Biosimilar Research Articles

Regulatory requirements for biosimilars as per CDSCO in India in comparison with Yemen

This study examines the regulatory requirements for biosimilars in India and Yemen, highlighting similarities and differences between the Central Drugs Standard Control Organization (CDSCO) and the Ministry of Public Health and Population (MOPHP). The regulatory landscape for biosimilars is evolving globally, with varying requirements across countries. This comparative analysis examines the regulatory requirements for biosimilars in India, governed by the Central Drugs Standard Control Organization (CDSCO), and Yemen. A comprehensive review of guidelines, regulations, and approval processes reveals both similarities and differences between the two countries. While both CDSCO and Yemen require a comparability exercise to demonstrate bio similarity, differences exist in the regulatory framework, clinical trial requirements, and approval processes. CDSCO has a separate regulatory framework and abbreviated pathway for biosimilars, whereas Yemen adopts the MOPHP guidelines and has a registration process. This analysis highlights the need for manufacturers to understand the nuances of each market's regulatory requirements to ensure successful approval and commercialization of biosimilars. The findings of this study can inform regulatory agencies, industry stakeholders, and researchers working in the field of biosimilars.

Biosimilars Versus Originators in Children With Juvenile Idiopathic Arthritis: A Real-World Experience

We aimed to evaluate the efficacy, safety, and immunogenicity profile of Etanercept (ETA) and Adalimumab (ADA) biosimilars (BIOs) compared to their originators in children with juvenile idiopathic arthritis (JIA). Eighty-one JIA children treated with ETA or ADA originators or BIOs were examined at baseline (T0) and after 3- (T1), 6- (T2), 12- (T3), and 24-(T4) months after starting treatment. Lower Juvenile Arthritis Disease Activity Score 10 (JADAS-10) scores were reported at T1, T2, T3, and T4 in JIA children treated with BIOs than originators (all p < 0.05). At T1 and T3, anti-drugs antibodies levels were lower in children receiving BIOs than originators (p = 0.04 and p = 0.0007, respectively), even after adjustments (both p < 0.05). Relapses were lower for BIOs compared to originators (p < 0.001). Safety profile was comparable between the groups (p > 0.05). A better overall profile of BIOs than originators was demonstrated in JIA children, but larger confirmatory studies are needed.

Effects of thermal treatment on quality of biosimilar and originator monoclonal antibodies

Investigating products under stress conditions provides valuable information for assessing stability, biosimilarity, and degradation behaviors during monoclonal antibody (mAb) development. Proper sample preparation is crucial for accurately evaluating the biosimilarity and effects of stress conditions in comparability assessment, where these studies guide biosimilar mAb development steps. Enzymatic and chemical treatments applied during sample preparation of mAbs generally require treatment of samples in temperatures higher than the storage temperatures of antibodies.In this study, samples of a TNF-α inhibitor IgG1 biosimilar (BIO) and its originator (OR) were treated for 7 days at commonly used temperatures during sample preparation. Alterations in the intact IgG, size variants, charge variants, binding kinetics, and post-translational modifications (PTMs) were investigated with CE-SDS, SE-UPLC, icIEF, SPR, and LC-MS/MS, respectively. Samples treated at 50 °C exhibited significant degradation, while minor differences were observed in samples treated at 37 °C. Monomer and intact IgG levels were decreased to levels below 97 % and 94 %, respectively, after 7 days of thermal treatment at 50 °C for both BIO and OR samples. Similar rates of degradation were observed between the treated biosimilar and originator samples. The percent monomer degradation rate between the biosimilar and the originators was similar at 50 °C (p = 0.32). Thermal treatment increased acidic variant levels in the products of the BIO (23.10 %) and OR (23.16 %). During post-translational modification monitoring, an increase in pyroglutamic acid formation and a decrease in C-terminal lysine were observed after thermal treatments. Acidic variant alterations were associated with asparagine deamidation and N-terminal pyroglutamic acid formation. Post-translational modifications were mainly located at the Fc domain, with methionine oxidation and asparagine deamidation as the main modifications occurring at the Fab domain.In conclusion, these results revealed that prolonged thermal treatment under elevated temperatures induces molecular alterations, thereby facilitating the degradation of IgG1. In addition, our findings indicate that both BIO and OR lots exhibit similar degradation profiles when subjected to thermal treatments.

