MENINGITIS C VACCINE

USE OF MENINGOCOCCAL GROUP C CONJUGATE VACCINE

KEY PHARMACEUTICAL/TECHNICAL ISSUES
(UPDATED AUGUST 2000)

Q1: What are the details of presentations and pack sizes?

A:  The vaccine is available in the following presentations:

1.Wyeth Vaccines (Brand name: Meningitec): A single pack containing 1 x 1 dose in glass vial (0.5ml suspension) and a multipack containing 10 x 1 dose in glass vials (0.5ml suspension).

The dimensions are:

2. Chiron Vaccines (Brand name: Menjugate): A single pack containing 1 x 1 dose glass vial of lyophilised powder and a glass vial containing 0.5ml diluent for reconstitution. There is also a single pack containing 1 x 10 dose glass vial of lyophilised powder and 1 glass vial of diluent.

The dimensions are:

The Wyeth brand is licensed for use in children and older people of any age and is being supplied through primary care in a single dose presentation.

The Chiron brand is currently licensed only for use in children over 12 months of age and the initial supply is mostly in a multi dose presentation and will be used only in the schools programme.

The North American Vaccine brand is currently licensed only for use in children over 12 months of age and is in a single dose syringe presentation and the initial supply will be used only in the schools programme.

We are advised that the marketing authorisation holder, North American Vaccine (UK) Ltd has recently been acquired by Baxter Healthcare Ltd. Further information is available from the Hyland Immuno division of Baxter Healthcare Ltd.

Q2:  Is there an overage in the presentations?

A:  There is adequate vaccine in each presentation to provide at least the full quantity of recommended dose/doses.

Q3:  Will the vaccines need to be transported under cold chain conditions?

A:  The meningococcal group C conjugate vaccine should be stored at temperatures of 2^o -8^oC at all times. It should be discarded if frozen, or if it is suspected to have been exposed to temperatures less than 2^oC. In addition it should be kept away from sources of direct heat, such as a radiator and out of direct sunlight.

When the vaccine is transported to, and used in a school, it may not always be practical to keep it stored between temperatures of 2^o-8^oC.

For the Wyeth product we have data to suggest that the stability of the vaccine will not be impaired if it is kept at temperatures not exceeding 25^oC for no longer than 24 hours.

On the basis of the above data, we would advise that for the Wyeth product, unrefrigerated vaccine does not have to be discarded on the day of issue but can be returned to appropriate refrigeration provided that:

1. Vaccine stored outside of the 2^o-8^oC recommended range is appropriately marked before being returned to refrigeration to ensure that when next issued it is used on that occasion.
   
   
2. Vaccine is only subjected to re-refrigeration on one occasion.
   
   
3. Total exposure time to temperatures between 8^o and 25^oC does not exceed 24 hours.

For the Chiron product we have data which demonstrates that the lyophilised vaccine is stable when held for 3 months at 30^oC, after storage at 2^o-8^oC for 18 months. The diluent is stable for 18 months at 30^oC.

On the basis of the above data for the Chiron product we would advise that unrefrigerated vaccine does not have to be discarded on the day of issue but can be returned to appropriate refrigeration provided that:

1. Vaccine stored outside of the 2^o-8^oC recommended range is appropriately marked before being returned to refrigeration to ensure that when next issued it is used on that occasion.
   
   
2. Total exposure time of the vaccine to temperatures between 8^oC and 30^oC does not exceed 3 months.

The Department of Health is advising that any multi-dose vaccine once reconstituted should be used within 4 hours.

For the North American Vaccine product we have data to suggest that the stability of the vaccine will not be impaired if it is kept at temperatures not exceeding 40^oC for no longer than 30 days.

On the basis of the above data for the NAVA product we would advise that unrefrigerated vaccine does not have to be discarded on the day of issue but can be returned to appropriate refrigeration provided that:

1. Vaccine stored outside of the 2^o-8^oC recommended range is appropriately marked before being returned to refrigeration to ensure that when next issued it is used on that occasion.
   
   
2. Total exposure time of the vaccine to temperatures between 8^oC and 40^oC does not exceed 30 days.

Q4: What is the shelf life of the vaccine?

