Biological Medicines Research Articles

Summary of Research: Effects of Adalimumab-adbm Versus Adalimumab Reference Product on Patient-Reported Outcomes in Rheumatoid Arthritis: Results from VOLTAIRE-RA.

This Summary of Research overviews the results of a study that looked at patient-reported outcomes in the VOLTAIRE-RA trial (NCT02137226), originally published in Rheumatology and Therapy. A biosimilar is a biologic medicine made to be very similar to the original biologic medicine (also known as the reference product). The VOLTAIRE-RA trial compared the efficacy and safety of an adalimumab biosimilar (Cyltezo®, adalimumab-admb) with the adalimumab reference product, Humira®, in people with rheumatoid arthritis. As part of the VOLTAIRE-RA study, participants took either adalimumab-adbm or adalimumab reference product for 24weeks. Patient-reported outcomes were captured after 12weeks and after 24weeks of treatment to assess the effects of treatment on each participant's health-related quality of life. People with rheumatoid arthritis who were given adalimumab-adbm or adalimumab reference product experienced similar clinically meaningful improvements in their health-related quality of life after 12weeks of treatment. A high proportion of people in this trial who were given adalimumab-adbm or adalimumab reference product reported greater improvement versus a reference US population matched by age and sex. This is notable, as it represents a treatment goal that was difficult to achieve in earlier rheumatoid arthritis trials of non-biologic treatments.

Systematic review with meta-analysis of the effectiveness of subcutaneous biologics versus intravenous biologics in inflammatory bowel diseases

Background Biologic therapies are commonly used for inflammatory bowel disease (IBD) patients. Multiple biologic medicines can now be given both intravenously and subcutaneously. The different administration routes present provide different advantages regarding dose escalation, healthcare resource utilisation, pharmacokinetics, convenience and safety. Comparator effectiveness studies between intravenous and subcutaneous administration are lacking. Aim Our primary outcome was to compare the effectiveness between intravenous and subcutaneous biologics in rates of clinical remission. Methods We performed a systematic review and meta-analysis to include all relevant articles from MEDLINE (Ovid), EMBASE, PubMed and Cochrane Central Register of Controlled Trials from 1 January 2003 to 28 January 2024. Studies that compared intravenous and subcutaneous administration of the same biologic therapy in IBD patients and reported effectiveness outcomes were included. This study was registered on PROSPERO (CRD42023442675). Results Twenty studies met the inclusion criteria for the systematic review. Nine vedolizumab cohort studies were meta-analysed for clinical remission and no difference was found in clinical remission rates between intravenous and subcutaneous administration (relative risk = 0.99; 95% confidence interval: 0.88, 1.11). Six infliximab cohort studies were meta-analysed for clinical remission and no difference was found in clinical remission rates between intravenous and subcutaneous administration (relative risk = 0.91; 95% confidence interval: 0.77, 1.08). Conclusions Our findings in the first meta-analysis comparing the effectiveness of intravenous and subcutaneous biologic therapies in IBD suggest there is no difference in the effectiveness between these two administration routes. However, further high-quality studies, particularly head-to-head studies are needed to confirm this finding.

Contemporary treatments for mid-substance achilles tendinopathy: a review

Mid-substance Achilles tendinopathy is primarily a degenerative condition that frequently affects quality of life, especially for patients wanting to continue a high level of activity. It can differ from insertional Achilles tendinopathy both in terms of its epidemiology as well as its management strategies. Currently, numerous treatment options exist in the literature for this fairly common musculoskeletal condition. However, many of these treatments remain experimental with no substantial evidence for efficacy. A number of these options, including regenerative and biologic medicines, have nonetheless demonstrated improvements in patient-reported outcomes and promising potential. As such, there remains no standard approach for management beyond stretching/exercise therapy. This article reviewed the current literature surrounding treatment options and provided summaries and recommendations of eight treatment modalities for this condition. It is intended to serve as a general review as well as an objective evaluation of recent evidence that may provide some guidance for healthcare providers when discussing treatment options with patients.

Regulation of exosomes as biologic medicines: Regulatory challenges faced in exosome development and manufacturing processes.

