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Introduction

Biological medicines including biosimilar medicines are highly complex, protein based medicines, made or derived from living organisms typically using recombinant DNA technology. Proteins are usually much bigger in size than medicines produced by chemical synthesis and have a higher complexity and variability than small chemical compounds. They can be tailor made so they bind to specific targets in the body.

Biosimilar medicines are biological medicines that have been developed to be highly similar and clinically equivalent to an existing biological medicine and are marketed after the expiry of the patent on the originator or reference biologic. Biosimilar medicines are comparable to their reference product as they have demonstrated no clinically meaningful differences in safety, efficacy, quality, structural characteristics and biological activity compared to that of the reference biologic.3

Biosimilar medicines are much more expensive and take longer to develop than a traditional generic.26

Treat complex and long term conditions

Typically biologics including biosimilars, are used to treat long term and complex conditions such as cancer, rheumatoid arthritis, psoriasis, Crohn’s disease and growth disorders. Worldwide, over 650 biologics have transformed the lives of over 350 million patients suffering from more than 100 diseases.2 

As a result of their complexity, biological medicines including biosimilars are considerably more expensive to develop and manufacture than conventional medicines. This can make it difficult for the NHS to afford these medicines and can limit patients' access to them.23 

Regulated to the same standards of safety, quality and efficacy as originator medicines

By definition, biosimilars are required to have the same amino acid sequence, as the reference products and to demonstrate high purity, and highly similar analytical and functional properties, pharmacokinetics / pharmacodynamics (PK/PD), clinical efficacy (potency) and safety, including immunogenicity.1,3,17

The European Commission (EC) has clearly expressed its confidence in the quality and consistency of biosimilars. In their 2013 consensus information document 'What you need to know about biosimilars' the EC states that “biosimilar medicinal products have been used safely in clinical practice in the European Union since 2006 and their market share has been growing at different rates across both EU member states and product categories.”17

The regulatory process for biosimilar medicines is fundamentally different than for generic products which require very limited  clinical development.  In the case of biosimilar medicines, the European Commission issues specific guidelines for each product which specify the procedures, including appropriate clinical trials, to be performed  in seeking regulatory approval of the product.  The main part of the evaluation is a detailed head to head comparison of the biosimilar medicine with its reference medicine to show there is no clinically significant differences between them. The size and duration of the clinical trials is set after a rigorous scientific advice process with the European Medicines Agency. The biosimilar pathway does not need to demonstrate safety and efficacy in each indication as this is done by reference to the originator product which has already satisfied these requirements. 6,16

Regulatory approval

Biosimilars are approved via stringent regulatory pathways so that they may be launched following loss of exclusivity of their originator reference products.4,5,11,12,13,14. The scientific review within EMA is carried out by the Committee for Medicinal Products for Human Use (CHMP), who take advice from the Biosimilar Medicinal Products working party. The UK medicines regulator MHRA, plays a leading role within CHMP and provides UK experts to carry out scientific assessment and be part of the decision making process.  The scientific and regulatory principles for demonstrating that biosimilars have no clinically meaningful differences to their reference product build on those used for assessing changes in the manufacturing process of a given biologic.8,9,10 These comparability principles have been in place for more than 25 years to address manufacturing changes and have been demonstrated to work.

Since 2006, biosimilars have been used effectively in clinical practice in the UK and other European countries where they are already making an impact in terms of cost-savings and patient access.7

Biosimilars are approved by regulators across the world, including the EU, only if they have demonstrated comparability to the originator product in terms of safety, efficacy and quality through an extensive and iterative comparability exercise, based on strict guidelines set by the authorities.4,5,11,12,13,14  Regulators such as EMA and FDA will only approve biosimilars for which companies provide information which allows them to conclude that there are no clinically meaningful differences between the reference product and the biosimilar.3,4,5

Competition, cost reduction and innovation

The use of biosimilar medicines offers the opportunity for increased access to these important medicines and by creating competition, reducing cost.20 Competition also provides an incentive for originator companies to develop new biological medicines; and biosimilars themselves maybe associated with additional patient support services.

