Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Similarity and Interchangeability of Biosimilars in Comparison to Generics

Anja Köstner (Abschlußjahr: 2013)

Summary
Language: English
Expenditures for healthcare systems are steadily increasing and leading to a high pressure to make medicinal products affordable in order to ensure access to new medicines for everybody. At the same time the market share of costly biological drugs is rising - offering treatment options for many and severe diseases but also burden the healthcare systems with high treatment costs.
Generic products, cheaper copy versions of small molecule drugs, have widely penetrated the market. But biosimilars, their biological analogues, have not gained as much acceptance in the market.
Generic products can refer to the efficacy and safety data of the innovator product by demonstrating sameness to this reference product. Usually, this is achieved by proving pharmaceutical equivalence and bioequivalence with the reference product. In most cases assessment of pharmacokinetic parameters is sufficient. Sometimes the program may be extended or even shortened if a biowaiver is applicable.
Biologicals cannot be comprehensively characterised due to inherent microheterogeneity and capability of analytical methods. Therefore, for a copy version pharmaceutical equivalence cannot be demonstrated but high similarity to the reference product. In contrast to generics these biosimilars have to complete an extensive similarity exercise comprising an analytical comparability program, comparative non-clinical studies and comparative clinical studies in order to bridge safety and efficacy data of the innovator product.
The comparison with the reference product and proof of bioequivalence of the generic usually leads to accepted interchangeability of the generic with its reference product. Only in some cases concerns remain. This acceptance of interchangeability is used in many healthcare systems to establish substitution policies and herewith reduce prices.
This does not hold true for biosimilars. Even though they have proven in the similarity assessment that no clinically meaningful differences to the reference product exist and they are approved on the basis of bridged safety and efficacy data, concerns remain on their  interchangeability. Especially with regard to immunogenicity all stakeholders are reluctant to accept the concept of interchangeability for biosimilars. Physicians hardly switch patients who are satisfyingly treated with the reference product to the biosimilar and also in healthcare systems substitution is not yet established for biosimilars. The US have already foreseen substitution in the legislation, but detailed guidance is still to come from FDA.
In order to achieve a more extensive market uptake of biosimilars interchangeability should be clearly communicated. As this may only be possible for a certain group of biosimilars directly with approval, additional requirements to receive interchangeability status should be defined. These should reflect knowledge on the molecule, data generated for approval and severity of possible immunogenic reactions and could range from routine pharmacovigilance to additional switch studies.
Substitution may be the next step only and require more experience with biosimilars but could be based on the previously established interchangeability.
The use of biological medicines will increase and so will the health care expenditures. Cost reductions by biosimilars’ market entry will not be as large as with generics due to higher development and manufacturing costs. But to make this progress affordable openness for biosimilars will have to grow as well.
Pages: 62