With advances in medical technology, extracellular vesicles, also known as exosomes, are gaining widespread attention because of their potential therapeutic applications. However, their regulatory landscape is complex and varies across countries because of their unique intracellular mechanisms of action. The diversity of manufacturing techniques renders their standardization challenging, leading to a fragmented regulatory landscape. The current global regulatory framework of exosomes can be broadly classified into two strategies: one involves elucidating constituent components within exosomes and the other involves examining the physiological repercussions of their secretion. When using exosomes as therapeutic agents, they should be governed similarly to biological medicinal products. Similar to biologics, exosomes have been analyzed to determine their particle size and protein composition. An exosome-based therapeutic agent should be clinically approved after understanding its molecular composition and structure and demonstrating its pharmacokinetics and therapeutic efficacy. However, demonstrating the pharmacokinetics and therapeutic efficacy of exosomes is challenging for regulatory agencies. This article reviews the technical characteristics of exosomes, analyzes the trends in regulatory laws in various countries, and discusses the chemistry, manufacturing, and control requirements of clinical applications.

Extracellular vesicles the delivery of drugs through genetic engineering

Researchers from a variety of disciplines are investigating the use of extracellular vesicles (EVs) as delivery vehicles for pharmaceutical solutions. In order to make the most of the therapeutic potential of EVs, various loading strategies have been devised. Despite the widespread application of exogenous methods, endogenous approaches are becoming increasingly preferred instead. Medicinal macro molecules such as proteins and nucleic acids can be loaded with relative ease using this technology that manipulates parental cells through genetic engineering. We examine the most effective ways for EV loading and demonstrate why endogenous is superior. Extracellular vesicles (EVs), which are able to transport pharmaceuticals, have the potential to tackle the problems of biologic therapeutic stability and off-target undesirable effects. In addition, we investigate the most recent findings and applications of this innovative method in order to shed light on the numerous potential therapeutic possibilities in the field of EV-based treatments. The possibility of endogenous loading of EVs with big biological medicines has been brought to light by recent research. In order to optimize the loading of biologic drugs in extracellular vesicles (EVs), researchers have been able to apply cargo selection and loading pathway molecules thanks to advancements in EV biogenesis. It has been established that endogenous EV loading is successful in preclinical in vivo trials, which demonstrates its promise in a variety of therapeutic situations.

Immune-related adverse events of antibody-based biological medicines in cancer therapy.

Recombinant antibodies (Abs) are an integral modality for the treatment of multiple tumour malignancies. Since the Food and Drug Administration (FDA) approval of rituximab as the first monoclonal antibody (mAb) for cancer treatment, several mAbs and antibody (Ab)-based therapies have been approved for the treatment of solid tumour malignancies and other cancers. These Abs function by either blocking oncogenic pathways or angiogenesis, modulating immune response, or by delivering a conjugated drug. The use of Ab-based therapy in cancer patients who could benefit from the treatment, however, is still limited by associated toxicity profiles which may stem from biological features and processes related to target binding, alongside biochemical and/or biophysical characteristics of the therapeutic Ab. A significant immune-related adverse event (irAE) associated with Ab-based therapies is cytokine release syndrome (CRS), characterized by the development of fever, rash and even marked, life-threatening hypotension, and acute inflammation with secondary to systemic uncontrolled increase in a range of pro-inflammatory cytokines. Here, we review irAEs associated with specific classes of approved, Ab-based novel cancer immunotherapeutics, namely immune checkpoint (IC)-targeting Abs, bispecific Abs (BsAbs) and Ab-drug-conjugates (ADCs), highlighting the significance of harmonization in preclinical assay development for safety assessment of Ab-based biotherapeutics as an approach to support and refine clinical translation.

Biological Medicines Prepared Using Vibration Processing Are Able to Influence Their Targets Without Direct Contact With Them.

Recently, there has been a radical change in understanding of the nature of drugs based on highly diluted solutions. It has been established that their activity does not depend on the content of the original substance in dilutions, but is a consequence of the technological processing (TP) of dilutions with vibration, which accompanies each dilution during the preparation of solutions and, among others, leads to the formation of nanoparticles with certain properties. Repeated vibration treatment leads to the appearance of modifying activity that is absent in the original substance, and these effects of TP solutions can be exerted without direct contact with their targets, which clearly indicates the physical nature of the TP solution's activity. In the framework of this article, a statistically significant effect of TP antibodies to the insulin receptor on glucose consumption by CHO cells both with and without contact exposure, as compared with control (P < 0.05) was shown in the vast majority of the experiments. The obtained results shed light on a possible source of activity of drugs based on TP antibodies, which should be associated with the applied vibration effect and can manifest itself both with contact exposure and without it.

