International collaborative study to assess candidate reference preparations to control the level of anti-D in IVIG for use in Europe and the United States

Specifications for anti‐A and anti‐B in intravenous immunoglobulin: history and rationale

“…By this time, we were collaborating with colleagues at CBER/FDA and the European Directorate for Quality of Medicines and Healthcare (EDQM) to harmonize tests and specifications for IVIG across the United States and Europe. To aid the implementation of our proposed specification for anti‐D in IVIG, and to overcome variation in hemagglutination titrations, we produced a lyophilized 5% (wt/vol) IVIG preparation containing the appropriate level of anti‐D (we spiked IVIG with the 2nd International Standard for anti‐D immunoglobulin, 01/572, to 0.0475 IU/mL) to define this proposed maximum limit, together with a negative‐control IVIG . The starting concentration of IVIG for testing in the direct method is 2.5% (wt/vol) corresponding to a 1‐in‐2 dilution of the reference preparations and 5% (wt/vol) IVIG products.…”

Intravenous Immunoglobulin and Autoimmune Disease

“…However, it is accepted that there are significant batch‐to‐batch variations in many different antibody titers 4,5 . It is very difficult to control for this, although some legislation is now in place for certain antibody specificities, for example, anti‐D 6 . Therefore, it is probable that there are batch‐to‐batch variations of contents responsible for the mechanisms of action of hdIVIg such as anti‐CD95 antibodies, which are discussed later.…”

“…healthy donors Natural antibodies for example, anti-D. 6 Therefore, it is probable that there are batch-to-batch variations of contents responsible for the mechanisms of action of hdIVIg such as anti-CD95 antibodies, which are discussed later. There are also likely to be manufacturer-to-manufacturer differences, as well as differences in plasma source with effects on repertoire dependent on endemic diseases and vaccination status.…”

Current clinical uses of intravenous immunoglobulin

“…2 Experiments in mice infected with WNV revealed both prophylactic and therapeutic efficacy of plasma and IVIG prepared from healthy Israeli donors, but not from US donors. 3,4 Clinical trials of IVIG in WNV infection are currently being planned by the National Institutes of Health. 5 This finding may also be generalisable as a model for treating other infectious, particularly viral, diseases with no specific treatment.…”

“…However, we accept that there are significant batch-tobatch variations in many different antibody titres. 3 It is very difficult to control for this, although some legislation is now in place for certain antibody specificities, for example anti-D. 4 It is not usually practicable to routinely measure the patients' specific IgGs and match this to antibody titres in IVIG batches. There may be occasional exceptions in replacement therapy for specific antibody deficiency syndromes (SPAD), but not usually for common variable immunodeficiency (CVID) where measurement of IgG levels and clinical assessment is currently the norm for determining the adequacy of replacement treatment.…”