Number of Biosimilars Available
14
Country Spotlight: EU
The European Union is a politico-economic union of 28 member states: Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Italy, Ireland, Latvia, Lithuania, Luxembourg, Malta, the Netherlands, Poland, Portugal, Romania, Spain, Slovakia, Slovenia, Sweden and the United Kingdom.
The European Medicines Agency (EMA) is responsible for the scientific evaluation of medicines developed by pharmaceutical companies for use in the EU.
Biosimilars Available
As of April 2016, there are 14 biosimilars approved for use in the EU:[1][2]
- Two medicines used to treat anemia in patients with chronic kidney failure or anemia due to chemotherapy (epoetin alfa and epoetin zeta, marketed regionally under 5 different brand names)
- Four medicines used treat a low white blood cell count due to chemotherapy, HIV or chronic conditions that cause a low white blood cell count; or to mobilize stem cells for transplantation (filgrastim, marketed regionally under 6 different brand names)
- Two medicines used treat a low white blood cell count due to chemotherapy (filgrastim)
- Insulin used to treat diabetes (insulin glargine)
- Two medicines used for in vitro fertilization (follitropin alfa)
- A growth hormone used to treat patients with growth deficiencies (somatropin)
- A medicine used to treat Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis Ulcerative Colitis, and Crohn’s Disease, (infliximab, marketed regionally under two different brand names)
- A medicine used to treat Axial Spondyloarthritis, Psoriatic arthritis, Plaque Psoriasis and Rheumatoid Arthritis (entanercept)
Score Overview
EU is Fully Compliant.
The overall score for the EU is 3.87/5. This means the EU guidance is partially or fully compliant with the WHO in most areas, in a few areas exceeds the WHO standards, and in some areas do not meet the WHO standards.
The graph below shows individual scores by each of the 28 components of biosimilar policy
There are seven areas where the EMA is not as specific as the WHO, being either non-compliant, minimally compliant, or partially compliant with the WHO biosimilar policy.
Scores by measured component
Gaps
Gap 1
Scope:
The EMA does not mention that DNA-derived therapeutic proteins are in scope, or that the biologics should be well established or well characterized. Vaccines can be considered for approval through the biosimilar pathway in the EU, while they are specifically excluded in the WHO guidances.
Gap 2
Reference Product:
When comparing the biosimilar to the original medicine, the EMA guidances do not specify that the same host cell should be used to produce the medicine.
Gap 3
Quality/Analytical, Biological Analysis:
The EMA guideline states that a comparability exercise should asses the biological properties of the biosimilar and the original biologic, not that this is a necessary step. .
Gap 4
Quality/Analytical, Immunological Analysis:
The EMA does not provide as much detail as WHO regarding how to compare immunogenicity between the biologic and the biosimilar
Gap 5
Quality/Analytical, Stability Studies:
The EMA does not require head to head studies to evaluate the stability of the biosimilar as compared with the original biologic
Gap 6
Naming:
When considering how to name biosimilar products such that clear product identification is possible, the EMA do not provide an appropriate level of specificity.
Gap 7
Labeling:
The EMA does not require biosimilar manufacturers to include the same level of transparency in the product label as the WHO.
Overall country score as compared to peers
History of Policy
The EMA were the first region to develop overarching biosimilar guidances in 2004, which were formally adopted in 2005. These have been updated and revised, with the most recent versions becoming effective in 2015. Additional guidelines have also been developed tackling specific issues related to biosimilar approval.
Many other countries have relied heavily on the EU guidances as a template for the development of their own biosimilar policies, eg Japan, or even adopted them wholesale, eg Australia.
Policy Guidelines
Overarching Guidelines
Guideline on similar biological medicinal products
- This guideline outlines general principles for demonstrating biosimilarity
- First issued June 2004; Most recent update April 2015
- This guideline gives advice on the quality requirements after a change occurs in the manufacturing process
- First issued February 2006; Most recent update December 2014
- This guideline describes the non-clinical and clinical requirements for demonstrating biosimilarity
- First issued February 2006; Most recent update July 2015
Specific Biosimilar Guidances
Immunogenicity assessment of monoclonal antibodies intended for in vivo clinical use
- This guideline addresses issues related to the unwanted effects on the immune system of monoclonal antibodies (mAbs) intended for clinical use.
- First issued December 2012; Most recent update December 2012
Immunogenicity assessment of biotechnology-derived therapeutic proteins
- This is a draft guidance that contains a list of issues to be considered when assessing the possible effects that biosimilars can have on a patient’s immune system
- First issued December 2007; Most recent update October 2015 (consultation period for the update ended Jan 2016)
- This guideline gives advice on the non-clinical and clinical requirements after a change occurs in the manufacturing process
- First issued December 2003; Most recent update November 2007
Medicine Specific Guidances
- These guidelines describe the non-clinical and clinical requirements for demonstrating biosimilarity for specific medicines
Similar biological medicinal products containing recombinant follicle-stimulating hormone
- First issued September 2013; Most recent update September 2013
Similar biological medicinal products containing interferon beta
- First issued September 2013; Most recent update September 2013
- First issued December 2012; Most recent update December 2012
Similar biological medicinal products containing recombinant erythropoietins
- First issued September 2010; Most recent update September 2010
- First issued July 2006; Most recent update July 2006
- First issued July 2013; Most recent update July 2013
Similar biological medicinal products containing low-molecular-weight heparins
- First issued October 2009; Most recent update October 2009
- First issued April 2009; Most recent update April 2009
- First issued July 2015; Most recent update July 2015
- First issued July 2006; Most recent update July 2006
- First issued July 2006; Most recent update July 2006
- First issued July 2006; Most recent update July 2006
- First issued September 2015; Most recent update September 2015
- Note: date of first issue refers to the date the guideline received final approval from the Committee for Medicinal Products for Human Use. Most recent update refers to the date the most recent version of the guideline came into effect.
Side by side comparison of each of the score components
For each of the 28 components of biosimilar policy evaluated, the specific wording in the FDA's biosimilar policy is listed, alongside the accompanying wording in the WHO policy (shown in the blue box).