Sustaining competition for biosimilars on the pharmacy benefit: Use it or lose it.

Congress passed the Biologic Price Competition and Innovation Act of 2009, specifically to offer market competition as a counterweight to the rising costs of biologic medicines. As of April 15, 2024, 49 biosimilars have been approved by the US Food and Drug Administration in 15 biologic categories. Biosimilar competition has been undeniably successful: Through 2022, biosimilars have saved the US health system $23.6 billion, without significant care disruption or reduced quality. Through 2023, adalimumab biosimilar competition has added an additional $6.5 billion to this total, primarily through greater rebates from the reference manufacturer. Despite launching at discounts as great as 85%, adalimumab biosimilars have not been given preferred formulary positioning in the vast majority of cases and have thus gained only 3% of market share through 2023, largely because of payers' and pharmacy benefit managers' preference for rebates over discounts. This situation may negatively influence future biosimilar development, posing a threat to a biosimilar pipeline that represents hundreds of billions in savings over the next 10 years.

RWD77 Time to Reimbursement in Kazakhstan for Novel Biologic Medicines Approved during the Period 2013-2022

RWD77 Time to Reimbursement in Kazakhstan for Novel Biologic Medicines Approved during the Period 2013-2022

The clinical assessment of changes in bone density in rheumatoid arthritis patients': Role of DEXA scan and bone turnover biomarkers

In addition to generalised of bone loss and a higher fracture risk, rheumatoid arthritis (RA) causes periarticular bone erosions. Improvements in bone density/erosion and turnover may not go hand in hand with a positive clinical response to biological anti-inflammatory drugs assesed by disease activity score 28 (DAS28) in RA patients. This study aimed to understand how biologic anti-inflammatory drugs affect bone density, erosion, and turnover in RA patients. We examined bone mineral density (BMD) and bone turnover biomarkers. The study population consisted of 62 RA patients, 49 (79%) of whom were female and 13 (21%) of whom were male. The patients ranged in age from 40 to 79 years old. The patients' BMD was measured using a DEXA scan, and their plasma levels of bone turnover biomarkers CTX and osteocalcin were quantified utilizing an ELISA. BMD of the hip and lumbar spine in responder patients rose after therapy by 0.001g/cm2 (0.11 percent, p0.001 vs. before treatment) and 0.0396g/cm2 (3.96 percent, p0.001 vs. before treatment), respectively. Clinically non-responder patients' DAS28 revealed minor reductions in hip BMD values of −0.008g/cm2 (−0.78 percent, p0.001 vs. before therapy), as well as an improvement in lumbar spine BMD of 0.03g/cm2 (3.03 percent, p0.001 vs. before treatment). After 12 weeks of therapy, the CTX levels in responder patients dropped from 164 125 pg/ml to 131 129 pg/ml. Osteocalcin levels in non-responder patients increased substantially from 11.6 ng/ml to 14.9 ng/ml after 12 weeks of therapy compared to baseline (p = 0.01). Treatment with biologic anti-inflammatory medicines decreases widespread bone loss in RA patients' hip and lumbar spine. The beneficial effects of therapy on BMD were not associated with changes in disease activity of RA patients. Changes in plasma levels of bone turnover biomarkers such as sCTX and osteocalcin confirmed the treatment's beneficial effects.

Plain language review: what are biosimilar medicines and how can they be used to treat people with cancer?

The aim of this plain language review article is to help you to understand biosimilar medicines (called biosimilars) by giving a summary of biologic medicines and biosimilars. It is based on the experience of an international panel of physicians with expertise on biosimilars who discussed and agreed on the topics and information included in this review article. Biologic medicines are medicines that come from living organisms such as bacteria and animal or plant cells. Biosimilars are a group of approved biologic medicines that are similar to original biologic medicines that are already available. This review explains how biosimilars are developed and approved, and how they are used to treat people with cancer. It also answers some common important questions people with cancer might have when taking biosimilars. The purpose of this plain language review is to help you to understand the findings from recent research. This review reports information from peer-reviewed literature and other sources available in the public domain (e.g., regulatory documents or product information labels). The findings may differ from those of other review articles. Health professionals should make treatment decisions based on all available evidence.

