Reference Biological Product Research Articles

Detection and isolation of Leishmania infantum from natural infected dog in Türkiye

Some clinical signs such as cachexia, alopecia, exfoliative dermatitis, hair loss, and swollen lymph nodes were observed in a one-year-old crossbred male dog living in a rural area of Kirikkale province, Türkiye, was presented to the veterinary clinic by its owner. Anaemia, leucopenia, hyperglobulinemia, and bilirubinemia were detected. Seropositivity was detected using Leishmania IgG/IgM Rapid Test. The amastigote forms of the parasite were observed in the lymph node aspirates. Viable promastigotes were observed in the samples obtained from the Novy-MacNeal-Nicolle medium (NNN) tubes. The parasite DNA was extracted from the promastigotes produced in the NNN medium using a DNA extraction kit according to the manufacturer's instructions. The specific bands indicating the gene regions of L. infantum (350 bp and 730 bp for HSP20 and HSP70, respectively) were observed. Additionally, BLASTn analysis revealed 100 % similarity with GenBank-deposited L. infantum sequences. The sequences were submitted to GenBank (Accession numbers: OR806945 and OR806946). According to the author's knowledge, it is the first dog isolate deposited in the collection of the Microbiology Reference Laboratories and Biological Products Department, General Directorate of Public Health, Ministry of Health, Ankara, Türkiye. The isolate (TR_L. infantum CanL-1_damla) has been preserved by cryopreservation at −150 °C for further studies.

Safety of Rituximab biosimilar (Riximyo®) following a single switch from the reference product in patients with Non-Hodgkin’s lymphoma: a retrospective study

Unlike small molecule drugs and generic products, the active component of biologics and biosimilars are not identical chemical entities. Despite bioequivalence, there is limited evidence in clinical practice (i.e. Phase IV post-marketing surveillance) regarding the safety of biosimilar rituximab and even less so for “switching therapy” with respect to safety. Drug substitution by switching aims to realise cost savings by changing therapy involving a reference (biologic) product to a biosimilar. A retrospective analysis of safety outcomes including treatment-emergent adverse effects (TEAEs), rates of death and discontinuation of therapy, for all patients that received switching therapy (from reference to biosimilar rituximab, n = 33) was compared to patients who did not did not switch therapy (received biosimilar rituximab only, n = 18) at an Australian metropolitan cancer centre, over a six-month period. There was no statistical significant differences for any safety outcomes examined. Switching therapy for patients receiving rituximab does not lead to poorer safety outcomes.

Concomitant Hidradenitis Suppurativa and Pyoderma Gangrenosum - Adalimumab Biosimilar can Help: A Case Report

Introduction: Systemic inflammation leading to various types of disorders with mainly cutaneous manifestations is not uncommon. Hidradenitis suppurativa (HS) and pyoderma gangrenosum (PG) may be the consequences of such situation and develop concomitantly in a single patient. Case Presentation: We present herewith a case of HS along with PG which was managed with Adalimumab biosimilar. Discussion: HS and PG are both uncommon inflammatory skin conditions linked to systemic inflammatory disorders. Adalimumab, a tumor necrosis factor-alpha antagonist, is used to treat a variety of inflammatory disorders. Biosimilars are biologics that are extremely similar to an already-approved reference biological product but are produced by a distinct company. Several biosimilar variants of adalimumab have been developed and approved by regulatory authorities in various countries. They can be used as alternatives to the reference product, resulting in potential cost-savings and increased treatment accessibility. Conclusions: Biosimilars of adalimumab have an important role in the management of HS and PS considering their favorable outcome.

Sustainable Integration of US Food and Drug Administration-Approved Biosimilars: Pharmacy- Versus Physician-Driven Change.