P884 Patient satisfaction and experience after a switch to an adalimumab biosimilar with high concentration and citrate-free: results from a multicentric prospective real-life study

Abstract Background Switching from a reference product (RP) to a biosimilar (BS) aims at generating cost savings. Patient adherence after a switch is linked to overall experience that can be impacted by patient or treatment characteristics. This study aimed to analyse patient-experience after a switch from an adalimumab (ADA) to CT-P171 (ADA BS high concentration, HC, citrate-free). Methods YU-MATTER (NCT05427942), a multicentric prospective observational study included patients with inflammatory bowel disease (IBD) or chronic inflammatory rheumatic disease (CIR), treated with ADA: either the RP (HC: 100mg/ml) or a BS with low concentration (LC: 50 mg/ml). Patients were switched to CT-P17 and followed-up for 3 months (M). Clinical characteristics were collected at M0, including beliefs (BMQ questionnaire2), patient-experience via 5 self-questionnaires designed in collaboration with patient associations to explore satisfaction regarding the injection (Likert 7), discomfort (pain [NRS 0-10], redness [Likert 4], itching [NRS 0-10], and haematoma [Likert 3]). Satisfaction and overall injection tolerance (pain &amp;lt; 4 AND absence of redness AND itching &amp;lt; 4 AND absence of haematoma) were assessed between M0 (just before switch) and M3 (3 months after switch). Factors associated with satisfaction improvement (Likert) were explored through multivariable logistic regression. Results Of the 232 patients analysed, 167 had IBD (CD =136); mean age 44±15 years; median IBD duration 9 years ([Q1; Q3]: [5; 15]) and 50.9% were men. The median differential score necessity-concern was of 5 [3; 7] suggesting that the perceived necessity of the treatment was higher than its concerns. 119 (51.2 %) patients were switched from a BS (45 with citrate) and 113 (48.7%) from the RP. At M3, 175 patients (75.4%) were satisfied with the injection and 145 (62.5%) had a stable or improved satisfaction versus the previous ADA. Among patients receiving a BS, the presence of citrate was significantly associated with an improvement of satisfaction after switching to CT-P17 (58.3% vs. 30.0%, p=0.006). Overall injection tolerance significantly improved after switching from 28.9 % at M0 to 57.7 % at M3 (p&amp;lt;0.0001). A significant decrease of pain related injection was observed after the first injection of CT-P17 (median -2 [-4; -1]) for patients switched from a BS and remained stable for patients switched from the RP (median 0 [-1;1]). In multivariable analysis, the switch from a LC ADA was an independent factor of satisfaction improvement (vs from the RP, odds ratio=3.03; p=0.003; Table). Conclusion The global experience of switching to CT-P17 was positive with an overall improvement in injection tolerance. Injection volume was an independent factor associated with a successful experience.

Advancing Subcutaneous Dosing Regimens for Biotherapeutics: Clinical Strategies for Expedited Market Access.

In recent years, subcutaneous administration of biotherapeutics has made significant progress. The self-administration market for rheumatoid arthritis has witnessed the introduction of additional follow-on biologics, while the first subcutaneous dosing options for monoclonal antibodies have become available for multiple sclerosis. Oncology has also seen advancements with the authorization of high-volume subcutaneous formulations, facilitated by the development of high-concentration formulations and innovative delivery systems. Regulatory and Health Technology Assessment bodies increasingly consider preference data in filing dossiers, particularly in evaluating novel drug delivery methods. The adoption of a pharmacokinetic-based clinical bridging approach has become standard for transitioning from intravenous to subcutaneous administration. Non-inferiority studies with pharmacokinetics as the only primary endpoint have started deviating from traditional randomization schemes, favoring the subcutaneous route and comparing with historical intravenous data. While nonclinical and computational models made progress in predicting safety and immunogenicity for subcutaneously dosed antibodies, clinical trial evidence remains essential due to inter-individual variations and the impact of formulation parameters on anti-drug antibody formation. Ongoing technological advancements and the expanding knowledge base on pharmacokinetic-pharmacodynamic correlation across specialty areas are expected to further accelerate clinical development of subcutaneous biologics.

Comparison of Immunochemical Reactions of Infliximab Innovator and Biosimilars on an Infliximab Detection Kit Used for Therapeutic Drug Monitoring.

Monitoring serum infliximab (INF) concentrations is crucial for designing appropriate doses for patients with rheumatoid arthritis. It is recommended to maintain the serum trough INF level at least 1.0 µg/mL. In Japan, an in vitro diagnostic kit using immunochromatography has been approved to determine whether the serum INF concentration is over 1.0 µg/mL or not, and to support the determination of the necessity of increasing the dose or switching to another drug. Biosimilars (BS) of INF may have immunochemical properties different from those of its innovator product, which may show different reactivities on the diagnostic kit. In this study, the responses of the innovator and five BS products on the kit were compared. Based on visually comparing the intensity of color development between the test and control samples, differences were found in the judgment results depending on the analyst. In particular, 1.0 µg/mL was not determined as positive in some cases, whereas 2.0 µg/mL was reliably determined as positive. Overall, no significant difference in reactivity was found between the innovator and five BS products. To further compare the differences in immunochemical properties, the reactivity of these products with three enzyme-linked immunosorbent assay (ELISA) kits was compared. The results confirmed that there were no significant differences among the innovator and BS products in reactivity with the examined kits. When using that diagnostic kit, the users need to be aware that the judgement around 1.0 µg/mL INF may differ depending on the test conditions, including the analyst.

