The first biosimilar in Europe was approved in 2006. As of date, Europe has released the highest number of biosimilars in the world and EMA was well acquiped with the knowledge on safety and efficacy of biosimilars.
Sice the biosimilars are produced in the living organisms, a slight change is expected. But the biosimilar should have same efficacy, safety and quality compared to the reference compound.
The manufactuer of the biosimilar should submit comprehensive compartitve studies comparing with reference compound.
If biosimilar has similar activity, safety compared to reference compound in one condition, then the biosimilar can be indicated for the other indications for which the reference compound was indicated.
Though the clinical trials are not required for extending the indication, comprehensive scientific evidence is required.
Regular pharmacovigilance studies are conducted for the purpose of safety.
Overview of biologics
Biologics are large molecules and their characterisation includes use of protein mapping, MS analysis and assays in cells. Control over the safety of the biologics is important.
Biosimilars are the compounds that are ‘hgihly similar’ to the reference compound. Manufacturers can make the biosimilars after patent expiry of the refence compound (genraally 10 years). Biosimilars may have slight variations in the structure compared to the reference comdpound, but these variations do not cause much change with respect to the safety and efficacy of the biosimilar.
There are certain characterstic features of the biosimilars that include
1. They are highly similar with reference compound with slighly changes which does not effect the safety and efficacy of the biosimilar
2. The changes should be minor, which is similar to the changes that are observed between the different batches of the reference compound
3. The quality should be same as reference compound
The protein should have same amino acid sequence and 3D structure.
Biosimilars will have same posology, route of administration as reference compound.
Different classes of biosimilars that are approved in EU
Polysaccharides: Enoxaparium sodium
Growth factors: Epeotin, Filgrastim
Hormones: Follitropin alfa, Insulin, somatotropin, teriparatide
Monoclonal antibodies: Adalimumab, Infliximab, Rituximab
Fusion protein: Etarncept
Biosimilars are not generic compounds
Biosimilars are not generic compouns. Generics are smaller molecules with less complex structure. However biosimilars have more complex structure and need more studies in order to establish their safety and efficacy.
Approval of biosimilars
Most of the biosimilars are approved centrally with onjly few heparins were approved at country level.
CHMP and PRAC will approve the drugs once the manufactuer submits approval from EMA.
There involves the 3 steps for theapproval of biosimilar
Step 1: Quality studies: Physical and chemical properties, safety and efficacy need to be proved
Step 2: Pharmacodynamic and toxicology studies are to be submitted
Step 3: Clinical studies: Pharmacokinetic, pharmacodynamic, efficacy, safety and immunogenecity need to be proved
Clinical trials comparing the safety and efficacy with the reference compound need to be submitted for the approvals of the biosimilars.
There is no need conduct all the pivotol trials for the biosimilar approval. However, the trials are conducted to check the differences if any in the safety, efficacy , immunogenicity and pharmacokinetic studies. Health population can be considered for conducting PK studies.
Immunogenecity is common study for all the biological compounds.
EMA report on biosimilars (http://www.ema.europa.eu/docs/en_GB/document_library/Leaflet/2017/05/WC500226648.pdf)