Biosimilars are clinically equivalent to branded products yet cost significantly less. Interchangeability is a US Food and Drug Administration (FDA) designation that allows generic drugs to be substituted for reference drugs at the pharmacy, without a physician's consent. Currently, no oncologic biosimilar has FDA approval for interchangeability. Building on pharmacy auto-substitution processes with therapeutic interchange, Plan-Do-Study-Act methodology was used to automate conversions from reference biological products to Pharmacy and Therapeutics-/Physician-approved biosimilars. After establishing the baseline metrics, cycle 1 focused on full staff education (completed July 2020) with systematic pharmacy-driven biosimilar conversion initiated in September 2020 for rituximab, trastuzumab, and bevacizumab. Physician-initiated conversion of Neulasta biosimilar products was encouraged but not mandated. During cycle 2 (May 1, 2021-November 30, 2021), pharmacy-driven Neulasta biosimilar conversion was mandated. In cycle 3 (December 1, 2021-April 30, 2023), stakeholder education was reinforced and the sustainability of conversions was confirmed. Systematic pharmacy-driven conversion to biosimilar products improved over cycles 1 and 2 from baseline: 1.8% to 90.3% for rituximab, 9.2% to 89.7% for trastuzumab, and 20.5% to 96.1% for bevacizumab. Physician-driven biosimilar conversion for Neulasta was lower at 12.7% through April 2021. Pharmacy-driven Neulasta biosimilar conversion was initiated during cycle 2, resulting in a conversion rate of 39.7%. The conversion rates remained sustainable through April 2023. Pharmacy-driven auto-substitution of biosimilar products results in rapid and statistically significant biosimilar adoption. The pharmacy-based substitution approach was found to be far more effective than physician-driven substitution. Rapid conversion from branded products to FDA-approved biosimilar is feasible, measurable, and sustainable and can be scaled. Barriers to Neulasta conversion warrant further investigation.

Potential for biosimilars in rheumatology in Africa

Biosimilars are products which are highly similar to a reference biologic product (RBP). In Africa, regulatory frameworks for biosimilar approval are still in development in many countries and few biosimilars...

Biosimilar of analogue of insulin glargin: proven safety, effectiveness, interchangeability

Diabetes mellitus (DM) is a global medical and social problem, its prevalence is steadily increasing throughout the world. The significance of DM is due to early disability and high mortality, primarily from macro- and microvascular complications of diabetes mellitus. Adequate therapy and its timely intensification in order to achieve an optimal individual level of glycemic control is an important aspect in this regard. Insulin therapy is indicated for all patients with type 1 diabetes mellitus. In type 2 diabetes the appointment of basal insulin is necessary if it is impossible to adequately control glycemia with oral drugs. Treatment of diabetes all over the world and in our country requires significant healthcare costs. The problem of reducing the cost of drug therapy in all countries of the world is currently being solved by the admission to the market of biosimilar drugs (biosimilars). A biosimilar (biosimilar) medicinal product (biosimilar, biosimilar) is a biological product similar in terms of quality, efficacy and safety to a reference biological medicinal product in the same dosage form and having an identical route of administration. Insulin glargine is one of the commonly used drugs in clinical practice and is of interest for reproduction. Biosimilar currently registered. This is a biosimilar of domestic production of insulin glargine with proven bio- and therapeutic equivalence, immune safety, good tolerance, recognized as interchangeable with the original insulin glargine. Indications and contraindications for use can be extrapolated to biosimilar without fear of reducing efficacy and the development of adverse events.

Evaluation of the drug utilization of biosimilar medicinal products containing monoclonal antibodies: A systematic review

Aim: The objective is to study the availability and affordability of biosimilar medicinal products containing monoclonal antibodies, measure their drug utilization, and evaluate the rational drug use globally through analysis and systematic review of scientific articles published in the scientific literature. Materials and methods: The documentary analysis of scientific publications was carried out by specific keywords in MEDLINE database, Central Medical Library, and national peer-reviewed scientific journals in Bulgaria for the period from January 2008 to May 2020. 100 scientific publications have been found for a period of 12 years. Articles were selected according to PRISMA. Analyses include 17 articles that fully meet the preset criteria. Descriptive and variational analyses were carried out as basic statistical analyses. Mean values, standard deviation, minimum, maximum, and 95% confidence intervals have been determined. Results and discussion: Studies on this topic in EU Member States are obviously of interest, but publication activity is not high—only 17 scientific publications over a 12-year period. All 17 studies reflect cost savings after switching from a reference biological medicinal product to a biosimilar medicinal product, and the reduction in budgetary costs as a weighted average is about 30% of the total budgetary costs of biological therapies for the first 5 years. All 17 studies have reported that the use of biosimilar medicinal products is rather low. Although the quality, safety, and efficacy of biosimilar medicinal products have been unequivocally established, their introduction to the market is still insufficient.

