Development and Execution of In Vivo Bioassays
January 8, 2022
Veeda through its V-Konnect series interacted with Dr. Susobhan Das and discussed about
“Current outlook of Biosimilar Development”
About the V- Konnect
V-Konnect interview series, is a program to get in touch with specialized industry experts to know their views on opinions on current relevant subject matters.
About Dr Susobhan Das – Founder & CEO at Amthera Life Sciences
Dr. Das is a Founder & CEO of Amthera Life Sciences Pvt. Ltd which is a preclinical stage Biosimilar Drug development company based at Bangalore.
Dr. Das has extensive techno-commercial experiences in early stage Biologics Development. He has 20 years of experience in advanced biotechnology research and Biopharmaceuticals development. He has served as a member of USP Biologics and Biotechnology Expert Panel and also worked as a Director at United States Pharmacopeia, India site. Dr. Das has also worked at
senior management level at Intas Pharmaceuticals developing Biosimilar for global markets.
Dr. Das has worked as member of Expert committee on Biologicals and rDNA Products: Indian Pharmacopeia Commission (IPC); Govt. of India. He has authored research papers which are published in peer-reviewed National and International journals
1. What are the key international developments with respect to EU and
USFDA biosimilar requirements?
A: One key development towards biosimilar acceptance has been the issuance of guidance on “interchangeability” by US-FDA in May this year. This will pave the way for the substitution of one product for the other without a prescriber’s involvement, as is the case for generic small molecule pharmaceuticals. This I believe, is a significant action and will promote competition in the biologic market in the US.
Another development is the issuance of a revised guidance by FDA titled “Development of Therapeutic Protein Biosimilars: Comparative Analytical Assessment and Other Quality Considerations” also in May this year. This is the revised version of an earlier guidance titled “Quality Considerations in Demonstrating Biosimilarity of a Therapeutic Protein Product to a Reference Product,” published on April 30, 2015. FDA says this revision is to reflect on agency’s recommendations on the design and evaluation of comparative
analytical studies intended to support a demonstration that a proposed therapeutic protein product is biosimilar to a reference product and in anticipation that this will provide additional clarity and flexibility for product developers on analytical approaches to evaluating product structure and function.
For Europe, although approval rate of Biosimilars are much higher that the US, uptake of biosimilars are somewhat country specific, with the large EU5 countries still do not have interchangeability options. However, payers have significantly employing various tools which may lead to higher biosimilar uptake. For example introduction of prescribing target i.e. prescribing biosimilars to a predetermined percentage of patients. NHS of UK introduced biosimilar adoption framework with the idea that switching of patients to a
biosimilar may be inserted into clinical practice with incentive offerings for staff to offset switc hing costs. This year in May, NHS has published a document titled “what is a biosimilar medicine” for clinical and nonclinical stakeholders about the role of biosimilars in the healthcare system. The document explains among many others aspects, on the overall savings from Biosimilars as well as suggest that a prescriber can switch from a reference to a biosimilar product. However, switching at the pharmacy level is still not permitted without the consent of the prescriber as of now.
2. What are the main attributes for higher market approvals of Biosimilars in Europe compared to the US?
A: The first biosimilar, Zarxio, approved in the United States only in 2015 whereas Omnitrope, another biosimilar was approved by the European Medicines Agency (EMA) way back in 2006. Since then, the EMA has approved more than 40 biosimilars as of 2019. Essentially this shows that EMA as the pioneering agency to advance biosimilars approval
and uptake for the world. To understand this one may refer the concept paper on the development of a guideline on the comparability of biotechnology-derived products published in 1998 which led to the introduction of a directive in EU legislation with the idea of “similar biological medicinal product” in 2001. Therefore, definition and a legal framework for market authorization for Biosimilars was first introduced in the world by the EU and is monitored and updated on an ongoing basis which is key for larger market approval rate of biosimilars in the EU. By now the EU has already an experience of over a decade of Biosimilar use and established the fact that biosimilars have similar efficacy and safety concerns as that of the reference products and can save a significant portion of healthcare costs. Only three official biosimilars is in the market in the US, although around 15 are approved and their uptake has been slower than anticipated. For example less than 15% for filgrastim biosimilar and 3% for the infliximab biosimilar holds as market share. This is partly due to the lack of pricing incentives from biosimilars as well as more attractive contract offers from the innovator product. A host of other reasons for this slow approvals and uptake could be considerations on overall quality, safety, and clinical efficacy of the biosimilar plus manufacturer reliability (supply without disruptions), reimbursement rates set by insurance companies or commercial payers, and support services for health care professionals and patients. In other words, assurance on the efficacy and safety from the providers as well as less out-of-pocket expenses is key to most US patients. Currently this is yet to happen in the US, although progress has been made to achieve these goals. On the contrary, a range of different policies to generate
pricing pressure, drive adoption, and ultimately yield cost-savings for their healthcare systems have been implemented in the EU countries which somewhat led to higher uptake rate for the biosimilars.
3. What is the scenario of prescribers’ acceptance of biosimilars over the
innovator biological products?
