Appendix 6: Passive immunisation

Human normal immunoglobulin for intramuscular use (available as Normal Immunoglobulin-VF) is a sterile, preservative-free, pasteurised solution containing 160 mg/mL human plasma proteins and 22.5 mg/mL glycine. The solution has a pH of 6.6. At least 98 percent of the protein comprises immunoglobulins, mainly immunoglobulin G (IgG). Normal Immunoglobulin-VF is intended for IM injection and is available in 5 mL preservative-free vials. It is prepared by Cohn cold ethanol fractionation of human plasma. The manufacturing process involves specific viral removal steps to reduce the possibility of virus transmission, and includes pasteurisation for viral inactivation and nanofiltration for virus removal.

Specific human immunoglobulin preparations for IM use are available, including those for tetanus, hepatitis B, varicella zoster and anti-D. These are manufactured from plasma pools containing donations from individuals known to have high levels of the appropriate antibody. These preparations are available in single vials containing the specific antibody. The volume of the product will be determined by the potency for the appropriate antibody. In unusual circumstances, when supplies of specific immunoglobulin products manufactured from New Zealand plasma are not available, commercial products from alternative donor sources may be supplied by NZBS.

RIG is imported from a commercial source and is held at NZBS sites in Auckland, Christchurch and Wellington. The product is not registered as a medicine in New Zealand. It may be accessed and supplied under section 29 of the Medicines Act 1981 after discussion with an NZBS medical officer.

For information about the current human normal immunoglobulins for intravenous use in New Zealand refer to immunoglobulin preparations section in the Transfusion Medicine Handbook. Further queries regarding usage and dosage of IVIG can be directed to the New Zealand Blood Service transfusion medicine specialists via the district blood bank.

Human normal immunoglobulin for subcutaneous use (Evogam) is produced by CSL Behring, Australia, from NZBS New Zealand-sourced plasma. It is a sterile solution containing 16 g per 100 mL of human immunoglobulin with a purity of at least 98 percent immunoglobulin G (IgG). At least 85 percent consists of monomers and dimers (typically >90 percent), and less than 10 percent of the IgG is aggregates. The distribution of the IgG subclasses closely resembles that found in normal human plasma.

The pH value of the solution is 6.6. It contains 2.25 g/100 mL of glycine as a stabiliser. It does not contain a carbohydrate stabiliser (eg, sucrose, maltose) and contains no preservative. Evogam contains only trace amounts of IgA, typically <0.025 mg/mL.

Evogam is produced by chromatographic fractionation of large pools of human plasma obtained from New Zealand’s voluntary blood donors. The manufacturing process involves special steps to reduce the possibility of virus transmission, including pasteurisation (heating at 60°C for 10 hours) and nanofiltration.

NZBS operates a 24-hour on-call service for medical advice and access to these products. Details of the medical officer on call can be obtained from any district hospital blood bank in New Zealand.

Product can be requested using the NZBS request form. This can be accessed online on the NZBS website, by contacting your local blood bank or writing to:

New Zealand Blood Service
Private Bag 92071
Victoria Street West
Auckland 1142

email: info@nzblood.co.nz

telephone (during normal office hours): 09 523 5744.

For advice on the use of immunoglobulin products and specific dosages of these products, please contact a medical officer at NZBS. Copies of the product data sheet are available on the NZBS website.

Normal Immunoglobulin-VF is available for passive immunisation (pre- or post-exposure prophylaxis) against measles (see section 12.8.2) and hepatitis A (see section 8.8) where active vaccination is not appropriate or is contraindicated. It is not recommended for the prevention of rubella or mumps. Guidance on the use of specific preparations is provided in other sections of this Handbook: for pre- or post-exposure prophylaxis against hepatitis B (section 9.5.2 and section 9.8.1), tetanus (section 22.5.5) and varicella zoster (section 24.8.2).

Recurrent infections can occur in individuals who have low or absent levels of circulating immunoglobulins – so-called humoral immune deficiency. This can arise as a congenital disorder, or it can be acquired as a consequence of a number of diseases. Humoral immune deficiency can exist alone or as part of a wider immune deficiency syndrome. Immunoglobulin products can be used to prevent recurrent infections in these patients.

Until recently, IVIG was the product of choice for managing these patients. A subcutaneous IgG product (Evogam) is also now available, which can be infused by patients at home. This avoids the need for outpatient or day-case admission for infusion of IVIG and is preferred by some patients. The subcutaneous preparation is not suitable for use in prophylaxis against hepatitis A or measles infection.

For replacement therapy in antibody deficiency disorders, monthly administration of IVIG is given, usually at a dosage of 0.2 to 0.6 g/kg of body weight.[1] Subcutaneous product is administered one to two times per week, with the overall monthly dosage similar to that of IVIG. For both types of product, the dosage and frequency of infusion should be based on the effectiveness in the individual patient. In general, however, the aim of treatment should be to maintain the serum IgG at or above a level of 5 g/L.

Immunoglobulin should not be mixed with other pharmaceutical products, except as indicated by the manufacturer.

Passively acquired antibody can interfere with the response to live attenuated virus vaccines. Live virus vaccines should be given at least two weeks before, or deferred for up to 11 months after, doses of human normal immunoglobulin or other blood products[2]. The interval will be determined by the blood product and dose received (see Table A6.1).

Table A6.1 gives the current recommendations for deferment of live parenteral vaccines, MMR and VV, after receipt of blood products. Note that the live vaccines will not cause harm if given earlier than this, but the immune response may be suboptimal, leaving a patient at risk for the relevant disease(s). In an outbreak situation (e.g. measles) immunisation may be given at any time as the benefit could outweigh the potential impaired response. If given earlier, then subsequent serological testing or repeating live vaccine dose at an appropriate time interval can be done.

Serological testing after the administration of immunoglobulin may detect transfused antibodies for several months after administration. Serological testing for any infection after immunoglobulin should therefore be discussed with an expert.

Injections of Normal Immunoglobulin-VF must be IM, and care should be taken to draw back on the plunger of the syringe before injection to be certain that the needle is not in a blood vessel (see section 2.2.3).

As with any injection, there is a risk of anaphylaxis. Adrenaline and other means of treating acute reactions should therefore be immediately available (see section 2.3.3).

1. NZ Blood. 2017 Immunoglobulins: CSL Product Data Sheets. New Zealand Blood Service; 2017 [updated 07 March 2017]; URL: https://www.nzblood.co.nz/Clinical-information/Transfusion-medicine/Health-professionals-medicine-datasheets/Immunoglobulins. (accessed 3 July 2020)
2. Freedman M ,Kroger A. 2023. General immunization practices. in Plotkin's Vaccines: Eighth edition, Orenstein W (eds). Philadelphia, US. p. 113-144.e6. (accessed 25 May 2023)
3. NZ Blood. 2016. Transfusion Medicine Handbook Third Edition, 2016: A guide to the clinical use of blood components, blood products and blood transfusion procedures in New Zealand (ed.), Epsom, Auckland: New Zealand Blood Service. URL: https://www.nzblood.co.nz/assets/Transfusion-Medicine/PDFs/111G122.pdf (accessed 3 July 2020)