Biosimilar development and review process in the BRICS-TM countries: Proposal for a standardized model to improve regulatory performance

ABSTRACT Objectives The current study is aimed at proposing a standardized regulatory model for biosimilar development and approval for adoption by BRICS-TM agencies, based on evaluation of regulatory guidelines and potential solutions to challenges. Methods An established validated questionnaire was used and the recommendations were collated. Propositions deemed critical for improving the regulatory pathway for biosimilar development were synthesized to design a new regulatory model. Results The key areas for improvement in BRICS-TM countries were: effective implementation of a step-wise approach; adoption of science-based regulatory evaluation for clinical efficacy studies and acceptance of analytical comparability studies in lieu of confirmatory clinical trials; a streamlined biosimilar development program for RBP sourcing; regulatory reliance for joint or shared review of the applications; and enhanced transparency and communication between the regulatory agencies and biosimilar developers. Based on these identified critical aspects, a simplified and standard regulatory model was developed to enable standardization of biosimilar guidelines across BRICS-TM countries for a common development program. Conclusions Effective implementation of the proposed standardized model for biosimilar development and approval processes across the BRICS-TM agencies will eliminate unwarranted studies, reduce the development costs, and enhance process efficiency thereby expediting patients’ access to new affordable biosimilar medicines. Plain language summary The studies presented in this article have identified key areas for improvement in biosimilar development and approval pathways in BRICS-TM countries, which have formed the basis for development of a model to standardize requirements for biosimilar development and the approval process, with a view to improve regulatory performance. Implementation of the proposed model by the BRICS-TM regulatory agencies with consideration of a stepwise approach and science-based evaluation of analytical data could reduce the duplication and unnecessary conduct of non-clinical studies, thereby reducing the development cost and review timelines. Data assessment based on reliance as considered in the proposed model would strengthen reliance networks and improve the process efficiency among the BRICS-TM regulatory agencies. Flexibility in regulatory requirements by the BRICS-TM agencies for the use of Reference Biologic Product (RBP) from other emerging economies and their interaction with the developers would enhance transparency and ease the challenges in sourcing RBP from different jurisdictions. This would further help in expediting a common biosimilar development process. Good Manufacturing Practice (GMP) inspection of the biosimilar manufacturing facilities by desktop audit or off-site audit and acceptance of GMP certifications from other reference agencies would improve the overall regulatory performance and reduce overall review timelines, leading to faster availability of biosimilar medicines for patient access.

Insulin biosimilars in clinical practice

Diabetes mellitus (DM) is an important medical and social problem throughout the world due to its high prevalence. At the same time, the majority of patients have type 2 diabetes. The onset of the disease is gradual, with a prolonged asymptomatic preclinical stage. Therefore, it is necessary to conduct screening among patients at risk. Therapy for type 2 diabetes is carried out with oral hypoglycemic drugs. If it is impossible with their help to achieve adequate glycemic control, it is possible to add basal insulin to therapy, and if the own insulin secretion is depleted, an intensive insulin therapy regimen must be prescribed. Insulin preparations differ in the source of receipt, as well as in the duration of action: background, or basal (insulin of medium duration, long-term or ultra-long-acting) and prandial, or food (ultrashort and short insulin). Currently, along with original insulin preparations, their analogues, or biosimilars (biosimilars), appear on the pharmaceutical market. Biosimilar (biosimilar) is a biological product similar in quality, efficacy and safety parameters to a reference biological medicinal product in the same dosage form and having an identical route of administration. Biosimilars are used all over the world, and this applies not only to insulin preparations, but also to other biological preparations. Proof of bioequivalence is a long-term process that ensures comparability and the absence of clinically significant differences between the study and the reference drug, and includes preclinical and clinical studies. The task of studies of biosimilars of insulin is to confirm the comparability with a reference, previously well-studied biological product. The efficacy and safety of domestically produced biosimilars has been studied in a number of clinical studies, during which the bioequivalence of the drugs was shown. These drugs are of high quality and safe, and their pharmacological characteristics, immunogenicity and effectiveness do not differ from the original drugs.