Factors Affecting Patients' Acceptance of Switching to Biosimilars Are Disease-Dependent: A Cross-Sectional Study.

Biosimilars (BS) are promoted worldwide because of the high cost of biologics. However, patients are apprehensive about switching to BS. For some diseases, several factors, which may be disease-dependent, influence patients' acceptance of switching to BS. Herein, we evaluated whether factors influencing acceptance for switching were disease-dependent among Japanese patients with different diseases. This cross-sectional study involved pharmacists' interviews with patients who used or planned to use biologics. Demographic and clinical characteristics were retrospectively investigated using the patients' medical records. Multivariate logistic regression showed that switch refusal was associated with a history of adverse reactions to biologics (odds ratio [95% confidence interval (CI)] = 3.38 [1.35-8.44]), history of complaints related to disease activity (3.57 [1.53-8.32]), and unacceptability of generic drugs (7.62 [2.70-21.60]). Subgroup analyses suggested that the unacceptability of generic drugs was a common factor, regardless of the disease. Concomitantly, histories of adverse reactions to biologics and complaints related to disease activity were disease-dependent factors. Healthcare professionals should help patients in selecting BS, considering these factors according to the disease.

The Global Landscape of Manufacturers of Follow-on Biologics: An Overview of Five Major Biosimilar Markets and 15 Countries.

Current knowledge is limited about which manufacturers are active in the global field of biopharmaceutical product development and how many unique follow-on biologics are approved in global markets. This study aimed to provide a cross-sectional overview of manufacturers of follow-on biologics approved in 15 large countries from different regions of the world, as well as in five major biosimilar markets with long established biosimilar frameworks. We screened national drug databases to identify follow-on biologics and their manufacturers approved in 15 countries in Asia, Africa, Latin America and the rest of the world, as well as five major biosimilar markets: the European Union (including the UK), USA, Canada, Australia and Japan. This study identified a total of 304 follow-on biologics from different manufacturers for 18 active substance classes included in the analysis. Of these, 67 products are approved as biosimilars in at least one of the five major biosimilar markets. A total of 140 (46%) follow-on biologics are manufactured in India or China, of which only eight (seven from India and one from China) are approved as biosimilars in any of the five major biosimilar markets. This study found that the majority of follow-on biologics are only approved in the respective country of manufacturing. A small number of manufacturers, primarily from India and Argentina, supply their products to other regions in the world. As some countries have less stringent regulatory approaches for biosimilars, or have only recently implemented biosimilar guidance in line with World Health Organization standards, follow-on biologics could have been approved that would not be considered biosimilars according to the World Health Organization standards. With this study, we try to contribute to discussions on creating more transparency about global approvals of follow-on biologics and promoting access to high-quality biosimilars in countries around the world.

Comparison of the efficacy and safety of the original rituximab and its biosimilar in routine clinical practice

Currently, a biosimilar (BS) of rituximab (RTM) Acellbia® is widely used in Russia for the treatment of rheumatoid arthritis (RA), however, a systematic study of this drug in routine clinical practice has not been conducted.Objective: to compare the results of the use of RTM BS (Acellbia®) and the original rituximab (oRTM) in the daily clinical practice of a large rheumatology center.Patients and methods. The study involved 127 patients predominantly with seropositive RA, who were divided into four groups. Groups 1 and 2 included 66 bionaive patients with active RA and ineffectiveness of previous therapy. 31 patients of the 1st group received 2 infusions of oRTM at a dose of 500 mg intravenously (IV) 2 weeks apart; 35 patients of the 2nd group – 2 infusions of RTM BS at a dose of 500 mg IV 2 weeks apart. Groups 3 and 4 included 61 patients who had previously received oRTM therapy. These patients received 4 courses of oRTM treatment on average before being included in the study. 30 patients of the 3rd group continued oRTM therapy: they received 2 infusions at a dose of 500 mg IV 2 weeks apart; 31 patients of the 4th group received 2 infusions of RTM BS at a dose of 500 mg IV 2 weeks apart.Results and discussion. During the observation period, the dynamics of the main indicators of RA activity in the 1st and 2nd groups did not differ significantly. Although the indication for rehospitalization was an exacerbation of the disease, 64.5% of patients in the 1st and 77.1% of patients in the 2nd group, preserved a 20% improvement according to the ACR criteria on re-examination. The condition of patients of the 3rd and 4th groups remained generally stable during the observation period. The change in the DAS28 index in most cases was clinically insignificant. There were no significant differences in the dynamics of inflammatory activity among patients who continued oRTM treatment and who received RTM BS.Conclusion. The results of the study show that both the prescription of RTM to bionaive RA patients and repeated courses of treatment with RTM BS and oRTM are comparable in terms of efficacy and tolerability.

