Statement on Immunoglobulin Utilization and Intravenous Immunoglobulin Brand Switching
Alan Tinmouth, MD (NAC)
Andrew Shih, MD (NAC)
Douglas Morrison, MD (NAC)
Oksana Prokopchuk-Gauk, MD (NAC)
Charles Musuka, MD (NAC)
David Conrad, MD (NAC)
Lakshmi Rajappannair, MD (NAC)
Kathryn Webert, MD (NAC)
Pamela Leclerc (Nova Scotia)
Lindy McIntyre (CBS)
Saba Teklehaimanot (CBS)
List of abbreviations
Immunoglobulin
Intravenous Immunoglobulin
National Advisory Committee on Blood and Blood Products
Subcutaneous Immunoglobulin
Summary of Revisions
Revision Date
Details
Intravenous immunoglobulin (IVIg) and subcutaneous immunoglobulin (SCIg) are used to treat primary and secondary immune deficiency disorders and a wide range of autoimmune disorders across various medical specialties. Immunoglobulin (Ig) utilization continues to grow year over year despite jurisdictional guidelines available across the country. This places continuous pressure on the supply and cost of these products for the Canadian health care system. As a result, there is need for ongoing monitoring of utilization and stewardship to ensure appropriate utilization of Ig across all regions.
The National Advisory Committee on Blood and Blood Products (NAC) endorses the appropriate use of IVIg and SCIg based on evidence based guidelines. In Canada there are currently four provincial/regional guidelines that exist to guide appropriate Ig use (listed and linked in Section 2.0). These more recent guidelines have superseded previous national guidelines published by NAC. To ensure the long term stability of IVIg supply, adherence to and enforcement of these guidelines is essential. Amalgamation of existing provincial/territorial/regional guidelines into a single national guideline would help ensure equity of Ig utilization for all Canadians.
The primary principles for appropriate Ig utilization include:
- Ig should only be prescribed where there is evidence to support use (see below); and,
- a) Alternative therapies have failed or are not feasible/available;
b) The dose of Ig is prescribed using an adjusted dose body weight calculator, where appropriate; and,
c) Maintenance Ig should only continue if benefit is demonstrated, regular clinical review occurs to ensure adjustment to the lowest effective dose and/or greatest treatment interval, and trials of alternative therapies are considered where appropriate.
Canadian Blood Services is the sole supplier of IVIg and SCIg for nine Canadian provinces and three territories through their pan-Canadian formulary of plasma protein and related products. As IVIg and SCIg are general listing products on the Canadian Blood Services formulary, IVIg and SCIg are provided at no direct cost to hospitals and patients. While Canadian Blood Services offers a substantial range of products, it manages a formulary, not an open formulary. Selective changes to product listings occur through product selection and tendering processes.
Ig utilization, including both IVIg and SCIg, should follow recommendations with respect to indications and dosing stated in the applicable provincial/territorial/regional guideline.
In cases where a specific indication is not listed in the applicable guideline, requests for Ig should be supported by an updated evidence review; initial approval, as appropriate, and ongoing assessments of effectiveness should be guided by established local or provincial/ territorial/regional processes. Guidelines from other jurisdictions may serve as a resource when condition specific indications are not listed in the applicable provincial/territorial/regional guideline.
During periods of shortage (Green Advisory, Amber, or Red), additional restrictions on use or dose adjustments as outlined in the National Plan for Management of Shortages of Immunoglobulin (found on the Blood Shortages page of the NAC website) should be followed.
For reference, links to the various Canadian regional/provincial guidelines are provided below:
- British Columbia IVIg Utilization Management Program Recommendations (July 2019)
- Prairie Collaborative Criteria for the Clinical Use of Immune Globulin (February 2022)
- Ontario Immune Globulin Utilization Management (January 2025)
- Atlantic Clinical Indications and Criteria for Intravenous and Subcutaneous Immunoglobulin (IVIg/SCIG) (April 2022)
NAC supports the use of an adjusted body weight calculator to calculate IVIg dosing in adult patients. Slight variation currently exists between available calculators. The clinical impact of these differences is not known but likely minimal. NAC recommends that locally applicable calculators are used.
- British Columbia: IVIg Dose Calculator
- Alberta and Saskatchewan: IVIg Dosing Based on Adjusted Body Weight Calculation
- Manitoba: Ideal Body Weight Calculator with IVIg Dosing
- Ontario: Immune Globulin (IVIG/SCIG) Dose Calculator
- Nova Scotia, Prince Edward Island, and New Brunswick: IVIG Dosing Calculator
- Newfoundland and Labrador: Ideal Body Weight Calculator with IVIg Dosing
The use of standard IVIg infusion rate tables applicable to all brands of 10% IVIg is strongly recommended. Standard infusion protocols help avoid confusion in terms of administration rates at the bedside. Examples of generic 10% IVIg infusion rate tables for adult and pediatric patients currently in use within Canadian jurisdictions include:
- British Columbia: Infusion Rate Tables
- Alberta: 10% IVIG Infusion Rate Tables – Adult | Pediatric
- Saskatchewan: Generic 10% IVIG Infusion Rates – Adult and Pediatric
- Manitoba: Pediatric & Adult IVIG Infusion Rate Table (see number 9)
- Ontario: Infusion Rate Tables
- Nova Scotia, Prince Edward Island, and New Brunswick: Intravenous Immunoglobulin – Gammagard S/D Adult | Adult | Pediatric
- Newfoundland and Labrador: IVIG Infusion Rate Tables
Local/jurisdictional transfusion medicine services should regularly review their IVIg by brand to ensure they align with Canadian Blood Services’ supply shares for IVIg. Changes to local utilization shares of IVIg products should preferentially be achieved through the selection of products for new patients to ensure that patient transition between brands is minimized. Patients who have been identified to have a history of IVIg adverse reactions but demonstrated tolerance to specific IVIg brands should preferentially not undergo IVIg brand switching.
