Automatic Substitution Research Articles

Use of Biosimilars: A Systematic Review of Published Position Statements and Recommendations from Health Organisations and Societies.

Hesitation about using biosimilars still exists among healthcare professionals (HCPs), despite extensive experience with their use. Globally, several health organisations and societies from various specialties have issued biosimilar position statements to guide the use of biosimilars in their specialties. However, it is uncertain how similar or different their positions or recommendations are or whether these positions have evolved with the increased experience and availability of new evidence. The study aimed to describe and assess the recommendations of published position statements regarding several aspects of biosimilars across specialties and determine whether these positions have changed with the emergence of new evidence. We systematically searched for published position statements of biosimilars in online databases and included statements written in English. The search was from the inception of the databases until May 2023. Two reviewers independently extracted the data. Only position statements that included recommendations to guide the use of biosimilars in clinical practice and were issued by health organisations and societies, including expert panels, were included. We synthesised recommendations on five aspects: prescribing practice, extrapolation of indication, interchangeability, treatment initiation with biosimilars in biologic-naïve patients, and pharmacovigilance. The review included 25 papers involving eight specialties, 16 of which were from European countries, 1 from an international organisation representing 49 countries, and 6 from various countries. The papers were published between 2009 and 2020, with 19 published between 2015 and 2020. Of the five aspects of biosimilars assessed, nearly half (11 of 25) of the papers at the time they were published did not base their positions on a scientific or evidence-based approach. Only 4 of the 25 position papers were identified as revisions of their previous papers. With increasing experience in biosimilars and the emergence of new evidence, about 60% (16 of 25) of the papers contained outdated recommendations, particularly on two aspects. They were extrapolations of indications and interchangeability (including switching). The recommendations for most papers for three other aspects were still appropriate. These were prescribing biosimilars by their brand name and active ingredient, initiating treatment with biosimilars in biologic-naïve patients, and monitoring the long-term safety of biosimilars through pharmacovigilance. For four of the revised papers, their position evolved from opposing indication extrapolation for biosimilars to accepting it, while the position of two papers shifted from not recommending biosimilar switching to permitting the practice. Meanwhile, most paperswere against automatic substitution by pharmacistsbecause the evidence for this practicewas still limited. Across specialties, the variability among the position statements is seen for extrapolation of indications for biosimilars and interchangeability (including switching). This requires a revision,considering the latest evidence and growing experience with the use of biosimilars in extrapolatedindications and with switching.

Relationships between the Visual Quality and Color Patterns: Study in Peri-Urban Forests Dominated by Cotinus coggygria var. cinerea Engl. in Autumn in Beijing, China

The spatial pattern of color patches plays a crucial role in affecting the visual quality of peri-urban forests dominated by Cotinus coggygria var. cinerea Engl. in autumn. The impact mechanism has been studied to facilitate algorithm-based automatic visual quality estimation. The color patterns of 120 photographs were calculated after color quantization and automatic color substitution. The scenic beauty of the forest was estimated by 698 respondents. Multiple correlations between visual quality and color pattern metrics were explored with stepwise regression. Principal component analysis (PCA) was also employed to investigate the impact mechanism of color patterns on visual quality. Number of patches (NP), largest patch index (LPI), mean patch area (AREA_MN), patch size standard deviation (AREA_SD), and Shannon’s evenness index (SHEI) were the main factors affecting the visual quality of the Cotinus coggygria forest. AREA_MN correlated positively with visual quality, while NP, LPI, AREA_SD, and SHEI correlated negatively. Moreover, AREA_SD had the most significant impact on the visual quality of the landscape, while SHEI, LPI, and AREA_MN had the second-highest impact. The evenness and the size of color patches significantly affected the visual quality of the forest landscapes. Balancing the diversity and evenness of color patches plays a decisive role in creating a forest landscape with high visual quality.

The price paradox of biosimilar-like long-acting insulin.

