An integrated approach to biosimilar development and commercialization

Deepa Dahal


Over the next 10– 15 years, the biosimilars industry is expected to explode as the patents on branded biologics begin to expire. Analysts agree that biosimilar market size will be fairly significant in the next few years, ranging between $2– 3 billion by 2015.1,2 This favorable market outlook is based on multiple forces driving the industry, including pressure to reduce healthcare costs, need for biopharma companies to explore new markets, and better-defined regulatory pathways.

The potential demand for biosimilars creates an enormous opportunity for biopharmaceutical companies. But unlike the development of innovator biologics—or generic versions of chemical-based medications—biosimilar development and commercialization is a uniquely challenging endeavour requiring precision, stepwise planning to ensure timely regulatory approval and optimal market access.

To expedite commercialization and optimize market access, biosimilar manufacturers must focus on addressing three major business challenges: meeting the regulatory requirements, outlining an adequate clinical development program, and optimizing commercialization and market access. Focusing on these areas can ensure competitiveness and optimizing return in the fast-growing biosimilars space. The following elements are recommended as part of such a comprehensive biosimilar business strategy:

Identify the requisite regulatory stipulations for every intended market

This process needs to follow a logical progression to ensure that a global development plan can be leveraged to satisfy regulators in each potential market. Although biosimilar regulations differ around the globe—and are still evolving—companies can and are still devising strategic development plans based on existing regulations and biologics / biosimilar products guidance. Regulatory strategies must address product, indication and market specific requirements.

“The potential demand for biosimilars creates an enormous opportunity for biopharmaceutical companies.”

 It is important to remember that each country is on its own maturity curve in terms of the biosimilar regulatory process. For countries with still-evolving regulatory pathways and guidelines, companies need to be aware of where they are currently in the cycle, and then anticipate likely future scenarios based on the existing regulations and their experience.

Focus clinical development strategies on patient selection and appropriate clinical endpoints

Key challenges relevant to the clinical development of biosimilars include maximizing patient recruitment and choosing the most sensitive patient population that is most likely to respond to therapy, while expediting clinical trials and minimizing sponsor cost. Patient recruitment can be accelerated by choosing the countries / markets in which to conduct the clinical studies with the greatest unmet need for the biosimilar (i.e., those that do not have access to the innovator biologic). Companies can also accelerate speed to market by selecting markets where regulatory agencies are willing to work with companies to bring biosimilars into market earlier (i.e. markets where governments are incentivized to reduce healthcare costs). Additionally, investing in education of both investigators and their patients on the potential benefit of participating in a biosimilar trial (i.e., better standard of care for patients with no access to the drug otherwise) can facilitate patient recruitment in all markets.

Selecting an appropriate patient population and sample size for the primary indication with which to demonstrate clinical similarity is critically important to obtain regulatory authority buy-in, especially to secure extrapolation to other indications. Incorporating the right clinical endpoints, including biomarkers or other surrogates predictive of clinical efficacy, may also obviate extensive clinical trials.

Ensure the commercialization strategy optimizes uptake of biosimilars by prioritizing the development pipeline, gathering outcomes data, engaging stakeholders and minimizing barriers for use

Companies need to prioritize their biosimilar development pipeline to maximize the commercial potential of their products, and engage stakeholders such as patients, physicians and payers / insurers to improve market uptake. To optimize commercial potential, they must consider market size, product price, reimbursement policies, healthcare policies, competing products and barriers for uptake.

“It is important to remember that each country is on its own maturity curve in terms of the biosimilar regulatory process.”

A concurrent work stream to regulatory and clinical plans should be to assess physician and payer willingness to prescribe and pay for the potential biosimilar. For cases in which reimbursement or adoption appear unlikely or challenging, biosimilar developers must design the development program to provide as much outcomes data as possible. This could include comparative effectiveness data, health technology assessments or even the potential effect on public health.

Biosimilars will likely not have the same uptake as small-molecule generics, and in fact, uptake varies greatly by the particular molecule, product class and regional market dynamics. Because of this difference, it is important to consider commercialization strategy early in the development process, which can help companies identify and prioritize which molecules to develop, which markets to prioritize and what the expected revenues and return on investment can be.

Because biosimilars differ from small-molecule generics by not being identical to the reference product, and the price differential is generally smaller (~20 – 50 percent) 3,4, effective commercial strategies for biosimilars tend to be more similar to the strategies employed for a branded biologic versus those of generic products. These strategies may include effective market and KOL development, device improvements, and patient support programs. Additionally, the role of real-world patient data (i.e., post-marketing observational studies) becomes more important, as potential risks inherent to biologic products, such as immunogenicity, are not always immediately evident.