Biosimilars: evolution of approaches to the development, regulation, life cycle control and interchangeability management

The legal framework for biosimilar medicinal product was first established in 2004 in the European Union and later in the USA. Since then, based on the scientific and regulatory experience with biosimilarity assessment, regulatory approaches have evolved considerably. A clear understanding of the capabilities of each development stage in assessing comparability in terms of power to identify differences and assess their relevance to the final clinical outcome gradually accumulated. In addition to the commitment to the biosimilarity approach, it is important to comply with the general requirements applicable to any drugs produced at an industrial scale. Experience showed that the demonstration of biosimilarity based on a range of analytical and functional tests and mainly clinical pharmacological studies is universal and allows extrapolating therapeutic indications. The establishment of biosimilar interchangeability, since the active substance by definition is a version of the active substance of the corresponding reference biological product, can introduce additional difficulties. A single approach to the establishment of biosimilar interchangeability has not yet been developed.

Scaled integration of FDA approved biosimilars: Closing the knowledge and adoption gaps.

15 Background: Biosimilars are clinically equivalent and highly similar to brand yet cost significantly less. Financial savings are shared by patients, practices and payers, ranging anywhere from 21-24% based on 10/01/20 ASP data from CMS. The effective conversion to biosimilar products is vitally important to total cost-of-care savings and can be achieved without negatively affecting patient outcomes. Physician understanding and confidence in biosimilar products is seen as a major conversion barrier. Methods: Interchangeability is an FDA designation that allows generic drugs to be substituted for reference drugs at the pharmacy, without a physician’s consent. Currently no biosimilar has that FDA approval for interchangeability. Building on previous pharmacy auto-substitution processes with therapeutic interchange, a formalized biosimilar policy and SOP was developed to automate conversion from the reference biologic product to the P&T/Physician approved biosimilar. Workflow changes were instituted to alleviate the provider burden of patient-by-patient decisions and placed them with the pharmacy review team. Full staff support and understanding on biosimilar usage was endorsed through mandatory biosimilar education of physicians, advanced practice providers, pharmacists, nurses, financial navigators and prior authorization team members and tracked using meeting attendance and the online E-learning system. Patient education was verified using established teaching visits by tracking documentation in the electronic health record (EHR). Quantitative metrics and reports were developed to assist in tracking the number of unique patients receiving the brand or biosimilar agents. Billed product units per month were also tracked to facilitate auditing and assure accuracy. Baseline brand/biosimilar utilization data for Rituximab, Trastuzumab, and Bevacizumab was collected from July 1, 2019 through December 31, 2020. Results: During the baseline period of 7/01/19 – 12/31/19, biosimilar conversion ranged from 0% (trastuzumab) to 8.4% (rituximab). Following full staff education and physician consent, systematic auto-conversion to biosimilar products was initiated on January 1, 2020. Conversion rates based upon billed biosimilar units likewise improved from 11.7% (baseline) to 90.2% (2021 Q1) for rituximab, 8.4% to 87.4% for trastuzumab, and 0% to 90.0% for bevacizumab. Conclusions: Rapid and near-complete conversion from brand product to FDA approved biosimilar is feasible, measurable and can be scaled.[Table: see text]

Current Regulatory Requirements for Biosimilars in Six Member Countries of BRICS-TM: Challenges and Opportunities.

Background: The aim of the study was to identify, interpret, and compare the current perspectives of regulatory agencies in six member countries of BRICS-TM (Brazil, Russia, India, China, South Africa, Turkey, and Mexico) on the different criteria used for biosimilar development and marketing authorisation process.Methods: A semi-quantitative questionnaire was developed covering the organisation of agency, biosimilar development criteria and marketing authorisation process and sent to seven regulatory agencies covering the BRICS-TM countries. All data was kept anonymous and confidential. Data processing and analysis was carried out; descriptive statistics were used for quantitative data and content analysis was employed to generate themes for qualitative data.Results: Out of the seven regulatory agencies included in the study, six representatives provided the responses. The perspectives of these six regulatory agencies varied on a number of aspects relating to the review criteria for biosimilar development and licencing process. The most prevalent model for data assessment is the “full review” of a marketing authorisation application. There is lack of a standard approach across the agencies on sourcing of the reference biological product, in vivo toxicity studies and confirmatory clinical studies. Most agencies restrict interaction with biosimilar developers and any scientific advice is non-binding. The marketing authorisation approval depends on scientific assessment of the dossier, sample analysis and GMP certification. The agencies do not issue any public assessment report specifying the summary basis of biosimilar approval.Conclusion: Regulatory agencies across the six emerging economies are steadily improving the regulatory mechanism in the area of biosimilars. However, there remains scope for increasing the effectiveness and efficiency of the processes by encouraging open and transparent interaction with developers, adopting a flexible approach toward accepting advanced analytical data in lieu of clinical studies and enhancing regulatory reliance amongst agencies. This will help to simplify the new biosimilar development programmes and make them more cost-effective.

