Biotherapeutic Medicines, A New Frontier, Face Regulatory Issues

Biotherapeutic medicines, engineered by living organisms, have opened a promising path to treat major diseases. Near copies of these medicines, called biosimilars, are slowly coming to market, as the originator products become free of intellectual property rights or data protection.

However, some regulatory issues are left to be addressed, in particular in developing countries, according to the pharmaceutical industry and the World Health Organization. For patients, information on those products and their affordability are key, said a patient group representative.

The International Federation of Pharmaceutical Manufacturers & Associations (IFPMA) organised an event on 15 March entitled: Biotherapeutic medicines: a winning formula for patients.

According to the Gino Grampp, director of R&D for Amgen and Biotherapeutics Group chair, a biotherapeutic is a medicinal product manufactured in, or extracted from, biological sources. They are designed to target specific pathways of diseases, he said.

Biotherapeutics have been around for over 100 years, he said, starting with the use of porcine or bovine insulin to treat diabetes.

WHO Leads Global Regulatory Efforts

According to the WHO, biotherapeutics, as well as biosimilars present technical issues such as the potential immunogenicity of active substances, in which the immune system of the patient will react adversely to the biotherapeutic medicines. The WHO has been working on global guidelines for both products.

Biotherapeutics cannot be exactly reproduced due to their manufacturing process. Biosimilars cannot thus be considered as generics to biotherapeutics, but as products with similar qualities.

HyeNa Kang, a scientist at the WHO but speaking in her personal capacity, said the WHO develops guidelines and recommendations for biological products, in particular through the WHO Expert Committee on Biological Standardization, and eight WHO Collaborating Centres for Biological Standardization.

WHO Global written standards promote regulatory convergence, she said, but leave space to national regulatory authorities to formulate specific requirements. WHO global measurement standards seek to define an internationally agreed unit to allow comparison of biological measurements worldwide, she said.

Challenges of a new standard include that it needs to fit into existing laws and regulatory frameworks, she said. Also, regulators may need training on the new standard, and industry may not be prepared to respond to it.

On biosimilar products, Kang said that an increasing amount of patents and data protection for biotherapeutic products are expiring, giving way to biosmilar products, which she described as “a copy version of an already licensed biotherapeutic with demonstration of similarity based on a comparability exercise expected to be licensed on reduced data package.” Biosimilars are expected to contribute to reduced priced and increase accessibility, she said.

For biosimilars, proof of similarity through head-to-head comparison with a reference product is necessary, she said, and on the basis of proven similarity, the licensing of a biosimilar relies on nonclinical and clinical data generated with an already licensed product, she said.

On biosimilars, an implementation strategy of the WHO guidelines is necessary, she said. Following several WHO implementation workshops, issues were identified, in particular the fact that most biotherapeutics in developing countries are licensed under a standalone approach with reduced data package rather than a strict comparability exercise, she said.

Some countries have a regulatory pathway, she said, but the requirements are generally unclear, and some biosimilars are licensed without adequate quality, safety or clinical data, she said.

On what should be done with already licensed products, Kang said it is essential to develop approaches so they are evaluated according to WHO guidelines, or be phased out in a “reasonable period of time.”

During a public hearing of the United Nation High-Level Panel on Access to Medicines last week, a civil society representative underlined the need for safety for biosimilar products but warned against too stringent regulatory measures. In particular, he said the head-to-head comparison with a reference product implies that the generic company acquires the originator product, which is generally highly priced and would prevent significant price reduction for biosimilars (IPW, Public Health, 19 March 2016).

A number of countries are now introducing new or updated regulations for biotherapeutics, like Mexico, Chile, Uruguay, and Peru, she said. During the 67^th World Health Assembly in 2014, a resolution on biotherapeutics was adopted (WHA6721), she said.

The resolution instructs the WHO to support member states in strengthening their capacity in the area of the health regulation of biotherapeutic products, including biosimilars. It also instructs the WHO to support the development of national regulatory frameworks promoting access to quality, safe, efficacious and affordable biotherapeutic products, including biosimilars.

Futhermore, the resolution asks that the WHO Expert Committee on Biological Standardization update the 2009 guidelines, and that the WHO report to the 2016 WHA on progress in the implementation of the resolution.

Among challenges of regulatory convergence, she said “expectations are growing to reduce regulatory and policy burden while expectations for more transparency is increasing.” However, in the context of a complex multinational supply chains, convergence of standards will be critical, she said.

Mexico Working on Regulation

Fernando Fon, director of Medical and Regulatory Affairs for the Mexican Association of Pharmaceutical Research Industries (AMIIF), said Mexico will be increasingly affected by non-communicable diseases, and that biotherapeutics will be sought to answer those diseases.

Mexico is currently undertaking a major reform of its health system, he said. Mexico has several institutions in the Mexican health system, each with its own area of medicine and its own resources. The Mexican regulatory authority, which is composed of several commissions. reviews all medicines, he said.

Mexico has a number of technical regulations on biotherapeutic medicines, he said, adding that all products need to be reviewed before being given the status of innovator product or biosimilar.

Ongoing issues regarding biosimilar products include clinical trials for bio-comparability, interchangeability, immunogenicity, and pharmacovigilance, he said.

Patients: Need Information and Access

Alison Lightborne, policy manager at the International Alliance of Patients Organizations (IAPO), said innovations and medicines should be patient-centred, and medicines should be safe and accessible.

There is a perceived lack of necessary expertise to understand the issues, she said, and whether it is relevant for patients to understand what is going on at the international level. There is also a lack of understanding of the value of patient involvement, she said.

 

Image Credits: Catherine Saez