In Vivo Recovery and Survival of Monoclonal-Antibody-Purified Factor VIII Concentrates

Abstract

SummaryIn response to reports of discrepant in vitro assays of high-purity concentrates, a double-blind crossover study of in vivo recovery and half-life of two brands of monoclonal-antibody-purified factor VIII concentrates (Monoclate and Hemofil-M) was performed in 23 patients with hemophilia A. In vivo recoveries were close to values predicted from the labelled unitage when plasma samples were assayed by a one-stage method. When a two-stage assay was used, lower recoveries were calculated and the recovery with Hemofil-M was slightly but significantly lower than that with Monoclate. The concentrates were re-assayed in vitro by the two-stage method. Monoclate (which is assayed by the manufacturer using a two-stage method) contained 97% of the labelled potency and Hemofil-M (which is assayed by the manufacturer using a one-stage method) contained 81% of the labelled potency. Differences in in vitro and in vivo assay methods contribute to disparities between expected and observed factor VIII recovery. Clearance of Hemofil-M was significantly faster than that of Monoclate, but volume of distribution at the steady state, mean residence time, and plasma half-disappearance times of the two concentrates were not significantly different.

Response to commercial factor VIII concentrate

“…These authors indicated that the Heniofil-M product did contain activated Factor VIII [ 11. Similar results were obtained in a more recent study using in vitro assays of Factor VIII vials as well as in vivo recoveries of these products [2]. With regard to the internal assay standard, ARUP did not use the MEGA I standard; however, we do not believe that this alone would explain the discordant results.…”

Allometry of Factor VIII and Informed Scaling of Next-Generation Therapeutic Proteins

“…The complete set of collected data is summarized in Table 1. A total of 60 publications were included representing mice, dogs, and humans with HA as well as normal mice, rats, rabbits, and monkeys 7–11,14–16,25–76. A summary of the NCA derived PK parameters CL, V ss , MRT, and half‐life ( t 1/2 ) are presented in Table 2.…”

Obtenção e caracterização de anticorpo monoclonal murino anti-fator VIII da coagulação sangüínea

“…A partir daí iniciaram-se inúmeras pesquisas com o objetivo de introduzir novos produtos na terapêutica da hemofilia. [3][4][5][6][7][8][9][10][11][12] …”

“…A partir daí iniciaram-se inúmeras pesquisas com o objetivo de introduzir novos produtos na terapêutica da hemofilia. [3][4][5][6][7][8][9][10][11][12] As novas técnicas de engenharia celular e biotecnologia avançaram muito nas últimas décadas e entre elas a produção de anticorpos monoclonais utilizados tanto para o aprimoramento diagnóstico em rotinas laboratoriais como na produção de medicamentos e purificação de proteínas utilizadas na terapêutica. [13][14][15][16][17] Os concentrados de FVIII purificados através de anticorpos monoclonais (denominados produtos ultrapuros) colocados no mercado no início dos anos 90 vieram solucionar complicações desastrosas no tratamento da hemofilia, pois se trata de terapêutica eficaz e segura apresentando alta especificidade, segurança viral e redução de efeitos colaterais.…”