Critical Quality Attributes

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

A deep understanding of the critical quality attributes of a reference product - how each attribute, alone and in concert with other attributes, impacts safety, efficacy (strength), pharmacokinetics (how the drug moves through the body), and overall quality – is fundamental to producing a high-quality biosimilar.


Like a human face, a biologic drug is enormously complex and has a large number of features.  For the biologic, we call these attributes, and there are typically a hundred or more. 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.  Features important to these functions are known as “critical quality attributes.” These critical quality attributes include structures that are determined both by the DNA used and by the cell line and manufacturing process. An understanding of which attributes are important to each function for each product is important in order to obtain the best possible match. This knowledge enables scientists to develop high-quality biosimilar products. 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.

Just like these pictures slightly differ, so will a biosimilar to its reference product.

Scientists and doctors are constantly learning more about human biology and the medicines used to treat patients. These medicines generally have three types of attributes: those known to be critical to molecule function (critical quality attributes), those known to be unimportant to molecule function, and those scientists are unsure about. One complicating 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.  This is when 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 nearly 100 attributes of a reference product and assess, for each attribute, the importance of matching the attribute to produce a high quality biosimilar.

Evaluating Critical Quality Attributes for Biosimilarity

Glossary
A Critical Quality Attribute

High mannose type glycans (carbohydrate structures) are often a critical quality attribute. This attribute reduces the amount of time the drug stays in the body. This attribute can also be important for how a biological medicine functions and treats a particular disease. To have similar efficacy, safety and immunogenicity to a reference product, a biosimilar needs to match all critical quality attributes.

Criticality Unclear

Afucosylated-type glycans (carbohydrate structures) are sometimes critical quality attributes. Depending on the biological medicine and the disease being treated, this attribute may be important, not important, or of unknown importance to biological function.  When scientists have not yet determined if the attribute is important, biosimilars should match the attribute to limit risk to the patient.

Not a Critical Quality Attribute

The last amino acid that a cell adds to an antibody remains there only temporarily and is later removed by the cell. It is acceptable for a biosimilar to have differences in this amino acid, as it does not impact how the antibody functions or how it moves through the body.