A biosimilar is defined as “a biological medical product that contains a version of the active substance of an already authorized original biological product”. Development of a biosimilar cannot follow the established generic regulatory pathway, because biological drugs have extremely complicated structure and character, and to produce the exact same molecule as an original biological product. Although a biosimilar molecule is not exactly same to that of its original product, high level similarity between them in terms of quality characteristics, biological activity, efficacy, and safety must be demonstrated for approval.
- (1) Production process establishment
- Biosimilar makers must establish their unique production process which includes cell line, culture condition, and purification methods, since those of an original product are not disclosed.
- (2) Analytical characterization and in vitro comparability
- Character and quality of a biosimilar in many aspects are analyzed by means of latest techniques. In order to prove comparability of a biosimilar to an original product, these analyses are required to be carried out in enough number of production lots. Therefore, much larger amount of analytical data is required for development of a biosimilar, compared to those required for an innovative biological drug.
- (3) Non-clinical study
- Comparability of biological character between a biosimilar and its original product is proved in non-clinical tests. Biological activities concerning to therapeutic effects of a biosimilar are proved to be comparable to those of its original product in many non-clinical studies such as biochemical tests and pharmacological tests using animal models.
- (4) Clinical study
- For approval of a biosimilar, clinical studies are required in addition to non-clinical studies. Comparability of pharmacokinetics/pharmacodynamics between a biosimilar and its original product is also proved in phase 1 clinical studies. After that, phase 3 clinical studies, which are not required for development generic drugs of small molecular drugs, are carried out to demonstrate their biosimilarity with respect to efficacy and safety in therapeutic indications for which its original product has been approved.
For all these reasons, much higher expense and time period are required in addition to highly advanced technology for development of a biosimilar compared to that of a small molecular generics drug.