During a shortage or period of reduced inventory for one or more IVIg product, switching IVIg brands for specific patients may be required. In these situations, a communication must be sent from the transfusion medicine service to the IVIg infusion clinic and prescribing physician, as per local policy. This communication must emphasize any potential impact to the IVIg infusion duration for the first exposure to a new IVIg brand.
To minimize risk of infusion reaction, the maximum infusion rate of any IVIg brand at initial exposure should not exceed that of the manufacturer recommendation (4-5 mL/kg/h in generic infusion tables). Patients receiving chronic IVIg will require a longer infusion duration upon first exposure to a different IVIg brand while the patient’s tolerance of this product is confirmed. Appropriate communication with patients, outpatient infusion clinic booking staff, and nurses is essential to ensure adequate infusion time is allocated for a new IVIg brand. For sample resources, please consult the following documents which may be customized for hospital or regional use:
- Appendix A: IVIg Brand Switch Communication Templates
- Patient Notification Template
- Physician Notification Template
- Appendix B: Canadian Ig Supply and IVIg Brand Switching Fact Sheet
Appendices
Patient Notification Template
[DATE]
[PATIENT FIRST] [PATIENT LAST]
[ADDRESS]
[ADDRESS]
Dear [PATIENT NAME]
RE: Notice of Intravenous Immunoglobulin Brand Switch
Over time, supply dynamics will impact the availability of specific immunoglobulin (Ig) brands. Availability of certain intravenous immunoglobulin (IVIg) brands and vial sizes may be limited due to supply chain constraints or changes in manufacturing contracts and will require some patients to switch IVIg brands. National and provincial/territorial planning is under way to develop and implement stewardship/conservation strategies and contingency shortage plans. To ensure an ongoing supply of IVIg, Canadian Blood Services regularly makes changes to the brands of IVIg that they carry.
You are one of many patients who receive [INSERT BRAND NAME] on a regular basis. You will need to be transitioned to a different IVIg brand by [INSERT DATE]. The replacement brand of IVIg is expected to be as effective for you as [INSERT BRAND NAME] has been. However, because side effects may vary across IVIg brands, the first time you receive the replacement brand of IVIg, the infusion rate will be slowed (given at the rate that would be used for a first-time patient) to watch for any side effects. This will mean that the time required to receive your first infusion of the replacement IVIg brand will be longer than you are used to.
The replacement brand of IVIg will be determined based on available IVIg inventory closer to your next infusion date.
Your prescribing physician and infusion clinic/site staff will be informed of this upcoming change. We kindly ask you to discuss the scheduling of your first infusion of the replacement brand of IVIg with the infusion clinic/site staff to ensure that everyone involved is prepared for this change.
Please contact your prescribing physician with any questions or concerns.
Sincerely,
[TRANSFUSION MEDICINE PHYSICIAN NAME & SIGNATURE]
Cc: [WARD – NAME OF OUTPATIENT INFUSION DEPARTMENT]
Physician Notification Template
[DATE]
Dr. [DOCTOR INITIAL] [DOCTOR LAST]
[ADDRESS]
[ADDRESS]
By fax: [FAX]
Dear Dr. [DOCTOR LAST]
Re: [PATIENT LAST], [PATIENT FIRST]
DOB: [DOB]
HSN: [HSN]
RE: IVIg Brand Switching for Chronic IVIg Infusion Patients
Over time, supply dynamics will impact the availability of specific immunoglobulin (Ig) brands. Availability of certain intravenous immunoglobulin (IVIg) brands and vial sizes may be limited due to supply chain constraints or changes in manufacturing contracts and will require some patients to switch IVIg brands. National and provincial/territorial planning is under way to develop and implement stewardship/conservation strategies and contingency shortage plans.
To ensure an ongoing supply of IVIg, Canadian Blood Services has recently made changes to the brands of IVIg that they carry. Further details are provided in the Customer Letter – [PROVIDE LINK TO MOST RECENT BRAND AVAILABILITIES]
[PATIENT NAME] is in a cohort of patients who receive this product on a regular basis and will need to be transitioned to an alternative IVIg brand [SELECT NEW IVIG BRAND] by [INSERT DATE]. The first time [PATIENT NAME] receives [SELECT NEW IVIG BRAND], the infusion time will need to be extended as slower maximal infusion rates are required while the patient’s tolerance of this new IVIg product is determined.
