Immunoglobulin stability.

Abstract

In this issue of Biotechnology and Applied Biochemistry, I have had the opportunity to review the following article by Rajesh Parti and Samia Mankarious entitled “Stability assessment of lyophilized intravenous immunoglobulin after reconstitution in glass containers and poly(vinyl chloride) bags” (pp. 13Ő18). This paper exemplifies the journal's Mission Statement as outlined by the Editor‐in‐Chief, Dr. Roger L Lundblad. As he expressed: “studies will be expected to address directly regulatory and clinical issues” and “issues impacting on the use of such macromolecules in therapeutics”.Over the last 20 years there have been a number of changes in technology which have accommodated modification in the delivery of therapeutic immune globulins. The intramuscular administration product was the hallmark of immune globulin application. However, the advent of intravenous infusion technology for immune globulins has expanded the usage and indication for these products. Many of these products are now provided in a liquid format which presents the manufacturer with a different set of parameters than for the lyophilized product, thus furthering the requirement for complex studies to address new objectives.Manufacturers of products, by they pharmaceutical or biopharmaceutical, are continually faced with issues associated with product stability and product compatibility. They are, at times, beyond the manufacturers' scope and need to be addressed at point of use. Therefore, the challenge remains in the hands of the clinician, the nurse and/or the pharmacist. As manufacturers, it is important to understand the ultimate practical usuage and application of products in a medical setting. With the advent of rapid changes in medical care and medical care delivery, the utilization may not be environmentally compatible or not always challenged through experimentation. If manufacturers explore compatibility of active ingredients, excipients and extractables, it is important that these findings be documented for wide‐spread distribution. This could be in the form of a publication such as the journal article and/or ultimately included as a package insert change or in a monograph.The authors, Parti and Mankarious, initiated their studies to address the importance of the intravenous immunoglobulin stability in the representative delivery care system. The study is complimented by the statistical significance of their data. The authors' approach could be used as a model for assessment of other product stability/compatibility protocols. It is quite clear that data of this nature will need to be collected by all manufacturers on an on‐going basis.The current article addresses licensed product and its utilization under various conditions. It is not uncommon for manufacturers to be faced with similar issues with clinical product used in a clinical trial and/or before initiation of a clinical trial. I have recently been faced with a similar challenge with an HIV hyperimmune g‐globulin product (HIV‐IGTM). This product is in Phase III clinical trials to assess the prevention of HIV transmission from HIV‐positive pregnant women to their infants. This study is being performed under the auspices of the National Institutes of Health for the AIDS Clinical Trials Group (ACTG 185).The control product for this study is a licensed intravenous immunoglobulin which is compatible in 5′ dextrose but not saline. HIV‐IGTM had demonstrated compatibility in only saline, as other diluents were not previously tested. In order to blind the study, it was required that both immune globulins be diluted in 5% dextrose. As a result of this requirement, a study was initiated to analyse stability in saline as compared with 5% dextrose. The product was diluted 50′ and stored in polypropylene tubes. Three different lots were tested at different times post release, including 4, 6 and 12 months. Table 1 demonstrates compatibility of HIV‐IGTM with saline and dextrose as shown by potency, pH, chromatographic purity and protein. The variances observed are within the expected range of the assay method. The appearance was unchanged between zero time and 24 h in saline and 5′ dextrose.In summary, it is incumbent upon investigators and manufacturers to continually analyse the usage of their product(s) in a changing medical environment. Furthermore, it is important that scientific data be shared and distributed to the medical community. Considering the importance of this type of data, it is remarkable that only limited scientific literature addressing intravenous immunoglobulin stability is available [1].