Finally, compress the timeline

The final element of a successful plan is a compressed timeline to accommodate the complexity of biosimilar development. Successful biosimilar companies will be those who collapse their clinical, commercial and regulatory thinking into a streamlined cohesive function and embrace the organizational change that such a framework necessitates.

“Companies need to prioritize their biosimilar development pipeline to maximize the commercial potential of their products…”

Perspectives on the US biosimilar landscape

In the past several months, the FDA has released three guidance documents on biosimilars focused on demonstrating biosimilarity to a reference product, quality considerations, and answering FAQs from biosimilar manufacturers. An understanding of this guidance confirms our earlier hypothesis that the FDA is aligned with the European Medicines Agency (EMA) in suggesting a “stepwise approach” to demonstrating biosimilarity to a reference product, including characterization studies, then functional assays, then preclinical / clinical studies. Although product-specific guidance has not been released by the FDA to date, it is clear the agency will evaluate biosimilar products case-by-case, via “a risk-based totality-of-the-evidence approach.”

The key to developing a biosimilar molecule for the US is understanding that early dialogue with the agency is necessary, in order to ensure complete agreement on the “biosimilarity and comparability” of the biosimilar molecule to the reference product, based on characterization and analytical studies. Based on this agreement, the FDA is willing to provide guidance throughout the rest of the development program. This is unlike the traditional development program for innovator drugs and biologics, where most regulatory guidance is provided prior to designing Phase III studies.

Another key, and unique, aspect of the FDA’s guidance include its willingness to define interchangeability, which means a biosimilar product can be substituted for the reference product without a physician’s approval, at the pharmacy level, as well as guidance around how to achieve interchangeability status – through switching studies. To-date, the EMA has not addressed the issue of interchangeability.

Other unique considerations the FDA suggests include: allowance of fewer indications than the reference product is licensed for, differing routes of administration and presentations (i.e. strengths, delivery devices, etc.), and using foreign reference products if an acceptable bridging study is conducted. The possibility of developing a biosimilar for just a single indication provides a potential fast to market strategy for developers. Lastly, the FDA also leaves the possibility open of requiring more robust post-marketing and REMS for biosimilars, compared to the reference products.

A detailed analysis of the FDA guidance and comments to the industry suggests that the agency is more than willing to work with biosimilar manufacturers throughout the development process, and is keen on bringing biosimilars to the US market faster (and with a less costly development program) than innovator biologics. Once the regulatory and clinical hurdles are crossed, two major factors will determine the commercial success of biosimilars – whether the FDA will actually declare biosimilars interchangeable, and whether pricing of these products will drop significantly enough to encourage switching to them. I In the meantime, it is clear that biosimilar manufacturers must continue to carefully consider the regulatory guidance, clinical requirements, and commercial considerations previously proposed in order to ensure optimal long-term outlook.

The FDA is currently accepting comments from the public on the draft guidance documents it has issued. Several biopharmaceutical companies as well as professional and patient advocacy organizations have called for more stringent guidelines and language than proposed in this version.


1. DataMonitor (2011), “Pharmaceutical Key Trends 2011–Biosimilar Market Overview”

2. IMS Institute for Healthcare Informatics (2011), “The Global Use of Medicines: Outlook Through 2015”

3. Grabowski HG, Ridley DB and Schulman KA. Entry and Competition in Generic Biologics. Manage. Decis. Econ. 28: 439–451 (2007)

4. Barclays Capital (2011), “European Pharmaceuticals: The Biosimilars Handbook”


About the author:

Deepa Dahal, MBA, is Principal Consultant, Commercial Strategy, Biosimilar Intelligence Team, Consulting at Quintiles. Deepa Dahal brings to Quintiles Consulting over six years of marketing and strategic consulting experience within the pharmaceutical and life sciences industries. Her background lies in commercial strategy, market development, brand planning, product launch, life cycle management, and managed care contracting. At Quintiles, she has focused on developing commercial strategies for multiple clients in the biologics and biosimilar space, including innovator biologics as well as biosimilars in development. She has also played a leading role in defining Quintiles’ own global biosimilar strategy.

Prior to joining Quintiles, Deepa was a Senior Consultant at both Campbell Alliance and IMS Health. At Campbell, she focused on Marketing and Brand Management strategy among pharmaceutical and biotech companies. At IMS, she worked on Managed Care Contracting and Compliance with pharmaceutical clients. Deepa has a bachelor’s degree in Business from the University of Idaho and an MBA from the University of New Hampshire.

About Quintiles’ Biosimilar Intelligence Team

Quintiles’ Biosimilars Intelligence Team supports the development and commercialization of clients’ biosimilar products globally. It is composed of global regulatory, clinical development, medical, therapeutic area, commercial and market access experts.

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