Access to Insulin Products in Pakistan: A National Scale Cross-Sectional Survey on Prices, Availability, and Affordability.

Background: Diabetes is among the top ten most prevalent diseases in Pakistan, and the availability of medicines to treat the disease is vital for a great percentage of the country’s population. Insulin was discovered a century ago; however, its access in several parts of the globe remains an issue. This study aims to evaluate prices, availability, and affordability (access components) of insulin and five comparator medicine access in Pakistan. Methods: A nationwide cross-sectional survey was conducted to evaluate the access to insulin and some comparator medicines in eight cities of Pakistan, using a modified WHO/HAI methodology. The survey included 80 medicine outlets, i.e., 40 private pharmacies and 40 public hospitals. Data for every unique insulin product available in the Pakistani market were obtained, including five comparator medicines. Percentage availability, median unit prices (MUPs), and affordability (the number of days’ wages (NDWs) required for a month’s course by the lowest-paid unskilled government worker) of all products were calculated, including originator brands (OBs) and biosimilar (BS) products. Results: Of all insulin products surveyed (n = 320), 87.5% were manufactured by foreign multinational companies (MNCs). None of the insulin products had an ideal availability of 80% in any of the surveyed health facilities. In the public sector, none of the insulin products had an availability of more than 50%. In the public sector, the overall availability of human insulin was 70% (including OB and BS). While in the private sector, the overall availability of human insulin was 90% and that of analog insulin was 62.5%. The analog insulin products were 72.8% costlier than the human insulin products. The median prices of BS insulin were 25.4% lower than the OB products, indicating that almost one-fourth of the cost could be saved by switching to BS human insulin from OB human insulin. All oral anti-diabetic medicines were found to be affordable, whereas none of the insulin was affordable. The NDWs for human and analog insulin were 1.38 and 5.06. Conclusion: In Pakistan, the insulin availability falls short of the WHO’s benchmark of 80%. Insulin continues to be unaffordable in both private and government sectors. To increase insulin access, the government should optimize insulin procurement at all levels, promote local production, enforce biosimilar prescribing, and provide financial subsidies for these products.

P017 Increased Level of Immunoglobulin G in the Development of Adverse Reactions in Patients With Ulcerative Colitis.

Goal: To identify the relationship between the level of immunoglobulins G and E and the development of adverse reaction (AR) in patients with ulcerative colitis (UC) receiving original infliximab (IFХ) and infliximab biosimilar (BS). 35 UC patients with moderate to severe course of the disease (according to Truelove-Witts) who received maintenance therapy with IFХ at a standard dose of 5 mg/kg of body weight for a year were retrospectively analyzed. There were 16 men (45.7%), 19 women (54.3%). The average age is 34±4.2 years. The duration of the anamnesis was from 3 to 7 years. Patients were divided into 3 groups depending on the development of AR and the received biological drug, without taking into account concomitant anti-inflammatory therapy. The 1st group (n=14) alternated the introduction of the original IFХ and its BS; The 2nd group (n=7) consisted of patients alternating between the original IFХ and BS, in whom AR was registered; the 3rd group (n=14) received BS by one trade name. Using enzyme immunoassay, the level of immunoglobulins in the groups of patients was assessed. In the 1st and 3rd groups, AR was not observed. AR in 2nd group was characterized by: bronchospasm 3 (42.8%), Quincke's edema 1 (14.3%), urticaria 1 (14.3%), rhinitis 1 (14.3%), anaphylactic shock 1 (14.3%). In patients of 1st group, the level of IgE is 44.8 ± 5.1 IU/ml, IgG is 16.5 ± 1.7 g/l. In 2nd group -IgE-44.5 ± 11.7 IU / ml, IgG-26.1 ± 2.1 g/l, while in patients in group 3-IgE - 31.5 ± 3.04 IU/ml, IgG - 9.46 ± 1.01 g/l. It was reliably established that the highest level of IgG was observed in the 2nd group, while in the 3rd group it was minimal (p < 0.05). The IgG level in 1st group is higher than in 3rd group, although in both groups the IgG level was within the reference values. In all groups, the IgE value remained normal. AR on the background of therapy with IFL and biosimilars are not associated with an increase in the level of IgE, but are caused by an increase in the level of IgG. The alternation of the original drug and the biosimilar increases the risk of developing AR due to increased IgG levels. Treatment with a biosimilar by one trade name does not increase the risk of developing AR.

