Anticipated patent expiry for the blockbuster biological medicinal products attracted most of the Biopharmaceutical companies to develop Biosimilars for global markets including European Union (EU) countries. While registering marketing authorization applications (MAA – Article 10(4) Applications) for those Biosimilars, companies must ensure that the applications are in line with legal requirements and procedures laid down in Directive 2001/83/EC and in Regulation (EC) No. 726/2004. MAAs of Biosimilars must be submitted through Centralized Procedure (CP) and are subjected to the European Medicines Agency’s (EMA’s) evaluation.

Even though Biosimilars Regulatory submission pathway facilitates certain advantages for product development and Regulatory approvals (no requirement of conducting full-fledged non-clinical and clinical studies that may involve additional time and money), product development goals still have strict limitations.

To evaluate Article 10(4) Applications (MAAs of Biosimilars), a robust comparability exercise involving head-to-head comparison between the similar biological medicinal product and the Reference Medicinal Product (RMP) is required considering the levels of quality, safety and efficacy. In addition, manufacturers are required to go through different expression systems or different excipients for developing biosimilars, which adds to the burden of establishing similarity. Other challenges like optimal planning of clinical trial strategy to cover multiple member states/ countries, and selection of reference member state to fulfil global registration requirements are also prevalent.

In such scenarios, Freyr with a team of Regulatory experts support Biosimilar manufacturers in studying and establishing the similarity to the RMP. Freyr provides Regulatory services for Article 10(4) application (MAAs) registration and life cycle management (LCM) in EU countries for all types of biosimilar products. With a comprehensive knowledge about EU product registrations, Freyr helps the applicant understand the marketing regulations of biosimilars in multiple nations and liaises with local Health Authorities (HAs) for addressing submission queries in a compliant way. 


Freyr Expertise

  • Strategic advice during biosimilar product development phase and guidance for development in line with current EU requirements
  • Regulatory strategy and selection of RMP for Biosimilars that are developed for commercialization in EU countries
  • Strategic support in identifying the optimal Regulatory submission pathway for submission of Biosimilars products
  • Regulatory support on preparation for HA interactions and representation for pre-submission meetings (scientific advisory meetings) to resolve product developmental issues and anticipated Regulatory queries/ issues
  • Pre-submission administrative activities for submission of MAAs (Article 10(4) Applications) for Biosimilars
  • GAP analysis of developmental data/ source data against current EU Regulatory requirements and provide mitigation plan for identified gaps and the Regulatory deficiencies
  • Performing head-to-head comparability of Biosimilar product and RMP, with extensive understanding on Regulatory requirements for different type of Biosimilars, (for example mAbs, recombinant human protein products like Insulin, G-CSF etc.)
  • Preparing, reviewing, finalization and submission of MAAs for various types of Biosimilar products as per EU specific requirements
  • Provide strategies for HA queries, preparation and submission of response to HA queries with scientific/Regulatory logical approach on time for quicker approval of MAA
  • Evaluation of change controls for post approval changes (PAC)
  • Regulatory assessment of PAC and preparation of variation submission strategy
  • Compiling, reviewing and submission of Variations (Type IA/Type IAIN/Type IB/Type II) to already approved MAA of biological / Biosimilar products for PAC and LCM