Critical Quality Attributes

Matching biological function and critical quality is the art of biosimilar development.1

The critical quality attributes of a reference product—how each impacts safety, efficacy, pharmacokinetics, and overall quality—is fundamental to producing a high-quality biosimilar.2

A biologic drug is extremely complex and typically has one hundred or more features or “attributes.” Some of these attributes are important to the different ways the body can recognize proteins and are therefore critical to the safety, efficacy, and pharmacokinetics of the drug. These are known as “critical quality attributes.” 

An understanding of which attributes are important to each function for each product is important in order to obtain the best possible match. Some attributes work individually to drive a function, and some work in a composite manner. A biosimilar will not be exactly like its reference product and some features will not match, but the critical quality attributes need to match so that the biosimilar medicine and the original biologic work in the same way, that is, have the same biological function for every patient. Similarly, structural match is also desirable, but it is feasible to not have a precise structural match while still preserving function. 

Just as the features of the face below differ slightly, so will the features or attributes of a biosimilar differ from its reference product.


In addition to “critical quality attributes,” biosimilar medicines have attributes that are known to be unimportant to molecule function, as well as attributes that scientists are unsure about. 

One extremely important factor in biosimilar development is understanding which attributes are most important to match where the biology is unclear. This is the art of biosimilar development and Amgen is able to draw from its more than 35 years of biologics experience to better understand where it is critical to match the reference product to ensure that the biosimilar medicine works as intended.

Scientists evaluate more than 50 attributes of a reference product and assess, for each attribute, the importance of matching the attribute to produce a high–quality biosimilar.2,3

References:

  1. Kozlowski S. US FDA Perspectives on Biosimilar Biological Products. Presented at 2014 Biotechnology Technology Summit; June 13, 2014; Rockville, MD.
  2. US Department of Health and Human Services. Q8(R2) pharmaceutical development. http://www.fda.gov/downloads/Drugs/.../Guidances/ucm073507.pdf. Accessed November 23, 2016.
  3. Holzmann J, Balser S, Windisch J. Totality of the evidence at work: The first U.S. biosimilar. Expert Opin Biologic Ther. 2016;16:137-142.