Formulation and Administration of Biological Medicinal Products".

Monoclonal antibody (Mabs) containing medicinal products are widely used in clinical practice. Prior to parenteral administration, licensed Mab containing medicinal products are transferred to the ready-to-administer (RTA) forms. Reconstitution and/or preparation should follow the guidelines for Good Reconstitution/Good Preparation Practice. Preparation in the pharmacy must take place within the framework of a suitable quality management system. The responsible pharmacist must apply a risk assessment on the process to ensure the appropriate quality of the RTA preparation, especially because the extent of quality testing is limited by batch size (often one single unit) and time restraints. In these cases, appropriate quality is to be assured by means of qualification activities, environmental monitoring, process validation with growth medium and in-process controls. Correct labelling of the Mab containing RTA preparations includes a suitable storage advice and a defined shelf life. Physicochemical stability of a given Mab preparation can be assessed based on a specific stability study (supplied by the manufacturer in the SmPC or scientific journals, study published by an expert in a peer-reviewed scientific journal). Physicochemical stability studies require the use of various orthogonal physicochemical methods to detect accurately the degradation changes that may result from the deamidation, oxidation, disulfide formation, aggregation or fragmentation during storage. Complementary, biological activity can be measured. Compatibility studies of Mabs and devices used for preparation and administration are still scarce. Microbiological stability of Mab preparations is related to the complexity of the preparation process, the growth supporting nature of the preparation and the integrity of the container or container/closure combination. In use viability tests revealed that the potential of Mab preparations to support microbial growth was similar to that of the pure vehicle solutions used as control solutions. The enumerated microbial counts varied according to the species utilized and the type of Mab preparation. If sterility testing of the individual preparation is impossible, maximum permitted shelf life can be assessed empirically with regard to the maximum shelf lives defined in the USP <797> monograph. Finally, microbiological and physicochemical stability are to be considered concurrently when determining the shelf life of an individual Mab preparation. In each case, shelf life should be limited according to the shorter period of proven stability, either derived from the microbiological or physicochemical stability data.