Biosimilars offer patients broader access to known therapies called reference biologic medicines. Unlike generics, which have simple chemical structures, biosimilars are not expected to be identical medicines to the reference products. Because biosimilars will have minor differences, a robust data package of analytical, pharmacological and clinical data is critical to demonstrate similar quality, safety and efficacy to the reference product.1 Moreover, biosimilars made by different manufacturers will differ from the reference product and from each other, making each biosimilar a unique therapeutic option for patients.2
Because of the structural and molecular complexity of biologic medicines, developing and manufacturing high quality biosimilars requires deep scientific and manufacturing expertise. The first step in developing a biosimilar is to select the right cell line to produce the right clone. This demands an intimate understanding of the reference product and how it works in the body. A biosimilar must be shown to be similar to the reference biologic on the basis of 1. analytical (testing in a lab for structural/physical similarity), 2. non-clinical (testing for function/activity/toxicity) and 3. clinical data (testing in humans for safety and efficacy) in terms of structural characteristics, safety and efficacy.
Regulatory agencies may have different requirements regarding the amount of analytical, non-clinical and clinical data necessary to prove analytical similarity and comparable safety and efficacy. Additionally, minor differences with the active ingredient are expected and permitted so long as any such differences are demonstrated not to have a clinically meaningful effect in patients.
Complexities in Manufacturing Affecting Quality of Biosimilars
Beyond demonstrating similarity, having high quality manufacturing capabilities is another critical aspect to bringing safe and effective biosimilars to a patient. The manufacturing process for any biologic, including biosimilars, needs to account for variability. Each step in biologic manufacturing is intricate, sensitive and often specific to a particular medicine since they are produced in living cells. Even minor alterations may lead to changes in the biologic’s structure, stability or other quality aspects of the end product. The complexity of biologic manufacturing requires significant expertise and finely tuned processes and procedures to ensure high quality final products for patients every time.
The patents of a growing number of biologic medicines are due to expire over the next few years, which has led to an increased interest in development of biosimilars. Biosimilars are more affordable therapeutic options, but, given the complexity and cost of development and manufacturing, are not expected to generate the same level of cost savings as generics. Amgen brings more than 35 years of biologics experience and manufacturing expertise that will assist in developing high quality, consistently and reliably supplied biosimilars in order to benefit patients in need of therapeutic alternatives.
Similar to snowflakes, biosimilars from different manufacturers differ from their reference biologic medicine and from each other. It is critical to understand the differences and to demonstrate that they are not clinically meaningful and thus can be expected to be as safe and effective as the reference product for that approved condition of use.
Biosimilars cost $100 to 250M and take 7 to 8 years to develop
Small molecule generics cost $2 to $3M and take 2 to 3 years to developGlossary