n w Using Inter Vax BCG vaccine a

n w Using Inter. Vax BCG vaccine a r d W ti h t c O b o r e 0 2 8 1

Bacillus Calmette–Guérin (BCG) vaccine immunisation programme • • 0 2 8 1 Bacillus Calmette–Guérin (BCG) vaccine is an attenuated live vaccine derived from a Mycobacterium bovis strain routine vaccination started in the UK in 1953 as a universal school programme following a continued decline in tuberculosis (TB) rates in the indigenous population, the schools based BCG programme was stopped in 2005 changed to a risk-based programme which targets infants who are most at risk from or exposure to TB the most effective use of BCG vaccine is to give it as soon as possible after birth to prevent infants at increased risk of exposure to TB from becoming infected http: //www. bmj. com/content/349/bmj. g 4643 these infants are at greatest risk of developing severe disease, such as miliary TB and TB meningitis the BCG is also offered to previously unvaccinated tuberculin-negative individuals under 16 years of age who are contacts of cases of respiratory TB, and individuals at occupational risk n w t c O b o r e a r d ti h W Reference: Trunz BB, Fine P, Dye C. Effect of BCG vaccination on childhood tuberculous meningitis and miliary tuberculosis worldwide: a meta-analysis and assessment of cost effectiveness. Lancet. 2006 Apr 8; 367(9517): 1173– 80. 2 Using Inter. Vax BCG vaccine

Current Statens Serum Institut (SSI) BCG supply constraints 0 2 8 1 • over the past three years, there has been a decline in global availability of BCG vaccine with on-going constraints to the global supply of BCG vaccine • during 2015, supply problems with the BCG vaccine to the UK from Statens Serum Institut (SSI), Denmark resulted in a shortage of BCG vaccine which have impacted upon the delivery of the BCG programme nationally • SSI are the only manufacturer of a UK licensed BCG vaccine and further supplies of this product are not currently guaranteed n w a r d ti h W 3 Using Inter. Vax BCG vaccine t c O b o r e

Risk of TB due to shortages of BCG vaccine 0 2 8 1 • the overall impact on the general population is considered to be low • however there is a risk of individual TB cases occurring amongst the eligible population who are more at risk of severe forms such as TB meningitis • BCG has been shown to be effective against childhood forms of TB • waiting for a licensed vaccine may mean that babies at high risk remain unvaccinated and at risk of severe forms of TB n w a r d ti h W 4 Using Inter. Vax BCG vaccine t c O b o r e

PHE Response to on-going supply constraints of SSI BCG 8 1 To ensure the continuation of the BCG immunisation programme in the UK in protecting those at increased risk of severe forms of TB disease or exposure to TB, PHE have secured an interim supply of BCG vaccine from Inter. Vax Ltd of Canada, which is manufactured in Bulgaria. • • 5 b o r e 0 2 this vaccine has been used extensively around the world for many years, but a UK licence has never been applied for, as a consequence this product does not have a UK a licence Inter. Vax BCG vaccine is the only suitable alternative vaccine currently available to the UK studies have shown Inter. Vax BCG vaccine to be highly potent (WHO, Expert Committee on Biological Standardization, Geneva, 19 -23 September 2009, WHO/BS/09. 2114) whilst there is a different BCG strain in the Inter. Vax vaccine compared to the UK licensed BCG vaccine made by SSI, it is not anticipated that there would be a major difference in effectiveness or adverse events n w a r d ti h W Using Inter. Vax BCG vaccine t c O

When should unlicensed BCG be prescribed? 8 1 • guidance from MHRA states an unlicensed medicinal product should not be supplied where an available equivalent licensed medicinal product can meet the needs of the patient • therefore, if a supply of a UK licensed BCG vaccine is available; the licensed product should always be used instead of the unlicensed BCG vaccine t c O b o r e 0 2 • if you have stocks of licensed BCG vaccine (from SSI) that have not expired, you should use these before using Inter. Vax BCG • once all in date stocks of licensed BCG vaccine have been used, Inter. Vax BCG vaccine should offered as an alternative • PHE is only recommending that Inter. Vax BCG is used until licensed BCG vaccine becomes available again n w a r d ti h W 6 Using Inter. Vax BCG vaccine

r e b o 0 2 8 1 t Information on Inter. Vax BCG c O n vaccine w a r d ti h W Using Inter. Vax BCG vaccine

