The biosimilars field is one of the fastest-growing global industries, largely because many blockbuster biologics will be coming “off patent” in the next few years. PRA is poised to help our clients capitalize on opportunities in the rapidly emerging biosimilars space. Our strong background in biosimilars and biologics/monoclonal antibodies affords us a thorough understanding of the challenges and success factors involved in biosimilar drug development.

we have contributed to the development of 14 key biological drugs and supported studies leading to FDA approvals for five biological drug products on the market today.

During the last 5 years, PRA has been involved in 25 clinical trials in biosimilars in various phases and is currently conducting 16 trials across the globe in endocrinology, genitourinary, immunology, oncology, and hematology indications. The 25 clinical trials involve nearly 5850 patients and 830 healthy volunteers at 1300+ sites globally.

      PRA has a dedicated Biosimilars Development team with years of experience across the globe in various roles including:

      • The development of global biosimilar clinical plans
      • Integrated development plan throughout life cycle from CMC to licensing
      • Interactions with EMA, FDA, and KFDA among many other Regulatory Agencies via guideline development workshops, scientific advice meetings, pre-IND and IND meetings, and general correspondence
      • Global conduct of biosimilar trials phases I-IV

PRA’s Biosimilar Development team is a cross functional collaboration across various functions within PRA in a structured, focused, and team driven approach. Understanding and keeping up to date with the ever evolving global regulatory landscape, the science of comparability across the development cycle, bioanalytical challenges, recruitment challenges, speed to market post patent expiration, and market dynamics are critical for success. Our Biosimilar Development team knows the science, understands the regulatory requirements and the challenges to deliver success. The team is flexible, accessible, and has the passion to deliver safe cost effective medicines through the increased uptake of biosimilar products. PRA understands how to develop and conduct customized biosimilar trial designs, and our experience by phase, therapeutic area, and subject type for the last 5 years is summarized below:


Therapeutic Areas I III IV No. of Clinical Studies No. of Clinical Sites No. of Clinical Patients No. of Healthy Volunteers
Immunology 4 6 10 580 2,050 369
Oncology 3 4 7 450 1,918 351
Genitourinary 1 4 5 213 1,401 60
Endocrinology 1 1 2 73 478
Hematology 1 1 1 46
Total Studies: 9 15 1 25 1,317 5,847 826

*Last updated January 2016

Key Biological Drug Study Experience

Our understanding of biosimilars is further enhanced by PRA’s successful track record of managing trials involving biological drugs (ie, biologics, monoclonal antibodies, biosimilars, and biobetters), which spans from early phase development through successful regulatory submission in a number of therapeutic areas. During the last 5 years, PRA’s clinical experience includes 152 trials in biologics, of which 48 were in monoclonal antibodies, involving 5300+ sites globally and 26,000+ patients. We have supported studies leading to FDA approvals for 5 biological drug products on the market today.

Study Experience in Key Biological Drugs Excluding Biosimilar Studies (5 Years*)

Therapeutic Area No. of Studies No. of Sites No. of Patients
Biologics (excluding Biosimilars & Monoclonal Antibodies)
Oncology 20 967 3,228
Hematology 18 579 1,975
Infectious Diseases 16 736 4,108
Immunology 13 289 1,414
Neurology 11 145 1,510
Cardio-Metabolic Diseases 7 91 277
Hereditary Disorders 7 162 848
Genitourinary 6 17 323
Endocrinology 2 19 42
Functional Services 1 1 6
Gastroenterology 1 12 47
Hematology 1 50 75
Ophthalmology 1 1 35
Sub Total: 104 3,096 13,888
Monoclonal Antibodies (excluding Biosimilars)
Oncology 18 928 3,713
Immunology 15 396 1,951
Neurology 7 794 5,761
Hematology 3 100 545
Cardio-Metabolic Diseases 1 1 1
Functional Services 1 8 40
Infectious Diseases 1 1 124
Laboratory 1 1 54
Respiratory 1 1 48
Grand Total 48 2,230 12,237

Total Studies:

