Biosimilars are biotherapeutic products that are similar to already approved reference biologics in terms of quality, safety and efficacy. They are developed to be highly similar but not identical to existing biologics. Regulatory agencies like EMA and FDA require extensive analytical, non-clinical and clinical studies including pharmacokinetic, immunogenicity and clinical efficacy trials to establish biosimilarity. While biosimilars could increase access and lower costs, issues related to efficacy, safety, substitution and labeling need to be addressed to ensure patient safety and appropriate use.
6. BIOSIMILARS: INTRODUCTION
•A biotherapeutic product similar in quality, safety and
efficacy to an already licensed reference biotherapeutic
product. (WHO, Guideline for Similar Biotherapeutic Products, 2013)
•A Similar Biologic product is that which is similar in terms
of quality, safety and efficacy to an approved reference
biological product. (CDSCO, Guidelines on Similar Biologics, 2016)
•Biological medicine developed to be highly similar and
clinically equivalent to existing biological medicine.(EMA, 2012)
•A biological product highly similar to an FDA-approved
biological product and has no clinically meaningful
differences in safety and effectiveness . (FDA, 2017)
7. The Synonyms…
•Follow-on Biologics (FoBs)
•Follow-on Protein
•Follow-on Biologic Similar Biomedicines
•Subsequent entry biologicals
•SBMP (Similar Biological Medicinal Product)
Biosimilars are not (Bio)generics.
8. How are they manufactured?
1. Develop host cell
2. Establish a cell bank.
No two master cell banks are exactly alike.
3. Protein production
4. Purification
5. Analysis
6. Formulation
7. Storage and handling
9.
10. FACTS AND FIGURES
•>500 million patients helped. (Karpusas M et al. Cell Mol Life
Sci1998;54:1203–1216).
•Biopharmaceuticals - fastest growing segments of
pharmaceutical industry (≈50% of the market).
•Global biosimilars market - $1.3 billion (2013) → $35
billion (2020) (Pharmaceutical Technology. 2015).
•Patent for original products is going to expire.
•418 new biopharmaceuticals being developed.
•↑ healthcare services, hopefully “price war” will ↓
expenditures.
11. [Calo-Fernández B, Martínez-Hurtado J (December 2012). "Biosimilars: Company Strategies to Capture Value
from the Biologics Market". Pharmaceuticals. 5 (12): 1393–1408]
15. THE EUROPEAN SCENARIO
First recommendation in 2005; Revision in 2015.
Europe forerunner in biosimilar legal framework
and regulations.
EMA guideline 2015 recommends a stepwise
conduct of non-clinical and clinical studies.
Non-clinical: binding capability, signal transduction
& potentially relevant differences compared.
16. Before approval, EMA requires studies which should
include:
a) Pharmacokinetic and Pharmacodynamic studies,
b) Clinical trials of appropriate patient populations,
c) Choice of clinical endpoints in efficacy trials,
d) Evaluation of the immunogenicity of the biosimilar,
e) Pharmacovigilance studies
aimed at extrapolating safety and efficacy of the new
biosimilar with respect to the already authorized
branded medicinal product.
19. INDIAN SCENARIO
•Regulatory bodies- Deptt. of Biotech. (DBT), & the CDSCO
– under the MoHFW.
•15th Aug 2016: “Guidelines on Similar Biologics:
Regulatory Requirements for Marketing Authorization
in India”
Salient features –
•If reference biologic not marketed in India, can be licensed
in other specific countries.
•Post-marketing : >200 patients; completed within 2 years.
20. •If immunogenicity evaluated in clinical studies, not
mandatory to carry out in post-marketing studies.
•If pre-approval studies >100 pts; no. of pts for safety data
can be reduced.
22. 2) Safety:
•Concerns regarding immunogenicity.
•Consequences: ↓ or ↑ of efficacy, neutralization of a
native protein & general immune effects (allergy,
anaphylaxis, serum sickness).
•Eg. Pure Red Cell Aplasia (PCRA) by Epoetin α.
•Prone for batch to batch variation. Need for continuous
robust pharmacovigilance monitoring to ensure the
traceability of the products.
23. 3) Substitution:
•↓ safety of therapy, causes therapeutic failure.
•Can confound pharmacovigilance.
•Should be made with physician’s consent.
4) Labeling:
•Labels should be different.
•A summary of product characteristics should be
transparent and clear.
•Reference products should be defined.
•Substitution advice should be provided.
A biosimilar contains a version of an active substance of an already approved biological medicine, which is referred to as the ‘reference medicine’ or ‘originator medicine’. Similarity to the reference medicine in terms of quality, structural characteristics, biological activity, safety and efficacy must be established based on a comprehensive scientific comparability exercise such that they do not have any clinically meaningful differences from the reference medicine in terms of quality, safety and efficacy. European Medicines Agency: Questions and answers on biosimilar medicines, 2012
Concept of SBMP adopted in EU pharmaceutical legislation in 2004
Biologics get a special exclusivity period (but it's basically useless for many drugs)As part of the negotiations that set up the law to allow biosimilars, biotech companies negotiated a 12-year exclusivity period after a biologic drug was approved before biosimilars could come onto the market. That's longer than the five years that small molecules get.
But the exclusivity period runs concurrent to the patents that the companies have on the drug. Since patents run 20 years, only drugs with long development times are going to get approved with less than 12 years of patent time remaining, especially since companies tend to pile on additional patents during clinical development.
FUTURE PROSPECTS:
The legal requirements of approval pathways, the costly manufacturing processes, escalates the developing costs for biosimilars that could be between $75–$250 million per molecule. This market entry barrier affects not only the companies willing to produce them but could also delay availability of inexpensive alternatives for public healthcare institutions that subsidize treatment for their patients.
Even though the biosimilars market is rising, the price drop for biological drugs at risk of patent expiration will not be as great as for other generic drugs; in fact it has been estimated that the price for biosimilar products will be 65%-85% of their originators.
Biosimilars are drawing market's attention since there is an upcoming patent cliff, which will put nearly 36% of the $140 billion market for biologic drugs at risk (as of 2011), this considering only the top 10 selling products.
[Calo-Fernández B, Martínez-Hurtado J (December 2012). "Biosimilars: Company Strategies to Capture Value from the Biologics Market". Pharmaceuticals. 5 (12): 1393–1408]
The 2012–2019 patent cliff. Period of market exclusivity up to date of patent expiration for the ten top-selling biologics for 2011.
[Calo-Fernández B, Martínez-Hurtado J (December 2012). "Biosimilars: Company Strategies to Capture Value from the Biologics Market". Pharmaceuticals. 5 (12): 1393–1408]
Somatropin= Growth Hormone
Omnitrope was the first ever approved biosimilar
EMU is European Monetary
Have a look at the nomenclature according to proposed US guidelines eg-sndz, dyyb, szzs etc
Overall, it is harder to ascertain fungibility between generics and innovators among biologics than it is among totally synthesized and semisynthesized drugs, which is why the name "biosimilar" was coined to differentiate these drugs from small-molecule generics. A simple analogy is that it is harder to say that two wines are "sufficiently interchangeable", because of differences in yeast strain, weather, grape harvest, or terroir, than it is to say that two soda pops are "sufficiently interchangeable" because they contain the same flavoring powder and salts.