Patient safety must be "a non-negotiable priority" for the US Food and Drug Administration (FDA) and drugmakers as they seek to bring biosimilar medicines to market, and that focus "does not end with drug approval," regulators have been told.
"Put patients first and sound policy will follow," Joseph Miletich, senior vice president of R&D at Amgen, advised the FDA, speaking at an agency hearing.
Noting the complexities of biological products and the potential differences in products created from different living cells, Dr Miletich emphasised that biotechnology is an evolving field. "While much more is known today than 30 years ago, FDA's guidance documents should candidly acknowledge that there are some things we still do not scientifically know today," he told the hearing.
As the FDA finalises its guidances for the development of biosimilars, it must adopt policies to facilitate attribution of adverse events and foster manufacturer accountability, he added. The arrival of biosimilars in the US marketplace will significantly increase the challenge and importance of accurate tracking and tracing, and the use of distinguishable established names will facilitate prompt identification and resolution of product problems, he suggested.
The FDA also needs to conduct a communications campaign about biologics and biosimilars. "It will be essential for FDA to clearly communicate to all stakeholders what biosimilar products are and are not. For example, there should be no perception, implied or otherwise, that an FDA-approved biosimilar is somehow less effective or less safe than the reference product. However, at this time, biosimilars are not appropriate for automatic substitution - that is, without the explicit consent of the prescribing physician - unless deemed interchangeable by FDA," said Dr Miletich.
He also emphasised that FDA policy should foster supply chain stability. "Recent medicine shortages have been an opportunity for some manufacturers to suggest that FDA's standards are overly rigorous and a source of the drug shortage problem. This is exactly wrong," he told the hearing.
"Complex products require high standards. It is by maintaining appropriately robust good manufacturing practices and facility inspection standards that FDA assures the public the reliable supply of high-quality products," said Dr Miletich.
Mark McCamish, head of global biopharmaceutical development at Sandoz, focused on the need for the FDA to apply a single, science-based regulatory standard across all biologics, irrespective of the sponsor's business model.
Several originator biologics have undergone manufacturing changes since their commercialisation, and Sandoz uses these data to create a "highly similar" biologic that overlaps with the originator's product attributes, said Dr McCamish, who was testifying on behalf of the Novartis Group. Such a "highly similar" product should justify an abbreviated clinical trial programme, as is outlined in the FDA's draft guidance documents, he added.
Discussing how the use of biosimilars can increase patient access and reduce expenditures on biologics, Dr McCamish pointed to a recent study by the IGES Institute in Berlin which forecast that, by 2020, eight European Union (EU) countries could save a cumulative total of 11.8-33.4 billion euros through the use of biosimilars. This is in line with the findings of the US Congressional Budget Office (CBO), which estimated in 2008 that implementation of the biosimilar pathway could reduce total US spending on biologics by $25 billion during 2009-2018.
Richard Dolinar, chairman of the Alliance for Safe Biologic Medicines, outlined five areas of concern that he said the FDA should resolve before they allow biosimilars onto the US market. These are: - the need for robust clinical testing; - the establishment of steps to monitor the global supply chain and manufacturing process; - the creation of track, trace and naming provisions; - the development of clear packaging, labelling and prescribing information; and - very close and deliberate scrutiny of a biosimilar before it is deemed interchangeable.
"We applaud the FDA's efforts to bring biosimilars to the US market, but would urge a deliberate approach that is becoming of FDA's critical role of ensuring the safety and efficacy of the nation's drug supply," Dr Doliar told the hearing.
No two biologics made from different cell lines or using different processes can be identical based on today's science, and they are also highly sensitive to the manufacturing process, said Dr Dolinar. "In fact, altering a single manufacturing parameter can change a compound's identity and/or the precise effect it has on the human body," he added.