To describe the uptake and out-of-pocket (OOP) costs of Basaglar, the first long-acting insulin biosimilar, in a commercially insured population in the United States. Retrospective analysis of commercial pharmacy claims and pharmacy co-payment offsets. We assessed Basaglar uptake by examining trends in the composition of the long-acting insulin market in the United States from 2014 to 2018. As patient demographics and plan type may be important determinants of biosimilar uptake, we also assessed characteristics of all long-acting insulin users by drug. We examined Basaglar OOP costs by assessing mean OOP costs per claim for users of Basaglar and other long-acting insulins, overall and by plan type, and the number and source of co-payment offsets for Basaglar and other insulin glargine products from Basaglar market entry through 2018. We used multivariate linear models to examine the relationship between Basaglar OOP expenditures and insurer-negotiated amounts, overall and by plan type. Basaglar experienced a rapid uptake. However, there was no evidence that Basaglar users had lower OOP costs than reference product (Lantus) users. Given our results and the approval of the first interchangeable biosimilar, we recommend the empirical evaluation of biosimilar cost savings to patients and insurers prior to promoting their automatic substitution.

Provider and patient knowledge gaps on biosimilars: insights from surveys

Beyond the legal and regulatory limitations associated with biosimilar availability in the United States, the adoption of biosimilars is contingent on the willingness of health care providers (HCPs) to prescribe them and of patients to accept them. In this dynamic market, it is of paramount importance to understand the current awareness, attitudes, and preferences of a broad spectrum of stakeholders if uptake of biosimilars is to be optimized. In this article, we highlight knowledge gaps among US HCPs and patients regarding biosimilars for immune-mediated inflammatory diseases as assessed in published survey literature over the last 5 years. Although HCP familiarity and understanding of biosimilars appears to have improved over the last 5 years, survey data suggest that some physicians and pharmacists still approach use of biosimilars with caution owing to concerns regarding nonmedical switching, interchangeability, pharmacist-led substitution, and the extent of any cost savings. Patients understand the potential cost benefits of biosimilars but share many of the HCPs' concerns. A large majority of patients were also concerned that biosimilars would not treat their disease as well as the reference product and that switching may cause more adverse effects. Consequently, nonmedical switching is a major concern for patients, with the majority reporting that they would attempt to avoid a switch. Although patients trust their physicians' treatment recommendations and express confidence in biosimilars, they have mixed views on automatic substitution by pharmacists. The areas of concern identified can be used to guide further education programs for HCPs and patients, and, in doing so, improve biosimilar uptake.

Real-world use of an etanercept biosimilar including selective versus automatic substitution in inflammatory arthritis patients: a UK-based electronic health records study.

ObjectiveBiosimilars are approved as an alternative treatment to their originators. We compared the clinical outcomes of etanercept (ETN) biosimilar compared with ETN originator in real-world practice, from two local health boards in Wales with different policies on switching: automatic vs selective.MethodsData from the Secure Anonymised Information Linkage (SAIL) databank in Wales were used to create a retrospective cohort study using linked primary and secondary care data. Patients aged ≥18 years with diagnosis codes for RA, PsA or AS were included. Outcomes included treatment failure and DAS-28 score (for RA). The local health board with a policy of automatic switching (i.e. clinician/nurse involvement not mandated) is labelled as automatic switch area, and the other, which required clinician/nurse supervision, as selective switch.ResultsOf 8925 individuals with inflammatory arthritis, 13.3% (365) received ETN biosimilar and 31.5% (863) ETN originator. The treatment discontinuation rate was similar for ETN biosimilar and originator by Kaplan–Meier analysis. More biosimilar failure patients were treated in the automatic switch area (15 vs 4.8%). In the automatic switch area, 28.8% (75 of 260) of patients switched automatically from ETN originator to biosimilar compared with 10.5% (11 of 105) in the selective switch area. ETN biosimilar reduced DAS-28 by 1.6 ± 1.8 in the selective switch area vs 0.4 ± 0.6 in the automatic switch area.ConclusionThe ETN biosimilar was well tolerated. Fewer people were switched using selective policy, but this was associated with lower failure rates. Automatic switch policy led to more patients being switched and did not lead to significant worsening of disease.