Novel bispecific nanobody mitigates experimental intestinal inflammation in mice by targeting TNF-α and IL-23p19 bioactivities.

Inflammatory bowel diseases (IBDs) pose significant challenges in terms of treatment non-response, necessitating the development of novel therapeutic approaches. Although biological medicines that target TNF-α (tumour necrosis factor-α) have shown clinical success in some IBD patients, a substantial proportion still fails to respond. We designed bispecific nanobodies (BsNbs) with the ability tosimultaneously target human macrophage-expressed membrane TNF-α (hmTNF-α) and IL-23. Additionally, we fused the constant region of human IgG1 Fc (hIgG1 Fc) to BsNb to create BsNb-Fc. Our study encompassed in vitro and in vivo characterization of BsNb and BsNb-Fc. BsNb-Fc exhibited an improved serum half-life, targeting capability and effector function than BsNb. It's demonstrated that BsNb-Fc exhibited superior anti-inflammatory effects compared to the anti-TNF-α mAb (infliximab, IFX) combined with anti-IL-12/IL-23p40 mAb (ustekinumab, UST) by Transwell co-culture assays. Notably, in murine models of acute colitis brought on by 2,4,6-trinitrobenzene sulfonic acid（TNBS) and dextran sulphate sodium (DSS), BsNb-Fc effectively alleviated colitis severity. Additionally, BsNb-Fc outperformed the IFX&UST combination in TNBS-induced colitis, significantly reducing colon inflammation in mice with colitis produced by TNBS and DSS. These findings highlight an enhanced efficacy and improved biostability of BsNb-Fc, suggesting its potential as a promising therapeutic option for IBD patients with insufficient response to TNF-α inhibition. A bispecific nanobody (BsNb) was created to target TNF-α and IL-23p19, exhibiting high affinity and remarkable stability. BsNb-Fc inhibited the release of cytokines in CD4+T cells during co-culture experiments. BsNb-Fc effectively alleviated colitis severity in mouse model with acute colitis induced by DSS or TNBS, outperforming the IFX&UST combination.

Epitope Identification of an mGlu5 Receptor Nanobody Using Physics-Based Molecular Modeling and Deep Learning Techniques.

The world has witnessed a revolution in therapeutics with the development of biological medicines such as antibodies and antibody fragments, notably nanobodies. These nanobodies possess unique characteristics including high specificity and modulatory activity, making them promising candidates for therapeutic applications. Identifying their binding mode is essential for their development. Experimental structural techniques are effective to get such information, but they are expensive and time-consuming. Here, we propose a computational approach, aiming to identify the epitope of a nanobody that acts as an agonist and a positive allosteric modulator at the rat metabotropic glutamate receptor 5. We employed multiple structure modeling tools, including various artificial intelligence algorithms for epitope mapping. The computationally identified epitope was experimentally validated, confirming the success of our approach. Additional dynamics studies provided further insights on the modulatory activity of the nanobody. The employed methodologies and approaches initiate a discussion on the efficacy of diverse techniques for epitope mapping and later nanobody engineering.

A Regulatory Perspective on Biosimilar Medicines.

By definition, biosimilar medicinal products are biological medicinal products that are similar to other biological medicinal products that are already on the market-the reference medicinal products. Access to biosimilar medicines is a current reality. However, to achieve this goal, it is extremely important to consistently and scientifically substantiate the regulatory requirements necessary for biosimilar medicines when accessing the market. Based on an analysis of the raw materials and the type of methods used in the manufacturing processes of biological medicines, it is known that this tends to be more complex for the quality of the finished product than the manufacture of molecules obtained through a chemical process. It is then relevant to highlight the main differences between both products: biological medicines manufactured using biotechnology and the current generics containing active pharmaceutical ingredients (APIs) obtained from synthetic processes. Once arriving at the approval process of these medicinal products, it is imperative to analyse the guidance documents and the regulatory framework that create the rules that allow these biosimilar medicinal products to come to the market. The present review aimed at documenting comparatively the specific provisions of European legislation, through the European Medicines Agency (EMA), as well as the legislation of the United States of America, through the Food and Drug Administration (FDA). This was then translated into a critical appraisal of what concerns the specific criteria that determine the favourable evaluation of a biosimilar when an application for marketing authorisation is submitted to different regulatory agencies. The gathered evidence suggests that the key to the success of biosimilar medicines lies in a more rigorous and universal regulation as well as a greater knowledge, acceptance, and awareness of health professionals to enable more patients to be treated with biological strategies at an earlier stage of the disease and with more affordable medicines, ensuring always the safety and efficacy of those medicines.

