Plain Language Summary
Biosimilars, which are also known as biopharmaceuticals, are drugs designed to be as efficient and as safe as original drugs and developed using biological products, such as bacteria, yeast, and cells. These biosimilar drugs tend to be cheaper and, for this reason, have gained much attention for the treatment of diseases such as multiple sclerosis (MS). However, the regulation of biosimilars is still a matter of discussion. This study brings a list of recommendations from the Latin American Forum of Experts in Multiple Sclerosis regarding this subject. Forum members agree that current regulations should be strictly applied; biosimilar products should be traceable; substitutions between biosimilar and original biological drugs should be controlled; programs must be implemented to detect any safety problems associated with the use of original and biosimilar drugs; national studies should be conducted in Latin America to identify possible differences in the use of these medications for MS; the well-being and safety of patients must be prioritized over economic aspects; and healthcare professionals should be trained and educated regarding the use of original biological or biosimilar products for the treatment of MS.
Introduction
Biosimilar drugs are biological products with an active ingredient that is highly similar, but not identical, to a reference biological product that has been authorized for use by a regulatory agency. These are new versions of reference products that have been developed independently after the patent of the original product has expired, driven by the high costs of reference biological drugs, which affect patients and the whole healthcare system [
1]. Biologic therapies were introduced over a decade ago for the management and treatment of chronic inflammatory diseases [
2] and their regulation remains a worldwide discussion.
Biosimilars differ from synthetic chemical generic products because they originate from a living organism, such as bacteria, yeast, and mammalian cells [
3]. This implies the occurrence of posttranslational modifications, such as glycosylation, which lead to heterogeneity and intrinsic variability [
2]. Moreover, biological products have high molecular weight and a complex, heterogeneous, and only partially characterized structure. They also present higher risk of immunogenicity, with variable composition, quality, pharmacokinetics, and pharmacodynamics, demanding robust characterizations of these molecules [
4].
Biosimilar drugs rely on an extremely complex manufacturing process that is impossible to reproduce without adequate information. Small changes to the manufacturing process can cause important alterations in pharmacokinetics, pharmacodynamics, quality, efficacy, and product safety. However, most of the information regarding the manufacturing process of biological products (e.g., cell line, cultures, fermentation temperature, pH, growth media, filtration, and purification) is not fully accessible because of proprietary status, which poses an important challenge to biosimilar developers [
3]. Although biosimilars and complex molecules (such as glatiramoids) cannot be expected to be identical to reference products with the current technology available, developers of biopharmaceuticals should seek to manufacture drugs of compatible quality levels [
1]. Beyond production, the whole scheme of packing, distributing, and storing the product may affect its final efficacy and/or safety.
The principles applied to generic drugs are not compatible to define equivalence between the original and biosimilar biological compound. A detailed evaluation is needed to compare, among other aspects, efficacy and safety to establish biosimilarity between two molecules. This distinction also affects the nomenclature used for biological products, with some stakeholders preferring that biosimilars have the same International Nonproprietary Name (INN) of their reference product—a clear misconception [
5].
The use of biosimilar drugs has become widespread in Latin America partially with the interest in reducing the costs of biological therapies. In some countries, biosimilar prices may be up to 40% lower than the branded product [
6]. This favors the sustainability of health systems and improves patients’ access to these therapies. Moreover, by reducing costs, one can redirect resources to other healthcare priorities [
7]. However, this precept may not always be respected and some countries may opt for drugs exclusively on the basis of the cost of the product.
With patents for some molecules used in the treatment of multiple sclerosis (MS) expiring, biosimilar options have emerged in Latin America. Original immunomodulatory drugs used for MS treatment have already lost their patent and newer drugs will lose their patents within the next decade [
8]. Biosimilars have become a reality for countries such as Argentina, Colombia, Ecuador, Mexico, and Peru, but these drugs are expected to also enter markets in other countries in the region. Regulations and decision-making processes regarding the approval and use of biopharmaceuticals vary in Latin America according to each country’s reality and public policies [
4].
The generalized use of biosimilar drugs entails the definition and fulfillment of requirements that can guarantee the efficacy, safety, and quality of these drugs during their commercialization, thus protecting the well-being and health of patients. In fact, the introduction of new treatment options in the market should be driven by the interest of patients, not the interest of governments regarding expenditure [
8]. Regarding the safety of these drugs, pharmacovigilance programs should encompass reports of adverse effects in the post-marketing phase. However, this is not always fulfilled, especially considering that few Latin American countries have adequate post-marketing monitoring systems actively in place [
5]. Recent new European legislation on pharmacovigilance has been implemented to guarantee adequate risk management through reports on adverse reactions and compilation of data from all patients [
9].
The Latin American Forum of Experts in Multiple Sclerosis has been active for nearly a decade and is completely independent from the pharmaceutical industry. It is a space for learning, discussion, and consensus on MS. The last couple of meetings of the forum have allowed us to address this new period of global changes observed in therapeutic indications.
The objective of the present study was to obtain current information from each Latin American country represented in the forum regarding (a) approval of biosimilar drugs by regulatory agencies; (b) use of biosimilars, pharmacovigilance plans, and risk management; and (c) updates in the knowledge of different molecules.