Comparison of BRICS-TM Countries' Biosimilar Regulatory Frameworks With Australia, Canada and Switzerland: Benchmarking Best Practices.

Objectives: The aim of this study was to identify, compare and evaluate regulatory requirements for the biosimilar development and review processes in BRICS-TM (Brazil, Russia, India, China, South Africa, Turkey, Mexico) countries with mature regulatory systems of Australia, Canada, Singapore and Switzerland. It is hoped that this benchmark study provides an opportunity for BRICS-TM agencies to identify the key areas for improvement in their regulatory processes.Materials and Methods: A semi-quantitative questionnaire was developed covering the different criteria used in biosimilar development and registration process. Eleven regulatory agencies from BRICS-TM and ACSS (Australia, Canada, Switzerland and Singapore) countries were invited to take part in this study. Data processing and analysis was carried out using descriptive statistics for quantitative data and content analysis to generate themes for qualitative data.Results and Discussions: Nine of the 11 regulatory agencies recruited for the study completed the questionnaire. China and Singapore did not meet the deadline due to lack of resources. The organisational structure of BRICS-TM agencies revealed support from external assessors by most of these agencies in comparison with ACSS agencies. There was absence of reliance approach and participation in harmonisation activities across most BRICS-TM agencies. Despite alignment over biosimilarity, the mandate for in vivo non-clinical studies and additional local clinical studies in some of the BRICS-TM countries illustrates a lack of effective implementation of a step-wise approach. Adopting flexible regulatory standards in the sourcing of a RBP (Reference Biologic Product) by BRICS-TM similar to ACSS, will facilitate cost-effective development of biosimilar products.Conclusions: Comparative assessment of the biosimilar regulatory framework of BRICS-TM with ACSS agencies reveals the scope for enhancing efficiency of the regulatory approval process. To achieve this, BRICS-TM agencies should consider relying on reference agencies for alternative review mechanisms such as abridged or verification models, streamlined processes for providing scientific advice to developers and for waiving local clinical studies in-lieu of advanced scientific data.

Overcoming barriers to biosimilar adoption: real-world perspectives from a national payer and provider initiative.

In response to a published national payer survey indicating striking needs for multistakeholder initiatives to increase biosimilar adoption, a focus workgroup meeting joining payers and providers was conducted in December 2019 in Boston, MA. Before the focus group meeting, a survey was sent to health care providers to collect perceptions about barriers to biosimilar adoption and gather input on best potential strategies for addressing these barriers. The focus group panel consisted of 5 managed care pharmacists and 3 physician experts in rheumatology, dermatology, and gastroenterology, representing large managed care organizations and health care systems in the Boston area. A clinical moderator facilitated discussions between the payers and providers regarding challenges to biosimilar adoption and potential collaborative strategies to overcome these barriers. The focus group participants identified hurdles to biosimilar adoption in 3 major areas: (1) the lack of confidence in biosimilar interchangeability and a need for education about biosimilars, (2) the lack of financial incentives to switch to biosimilars from the reference biologic product, and (3) administrative burdens that impair the prescription of biologics. Learning from their mutual experiences, the focus group participants formulated action plans to address these barriers. The top strategies recommended by the participants included advancing biosimilar education, facilitating administrative processes related to biosimilar prescriptions, and increasing provider reimbursement while reducing cost sharing to patients receiving biosimilars. DISCLOSURES: The study reported on in this article was part of a continuing education program funded by an independent educational grant that was awarded by Sandoz Inc., a Novartis Division, to PRIME Education, LLC. The grantor had no role in the study design, execution, analysis, or reporting. The Academy of Managed Care Pharmacy (AMCP) received grant funding from PRIME to assist with participant recruitment and content review for the continuing education program. Bandekar, Cheifetz, Edgar, Helfgott, Hoye-Simek, Liu, and Smith received an honorarium from PRIME for serving as faculty for the continuing education program. Cheifetz has received research grants from Inform Diagnostics and consulting fees from AbbVie, Bacainn, BMS, Grifols, Janssen, Pfizer, Prometheus, Samsung, and Takeda unrelated to this work. Smith has received consulting fees from Boehringer-Ingelheim, has served as an investigator on industry-initiated trials for AbbVie and Pfizer, and has served as an investigator on investigator-initiated trials for Novartis and Regeneron. Carter, Fajardo, and Simone have nothing to disclose.