P30 Potential Impacts of the New MHRA Policy for Biosimilar Approval for the Industry and Patients

To understand the potential impact of the new MHRA guidance for biosimilar licensing in the UK and other key markets, in terms of accelerating biosimilar development, time to market, prescribing limits (e.g. automatic substitution) and, patient access to biologics. We reviewed the MHRA guidance on biosimilar licensing, alongside that from the FDA/EMA, and country-specific guidance on biosimilar use. We also analysed FDA/EMA approvals for biosimilars approved without confirmatory efficacy trials. Finally, a virtual iAdBoard was organised with payers/KOLs from France, the UK and US to capture different perceptions on the new policy and downstream impacts on biosimilar access. The MHRA has discontinued the requirement for biosimilars to undergo confirmatory efficacy trials as a licensing condition. Although the new policy was celebrated by the biosimilar industry, one must note the FDA and EMA do not explicitly state a Phase 3 trial requirement for biosimilar approval, and to date, two pegfilgrastim biosimilars have been approved without a Phase 3 trial (Udenyca, Nyvepria), given their robust chemical characterization and Phase 1 trials’ Results: Additionally, the new MHRA guidance contemplates exceptions where comparative trials are required, leaving uncertainty around for how many biosimilars, particularly monoclonal antibodies, chemical characterization plus PK/PD trials will suffice. The virtual iAdboard revealed payer differences in opinion regarding impacts on biosimilar development timelines (vs agreement on economic viability), and in future policies encouraging biosimilar uptake, with EU payers more receptive to the change than US counterparts, but concerned with backlash from HCPs. If the FDA/EMA endorse the MHRA decision, in the future, a strong CMC/Phase 1 package could replace Phase 3 studies for biosimilar licensing. However, it is yet unclear whether this abbreviated data package will result in faster times to market or if it will have negative impacts on prescribing freedom and patient access to biosimilars.

How Should Synthetic Follow-Ons of Biological Products Be Regulated? What Are the Implications for Automatic Substitution?

How Should Synthetic Follow-Ons of Biological Products Be Regulated? What Are the Implications for Automatic Substitution?

The Automatic Substitution of Biosimilars: Definitions of Interchangeability are not Interchangeable

In the USA, an interchangeability designation provides biosimilar sponsors with a pathway for achieving what is standard for small-molecule generics: pharmacy-level auto-substitution for an innovator. No other major health authority links interchangeability to automatic substitution, as all require the involvement of the prescriber or patient in a medication change. This editorial considers the clinical impact and practicality of auto-substitution. First, interchangeability is linked to non-medical switching (NMS), the practice of switching treatment in patients with stable disease for non-clinical reasons. NMS may generate negative sentiment in those unwilling or reluctant to switch, which can adversely impact treatment outcomes (i.e., nocebo effect). Indeed, in real-world studies of tumor necrosis factor inhibitors, discontinuation rates have been shown to be higher in patients switched to biosimilars for non-medical reasons than in historical cohorts maintained on innovators. Second, interchangeability may impede pharmacovigilance and traceability, as not all jurisdictions require innovators and biosimilars to have distinct biologic names. Third, an interchangeability designation from the US Food and Drug Administration only permits a biosimilar to be automatically substituted for its innovator, not other biosimilars (if available). Pharmacist education would be needed to avoid off-label, automatic substitution among biosimilars of a single innovator. Last, once granted, an interchangeability designation exists in perpetuity under current US federal law. However, the supply chains of innovators and biosimilars are maintained independently, with no requirement for reconfirmation of biosimilarity or interchangeability. We feel that additional guidance is needed for the auto-substitution of biosimilars and innovators to become a reality.

