Development challenges and validation of fill and finish processes for biotherapeutics
INTRODUCTION The therapeutic antibodies presently sold on the international markets are all administered via parenteral route, that is, by subcutaneous or intramuscular injection or intravenous infusion, with one product injected into the vitreous humor of the eye (Table 1). Approximately, twothirds of these preparations are liquid-stable preparations with 1 to 100 mL nominal volume; one-third of the preparations are marketed as lyophilized powder for reconstitution. With this selection of routes of application and dosage forms, it becomes quickly clear that the manufacturing procedure of choice for therapeutic antibody products is a liquid filling process under aseptic conditions, optionally with an additional freeze-drying process directly in the vial. Sterilization in the final container is practically excluded because of the thermolability of proteins.