152 5,326 26,125

*Last updated January 2016

Data Package and Regulations

The production of a biologic is a lengthy and complex process; each step is sensitive and even minor alterations to the overall process may result in differences in the structure, stability or other quality aspects of the end product. Because of the potential for subtle differences between a biosimilar and the originator product, the simplified procedures for the assessment/approval of small-molecule generics are not appropriate. Therefore, specific guidelines have been developed for the assessment and approval of biosimilars across the globe. Like the manufacturers of an originator reference product, biosimilar manufacturers must demonstrate a product’s efficacy and safety. The difference between biosimilars and an originator product is that approval is based on a demonstration of similarity to the previously approved originator product rather than a de novo demonstration of safety and efficacy. Regulatory authorities recommend that similarity to the originator product should be assessed in a step-wise approach throughout the development program, from production to non-clinical and subsequent clinical development, ensuring that any uncertainties are identified and addressed on an ongoing basis.
Biosimilars Data Package Although a reduction in the data package for a biosimilar product may be possible, it is still quite substantial when compared to small molecule chemical generic products. The “Quality” dossier required is extensive; first, a full-quality dossier that meets all regulatory standards similar to that of a novel biological product has to be provided; in addition, a comprehensive comparability exercise to the reference product is required for both the drug substance and drug product. The amount of non-clinical and clinical data required depends on how well the molecule is characterized, potential differences between the biosimilar and the reference product and clinical experience with the substance class. The type and extent of clinical data requirements for biosimilars vary based on three factors;
  • complexity of the active substance and how well it can be characterized
  • availability of an accepted surrogate end point to compare efficacy
  • type and seriousness of safety concerns that have been seen with the reference product or the substance class.
The clinical data required may include:
  • Robust and extensive comparative Phase I pharmacokinetic/pharmacodynamic (PK/PD)
  • Phase III efficacy and safety studies with immunogenicity assessed throughout the clinical program. Immunogenicity, in particular, is critical to the development of biosimilar medicines
  • Post-Authorization Safety Study (PASS)
The originator manufacturer will have undertaken a Phase III study for each applied therapeutic indication; however for a biosimilar, there is the possibility to extrapolate therapeutic similarity shown in one indication to other approved indications of the reference product. In summary, the development of biosimilar medicines is guided by stringent regulatory requirements ensuring the highest standard of quality, non-clinical and clinical comparability data. The type and extent of this data depends on the complexity of the molecule and, therefore, is decided on a case-by-case basis.
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Program Development

PRA understands the specific requirements and challenges of biosimilars clinical development programs (when compared to that of a new chemical entity), thereby providing sponsors with a tailored, cost-effective service. We can provide comprehensive, cross-functional support for biosimilar development programs, including consultation, regulatory, early development services, bioanalytical services (Phase I-IV), study conduct, safety and license application.
Therapeutic_Expertise_Biosimilars_Successful_Development_Program_Graphic To ensure effective cross-functional management, PRA has a dedicated Biosimilars Development Team. PRA has established a Biosimilars Task Group, consisting of senior representatives from a variety of roles to provide cross-functional collaboration in a structured, focused and team-driven approach that we feel is critical in supporting our clients’ needs. This group establishes a customized strategy for sponsors and identifies PRA’s differentiating capabilities to transform biosimilar trials; as such, PRA is able to deliver projects of the highest quality and minimize cost and time to market. Therapeutic_Expertise_Biosimilars_Integrated_Program_Graphic
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Patient Recruitment Strategies

Patient recruitment is the most challenging aspect of the clinical trial process, consuming approximately 30%* of the clinical timeline and often leading to trial delays. In addition to the standard clinical trial recruitment challenges biosimilar trials face a new set of challenges including:
  • Competition against new biological molecules for the same disease area
  • Changes in standard of care
  • Lack of incentives for both investigators and patients
  • Need for a large number of patients
  • Lack of understanding of what biosimilars are
Site and patient education is critical. Key for success is understanding the regulatory framework and the potential value of biosimilars including providing affordable alternatives to innovator specialty medications, increasing patient access to treatments that would otherwise be beyond their financial means and expanding access. Investing in education of both investigators and their patients can facilitate patient recruitment. PRA has developed general education materials tailored for patients and investigators which are regularly updated to reflect current thinking. Patient recruitment can be accelerated by choosing the countries/markets in which to conduct the clinical studies with the greatest unmet need for biosimilars (i.e., those that do not have access to the innovator biologics). PRA leverage’s the expertise of our dedicated in-house Feasibility, Medical Informatics and Site Recruitment teams to identify countries/ sites with the greatest potential for recruitment for a biosimilar trial. The time between feasibility, site selection and start up can be very long. In order to maintain interest and motivation, targeted “engagement communication” with sites are developed. The information is tailored on a case by case and can be general such as the quarterly Biosimilar Newsletter providing up to date information on the evolving regulations or disease specific updates.