For example, data based on 2010 usage of human growth hormone (hGH) at The North Central London Formulary and Medicines Management Group at University College London Hospitals NHS Trust suggests, annual cost savings in excess of £200,000 per annum are possible from a single centre if all patients were switched from originator hGH to biosimilar hGH.15,21 Savings generated through biosimilars can be reallocated in the same disease area to help fund access to recent innovative products or help fund access in other disease areas.19

The cost saving due to competition from biosimilar medicines and the resultant reduction in cost per Quality Adjusted Life Year (QALY)24 may lead to biosimilar medicines being approved by Health Technology Appraisal agencies when the pricing of the equivalent originator product was found not to be cost-effective for example, NICE approval of biosimilar infliximab in Ankylosing Spondilitis in February 2016.25

There is thus scope for biosimilar medicines not just to save the NHS money which can be made available to fund other treatments but also to make specific medicines available to patients within the NHS which might otherwise not be approved for use. 

Biosimilars will usually form part of a NICE multiple technology appraisal (MTA) alongside their reference products, in the indication under consideration.The Department of Health has confirmed that a technology appraisal remit referred to NICE enables NICE to decide to apply the same remit, and the resulting guidance, to relevant licensed biosimilar products which subsequently appear on the market.18 

References

1. Schneider CK, et al. Setting the stage for biosimilar monoclonal antibodies. Nat Biotech 2012;30:745–748
2. EuropaBio: Guide to Biological Medicines- A Focus on Biosimilar Medicines, Oct 2011
3. Weise M, et al. Biosimilars: what clinicians should know. Blood 2012;120(26): 5111–7
4. EMA Guideline on “Similar biological medicinal products containing biotechnology-derived proteins as active substance: non-clinical and clinical issues, EMEA/CHMP/BMWP/42832/2005 Rev. 1. Available for download here; accessed 20th January, 2015
5. FDA Draft Guidance for Industry: Scientific Considerations in Demonstrating Biosimilarity to a Reference Product. FDA, February 2012. Available for download here: accessed 20th January, 2015 
6. What is a biosimilar medicine? Guide. NHS England Medical Directorate 24 September 2015. Available for download here 
7.
EC Consensus document: What you need to know about biosimilar medicinal products. Please click here to access.
8. EMA guidelines on “Similar biological medicinal products containing biotechnology-derived proteins as active substance: quality issues”. EMA/CHMP/BWP/247713/2012. Available for download here 
9. US Food and Drug Administration Guidance: Demonstration of Comparability of Human Biological Products, Including Therapeutic Biotechnology-derived Products, Center for Biologics Evaluation and Research (CBER), Center for Drug Evaluation and Research (CDER) April 1996. Available for download here
10. International Conference on Harmonisation. ICH Q5E: Comparability of Biotechnological/Biological Products Subject to Changes in Their Manufacturing Process. Available for download here
11. Authority of the Minister of Health. Guidance for Sponsors: Information and Submission Requirements for Subsequent Entry Biologics (SEBs); Health Canada: Ottawa, Canada, 2010. Available for download here
12. MHLW. Guidelines for the Quality, Safety and Efficacy Assurance of Follow-On Biologics; MHLW: Tokyo, Japan, 2009.
13. Arato T. Recent regulations of biosimilars in Japan. Pharmaceuticals and Medical Devices Agency. 47th Annual Meeting, DIA 2011; 2011 Jun 19–23, Chicago, USA
14. PPDI Whitepaper: 'Developing Biosimilars in Emerging Markets: Regulatory and Clinical Considerations', 2013: Available for download here
15. Drug appraisal. Assessing the efficacy and safety of Omnitrope, British Journal of Clinical Pharmacy 2010; Volume 2 pg. 298-301, 2nd November 2010
16. Blood Biosimilars: The Science of extrapolation Nov 20 2014: Blood 124(22)
http://www.bloodjournal.org/content/124/22/3191?sso-checked=true

17. European Commission, Enterprise and Industry Directorate-General. Consensus Information Paper 2013. What you need to know about Biosimilar Medicinal Products. 2013 [cited 2014 Feb 7]. Available for download here
18. NICE 's position on biosimilars available here 
19. GfK EGA Sustainability Study 2014 September 9, Pg. 36
 20. Delivering on the Potential of Biosimilar Medicines, IMS, March 2016. Available here

21  Lessons learnt can inform the use of a new generation of biosimilar products, The Pharmaceutical Journal, June 2011. Available here

22  Biosimilars and inflammatory bowel disease: a switch programme using CT-P13, The Pharmaceutical Journal, September 2016. Available here

23 EC Consensus document: What i need to know about biosimilar medicines: Information for patients. Available here

24 NICE glossary for QALY Available here

25 NICE Technology Appraisal guidance, TNF-alpha inhibitors for ankylosing spondylitis and non-radiographic axial spondyloarthritis, 1st February 2016; please click here to access

26 Future Focused Finance Available here ​