The term “Follow-on biologics” is often used to refer to biosimilars, and/or biobetters and/or me-too biological products. Biosimilars are medicinal products that contain biological active substances which are demonstrated to be similar in terms of quality characteristics, biological activity, safety and efficacy to already authorized biological drugs (the so-called “reference medicinal products”). The similarity to the reference medicinal products is demonstrated through a comprehensive comparability exercise.
How similar is similar?
Developing a biosimilar drug is absolutely different – and can sometimes be more complex – than developing a ‘regular’ biological drug. For a biosimilar, demonstrating the quality, efficacy and safety of the product is not sufficient – proving similarity to the reference product is an additional requirement. This implies to design the pharmaceutical, nonclinical and clinical studies in a different way, with a different mindset. Also, assessing the degree of dissimilarity between the biosimilar candidate and the reference product and evaluating its impact on the overall development plan can be a challenging exercise.
When does a follow-on biologic become a biobetter?
Some differences can prevent biosimilarity between a reference product and a follow-on version of this product. When a biological drug is structurally and/or functionally altered to achieve an improved or different clinical performance, it may be referred to as a biobetter (or biosuperior). A number of biobetter products are already marketed. As there is no formal regulatory definition for biobetters, they should legally be considered as new biological products. Experience proves nonetheless that certain levels of simplification in their development may be possible based on sound scientific justifications. With new opportunities arising from biologics patent expiry, the potential for growth of the global market for follow-on biologics is unparalleled.
Key challenges encompass:
- Regulatory positioning and strategy
- CMC comparability plan
- Quality Target Product Profile (QTPP)
- Manufacturing strategy, Quality-by-Design (QbD) and scale-up
- Development and validation of bioassays for potency and test release
- Comparative development plan (nonclinical and clinical)
- Interpretation of CMC, biological and clinical differences between product in development and reference product
- Reference standard strategy
- Pricing strategy and reimbursement optimization