ABSTRACT
The clinically inactive components are formulation related. Preservative, buffer, and antioxidant changes in generic parenteral drug products are referred to as exception excipients, which may qualitatively or quantitatively differ from the reference product formulation. To demonstrate the similarity of formulation, the sponsor needs to show the equivalent stability of the active ingredient; this may require demonstrating the stability of the originator formulation and the stability of the originator drug substance in the proposed biosimilar formulation. Establishing biosimilarity becomes more complex when the biosimilar developer is forced to adopt a formulation different from that used by the originator. A deep understanding of the formulation of proteins is required to overcome this great hurdle and satisfy the Food and Drug Administration requirements of "no clinically meaningful difference." Various formulation excipients and buffers can be utilized and must, therefore, be chosen to maximize the pharmaceutical quality of the product without introducing significant side effects.