Leveraging the holistic benefits of biosimilars in Europe – part 2: how payers can safeguard the future of a healthy biosimilar market environment

ABSTRACT Introduction Biosimilars have improved access to biologic medicines; however, historical thinking may jeopardize the viability of future markets. Areas covered An expert panel of eight diverse European stakeholders provided insights about rethinking biosimilars and cost-savings, reducing patient access inequalities, increasing inter-market equity, and improving education. The insights reported here (Part 2) follow a study that provides perspectives on leveraging the holistic benefits of biosimilars for market sustainability based on independent survey results and telephone interviews of stakeholders from diverse biosimilar markets (Part 1). Directional recommendations are provided for payers. Expert Opinion The panel’s market maturity framework for biosimilars has three stages: ‘Invest,’ ‘Expand’ and ‘Harvest.’ Across market stages, re-thinking the benefits of biosimilars beyond cost-savings, considering earlier or expanded access/new indications, product innovations, and re-investment of biosimilar-generated cost-savings should be communicated to stakeholders to promote further engagement. During ‘Expand’ and ‘Harvest’ stages, development of efficient, forward-looking procurement systems and mechanisms that drive uptake and stabilize competition between manufacturers are key. Future biosimilars will target various therapy areas beyond those targeted by existing biosimilars. To ensure a healthy, accessible future market, stakeholders must align their objectives, communicate, collaborate, and coordinate via education, incentivization, and procurement, to maximize the totality of benefits.

An Overview of Biosimilars-Development, Quality, Regulatory Issues, and Management in Healthcare.

Biological therapies have transformed high-burden treatments. As the patent and exclusivity period for biological medicines draws to a close, there is a possibility for the development and authorization of biosimilars. These products boast comparable levels of safety, quality, and effectiveness to their precursor reference products. Biosimilars, although similar to reference products, are not identical copies and should not be considered generic substitutes for the original. Their development and evaluation involve a rigorous step-by-step process that includes analytical, functional, and nonclinical evaluations and clinical trials. Clinical studies conducted for biosimilars aim to establish similar efficacy, safety, and immunogenicity, rather than demonstrating a clinical benefit, as with the reference product. However, although the current knowledge regarding biosimilars has significantly increased, several controversies and misconceptions still exist regarding their immunogenicity, extrapolation, interchangeability, substitution, and nomenclature. The development of biosimilars stimulates market competition, contributes toward healthcare sustainability, and allows for greater patient access. However, maximizing the benefits of biosimilars requires cooperation between regulators and developers to ensure that patients can benefit quickly from access to these new therapeutic alternatives while maintaining high standards of quality, safety, and efficacy. Recognizing the inherent complexities of comprehending biosimilars fully, it is essential to focus on realistic approaches, such as fostering open communication between healthcare providers and patients, encouraging informed decision-making, and minimizing risks. This review addresses the regulatory and manufacturing requirements for biosimilars and provides clinicians with relevant insights for informed prescribing.

Biosimilars Would Reduce Health Care Costs But Are Yet Poorly Known - Patient Survey Study Among Biological Medicine Users.

From the beginning of the year 2024, gradually implemented amendment to the Medicines Act will enable interchange of biological medicines in pharmacies in Finland. The legislative change aims to reduce health care costs. Opinions of the biological medicine users regarding substitution in pharmacies and knowledge about biological medicines were determined by a patient survey in community pharmacies and via patient organizations in Finland. In total, 199 users of biological medicines responded to the survey. The respondents did not always know which product they were using, an originator or a biosimilar. This was more prominent among patients with biosimilars determined according to brand names. The more recently the biological medicine had been prescribed, the more likely a biosimilar was in use. Only about 40% of the respondents would enable pharmacies to substitute their biological medicine to a lower cost product. The most common obstacle to the idea of interchange in pharmacies was that the respondents wanted to keep the product the doctor had prescribed for them. In general, biosimilar users were more accepting towards possible interchange than originator users. Although the most recent treatments appear to be initiated with biosimilars, interchange in pharmacies could enable an efficient way to lower health care costs. However, guidance and awareness regarding biosimilars and biological medicines in general would improve patients' willingness towards the change, but also help pharmacists and prescribing doctors in their meaningful role.