A:  The Wyeth and Chiron vaccines have a shelf life of 18 months.

The North American Vaccine product has a shelf life of 12 months.

Q5:  What are the possible side effects? eg headaches

A:  Meningococcal Group C conjugate vaccines are well tolerated in all age groups. The rates of local reactions and systemic reactions are similar to those seen previously with Hib vaccines. Further information is available in the CMO Update 27 (August 2000), the joint CMO/CNO/CPhO Letter (PL/CMO/99/4, PL/CNO/99/8,PL/CPHO/99/3 issued in October 1999), the replacement chapter on Meningococcal Group C conjugate vaccine for "Immunisation against Infectious Disease 1996", the leaflet 'Reduce the risk: Your guide to the new meningitis vaccine' and in the Fact Sheet for health professionals on Meningitis C conjugate vaccine.

The following side effects sometimes happen one to three days after immunisation in the age groups shown below.

• Some redness or swelling where the injection was given.
• One in two babies may become irritable.
• One in 20 babies may have a mild fever.

• Some redness or swelling where the injection was given.
• One in five toddlers may become irritable.
• One in 20 toddlers may have a mild fever.

• One in 10 children may have redness or swelling where the injection was given.
• About one in 100 children may have a mild fever.
• One in 25 children may become irritable.

• About one in three may have some redness or swelling where the injection was given and one in 100 may have a very sore arm from the injection which may last a day or so.
• About one in 50 may have a mild fever.
• About one in 20 primary school children and one in seven secondary school children may have a headache.

Following injections some young people may experience nausea, vomiting, minor skin rashes, dizziness and tiredness and some young people may faint at the time of the injection.

There have been very rare reports of people having fits: these have usually been febrile or associated with fainting and recovery has usually been very quick. Fits have not been shown to be caused by the vaccine.

Q6:  How should any suspected adverse reactions be reported?

A:  As this vaccine is a new product, it carries a 'black triangle' symbol.

If a doctor or pharmacist suspects any adverse reaction (ADRs) to the vaccine, however minor, he/she should report this to the Medicines Control Agency through the Yellow Card spontaneous reporting scheme in the normal manner.

Reports of suspected ADRs will now be accepted by MCA directly from nursing staff who are involved in administering the vaccine or involved in the care of individuals receiving the vaccine, for the period of the meningitis vaccine campaign. Nursing staff should complete and sign the Yellow Card and include the doctor's name and address. When including the name and address of the doctor the nurse does not need to obtain the doctor's signature.

As there are now three suppliers of the vaccine it is important to identify both the brand and the batch number of the vaccine when reporting an adverse reaction.

Q7:  Does the vaccine contain thiomersal, human albumin, bovine components or human fetal material?

A:  Manufacturers have been asked for answers to these points.

According to Wyeth, one of the components used in the manufacture of the vaccine is derived from cow's milk but no bovine material is added to the final product. The milk-derived components used in the production of the vaccine comes from countries where no BSE has ever been reported. The vaccine does not contain any thiomersal, human albumin or human fetal material.

Chiron have stated that one of the components used in the manufacture of the vaccine is derived from cow's milk but no bovine material is added to the final product. The milk-derived component used in the production of the vaccine comes from countries where no BSE has ever been reported (Australia and/or New Zealand). The finished product does not contain thiomersal, human albumin or human fetal material.

North American Vaccine has confirmed that the finished product does not contain thiomersal, human albumin or human fetal material. Semi-solid special agar containing beef broth is used for the initial propagation of the Clostridium tetani seed cultures prior to inoculation of the fermentor. No bovine material used in the early stages of the production is present in the final product. A component derived from cow's milk is also used in the vaccine manufacture, but not added to the final product.

Bovine materials used in production comply with the European CPMP recommendations and are sourced from 'BSE-free' countries according to the current criteria.

Q8:  Is the vaccine genetically modified?

A:  Two of the vaccines are manufactured using a natural genetic variant as a carrier protein.

This component has been used for many years in other vaccines.

Q9:  Are the different brands of Meningitis C vaccine interchangeable?