Legal Obstacles to Biosimilar Market Entry

Improving the market availability and penetration of biosimilars, “follow-on” versions of biologic products, will require attention to key legal obstacles. Because biosimilars offer the potential for sizeable cost savings to payors and improved access to biologic drugs for patients, obstacles to the timely licensure and market availability of biosimilars are of major public health significance. Issues around intellectual property, potentially anticompetitive contractual arrangements with purchasers and insurers, and laws governing automatic substitution of biosimilars for biologics merit particular attention. This Article examines several key legal obstacles to biosimilar market entry in the United States, including (1) the complexity and imprecise boundaries of the exchange of patent information codified in the BPCIA; (2) patent thickets that protect biologic reference products; (3) unsettled antitrust law surrounding reverse payment patent settlements (i.e., “pay-for-delay” agreements); (4) contractual arrangements such as bundled purchase agreements and formulary exclusivity provisions; and (5) state laws that regulate substitution of biosimilars for biologics at the pharmacy level. Strategies to address these obstacles include reforms to the patent system to curb issuance of ancillary secondary patents intended to delay competition, greater transparency around biologic patents, reconsideration of the need for a regulatory designation of interchangeability, and better detection and enforcement of deliberately anticompetitive practices.

Economic and workload impact of therapeutic interchange of inhaler medications and nebulizer solutions.

To examine the financial impact of automatic formulary substitution of nebulization solutions for pressurized metered dose inhalers and dry powder inhalers and the effect of the automatic substitution initiative on respiratory care practitioner (RCP) workload at a community hospital. A retrospective observational study was conducted in a 326-bed nonacademic community hospital. Adult patients who received respiratory medications and had an inpatient stay, were admitted for observation, or had an emergency room visit from December 2016 through February 2017 (the control group) or from December 2017 through February 2018 (the study group) were included in the analysis. The primary outcomes were the cost of respiratory medications per hospital stay and the number of RCP visits per hospital stay. The secondary outcome was the cost of wasted doses per hospital stay. A total of 3,766 patients were included in the study: 2,030 in the study group and 1,736 in the control group. The mean cost of respiratory medications per hospital stay was significantly lower in the study group vs the control group ($13.29 vs $36.48, P < 0.001). The mean number of RCP visits per hospital stay was also statistically lower in the study group vs the control group (11.6 vs 12.9, P = 0.04). The mean cost of wasted doses was significantly lower in study group vs the control group ($0.25 vs $22.91, P < 0.001). Automatic formulary substitution of nebulization solutions for inhaler medications significantly decreased medication costs without increasing the average number of RCP visits per hospital stay.

European prescribers’ attitudes and beliefs on biologicals prescribing and automatic substitution

Introduction: The European Union (EU) and the European Medicines Agency (EMA) have led the development of a regulatory framework for biosimilars since 2004. By end of December 2019, 64 biosimilars of 15 originator biological medicines have a marketing authorization in Europe. Now, for the second time, the Alliance for Safe Biologic Medicines (ASBM) asked European prescribers for their views on the prescribing, adverse drug reaction reporting, automatic substitution and switching of biologicals and biosimilars. Methods: In March 2019, the ASBM surveyed 579 prescribers in France, Germany, Italy, Spain, Switzerland and the UK. Prescribers were asked for their views on authority over prescribing and dispensing of biologicals/biosimilars, reporting biological/biosimilar use and adverse drug reactions (ADR) and switching. There were also questions related to their familiarity with, knowledge of, attitudes to, and beliefs in, biosimilars. Results: Since the previous European prescriber study conducted in 2013, the percentage of respondents considering themselves highly familiar with biosimilar medicines has increased from 76% to 90%. Four out of five prescribers said they are legally required to report ADR that are brought to their attention and they file detailed ADR reports taking 10‒20 minutes. Four out of five prescribers feel very strongly about having control over what is prescribed and dispensed to their patients. While highly comfortable prescribing biosimilars to naïve patients, physician comfort level decreased when switching a stable patient to a biosimilar. Comfort level decreased further when prescribers were asked about switching a patient to a biosimilar for non-medical reasons, e.g. cost, and further still if the switch is initiated by a third party. Conclusion: European physicians have increased their familiarity with biosimilars since the 2013 survey. Physicians increasingly believe they should always have control of treatment decisions including the decision to switch to a biosimilar. It was also highlighted that governments should make multiple therapeutic options available through tenders.