Inter. Vax BCG vaccine • • • n w a r d ti h W 8 0 2 8 1 the unlicensed BCG Vaccine (Freeze Dried) is supplied by Inter. Vax Ltd, Canada and is manufactured by BB NCIPD Ltd, Bulgaria Inter. Vax BCG vaccine is supplied to over 100 countries world-wide including the Netherlands, France, Belgium, Norway and Sweden the vaccine has been a World Health Organisation (WHO) prequalified vaccine for 25 years, meaning it can be used by United Nations organisations for immunisation against TB in 2015, over 51 million doses were distributed globally the Inter. Vax BCG vaccine has a good safety record it does not have a marketing authorisation (a licence) for use in the UK therefore a Patient Group Direction (PGD) cannot be used Using Inter. Vax BCG vaccine t c O b o r e

How should Inter. Vax BCG vaccine be prescribed 8 1 • this unlicensed BCG vaccine has to be individually prescribed using a Patient Specific Direction (PSD) or a prescription / patient medicines administration chart • a PSD is the traditional written instruction, signed by a doctor, dentist, or non-medical prescriber for medicines to be supplied and/or administered to a named patient after the prescriber has assessed the patient on an individual basis • more information about PSDs can be found here: http: //webarchive. nationalarchives. gov. uk/20141205150130/ht tp: /www. mhra. gov. uk/Howweregulate/Medicines/Availabilitypr escribingsellingandsupplyingofmedicines/Frequentlyraisediss ues/Patient. Specific. Directions/index. htm n w a r d ti h W 9 Using Inter. Vax BCG vaccine t c O b o r e 0 2

What should I explain about using Inter. Vax BCG vaccine? • • • 10 0 2 8 1 the responsibility that falls on healthcare professionals when prescribing an unlicensed medicine is greater than when prescribing a licensed medicine. It is good practice to give as much information as parents or carers require or which they may see as relevant as part of the normal consent process, you should give the parent, or those authorising immunisation on the baby’s behalf, sufficient information about the proposed immunisation, including known serious or common adverse reactions, to enable them to make an informed decision you should explain the reasons for prescribing an unlicensed medicine. For example, there is currently a global shortage of BCG vaccine with no licensed product currently available in the UK. data from the manufacturer has been assessed and indicates satisfactory quality and safety and use of unlicensed BCG vaccine is currently the only way to offer immunisation against TB further information for prescribers can be found here: https: //www. gov. uk/drug-safety -update/off-label-or-unlicensed-use-of-medicines-prescribers-responsibilities n w a r d ti h W Using Inter. Vax BCG vaccine t c O b o r e

Legal liabilities when using Inter. Vax BCG r e 0 2 8 1 • liability for clinically appropriate prescribing and administration of Inter. Vax BCG vaccine lies with the prescriber and immuniser respectively b o • 11 t c for example, if the wrong dose was prescribed or O administered, liabilitynlies with the responsible healthcare w professional a r d ti h W Using Inter. Vax BCG vaccine

r e Priority groups for BCG b o t immunisation c O n w a r d ti h W Using Inter. Vax BCG vaccine 0 2 8 1

Who should I prioritise for BCG immunisation during this period of constrained supply of BCG Vaccine 8 1 PHE endorses the World Health Organisation’s statement to limit BCG vaccination to neonates and infants of recognised high-risk groups for TB. r e 0 2 Therefore, during this period, the priority groups to prioritised are: b o A. all infants (aged 0 to 12 months) with a parent or grandparent who was born in a country where the annual incidence of TB is 40/100, 000 or greater t c O B. all infants (aged 0 to 12 months) living in areas of the UK where the annual incidence of TB is 40/100, 000 or greater n w C. previously unvaccinated children aged one to five years with a parent or grandparent who was born in a country where the annual incidence of TB is 40/100, 000 or greater. These children should be identified at suitable opportunities, and can normally be vaccinated without tuberculin testing a r d ti h Older children who are eligible for BCG vaccination may be opportunistically vaccinated alongside younger children to optimise clinic size and avoid any wastage of the vaccine. W 13 Using Inter. Vax BCG vaccine

0 2 8 1 r e What you need to know about b o t using Inter. Vax BCG Vaccine c O n w a r d ti h W Using Inter. Vax BCG vaccine

Similarities between SSI BCG vaccine and Inter. Vax vaccine SSI BCG Vaccine 0 2 r e b o t c O n w a r d ti h W 1. The powder must be reconstituted with 1 ml of diluent supplied by the manufacturer 2. The vaccine & diluent must be stored in a refrigerator (2ºC - 8ºC) and protected from light 3. For Infants under 12 months of age a dose of 0. 05 ml 4. For adults and infants aged 12 months and over a dose of 0. 1 ml 5. Administration by intradermal route only 6. Same local reaction process leaving a small, flat scar 15 Using Inter. Vax BCG vaccine 8 1 Inter. Vax BCG vaccine

