a school-based strategy for HPV vaccine delivery, the following conditions must be met: The minimal proportion of girls of the target vaccination cohort or target grade that is enrolled in school must be 75%. If the strategy targets girls enrolled in a selected grade, the majority of girls must be between the ages of 9-13 years old with no more than 20% of girls aged 14 years old or above. A strategy or strategies for vaccinating girls not in school must also be planned and described. Additional information describing the educational system for girls and any existing school-based health programming will need to be described. Documentation that the Ministry of Education (MoE) is an ICC member and/or the signature of the Minister of Education is also needed with the application.

23. TITLE from VIEW and SLIDE MASTER | September 19, 2015 23 | HPV vaccine delivery costs Available estimates quantify HPV vaccine operational costs as higher than recurrent delivery costs for other GAVI vaccines. GAVI provides introduction grant of 2.40 USD per eligible girl. GAVI will not provide financial support for recurrent operational costs related to vaccine delivery. Countries are encouraged to seek other national or partner financial resources to cover these costs. The country report on the costing analysis of the proposed delivery strategy for the national application to GAVI must provide evidence of these non-GAVI resources to support delivery costs.

24. TITLE from VIEW and SLIDE MASTER | September 19, 2015 24 | HPV vaccine demonstration projects Countries unable to demonstrate ability to vaccinate 9-13 year old girls but wishing to introduce HPV vaccines have an opportunity to apply for a HPV Vaccine Demonstration Project. Learn by doing –Asses potintial HPV vaccine, delivery strategies, adapting necessary tools –Explore feasibility of integrating selected adolescent health interventions –Encouraging HPV vaccination in national cervical cancer control approach 2 year proogramme Max. 20,000 girls Vaccination with selected strategy and evaluation of coverage, acceptability, feasibility, costs Assessment of feasibility of integrating adolexcent health or sexual and reproductive health interventions Develop or strengthen comprehensive cervical cancer prevention and control strategy Multi stakeholder TAG required No co-financing, programmatic grant provided