The Challenges of Switching Therapies in an Evolving Multiple Biosimilars Landscape: A Narrative Review of Current Evidence.

With the increasing availability of biosimilars, the practice of switching therapies for non-medical reasons between an originator biologic and an analogous biosimilar has become more common. The evidence to support this practice mostly comes from single-switch randomized controlled trials (RCTs) and real-world (RW) evidence studies. However, as more biosimilars of the same originator enter the market, multiple switching events between originators and biosimilars is becoming a reality, despite limited evidence to support the efficacy and safety of such practice. Some countries have established guidelines, policies, or laws related to interchangeability and/or automatic substitution, whereas others have left these practices unregulated or controlled by other components of the healthcare system. Collectively, guidelines on single non-medical switching are often vague, with even less focus given to multiple non-medical switching, leaving this practice mostly unregulated. This narrative review will first discuss the current regulatory perspectives on non-medical switching and challenges associated with switching therapies, particularly with the availability of multiple biosimilars. We will then review the current evidence from RCTs and RW studies in the light of three different multiple-switch scenarios currently taking place in clinical practice: switching between an originator and a single biosimilar, switching between biosimilars of the same originator, and the clinical practice of switching back to the originator (i.e., switchbacks) after a failure of the initial non-medical switch to the analogous biosimilar.

Evaluating and prioritizing antimicrobial stewardship programs for nursing homes: A modified Delphi panel.

Antibiotic use in nursing homes is often inappropriate, in terms of overuse and misuse, and it can be linked to adverse events and antimicrobial resistance. Antimicrobial stewardship programs (ASPs) can optimize antibiotic use by minimizing unnecessary prescriptions, treatment cost, and the overall spread of antimicrobial resistance. Nursing home providers and residents are candidates for ASP implementation, yet guidelines for implementation are limited. To support nursing home providers with the selection and adoption of ASP interventions. A multiphase modified Delphi method to assess 15 ASP interventions across criteria addressing scientific merit, feasibility, impact, accountability, and importance. This study included surveys supplemented with a 1-day consensus meeting. A 16-member multidisciplinary panel of experts and resident representatives. From highest to lowest, 6 interventions were prioritized by the panel: (1) guidelines for empiric prescribing, (2) audit and feedback, (3) communication tools, (4) short-course antibiotic therapy, (5) scheduled antibiotic reassessment, and (6) clinical decision support systems. Several interventions were not endorsed: antibiograms, educational interventions, formulary review, and automatic substitution. A lack of nursing home resources was noted, which could impede multifaceted interventions. Nursing home providers should consider 6 key interventions for ASPs. Such interventions may be feasible for nursing home settings and impactful for improving antibiotic use; however, scientific merit supporting each is variable. A multifaceted approach may be necessary for long-term improvement but difficult to implement.

Biosimilars and Novel Insulins.

Insulin therapy is the mainstay of treatment for type 1 diabetes and may be necessary in type 2 diabetes. Current insulin analogues present a more physiological profile, are effective, and with less risk of hypoglycemia, but they are expensive. Biosimilar insulins should offer the advantages of insulin analogues at reduced costs. In addition, current rapid-acting insulin analogues are not fast enough to control excessive postprandial glucose excursions in many patients. Biosimilar insulins demonstrated that are safe and effective, but interchangeability and automatic substitution remain an issue. Ultrafast-acting insulins should reduce postprandial hyperglycemia and improve flexibility in insulin dosing. This systematic review was conducted following widely recommended methods. We searched for each topic in Medline, Embase, the Cochrane Library, and SCISEARCH for relevant citations for the appropriate period. LY2963016 and MK-1293 are biosimilar insulins of insulin glargine, and SAR342434 is a biosimilar of insulin lispro. The abbreviated developed program demonstrated comparable efficacy and safety and supports their use for treatment of people with diabetes but no interchangeability. Faster-acting insulin aspart is a new formulation of insulin aspart with accelerated subcutaneous absorption. Faster aspart demonstrated noninferiority in reducing HbA1c as compared to insulin aspart with superiority in controlling postprandial hyperglycemia without increasing hypoglycemia, and flexible insulin dosing. Biosimilar insulins have comparable PK-PD profiles and equivalent efficacy and safety to original insulins at a lower price, making them available for more people with diabetes. Faster aspart is the first ultrafast-acting insulin. New upcoming clinical trials and more clinical experience with faster aspart will show the real potential of this new insulin.