Differences between SSI BCG vaccine and Inter. Vax vaccine • • • The Inter. Vax BCG vaccine and diluent comes in a different presentation to SSI BCG vaccine /diluent vial Both are presented in glass ampoules not in vials so the preparation of the vaccine is different to SSI BCG vaccine The freeze-dried powder in the brown ampoule is sealed under vacuum, a sheet of plastic film must be used to wrap around the ampoule before snapping the top off Inter. Vax BCG vaccine has a vial monitor (a colour time-temperature sensitive dot that provides an indication of the cumulative heat to which the vial has been exposed) Reconstituted Inter. Vax BCG vaccine can be used up to 6 hours instead of 4 hours as with the SSI BCG vaccine n w a r d ti h W 16 Using Inter. Vax BCG vaccine t c O b o r e 0 2 8 1 vial monitor

• The vaccine vial monitor on the ampoule of freeze dried vaccine Inner square lighter than outer circle. If the expiry date has not passed, USE the vaccine • At a later time, inner square still lighter than outer circle. If the expiry date has not passed, USE the vaccine n w t c O • Inner square matches colour of outer circle. DO NOT use the vaccine x • Inner square darker than outer ring. DO NOT use the vaccine x a r d ti h W 17 Using Inter. Vax BCG vaccine b o r e 0 2 8 1

0 2 8 1 r e Reconstituting Inter. Vax BCG b o t vaccine c O n w a r d ti h W Using Inter. Vax BCG vaccine

Advice for immunocompromised healthcare workers r e 0 2 8 1 As an added precaution, it is recommended that healthcare workers who are severely immunosuppressed, should not reconstitute or administer Inter. Vax BCG vaccine (note this advice is specific to Inter. Vax BCG only and not for other live vaccines) t c O b o For details of immunocompromised, see pages 43 to 45 in the link below: https: //www. gov. uk/government/uploads/system/uploads/attachment_data/fi le/147824/Green-Book-Chapter-6 -v 2_0. pdf n w a r d ti h W 19 Using Inter. Vax BCG vaccine

Equipment • PSD/Prescription • Information leaflet for parents/carers • Disposable gloves • Vaccine, diluent (check expiry date and vial monitor) • Sheet of plastic film • Syringes with 21 G needles for mixing and drawing up • 1 ml graduated syringe with 26 G 10 mm short bevelled needle for intradermal injection • Cytotoxic (purple lidded) sharps bin • After care instructions n w a r d ti h W 20 Using Inter. Vax BCG vaccine t c O b o r e 0 2 8 1

Before opening the ampoule, check the vial monitor, expiry date and content of freeze dried powder n w a r d ti h W 21 Using Inter. Vax BCG vaccine t c O b o r e 0 2 8 1

Before opening the ampoule, record the date and time on the ampoule and your initial n w a r d ti h W 22 Using Inter. Vax BCG vaccine t c O b o r e 0 2 8 1

Tap the ampoule gently with your finger so that the freeze dried vaccine falls to the bottom of the ampoule n w a r d ti h W 23 Using Inter. Vax BCG vaccine t c O b o r e 0 2 8 1

Do NOT attempt to open the ampoule without a sheet of plastic protective film Take the sheet of plastic film which is supplied with the vaccine and wrap it around the ampoule n w a r d ti h W 24 Using Inter. Vax BCG vaccine t c O b o r e 0 2 8 1

With the sheet of plastic film wrapped around the ampoule place your thumb on the white ring around the neck of the ampoule and snap off the top Do this carefully to avoid any loss of the freeze dried vaccine and to avoid any sharps injuries to yourself n w a r d ti h W 25 Using Inter. Vax BCG vaccine t c O b o r e 0 2 8 1

To avoid sharps injuries to yourself and others, take care & caution when handling the opened ampoule and broken top of the ampoule 8 1 Discard the broken off top of the ampoule into a cytotoxic (purple lidded) sharps bin 0 2 To ensure the opened ampoule remains upright you may find placing it test tube or blood tube rack useful n w a r d ti h W 26 Using Inter. Vax BCG vaccine t c O b o r e

Opening the ampoule of diluent Place your thumb on the white dot and snap off the top carefully at the neck of the ampoule 0 2 Place the top of the ampoule into a locally approved sharps bin n w a r d ti h W 27 Using Inter. Vax BCG vaccine t c O b o r e 8 1

