title: An approach to study the viral safety of plasma-derived products in previously treated, non-infected patients.
abstract: Using the polymerase chain reaction (PCR), we designed a study concept to evaluate the safety of plasma derivatives in previously treated patients who are non-infected by the specific viruses studied. Several product lots can be studied in a single patient, with a study period for each lot of 3 months. In the present study 19 patients were included for treatment with Baxter Hyland Immuno's PCR-screened factor VIII concentrate Immunate (n=7), factor IX concentrate Immunine (n=10), the by-passing agent FEIBA plus Immunine (n=1), and the protein C concentrate Ceprotin (n=1). PCR testing for hepatitis B, C or HIV genomic material in patient samples was done as well as serological testing. All patients remained negative for the tested markers. All seven Immunate patients completed three treatment periods with three different lots of the study drug. The median study period was 282 days and the median dose 115 000 units, with a median of 115 exposure days. Five of the 10 Immunine patients completed three treatment periods and four patients, two treatment periods. One Immunine patient was discontinued from the study for reasons unrelated to the study drug administration. The median study period was 305 days and the median total dose 82 200 units, with a median of 88 exposure days. Our study presents a new design to approach the evaluation of viral safety of new plasma derivatives in previously treated, non-infected patients (NIPs) and offers several advantages over the currently recommended studies using testing for serological markers of infection in previously untreated patients (PUPs).
authors.affiliation: Department for Coagulation Disorders, Lund University, University Hospital, Malmö, Sweden. erik.berntorp@medforsk.mas.lu.se
authors.forename: E
authors.initials: E
authors.lastname: Berntorp
authors.forename: P
authors.initials: P
authors.lastname: Petrini
authors.forename: G
authors.initials: G
authors.lastname: Dockter
authors.forename: L
authors.initials: L
authors.lastname: Tengborn
authors.forename: I
authors.initials: I
authors.lastname: Wendisch
authors.forename: W
authors.initials: W
authors.lastname: Eberl
authors.forename: V
authors.initials: V
authors.lastname: Aumann
authors.forename: G
authors.initials: G
authors.lastname: Frade
authors.forename: I
authors.initials: I
authors.lastname: Seliger
authors.forename: W
authors.initials: W
authors.lastname: Engl
authors.forename: H
authors.initials: H
authors.lastname: Ehrlich
mesh_terms: D001779:Blood Coagulation Factors / Q000009:adverse effects / Q000627:therapeutic use*; D006467:Hemophilia A / Q000150:complications / Q000188:drug therapy*; D002836:Hemophilia B / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D011486:Protein C / Q000009:adverse effects / Q000627:therapeutic use*; D014777:Virus Diseases / Q000175:diagnosis / Q000517:prevention & control / Q000635:transmission
chemical_list: D001779:Blood Coagulation Factors; D011486:Protein C