EMA Releases Guide on Biosimilars in the EU

The European Medicines Agency (EMA) and the European Commission have released new guidelines on biosimilar medications to provide health care professionals with reference information on the science and regulation on the use of biosimilars.

“Today, biosimilars are an integral part of the effective biological therapies available in the EU, supported by adequate safeguards protecting patient safety,” Professor Guido Rasi, executive director of the EMA said in a press release earlier this month. “As health care professionals are at the forefront of patients’ care, it is vital that they have access to reliable information on these medicines: what they are and what scientific principles support their clinical development, approval, and safety monitoring.”

Biosimilars have physical, chemical, and biological properties highly similar to the biologic. In the EU, drug manufacturers can market approved biosimilars once the period of market protection for the reference medication expires—–after 10 years.

The first biosimilar was approved in the EU in 2006, and since then the EU has approved the highest number of biosimilars worldwide. The EMA has issued scientific guidelines over the years to help developers conform to the strict regulatory requirements for biosimilar approval.

“The expertise acquired over the last 10 years has enabled EU regulators to integrate experience-based knowledge with the initial science-driven concept,” according to the guide. “This has helped to shape current requirements for approval.”

In the EU, all medications produced using biotechnology must be approved through EMA. Thus far, nearly all biosimilars approved for use in the EU have been approved centrally because they use biotechnology for production. However, some biosimilars can be approved at a national level, such as low-molecular weight heparins derived from porcine intestinal mucosa.

Once a manufacturer applies for marketing authorization at the EMA, the data are evaluated by the CMP and PRAC, in addition to experts in the Biologics Working Parting and Biosimilar Working Party.

The EMA review results in a scientific opinion that is sent to the EU, and is ultimately granted an EU-wide marketing authorization.

For biosimilars, a positive benefit-risk balance is based on demonstrating biosimilarity and is achieved via comprehensive comparability studies with the reference medicine. Demonstrating high similarity with the biologic allows the biosimilar to largely rely on the safety and efficacy experience gained with the reference medication, according to the paper.

Additionally, companies developing biosimilars must demonstrate that the medication is manufactured to agreed standards using a large body of data, and that it is suitable for intended clinical use.

Comparability studies are crucial to establish biosimilarity to the reference medication and is the cornerstone of biosimilar development. They are designed to confirm biosimilarity and clinical performance.

If a biosimilar is found to be highly similar to a reference product and has comparable safety and efficacy in one therapeutic indication, the data can be extrapolated to other indications approved for the reference medication.

“Extrapolation is not a new concept, but a well-established scientific principle used routinely when biological medicines with several approved indications undergo major changes to their manufacturing process,” the paper said.

For the safety of biosimilars, the EU has a well-established system to monitor, report, assess, and prevent adverse drug reactions. Authorities continue to evaluate the benefit-risk balance of all medications, including biosimilars, and take necessary regulation action to help protect patients.

“Over the last 10 years, the EU monitoring system for safety concerns has not identified any relevant difference in the nature, severity or frequency of adverse effects between biosimilar medicines and their reference medicines,” the authors of the paper wrote.

A critical requirement for the safety monitoring of biological medications is the need for product and batch traceability during clinical use and at all levels in the supply chain. EU law requires all medications to have a trade name or brand name with the international nonproprietary name assigned by the World Health Organization.

“It is important that the medicine’s trade name and batch number are recorded by health care professionals at all levels, including dispensing and patient information,” the authors wrote. “Prescribers should include the trade name of the medicine in the prescription.”

Requirements for biosimilar approval in the United States by the FDA are based on the same scientific rationale as the EU, but specific data requirements may differ.

“The EU’s regulation of biosimilars has shaped biosimilar development globally, by establish the core principles that underpin biosimilar development in other highly regulated areas of the world,” the paper concluded. “EMA continues to share the extensive experience gained in the EU on biosimilars with other regulators around the world and participates in a number of international forums.”

The guide was launched at the EU’s third stakeholder event on biosimilar medicines.