A: In the beginning of biosimilar era, it was the differences between lots in quality characteristics were cited to be reason enough for great concerns on efficacy and safety of the product. From this we have come to a stage where regulatory agencies have formalized acceptable changes of quality characteristics in the “innovator products” with no impact on efficacy and safety. We also have for more than a decade of real world
experiences of biosimilar use with comparable efficacy and safety concerns in the EU. Moreover, we now have the outcome of NOR-SWITCH trial which demonstrated that “switching from infliximab originator to CT-P13 [a biosimilar] was not inferior to continued treatment with infliximab originator”. All of these experiences I believe, has led to higher prescribers’ acceptance of biosimilars over the innovator product given there is incentives attached all through the stakeholders chain (for example for the provider, prescriber, payer and insurer). The EU is clearly way ahead in implementing policies with
the above considerations and will reap benefits hugely in the healthcare cost savings. Although slow, the US has finally initiated action that may eventually allow biosimilars to be interchangeable with the innovator product. First to this idea was the finalization of the guidelines on interchangeability this year in May.
4. What is your opinion on Indian biosimilar industry, whether it attained its
potential or this just the beginning of the journey?
A: Indian biosimilar industry has now been very firmly established with defined
regulatory path and a number of large and medium manufacturers with more than 70 biosimilars approved. India is also the first country to approve a biosimilar monoclonal antibody to Rituximab in 2007 and interestingly without having a published guideline which first appear in the year 2012 and in a revised form in 2016. This approval has tremendously helped the patients to have access to the product with almost half the cost of the innovator product. Interestingly, another mAb, Trastuzumab indicated for HER2 positive breast cancer is now available at almost 65% less than the innovator price, due to the launch of an Indian biosimilar. Moreover, 3 companies from India has biosimilar
products registered in the US, the EU and Japan. This shows the maturation of Indian biosimilar industry as a global player. These facts although very positive, India still has huge gaps in filling up the affordability factor with its very low per capita income populace.
On the contrary, India has very high number of incidences and disease burden in most therapeutic segments such as Cancer, Diabetes, Infections, Arthritis, Blood factor disorders etc. Therefore, affordable and quality biosimilars is a big opportunity for India. However, what is critically needed is a policy framework somewhat similar to that is being followed in the EU which incentivizes all the stakeholders involved with biosimilar use including the insurance sector. Unfortunately, medicine costs in India is largely an out-ofpocket expense and this needs to change very rapidly. Given these policies are implemented, Indian biosimilar industry has tremendous potential to impact healthcare in a significant way.
5. Where does China stand with biosimilar approvals and the regulatory
A: This year in February Chinese regulators approved their first biosimilar. A biosimilar Rituximab indicated for non-Hodgkin’s Lymphoma. Although biotherapeutics development in China continue to grow exponentially over the past decade, no biosimilar drug however was approved until 2019. This is primarily because of lack of a national regulatory guidance which was first published in February 2015. This guidance document followed the same principles and requirements consistent to that as formalized by FDA and EMA. Some other changes also happened simultaneously to foster pharmaceutical
approvals and market authorizations such as China Food and Drug Administration (CFDA) is now National Medical Product Administration (NMPA) which falls under the State Administration for Market Regulation (SAMR). The Centre for Drug Evaluation (CDE) which reviews applications under NMPA remains without change in function. China currently has more than 200 biosimilars under clinical development. Interestingly two key recent development in policy setting by NMPA can be seen either as a barrier to biosimilar growth or bring serious competition : One is listing of foreign made drugs for urgent unmet medical needs which can be approved for registration without any clinical trials being conducted in China. 48 such drugs have been listed for public review, out of which 11 are biologic drugs. The second one is reduced or no import cost of new cancer drugs or drugs for hard to treat cancer. Another very interesting development is the Market Authorization Holder [MAH] program implemented by the Chinese regulatory agency as
a pilot program which allows holders of a NMPA biologics approval will have an option to manufacture the drugs on their own or use any contract manufacturer. This policy has given significant boost to the CMO industry inside China and will surely foster growth in the Chinese Biosimilar industry along with new drug development.
6. How switching and interchangeability affect biosimilars access and its
A: EMA and EU commission defines 3 terms related to biosimilar switching:
interchangeability, switching and automatic substitution. Interchangeability is a general term which includes both switching, when the prescriber decides to use one over another and substitution when this exchange happens at the pharmacy level without the consultation of the prescriber. In the US though FDA designated interchangeability may refer to automatic substitution at the pharmacy. Europe has been at the fore front in terms of interchangeability and currently allow physician guided transitions of biosimilars restricting pharmacy level substitution and this is without any separate or additional
regulatory guideline or drug development criteria. As a result we see a very high uptake of Biosimilars in some select EU countries. Therefore, we may envisage that interchangeability or substitution will surely bring competition as well as uptake and cost savings. Indeed a follow-on-biologic to Lantus like Basaglar has gained a market share of around 30 percent and the Neupogen market share is down by 20 percent from the competition of Zarxio a biosimilar.
The opinions expressed in this publication are those of the Interviewee and are not intended to malign any ethic group, club, organization, company, individual or anyone or anything. Examples of analysis performed within this publication are only examples. They should not be utilized in real-world analytic products as they are based only on personal views of the Interviewee. They do not purport to reflect the opinions or views of the VEEDA CRO or its management. Veeda CRO does not guarantee the accuracy or reliability of the information provided herein.