Challenges Faced by the Biopharmaceutical Industry in the Development and Marketing Authorization of Biosimilar Medicines in BRICS-TM Countries: An Exploratory Study.

BackgroundBiosimilars are expected to emerge as a rapidly growing segment of the biopharmaceutical industry. However, the biosimilar industry faces multiple challenges and obstacles in developing and marketing these complex products. Divergent regulatory framework in emerging countries adds to repetitive trials and increased cost of biosimilar development, delaying the approval process. Due to such roadblocks, healthcare systems and patients are yet to realize the full benefits of biosimilars.ObjectivesThe aim of this exploratory study was to specifically identify the challenges faced by the industry in emerging countries including Brazil, Russia, India, China, South Africa, Turkey and Mexico (BRICS-TM), pertaining to biosimilar development and the regulatory approval process. In particular, this study aims to understand the perceptions of industry on the barriers faced by them in terms of complexity, costs for biosimilar development and time-to-market for biosimilar product.MethodsA semi-quantitative questionnaire was designed based on secondary research. A total of 93 industry personnel and representatives from 14 trade associations from the BRICS-TM countries with 15-year minimum experience were identified and invited to take part in the study and participate in interviews, which were recorded verbatim. Data processing and analysis was carried out; descriptive statistics were used for quantitative data and content analysis was employed to generate themes for qualitative data.ResultsOf the 107 biopharmaceutical industry and trade association representatives invited to participate in the study, respondents from 33 biopharmaceutical companies agreed to take part and underwent the interviews. The industry personnel perceived biosimilar guidelines and approval processes as being protracted and in a state of evolution. The absence of an abridged approval pathway limited effectiveness of the regulatory process. The biggest hurdles in the development of biosimilar dossiers were the sourcing of the reference biological product and expectations around confirmatory clinical trials by the agencies. The non-comprehensive implementation of a stepwise approach resulting in unnecessary toxicity studies was also reported as a major challenge. The authors recommend further primary research with BRICS-TM regulatory agencies in order to propose a simplified pathway for development and approval.ConclusionsLack of standardized biosimilar development criteria and regulatory convergence across BRICS-TM agencies has led to challenges in multi-country development programmes for these medicines, in turn impacting the ability of industry to launch newer and more affordable biosimilars.Supplementary InformationThe online version of this article (10.1007/s40290-021-00395-8) contains supplementary material, which is available to authorized users.

Regulatory Prototype for Biological Products in the United States

Biological products are used for the treatment of many disease, so the biological application submitted for the approval of products are also increasing. The progress of a biosimilarproduct is more difficult and expensive than a small molecule generic product. Biosimilars are not true generic drugs, but demonstrate a high degree of similarity to the reference biological product. In order to improve access to costly biological treatments, a biosimilar pathway in the US was established under the Biologics Price Competition and Innovation Act of 2009. The study highlighted the “Regulatory prospective for the registration of Biological products in US” and a brief description about the development, Manufacturing and approval process of biosimilar products. This article is also focused on the regulatory framework, Biological License Application, Purple book, and Pharmacovigilance of biological products.

"Biosimilar" generic version of biologic products?

