TGA发布澳大利亚市场13个免疫球蛋白产品实验室检测调查报告

Immunoglobulins, commonly known as antibodies, are specialised glycoproteins produced by plasma cells in response to the presence of antigens – foreign substances such as viruses, bacteria, or toxins. These antibodies are a key component of the adaptive immune system, responsible for identifying and neutralising pathogens. 

Immunoglobulin products are regulated as biological medicines and are used to treat a range of immunodeficiency, autoimmune and inflammatory condition.  They provide patients with essential antibody-mediated protection. These products are subject to rigorous quality control and regulatory oversight by the TGA to ensure their safety and efficacy. Independent quality monitoring is important to ensure they continue to meet appropriate standards of safety, quality and efficacy.  

To support post-market surveillance activities, the Therapeutic Goods Administration (TGA) Laboratories conducted testing on a range of immunoglobulin products supplied to the Australian market, including Privigen, CSL Normal Immunoglobulin, Hizentra, Cuvitru, Kiovig, Gamunex, Xembify, Flebogamma, Octagam and Kamrab.

In a healthy individual, when an antigen enters the body, the immune system recognises it as foreign and initiates a targeted response. Immunoglobulins bind to the antigen, forming an antigen-antibody complex. Once bound, they play a crucial part of the immune response, including neutralising the pathogen, marking it for destruction by phagocytes, or activating the complement system which further enhances the clearance of microbes and damaged cells. After an infection is resolved, memory B cells retain information about the antigen. This enables the immune system to mount a faster and stronger immunoglobulin response upon future exposure to the same pathogen - a principle that underpins the mechanism of vaccine-induced immunity (1).

In immunodeficiency disorders, the production of immunoglobulins may be reduced or their function impaired, increasing susceptibility to infection. Therapeutic immunoglobulin products are used to replace or supplement these antibodies and are also indicated for a range of other conditions, including post‑exposure prophylaxis, acquired immunodeficiencies, and autoimmune or inflammatory diseases (Table 1) These products provide passive immunity through the administration of pre-formed antibodies. Unlike active immunity, which depends on the body's own immune response to generate antibodies following exposure to an antigen, passive immunity provides immediate but temporary protection.

Table 1. Immunoglobulins as therapeutic goods in Australia (2) 

Immunoglobulin products are widely used in Australia, with tens of thousands of units supplied annually for the treatment of a range of immune deficiencies and autoimmune disorders. Given their extensive utilisation and critical therapeutic role, the Therapeutic Goods Administration (TGA) undertook a laboratory survey to provide independent assurance of product quality and safety.

The survey was designed to verify that immunoglobulin products supplied in Australia continue to meet established quality standards and do not contain impurities or unwanted substances that could adversely affect patient safety. In particular, the testing focused on characteristics that may influence coagulation pathways, as well as overall product integrity and compliance with regulatory requirements.

Method

Samples

The survey included products from multiple sponsors and was designed to provide representation across a range of routes of administration and therapeutic uses, providing a representative assessment of immunoglobulin products supplied in Australia. (Table 2). 

The survey involved the assessment of 13 immunoglobulin products available on the Australian market. Laboratory testing was conducted in accordance with internationally recognised pharmacopoeial standards. Testing included evaluation of procoagulant activity using a Prekallikrein Activator (PKA) assay and assessment of product purity through High Performance Liquid Chromatography (HPLC). These analyses were undertaken to confirm that the products complied with relevant quality specifications and did not contain unacceptable levels of impurities. 

In addition to laboratory testing, product labels were reviewed for compliance with Therapeutic Goods Order No. 91 (TGO 91), which specifies medicine labelling requirements in Australia. Supporting documentation, including shipping records and manufacturers’ certificates of analysis, was also reviewed to verify compliance with approved specifications and supply chain requirements.

Compliance assessment summary

Following comprehensive testing and documentation review, each product was evaluated for regulatory compliance and classified into one of the following categories: 

• Compliant: The sample meets all applicable quality and regulatory standards.
• Non-Compliant: The sample fails to meet one or more critical quality requirements, rendering it unsuitable for use.
• Minor Non-Compliance: The sample exhibits minor deviations from standards that are potentially correctable and do not pose immediate safety concerns.

Test methods

Products were analysed by size-exclusion HPLC to assess molecular distribution. Products were also tested for Prekallikrein Activator (PKA). Testing was performed in accordance with the following monographs:

• Ph. Eur. Monograph 11.8 07/2025:2788 – Human Normal Immunoglobulin for Subcutaneous Administration
• Ph. Eur. Monograph 11.8 07/2025:0918 - Human Normal Immunoglobulin for Intravenous Administration
• Ph. Eur. Monograph 11.8 07/2025:0338 - Human Normal Immunoglobulin for Intramuscular Administration
• Ph. Eur. Monograph 11.0 - 01/2015:0723 - Human Rabies Immunoglobulin 
• Ph. Eur. Monograph 11.0 - 04/2016:20615 corrected 11.0 - Prekallikrein Activator
• Ph. Eur. Monograph 11.1 - 04/2023:20230 - Size-Exclusion Chromatography

Labelling of all drug products were visually examined, photographed, and analysed according to the TGO91 for medicine labelling.

Results

Table 2 summarises the outcomes of product testing. All products met the required specifications outlined in their respective pharmacopoeial monographs and/or approved product specifications. 

Where labelling deficiencies were identified, sponsors were requested to implement appropriate corrective actions. Depending on the nature of the issue, this may include updating product information in the Australian Register of Therapeutic Goods (ARTG), applying for a Section 14 exemption, or revising product labels to achieve compliance with current regulatory requirements.

Table 2. Results of Immunoglobulin Survey

* Product Label Reviews were not performed on these batches, as batch# P100803191 was used as representative of Privigen AU product.

Conclusion

The survey confirmed that all immunoglobulin products evaluated met the quality requirements assessed by the TGA. While minor labelling deficiencies were identified, no quality or safety concerns were detected. The findings support continued confidence in the quality of immunoglobulin products supplied in Australia and reinforce the importance of ongoing post-market monitoring and stability surveillance.

References

1. Arumugham VB, Rayi A. Intravenous Immunoglobulin (IVIG). 2023 Jul 3. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan–. PMID: 32119333.

2. National Blood Authority Australia Immunoglobulin products | National Blood Authority

3. National Report on the issue and use of Immunoglobulin Annual Report 2023-24 https://www.blood.gov.au/report-issue-and-use-immunoglobulin