P162 The Biosimilar Switch: IBD nurse's experience in Our Lady of Lourdes Hospital

Abstract Background A biological medication contains an active substance that is produced from a biological source such as living cells, hormones or enzymes. The active substance in a biological medicine is what makes the medicine work. Biological medicines are also called biologics. A biosimilar medicine is a biological medicine that is developed to be highly similar to an existing biologic but they are not identical and so cannot be considered to be generics. Biosimilars were introduced in Ireland in 2014. In 2018, Our Lady of Lourdes Hospital commenced a procurement programme to decide which Infliximab biosimilar to switch our patients to. This process would allow for a huge cost-saving to the hospital budget and also allowed for the allocation of a whole-time clinical nurse specialist to add the IBD nursing team. The infliximab biological switch was then carried out starting in October 2019. All patients received a letter explaining the switch and a booklet to explain the meaning of biosimilars. The patients were then either phoned or spoken to in person by either the IBD nurse or a GI pharmacist, and any questions or concerns addressed. Methods A patient satisfaction survey was sent to each patient 6 months after the switch. Each questionnaire was sent with a prepaid return envelope. The questionnaire consisted of 7 questions with tick box answers. 1. Gender? 2. Age? 3. Did you receive a letter and information booklet in the post prior to the day of your infusion switch. 4. Did you get the opportunity to talk to someone on the phone prior to your infusion? 5. Did you get the opportunity to speak to a nurse or pharmacist on the day of your infusion? If so who? 6. Were you given a named person to contact if you had any issues after our first infusion? 7. Were you happy with the overall experience of the infliximab biosimilar switch? Results 86 patients were switched from the originator to the biosimilar Flixabi. 22 responses were received. 1. 11 male; 11 female 2. Age 16-19 - 2; 20-29 - 1; 30-39 - 4; 40-49 - 4; 50-59 - 9; 70-79 - 1; preferred not to answer - 1. 3. 20 received the letter and booklet; 2 did not. 4. 15 spoke to someone on the phone; 6 did not and 1 could not remember. 5. 22 - spoke to a nurse; 0 - pharmacist. 6. 20 - yes; 2 - no. 7. 21 - yes; 1 - unsure. Conclusion Of the 86 patients who were switched 22 responded to the questionnaire. 21 patients were happy with their overall experience with how the switch was conducted.

Biologic and Chemical Medicines – Differences in Terms of Basic Scientific and Regulatory Aspects

Biologic and Chemical Medicines – Differences in Terms of Basic Scientific and Regulatory Aspects

Comparative price analysis of biological medicines: disparities generated by different pricing policies.

Introduction: Biological medicines have been assuming an important role among the therapeutic options for several diseases, however, due to their complex production process, the products obtained from this technology have a high added value and do not reach the purchasing power of most patients, which overwhelms the budget of health systems. With the development of biosimilars, which have reduced production costs, it is expected that access to biological medicines will become broader. However, in Brazil, the criteria for determining the price of biosimilars, unlike the generic policy in the country, do not foresee a price reduction due to the reduction of development costs. Objective: To understand the impact of the current model of economic regulation on the availability and access of these products in the country, based on a comparative analysis in selected countries, and identify trends that can help to expand the availability and access to biological medicines. Method: Quantitative and qualitative study, to identify the variation between the entry prices of biological medicines in Brazil and in selected countries, as well as the differences in the economic regulation policies established in these countries. Results: The results demonstrate that the current pricing model in Brazil has generated distortions in the prices of biosimilars in the market, which, consequently, makes it difficult for the population to access this category of products, in addition to allowing unsustainable market practices for the systems of public and private health in Brazil. It was also found that most of the analyzed countries, unlike Brazil, seek to harmonize the prices of different brands of the same molecule marketed in the country and with the international market, in addition to establishing incentive policies for indication and replacement by biosimilars, which expands the participation of biosimilars in the market significantly. Conclusion: Based on the data presented, it is concluded that it is essential to build a broader political and regulatory debate on the market for biologicals and biosimilars in the country to guarantee the access of the Brazilian population to more cost-effective technologies, generate a more competitive market and consequently contribute to the financial sustainability of health systems.