Biosimilars are currently popular after the expiry date of patents for biological reference products have expired or soon will expire. Besides, this ‘copycat’ version of biologic products offers much lower costs as compared to the reference products, thus promoting better patient access to the treatment of certain diseases such as cancer, inflammatory diseases, skin disorders, and diabetes. This review aims to determine the differences between biosimilars and generic drugs and highlight some issues related to biosimilar products such as comparability, interchangeability, immunogenicity, extrapolation of indication, current legislation, pharmacovigilance, and naming system. Scientific sources from PubMed, Google Scholar, ScienceDirect, and Elsevier were accessed for preparation of this review article. Biosimilars are not generic drugs as they have a larger and complex structure as compared to generic drugs. Due to that, biosimilars are highly similar but not identical to the reference products. Many regulatory authorities have authorized biosimilars under a distinct regulatory process from that of the generic drugs and subjected them to comprehensive comparability studies with their reference products (analytical, nonclinical in vitro, in vivo studies, and clinical trials). Additional evidence from interchangeability studies, extrapolation of indication studies, immunogenicity profile assessments, and pharmacovigilance studies are also beneficial to assess the efficacy, safety, and quality of the biosimilar before and/or after receiving their regulatory approval. Biosimilars are different from generic drugs due to their complexity in structure and manufacturing process. More comprehensive studies are required to ensure their benefits outweigh the risks.

Epoetin alfa-epbx: a new entrant into a crowded market. a historical review of the role of erythropoietin stimulating agents and the development of the first epoetin biosimilar in the United States

ABSTRACT Introduction: Erythropoietin stimulating agents (ESAs) have been established both to correct anemia and provide the clinical benefits of increased exercise capacity, reduced transfusion requirements, and improved quality of life. An increase in physician and patient adoption of biosimilars, as well as changes to healthcare reimbursement policies, have driven market competitors to innovate and expand the range of biosimilar products. While erythropoietin biosimilars have been approved by the EMA since 2007, the FDA’s approval of epoetin alfa-epbx in 2018 marks the first erythropoietin biosimilar approved in the United States. Areas covered: In this article, we critically review the biology, clinical use, manufacturing, safety, and efficacy of ESAs and erythropoietin biosimilars. We then review the regulatory framework and potential impact on healthcare costs offered by erythropoietin biosimilars. Expert opinion: Due to the complex nature of manufacturing large-molecule biologics, it is important to recognize the challenges to quality assurance and overall safety posed by the introduction of biosimilars, which undergo much more limited clinical testing than their reference biologic product before coming to market. With many biologic therapies nearing patent expiration, biosimilars will become increasingly common in clinical practice. Ensuring patient safety with these products will require increased post-marketing surveillance and awareness from prescribers.

The Efficacy, Safety, and Immunogenicity of Switching Between Reference Biopharmaceuticals and Biosimilars: A Systematic Review.

To date, no consensus exists among stakeholders about switching patients between reference biological products (RPs) and biosimilars, which may have been curbing the implementation of biosimilars in clinical practice. This study synthesizes the available data on switching and assesses whether switching patients from a RP to its biosimilar or vice versa affects efficacy, safety, or immunogenicity outcomes. A total of 178 studies, in which switch outcomes from a RP to a biosimilar were reported, was identified. Data were derived from both randomized controlled trials and real‐world evidence. Despite the limitations stemming from a lack of a robust design for most of the studies, the available switching data do not indicate that switching from a RP to a biosimilar is associated with any major efficacy, safety, or immunogenicity issues. Some open‐label and observational studies reported increased discontinuation rates after switching, which were mainly attributed to nocebo effects. Involvement of the prescriber in any decision to switch should remain and attention should be paid to the mitigation of a potential nocebo effect.

Naming Convention, Interchangeability, and Patient Interest in Biosimilars.

Although biosimilars may offer cost savings over their comparable biologics, use of biosimilars in the United States remains relatively low. This study investigates two barriers to uptake of biosimilars in the United States. First, the U.S. Food and Drug Administration requires that four-letter suffixes be added to the nonproprietary names of all biosimilars, as well as to the nonproprietary names of all biologics approved after March 2020. Second, biosimilars are not interchangeable with their reference biologic product at the pharmacy counter; a new prescription is needed for the biosimilar to be dispensed in place of the biologic. We conducted two behavioral experiments to examine the effects of the naming convention and interchangeability designation on patients' interest in biosimilars. We found that, absent the mention of needing a new prescription, adding four-letter suffixes to biosimilars' nonproprietary names decreased participants' likelihood of using the biosimilars. When participants were told whether a biosimilar required a new prescription, they were more interested in the biosimilar when it did not require a new prescription, and this effect was driven by participants' perceived similarity of the biosimilar to the biologic. The effect of interchangeability dominated the suffix effect. Our results suggest that both biosimilar suffixes and interchangeability issues provide signals to patients regarding the perceived similarity of biosimilars to their reference biologics and influence patient usage of biosimilars.