Drawing up the diluent • Use a syringe with a 21 G needle to draw up the diluent • Hold the ampoule at an angle and put the needle into the open top • Pull back the plunger to draw up the entire content of diluent from the ampoule into the syringe n w a r d ti h W 28 Using Inter. Vax BCG vaccine t c O b o r e 0 2 8 1

Reconstituting Inter. Vax BCG vaccine • Reconstituting of the Inter. Vax BCG vaccine should occur immediately after opening • At arms length, slowly add the diluent to the BCG freeze dried powder • The diluent is best added by angling the ampoule containing the freeze dried powder slightly, so that the diluent slowly trickles down the side, inside of the glass ampoule, into the freeze dried powder t c O • Very gently mix the content of the ampoule by drawing up the mix slowly into the syringe and inject the mix back slowly into the ampoule • Repeat this mixing step several times until the vaccine powder is thoroughly dissolved • The reconstituted vaccine should be inspected for any particulate matter, if there is any the vaccine should be discarded n w a r d ti h W 29 Using Inter. Vax BCG vaccine b o r e 0 2 8 1

Reconstituting Inter. Vax BCG vaccine NB Injecting diluent rapidly into the vaccine may cause displacement of dried freeze powder and frothing, which can affect the dilution and consequent potency of the vaccine. Shaking the ampoule may have a similar effect n w a r d ti h W 30 Using Inter. Vax BCG vaccine t c O b o r e 0 2 8 1

Use a needle gauge no larger than 21 G to eliminate the possibility of glass fragments being drawn up Attach , a 21 G needle to a new 1 ml graduated syringe to draw up the appropriate amount of vaccine into the syringe Ensure that the ampoule remains upright when placing the ampoule down n w a r d ti h W 31 Using Inter. Vax BCG vaccine t c O b o r e 0 2 8 1

Firmly attach a short bevelled 26 G (10 mm) needle to the syringe holding the reconstituted vaccine Ensure you have the correct dosage of reconstituted vaccine, when you are ready administrator the BCG vaccine intradermally with the bevel of the needle uppermost. Record administration of Inter. Vax BCG vaccine in the usual way 0 2 8 1 NB: Only those trained in intradermal injection technique should administer BCG vaccine. t c O b o r e Correct dosage For Infants under 12 months of age a dose of 0. 05 ml n w a r d ti h W 32 Using Inter. Vax BCG vaccine For infants aged 12 months and over a dose of 0. 1 ml

Storage of unused reconstituted vaccine • Ideally, the reconstituted vaccine should be used immediately or within a short period of time. • However, if not used immediately, the reconstituted vaccine should be stored away from light, at between at 2 o. C to 8 o. C in an appropriate refrigerator up to 6 hours and must be discarded after 6 hours. • Care should be taken when storing the reconstituted vaccine to ensure it remains upright. • Any other staff needing to access the fridge contents should be made aware of ampoule’s presence in the refrigerator. n w a r d ti h W 33 Using Inter. Vax BCG vaccine t c O b o r e 0 2 8 1

Where should I report adverse incidents? 8 1 • As with any vaccine, suspected adverse reactions to Inter. Vax BCG should be reported to the MHRA using the Yellow Card scheme t c O b o r e 0 2 • More information about the Yellow Card scheme can be found here: https: //yellowcard. mhra. gov. uk/ n w a r d ti h W 34 Using Inter. Vax BCG vaccine

What should I do? . . if there has been a spillage of either un-reconstituted or reconstituted BCG vaccine 0 2 8 1 • Deal with the spillage promptly following local procedures for the management of medicines spillages • Universal standard precautions should be applied including wearing non-sterile gloves, apron and facemask • After removing and safely disposing of all PPE, wash hands using soap and water (not alcohol hand gel) n w a r d ti h W 35 Using Inter. Vax BCG vaccine t c O b o r e

What should I do? …if there has been an accidental exposure to the vaccine, e. g. needle- stick injury, splash onto mucous membranes r e 0 2 8 1 • Following local procedures for the management of needle-stick injury/splash onto mucous membranes. • b o Refer to a TB specialist for assessment of risk and t possible anti-TB medicationc O n w a r d ti h W 36 Using Inter. Vax BCG vaccine

t c O b o r e 0 2 8 1 These slides were prepared by Surinder Tamne & Dominik Zenner, PHE TB section in conjunction with the BCG project board n w a r d With thanks and acknowledgment to the Birmingham & Solihull TB nursing team for their input in the preparation of these slides ti h W Using Inter. Vax BCG vaccine