PBI55 FUTURE TRENDS ON THE BIOSIMILAR UPTAKE IN THE EU5 AND THE US

Biosimilar use creates an opportunity for increased patient access, drug competition and cost-savings, especially in a landscape driven by imminent patent-expiration of biologics. Study aimed to assess anticipated trends and incentives to enhance biosimilar uptake in the United States (US) and Europe’s big 5 (EU5: France, Germany, Italy, Spain, the United Kingdom). Targeted literature review was conducted in Medline/Embase, complemented with desk research. Differences in supply- and demand-side policies for biosimilars are impacting global market uptake. Successive policy shifts are seen following collection of biosimilar switching evidence and continuous debate to support further penetration of biosimilars to generate more economic savings. In France, biosimilar use became a part of the health strategy (2018-2022), aiming to achieve 80% of biosimilar penetration in 2022. Although automatic substitution was introduced by law in France (2014), it is still not implemented due to the lack of a published decree. In Germany, a bill allowing biosimilar substitution by pharmacists awaits for the legislative approval since 2018; due to criticism and revisions, implementation of this reform will be postponed by 3 years. Meanwhile, G-BA was mandated to introduce a list of interchangeable biosimilars to support physician-authorised switching. In Spain and the UK, hospital pharmacy stocking of a one preferred drug over tendering for multiple products is expected. Real-world evidence for Italy shows the increasing trend for biosimilar use with great variability among regions. Despite infancy in the US biosimilar uptake, the FDA released the Biosimilars Action Plan (2018) outlining 11 key actions to boost the biosimilar industry and facilitate access, with a guideline for demonstrating interchangeability (2019). Even though market share of biosimilars remains low, with except to some drug-tendering processes, regulations are evolving rapidly and a number of tools should be implemented in the near future to boost the biosimilar uptake in the following years.

Medication safety risks to be managed in national implementation of automatic substitution of biological medicines: a qualitative study

ObjectivesTo explore relevant Finnish stakeholders’ perceptions on the automatic substitution of biological medicines with particular focus on medication safety and issues that need to be considered to create an appropriate...

Challenges in Post-marketing Studies of Biological Drugs in the Era of Biosimilars: A Report of the International Society for Pharmacoepidemiology 2019 Mid-Year Meeting in Rome, Italy.

Several controversial issues related to challenges in the post-marketing studies of biological drugs, including biosimilars, were discussed at the International Society for Pharmacoepidemiology (ISPE) 2019 Mid-Year Meeting in Rome (Italy) in April. In recent years, the marketing of biosimilars has been growing, thus offering opportunities for wider access by patients to high-cost biological drugs as well as ensuring the economic sustainability of national healthcare systems. Through the comparability exercise required for marketing approval, the similarity of biosimilars to the reference products in terms of efficacy, safety and quality has to be demonstrated in pre-marketing studies. In Europe, the 15years of experience of marketing of biosimilars has allowed the accumulation of a significant amount of scientific evidence confirming the comparability of the benefit-risk profile of biosimilars and originators. However, some aspects remain to be addressed both from a scientific and regulatory perspective, such as interchangeability and the automatic substitution of originators and biosimilars. The (long-term) monitoring of all biological drugs, including biosimilars, in real-world settings is warranted, with the ultimate goal of integrating pre- and post-marketing evidence relating to the aforementioned open questions. This conference report describes priorities, data sources and methodological strategies for the post-marketing surveillance of biological drugs in the era of biosimilars.