A:  The new meningococcal C vaccines use the same technology as that applied to the development of Hib conjugate vaccines. Experience from the use of Hib vaccines suggests that different brands of the Meningitis C vaccine are interchangeable.

Q10: Can this vaccine be given with other vaccines including travel vaccines?

A:  As we have advised in the DH fact sheet for health professionals on Meningitis C vaccine, studies have shown that this vaccine can be safely given with routine childhood immunisations including DTP/Hib, MMR, DT, Td, oral polio vaccine and IPV.

There are no studies to date on hepatitis B or BCG vaccine being given at the same time although there is no reason to suspect an interaction. BCG vaccine has been given within a month of meningococcal C conjugate vaccine with no adverse effects.

Travel vaccines other than the meningococcal plain polysaccharide A and C vaccine can be given at the same time as the meningococcal C conjugate vaccine but as with other vaccines, it is preferable to administer them at different sites.

Q11: Should the meningococcal C conjugate vaccine be given to patients who have received the meningococcal plain polysaccharide A and C vaccine in the past?

A: A gap of six months is suggested between the administration of the meningococcal plain polysaccharide A and C vaccine and the subsequent meningococcal C conjugate vaccine except in conditions of very high risk in young children (under five years of age) who would not be expected to have responded well to the earlier administration of the C component of the polysaccharide vaccine. Such children may receive the meningococcal C conjugate vaccine at least two weeks after the plain polysaccharide A and C vaccine.

Q12: How long after the administration of the meningococcal C conjugate vaccine can the meningococcal plain polysaccharide A and C vaccine be given?

A: A minimum of two weeks should be left after the administration of the meningococcal C conjugate vaccine before the meningococcal plain polysaccharide A and C vaccine is given.

Q13:  Can the new meningococcal vaccine be given for travel purposes?

A:  Meningococcal plain polysaccharide A & C vaccine (ACVax or Mengivac A + C) is still recommended for people travelling to high risk countries. Vaccine required for travel immunisation must be ordered from the manufacturers in the usual way.

Q14:  What advice do we give if asked about interactions between the vaccine and drinking alcohol and the use of illicit drugs?

A:  There are no known interactions with consumption of alcohol. We have no information on any interactions between meningococcal C vaccine and illicit drugs.

Q15: Are there adequate patient information leaflets supplied with multidose presentations?

A.  We understand that there are adequate patient information leaflets for each dose of vaccine.

Q16: How are consumables supplied?

A:  Consumables such as needles, syringes and 'sharps' bins are obtained locally and distributed through the normal channels.

Q17: Are anaphylactic packs available?

A:  These are provided locally as for any routine immunisations.

The advice on the management of anaphylaxis provided in 'Immunisation against Infectious Disease 1996' remains current.

Q18: What funding is available?

A:  Resources are allocated to Health Authorities, according to the school aged target population, through a Cash Limit Adjustment. Across all English Health Authorities a total of £1.8m last year and around £6.5m this financial year has been allocated. This represents an allocation of £1 per child aged 5 to 17 years and is used to support the schools' programme. Trusts will need to contact Health Authorities to see how the money is allocated within Health Authorities.

Q19: How is the input of pharmacy services to this campaign supported?

A:  Trust Chief Pharmacists negotiate with Health Authorities/Trusts to ensure that the programme is appropriately resourced.

Details of the additional activities which need to be resourced were given in the joint professional letter from CMO/CNO/CPhO(PL/CMO/99/2,PL/CNO/99/4,PL/CPHO/99/1) dated 20 July 1999.

Further information

For details of other questions which have been asked it would be best to contact your local Drug Information Pharmacist.

There is a factsheet on meningococcal C vaccine as part of the HEA - now Health Promotion England - series for health professionals. This was sent directly to all health professionals on the HEA/HPE database. There is also available a parent information leaflet 'Meningitis C Reduce the Risk. Your guide to the new meningitis C vaccine' available through local suppliers or from Health Promotion England. Details can be found on the HEA/HPE website at www.immunisation.org.uk.

This Q and A is available on the Department of Health website at: http://www.doh.gov.uk/meningitis-vaccine.htm.

DEPARTMENT OF HEALTH
AUGUST 2000