While supply of subcutaneous immunoglobulin (SCIg) may be similarly impacted by supply chain constraints it is often different than IVIg. In the event of IVIg shortages, it may be an opportune time to consider whether [PATIENT NAME] would be a good candidate for transitioning to SCIg.
The attached letter will be sent to [PATIENT NAME] shortly, so you may get some questions.
Thank you for your attention. My contact information is [INSERT HERE OR REFER TO HEADER DETAIL], should you have any questions or concerns.
Sincerely,
[TRANSFUSION MEDICINE PHYSICIAN NAME & SIGNATURE]
Cc: [WARD – NAME OF OUTPATIENT INFUSION DEPARTMENT]
Canadian Immunoglobulin Supply
- What is the current state of Ig supply globally?
Canada is part of a global supply chain, and the international supply of Ig is tight due to increasing demand. There is an ongoing global shortage of Ig as demand for the product is outpacing the plasma collections necessary to make them. The COVID-19 pandemic further disrupted global supply chains and decreased plasma collections worldwide.
- Is there a national shortage of Ig?
No. There is no national shortage of Ig. However, today’s rapidly shifting global market for Ig necessitates a proactive and ongoing approach to ensure an adequate supply of Ig for Canada.
- If an Ig shortage does occur in Canada, how will this be handled?
In the event of a shortage, planning to safeguard the supply of blood and blood products is led by the National Emergency Blood Management Committee, which includes representation from provincial/territorial health systems, the National Advisory Committee on Blood and Blood Products, and Canadian Blood Services. It’s expected that provincial/ territorial jurisdictions and hospitals implement actions that are complementary and congruent to national recommendations.
For further information, please refer to the National Plan for the Management of Shortages of Ig Products found on the Blood Shortages page of the NAC website.
- What steps have been taken to try to prevent a shortage of Ig?
Canadian Blood Services works to protect an appropriate stockpile of Ig, and the national Ig supply is closely monitored by Canadian Blood Services and transfusion medicine (blood bank) leaders. Provincial/territorial ministries of health and hospitals may also have established programs to review Ig product requests for appropriateness and track the proportions of different Ig brands used by hospitals. Throughout all these various activities, minimization of patient impact remains a priority.
Per the National Plan for the Management of Shortages of Ig Products, a Green Phase Advisory would also be issued by the National Emergency Blood Management Committee if Ig inventory is low or there is a potential supply of disruption. This phase triggers several actions to mitigate the risk of a shortage, including implementation of any potential conservation strategies.
Intravenous Immunoglobulin Brand Switching
- What is the impact of the tightening of global Ig supply on IVIg distribution by Canadian Blood Services?
As Canadian Blood Services buys Ig from several different global manufacturers, tightening of global Ig supply may result in Canadian Blood Services’ inventory of Ig brands and vial sizes fluctuating over time.
As a result, Canadian Blood Services works in partnership with hospitals across the country to manage IVIg inventory. Hospitals and Canadian Blood Services are in regular communication and hospital blood banks are prepared to accept all IVIg brands and vial sizes provided by Canadian Blood Services. Hospitals are encouraged to select IVIg brands for patients with acute IVIg needs carefully to help with balancing between IVIg brand percentages.
- Are all IVIg brands similar in terms of effectiveness and adverse reactions?
Yes. There are no known differences in the clinical effectiveness of the different IVIg for different medical conditions, despite slight differences in the licensed indications and adverse reactions seen with all IVIg products. Canadian hemovigilance data does not suggest the rates of specific adverse reactions are different between products. However, individual patients may have adverse reactions to a specific IVIg brand but tolerate a different brand.
- Should all patients be considered for brand switches of IVIg?
Many factors are important in deciding if a brand switch of IVIg is appropriate, including a history of previous serious reactions to a specific IVIg brand. The decision regarding IVIg brand switching in specific patient cases will be made by local transfusion medicine experts, together with physician prescribers.
- Will patients be involved in the IVIg brand switching decision?
IVIg prescribers may contact patients in some cases to discuss IVIg brand switching.
- Who will be notified if a patient IVIg brand switch is needed and how will this happen?
In situations where an IVIg brand switch is necessary for a patient, a written communication must be sent from the hospital transfusion medicine (blood bank) service to the prescribing physician. The transfusion medicine physician and/or the prescribing physician is responsible for notifying the patient and IVIg infusion clinic in writing, as per local policy. Communications must emphasize the potential impact to the IVIg infusion duration for the first exposure to a new IVIg brand.
- What is the impact to the patient if an IVIg brand switch is needed?
The manufacturers of all IVIg brands recommend that the first infusion takes place at a slower maximum rate. This means that patients who are used to receiving IVIg will have a longer infusion time at their first infusion of a different IVIg brand. It is important that patients and infusion clinics take this time into account when preparing for administration of a different IVIg brand to a patient on chronic IVIg therapy. To minimize patient and healthcare impacts, switching IVIg brands more than once is discouraged, unless necessary.