Are we ready to close the discussion on the interchangeability of biosimilars?

Since the introduction of the first biosimilar the discussion about their interchangeability has persisted. The body of evidence gathered for biosimilars provides reassurance that they are approved based on a rigorous comparability exercise and do not show clinically meaningful differences to their reference products. There are no data suggesting that the risk of switching to a biosimilar in terms of increased immunogenicity is greater than switching between two batches of any biologic. The key concern around switching biosimilars is the nocebo effect, which reinforces the need for physician involvement when switching. Whereas this might argue against automatic substitution of biosimilars, it is not a biosimilars-specific concern. To increase physician confidence in biosimilars, regulators should acknowledge that biosimilars are interchangeable.

Barriers towards effective pharmacovigilance systems of biosimilars in rheumatology: A Latin American survey

PurposeThis review summarises the current status of regulatory guidelines for the approval of biosimilars in Latin America and highlights the main barriers to effective pharmacovigilance in this region. We also report results from a survey of Latin American rheumatologists assessing their understanding of prescribing biosimilars and the pharmacovigilance of these drugs.MethodsWe reviewed the current guidelines for the regulatory approval of biosimilars and barriers to effective pharmacovigilance in Latin American countries. Rheumatologists attending the II Pan‐American League of Rheumatology Associations PANLAR Review Course (Biosimilars update) in Lima, Peru were asked to complete a short survey to determine their knowledge of biosimilars.ResultsMany Latin American countries continue to lag behind Europe and the United States in establishing regulatory guidance and effective pharmacovigilance systems for biosimilars. Results from our survey also highlight a lack of awareness regarding the availability of biosimilars, their nomenclature, automatic substitution, and reporting adverse drug reactions because of these drugs.ConclusionsThe main barriers to effective pharmacovigilance in Latin America are the lack of consensus on the interchangeability of reference biologics and biosimilars, and the need for more suitably trained personnel to carry out effective postmarketing pharmacovigilance of biosimilars. Inconsistencies in biosimilar nomenclature make it difficult to adequately trace drugs and record adverse drug reactions associated with their use, creating a barrier to the global pharmacovigilance of biologics.

PANLAR consensus statement on biosimilars

IntroductionBiologics have improved the treatment of rheumatic diseases, resulting in better outcomes. However, their high cost limits access for many patients in both North America and Latin America. Following patent expiration for biologicals, the availability of biosimilars, which typically are less expensive due to lower development costs, provides additional treatment options for patients with rheumatic diseases. The availability of biosimilars in North American and Latin American countries is evolving, with differing regulations and clinical indications.ObjectiveThe objective of the study was to present the consensus statement on biosimilars in rheumatology developed by Pan American League of Associations for Rheumatology (PANLAR).MethodsUsing a modified Delphi process approach, the following topics were addressed: regulation, efficacy and safety, extrapolation of indications, interchangeability, automatic substitution, pharmacovigilance, risk management, naming, traceability, registries, economic aspects, and biomimics. Consensus was achieved when there was agreement among 80% or more of the panel members. Three Delphi rounds were conducted to reach consensus. Questionnaires were sent electronically to panel members and comments about each question were solicited.ResultsEight recommendations were formulated regarding regulation, pharmacovigilance, risk management, naming, traceability, registries, economic aspects, and biomimics.ConclusionThe recommendations highlighted that, after receiving regulatory approval, pharmacovigilance is a fundamental strategy to ensure safety of all medications. Registries should be employed to monitor use of biosimilars and to identify potential adverse effects. The price of biosimilars should be significantly lower than that of reference products to enhance patient access. Biomimics are not biosimilars and, if they are to be marketed, they must first be evaluated and approved according to established regulatory pathways for novel biopharmaceuticals.Key Points• Biologics have improved the treatment of rheumatic diseases.• Their high cost limits access for many patients in both North America and Latin America.• Biosimilars typically are less expensive, providing additional treatment options for patients with rheumatic diseases.• PANLAR presents its consensus on biosimilars in rheumatology