Biosimilars: Not quite the same
Biosimilar medicines become more of a reality globally, but several questions remain.
It has been a busy time in the world of biosimilars. While regulatory bodies are getting their heads around developing clear-cut rules to ensure the safe introduction of biosimilar monoclonal antibodies, some countries are already seeing the first of these medicines enter the market.
Globally, there are many emerging countries in the process of developing or implementing regulatory pathways for the approval of biosimilars, using the WHO guidance document as a reference. “One of the most recent developments is that the Chinese regulatory agency has communicated their intent to engage with key stakeholders and develop a local pathway for the approval of biosimilars,” says Fermín Ruiz de Erenchun, Global Head Biologic Strategy Team at Roche.
“The challenge for many of these countries,” he adds, “will be the implementation and adaptation of the guidelines to the local situation. We still need to see a further convergence on this issue.”What’s in a name?
The naming of biosimilars and biotherapeutics in general is another topic that has over the past couple of years received the attention of the WHO and regulatory agencies. This has been intensely debated in several fora, and Roche also attended the open meeting organized by the WHO to explore whether or not such products be allowed to use the same International Nonproprietary Name (INN) as the innovator product.
The best way to improve the outlook for patients is to keep developing innovative medicines
“Patient safety is of paramount importance. So Roche and other companies believe that all biopharmaceutical medicines need to be identifiable throughout the prescribing and dispensing processes, a practice that would not be possible under the current INN system if biosmilars were to use the same INN as the innovator product,” stresses Fermín. He states that a unique and universally available identifier system could ensure that all approved biopharmaceutical medicines are individually identifiable.
The WHO has also recently issued a draft document on Regulatory Expectations and Risk Assessment for Biotherapeutic Products that specifically addresses biopharmaceutical products which have been approved in markets that have either no biosimilar guidelines, or that do not necessarily meet the global recommendations issued in 2010.
Ironing out the questions
Despite the progress, a number of key questions remain unanswered. For Fermín, the absence of a scientific position regarding the possibility of automatically substituting between a biosimilar and the innovator product remains a key issue. “This is a well-established practice for most of generic medicines, but the principles are different for biopharmaceutical products,” he explains.
“For biopharmaceutical products to be declared automatically substitutable, it has to be demonstrated that switching back and forth between the reference and the biosimilars product has no impact on efficacy and safety at the patient level, and the products are then interchangeable. In most cases, there is little, if any, data to support the automatic substitution of these products. Despite this, there remains no global position on this point.”
Illustrative of the inconsistencies that remain, Health Canada has issued guidelines declaring biosimilars as non-interchangeable products and the US FDA will issue guidelines this year, yet the European Medicines Agency (EMA) is not expected to provide guidance on this issue anytime soon.
The Roche position
“Roche has demonstrated that the best way to improve the outlook for patients is to keep developing innovative medicines and diagnostics. Today, we have developed nine innovative cancer medicines which have been proven to improve and, in many cases, extend the lives of people with 12 common cancer types,” comments Fermín.
According to him, “The availability of biosimilar medicinal products enhances competition, and their availability could offer potential economic benefit to healthcare systems while addressing the issue of new treatment options brought about by advances in medical science. However, whether approved biopharmaceuticals or non-comparable biologics patient safety must be the first priority for all products.”
“This assurance can only be had when products have been subject to thorough and extensive analytical, non-clinical and clinical comparative assessments and if there are well, regulated processes in place. It is our strong belief that biosimilar regulations should not impede, but instead promote and provide an incentive for innovative research towards new medicines,” Fermín says.
The EMA states that “a biosimilar is a biological medicinal product that contains a version of the active substance of an already authorized original biological medicinal product (reference medicinal product). A biosimilar demonstrates similarity to the reference medicinal product in terms of quality characteristics, biological activity, safety and efficacy based on a comprehensive comparability exercise.”
Non-comparable biological products
According to the IFPMA, “prior to the implementation of a science-based pathway for the approval of biosimilars, some biological products have been introduced on the market in some countries. Because the adequacy of the comparative studies to an appropriate reference biotherapeutic product and the basis for approval are unclear, these products are best described as non-comparable biological products.”