Role of public standards in the safety and efficacy of biologic medicines

Abstract

In this report, we emphasize the importance of public monographs with reference materials, coupled with careful process and change control and attention to GMPs, as a means of advancing access to good quality, safe, and effective medicines, with emphasis on available and incoming biologic medicines. With adequate control of articles covered by a monograph, these public standards can form the basis for a global public quality platform that covers reference products, non-interchangeable reference products, biosimilars, and interchangeable biosimilars. Working collaboratively with all stakeholders, new approaches allow these public standards to emerge nationally and globally in a timely way. Yet, there are increasing limitations in the availability of public standards for biologic medicines, which may reverse many decades of progress. Solutions are considered in this report.

Fig. 1

Four categories are emerging globally for a biologic product: (1) reference product, (2) one or more non-interchangeable reference products, (3) one or more biosimilar products to each reference product, and (4) interchangeable biosimilar reference products (USA only). All can be linked via common unitage traceable to an available WHO biological reference material with specified unitage. For categories 1 and 2, clinical trial designs might be based either on demonstrating a difference (two-sided) or non-inferiority (one-sided). For categories 3 and 4, designs are based on demonstrating similarity with criteria for population or individual equivalence. The dark shaded area in the figure denotes varying degrees of intellectual property protection via either patent or exclusivity, ranging from none to a minimum of 12 years exclusivity in the USA via BPCIA

Fig. 2

General chapters in the pharmacopeia, sometimes termed horizontal standards, can support public or private specifications for non-interchangeable biologic reference products and/or for biosimilars

Fig. 3

Assuming one reference product (RP), one follow-on non-interchangeable reference product (NI-RP), and two biosimilars for each, coupled with a further decision of interchangeability for each, a name might signal up to 10 regulatory decisions, e.g., 1 [NAME]-RP1; 2 [NAME]-RP2 (non-interchangeable); 3, 4 [NAME]-BS1 and [NAME]-BS2 to RP1; 5,6 [NAME]-BS1 and [NAME]-BS2 to RP2; and 7, 8, 9,10 signal interchangeability for each biosimilar