Djuro Josić, Andrea Buchacher, Christoph Kannicht, Yow‐Pin Lim, Klemens Löster, Katharina Pock, Stephen Robinson, Horst Schwinn, Monika Stadler
{"title":"Degradation Products of Factor VIII Which Can Lead to Increased Immunogenicity","authors":"Djuro Josić, Andrea Buchacher, Christoph Kannicht, Yow‐Pin Lim, Klemens Löster, Katharina Pock, Stephen Robinson, Horst Schwinn, Monika Stadler","doi":"10.1111/j.1423-0410.1999.tb00024.x","DOIUrl":null,"url":null,"abstract":"The biochemical and immunochemical aspects of the development of inhibitors with a plasma‐derived, double‐virus inactivated factor VIII (FVIII) concentrate (marketed as Octavi SDPlus in Germany and Bisinact in Belgium) are described. A total of 12 cases of inhibitor formation (predominantly type II) were reported in Germany, 8 in Belgium but none in Portugal. Initially, the only difference between the non‐pasteurised, SD virus‐inactivated product Octavi and the pasteurised product Octavi SDPlus appeared to be pasteurisation, though subsequently, the quality of source material for the product was found to differ in different countries. Separation studies revealed the presence of a 40 kDa peptide fragment in some batches. It was subsequently shown that there was a strong correlation between inhibitor development and batches containing the 40 kDa marker, and a relationship between elevated markers of coagulation activation (FPA in particular) and the occurrence of the 40 kDa marker. Further work revealed that analytical methods commonly used for quality control were not suitable to highlight batch‐to‐batch differences. It was concluded that inhibitor potential (neoantigenicity) in Octavi SDPlus arose due to two effects; degradation of FVIII already present in source material; and heating of unstable FVIII degradation products. In this case, inhibitors were not caused by the overall production process, nor by GMP failures. The problem of inhibitor potential can be avoided if appropriate preventive measures are taken. Further work is needed to prove non‐neoantigenicity and to reinforce the scientific findings, and to characterise pilot batches.","PeriodicalId":23631,"journal":{"name":"Vox Sanguinis","volume":null,"pages":null},"PeriodicalIF":1.8000,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Vox Sanguinis","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/j.1423-0410.1999.tb00024.x","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
The biochemical and immunochemical aspects of the development of inhibitors with a plasma‐derived, double‐virus inactivated factor VIII (FVIII) concentrate (marketed as Octavi SDPlus in Germany and Bisinact in Belgium) are described. A total of 12 cases of inhibitor formation (predominantly type II) were reported in Germany, 8 in Belgium but none in Portugal. Initially, the only difference between the non‐pasteurised, SD virus‐inactivated product Octavi and the pasteurised product Octavi SDPlus appeared to be pasteurisation, though subsequently, the quality of source material for the product was found to differ in different countries. Separation studies revealed the presence of a 40 kDa peptide fragment in some batches. It was subsequently shown that there was a strong correlation between inhibitor development and batches containing the 40 kDa marker, and a relationship between elevated markers of coagulation activation (FPA in particular) and the occurrence of the 40 kDa marker. Further work revealed that analytical methods commonly used for quality control were not suitable to highlight batch‐to‐batch differences. It was concluded that inhibitor potential (neoantigenicity) in Octavi SDPlus arose due to two effects; degradation of FVIII already present in source material; and heating of unstable FVIII degradation products. In this case, inhibitors were not caused by the overall production process, nor by GMP failures. The problem of inhibitor potential can be avoided if appropriate preventive measures are taken. Further work is needed to prove non‐neoantigenicity and to reinforce the scientific findings, and to characterise pilot batches.
期刊介绍:
Vox Sanguinis reports on important, novel developments in transfusion medicine. Original papers, reviews and international fora are published on all aspects of blood transfusion and tissue transplantation, comprising five main sections:
1) Transfusion - Transmitted Disease and its Prevention:
Identification and epidemiology of infectious agents transmissible by blood;
Bacterial contamination of blood components;
Donor recruitment and selection methods;
Pathogen inactivation.
2) Blood Component Collection and Production:
Blood collection methods and devices (including apheresis);
Plasma fractionation techniques and plasma derivatives;
Preparation of labile blood components;
Inventory management;
Hematopoietic progenitor cell collection and storage;
Collection and storage of tissues;
Quality management and good manufacturing practice;
Automation and information technology.
3) Transfusion Medicine and New Therapies:
Transfusion thresholds and audits;
Haemovigilance;
Clinical trials regarding appropriate haemotherapy;
Non-infectious adverse affects of transfusion;
Therapeutic apheresis;
Support of transplant patients;
Gene therapy and immunotherapy.
4) Immunohaematology and Immunogenetics:
Autoimmunity in haematology;
Alloimmunity of blood;
Pre-transfusion testing;
Immunodiagnostics;
Immunobiology;
Complement in immunohaematology;
Blood typing reagents;
Genetic markers of blood cells and serum proteins: polymorphisms and function;
Genetic markers and disease;
Parentage testing and forensic immunohaematology.
5) Cellular Therapy:
Cell-based therapies;
Stem cell sources;
Stem cell processing and storage;
Stem cell products;
Stem cell plasticity;
Regenerative medicine with cells;
Cellular immunotherapy;
Molecular therapy;
Gene therapy.