World Health Organization 28 February, 2019 Essential Training Package for HPV Vaccine Introduction Module 2 HPV vaccine attributes and storage conditions GardasilTM

Learning objectives At the end of the module, you will have learned to: Describe HPV vaccine characteristics (GardasilTM) Discuss the presentation of HPV vaccine Apply vaccine cold chain requirements Duration 25’

Key issues 1 2 3 4 5 What is HPV vaccine, GardasilTM, presentation? How effective is the vaccine? 2 How safe is the vaccine? 3 At which temperature should the vaccine be stored? 4 Explain to the participants the key issues raised in this module: What is GardasilTM, presentation? How effective is the vaccine? How safe is the vaccine? At which temperature should the vaccine be stored? Where in the refrigerator should HPV vaccines be stored? Where in the refrigerator should HPV vaccines be stored? 5

What is the presentation of GardasilTM? GardasilTM (or SilgardTM) is available in a liquid formulation: as a single dose vial intramuscular injection 1 vial has 0.5mL suspension Each vial contains a Vaccine Vial Monitor (VVM) Vaccine vials are available in pack sizes of 1, 10, and 100 Gardasil vaccine is available as a single dose vial in a liquid formulation for intramuscular injection Each vial contains 0.5 ml suspension Each vial contains a vaccine vial monitor (VVM) to indicate cumulative exposure to heat Vaccine vials are available in pack 1, 10, and 100 4

Is GardasilTM effective? GardasilTM is a quadrivalent vaccine to prevent from: Infection due to HPV types 16 & 18 that cause the majority of cervical cancers Infection due to HPV types 6 & 11 that are responsible for genital warts High efficacy of GardasilTM against persistent infection with HPV types has been demonstrated in females There is no evidence of waning immunity Data from several large clinical trials of HPV vaccine have demonstrated very high efficacy of GardasilTM against persistent infection with HPV types in females aged 15-26 years who had not been exposed to the HPV types targeted by the vaccine prior to the vaccination GardasilTM is a quadrivalent vaccine that protects from HPV infection types 16 & 18 that cause most of the cervical cancers worldwide as well as HPV infection types 6 & 11 responsible for benign anogenital warts & recurrent respiratory papillomatosis There is no evidence of waning immunity 9 years after vaccination in females who were vaccinated as part of the clinical trials conducted in the early 2000’s.

Is GardasilTM safe? GardasilTM is well-tolerated with no major safety concerns Injection site reactions such as redness, pain and swelling can occur Mild adverse events include fever, dizziness and nausea Syncope can occur after any medical procedure and is not uncommon in adolescents following receipt of a vaccine. It is recommended that adolescents be seated during HPV vaccine administration and observed for 15 minutes afterwards Safety studies of HPV vaccine were conducted in thousands of women around the world prior to licensure. Results of the studies demonstrated that vaccines were well tolerated with no major safety concerns for either vaccine. Post licensure, millions of girls have received the HPV vaccine. The most common adverse events reported in vaccinated girls have involved injection site reactions such as pain and swelling Other mild adverse events reported following HPV vaccination included fever, dizziness and nausea Syncope (fainting) has also been reported after HPV vaccine administration. Syncope can occur after any medical procedure and is not uncommon in adolescents following receipt of a vaccine (see following modules). It is recommended that adolescents be seated during HPV vaccine administration and observed for 15 minutes afterwards 6

HPV vaccine storage conditions HPV vaccines should be stored between +2oC and +8oC HPV vaccine is freeze sensitive HPV vaccine is light sensitive Handling vaccines requires great care. Careful storage and transport conditions are needed to protect vaccines from becoming ineffective and unusable. HPV vaccine must be transported and stored at +2°C to +8°C HPV vaccine is sensitive to temperatures lower than 0°C and loses efficacy if frozen It is sensitive to light and should be stored in the original package in order to protect from light 7

Temperature sensitivity of vaccines Freeze dried Liquid, no adjuvant Liquid, with alum adjuvant Vaccine formulation Rotavirus HPV Pneumo PS-PCV Measles OPV BCG HepB Penta- valent Least sensitive Most sensitive Vaccines to the left of the line are not damaged by freezing Most sensitive Heat sensitivity Freeze sensitivity MMR This slide shows the overall temperature sensitivity of common vaccines. Each bubble represents the overall or “representative” heat/freeze sensitivity for a type of vaccine. As you can see from this slide, HPV is one of the most freeze sensitive vaccines, along with HepB and PCV and Pentavalent vaccines. If freezing is suspected, perform shake test.

Where to place HPV vaccine in the refrigerator? Good temperature control during the storage and transport of vaccines is critical to ensure their potency and safety. As we have mentioned before, HPV vaccines must be refrigerated at+2°C to +8°C. The vaccine should be administered as soon as possible after being removed from the refrigerator HPV vaccine should not be placed in or near the freezer portion of the refrigerator nor directly on a frozen ice pack. Keep the HPV vaccine away from all cold air vents If the refrigerator is a side opening model, no vaccine should be stored in the door as the temperature is more likely to fluctuate when opening and closing the refrigerator The temperature inside the refrigerator should be monitored regularly 9

Which vaccine vials should be stored in front? Vaccine vials with early expiration dates and vials with VVM that has started to change color should be kept in front to be used first Further expiry date in back Closer expiry date in front Vaccines vials with early expiration dates should be kept in front for first use Vaccine vials with the Vaccine Vial Monitor (VVM) that has started to change color (i.e. inner square getting darker) should be used first Vaccine vials with VVM reaching discard point should not be used even if the expiration date is valid. Keep a “use first box” in the refrigerator to put vaccine vials that were taken out of the refrigerator (for fixed or outreach session) and were brought back unused. Vaccines in the “use first box” must be used first in the next session Do not open the refrigerator door often and regularly monitor the temperature of the refrigerator 10

Cold boxes and vaccine carriers If transport of vaccine is required, only conditioned ice packs should be used to maintain a cold chain at +2°C to +8°C . Frozen icepacks should be kept at room temperature for 5-10 or more minutes until the ice inside can be heard to move when shaken before placing the vaccines in them. This is called “conditioning” the ice packs and prevents the vaccine from freezing when it is placed near the packs HPV vaccine is sensitive to light and should be stored in the original boxes until ready to use

Key messages GardasilTM vaccine is safe and effective GardasilTM is available as a single dose vial (0.5mL) in a liquid formulation with VVM HPV vaccine is freeze sensitive and light sensitive HPV vaccine must be stored at +2oC to +8oC HPV vaccine should be stored in their original package When using icepacks in cold boxes and vaccine carriers, they should be conditioned to reduce the risk of vaccine freezing GardasilTM or SilgardTM is available as a single dose vial (0.5mL) in a liquid formulation for intramuscular injection Each vial contains a VVM GardasilTM is very safe and effective against diseases caused by HPV types 16 and 18 Store vaccines at +2°C to +8°C and administer as soon as possible after being removed from the refrigerator HPV vaccines are sensitive to temperatures lower than 0°C and lose efficacy if frozen HPV vaccines are sensitive to light and should be stored in the original packaging in order to protect from light When using icepacks in cold boxes and vaccine carriers, they should be conditioned well to reduce the risk of vaccine freezing

End of module for your attention! Thank you This is the end of the module, thank you for your attention!

References HPV vaccine introduction into national immunization programmes: Information for programme managers and health workers. WHO 2013 Gardasil/SilgardTM package inserts. Merck & Co, Inc. 2009