The regulatory landscape of biosimilars: Algeria's efforts and progress made from 2006 to 2021

Biologics are tremendously efficacious biological molecules that have enabled the treatment of many life-threatening diseases, which have previously been hard to treat. Biosimilars, also known as “follow-on biologics”, are highly similar versions of another already approved biologic, called the Reference Product. The European Union has been a pioneer in the regulation of biosimilars. WHO guideline on evaluation of biosimilars published in 2009 was an important landmark in biosimilar regulations worldwide, and several countries have adopted its principles in the development of their own regulatory pathway for the approval of biosimilars. Most countries in the Middle East North Africa (MENA) region still lack official and scientific guidelines for biosimilar approval pathways. This article explores the regulatory situation of biosimilar registration pathways in Algeria and describes the progress made and the regulatory landscape changes for biosimilars in Algeria during the past ten years. Our findings indicate that the development of biosimilar regulation in Algeria went through three major phases between 2006 and 2021, during which there has been much progress in drafting guidance documents for biosimilars. Since 2016, Algeria has used the EMA, FDA and WHO guidelines as the basis for approval of several biosimilars and no national guidelines or regulations have been adopted to date. Additionally, there has been no regulation on substitution/interchangeability. The Algerian regulatory authority has gained considerable experience with approval and use of increasingly complex biosimilars over the past 5 years and has the potential to create its own biosimilar-specific regulatory pathway in the near future.

OBSIDIAN - real-world evidence of originator to biosimilar drug switch in juvenile idiopathic arthritis.

Limited data about use of biosimilars (BIOs) are available in children with JIA. This study therefore aimed to evaluate long-term efficacy and safety of switching from etanercept (ETA) and adalimumab (ADA) originators to their biosimilars (BIOs), in children with JIA, in a real-world setting. This is a retro-prospective non-interventional multicentre Italian comparative cohort study. Medical charts of JIA children treated with biosimilars of ETA or ADA were included. Efficacy and safety of TNF-inhibitors therapy was evaluated at last follow-up during originator and at 3, 6 and 12 months following the switch to biosimilar. A total of 59 children (42 female, median age at onset 88 months) were treated with biosimilar of ETA (21) and ADA (38). Forty-five switched from the originator to the BIO (17 ETA, 28 ADA). At time of switch, 12/17 patients on ETA and 18/28 on ADA were in remission. No significant difference has been found at 3, 6 and 12 months after the switch. Ten patients discontinued biosimilars due to disease remission (4 ETA, 3 ADA), family willing (1 ETA), occurrence of burning at injection site (1 ETA) and persistent activity (1 ADA). No statistically significant difference was observed between originator and BIOs, nor between originator and BIOs, and between ADA and ETA in time to disease remission achievement, time to relapse and number of patients who experienced adverse event (AE). Our real-life results seem to confirm the efficacy and safety profile of switching from originator of ADA and ETA to their respective BIOs, also in paediatric patients with JIA.

AB0222 COMPARISON OF SELF-INJECTION DEVICES FOR ADMINISTERING ANTI-TUMOR NECROSIS FACTOR AGENTS USING THE ORIGINAL QUESTIONNAIRE IN PATIENTS WITH RHEUMATOID ARTHRITIS

Background:Self-injection of biological agents has become a general practice in the treatment of rheumatoid arthritis (RA). Self-injectable biological agents differ in shape, needle thickness, drug fluid volume, and so on. These differences may affect patients’ evaluations of self-injection devices. Five kinds of anti-tumor necrosis factor (TNF) agents can be administered by self-injection in clinical practice in Japan. Information on patients’ evaluations of self-injection devices is important in choosing the agent for the treatment of RA among several agents with the same mechanism of action.Objectives:The aim of this retrospective cross-sectional study was to compare patient evaluations of anti-TNF self-injection devices in the treatment of RA.Methods:RA patients in whom etanercept (ETN) pen 50 mg (Embrel Pen) was switched to ETN biosimilar (BS) 50 mg (ETN-BS [MA]), adalimumab (ADA) syringe 40 mg (Humira syringe) was switched to ADA pen 40 mg (Humira pen), golimumab (GLM) syringe 50 mg (Simponi syringe) was switched to GLM autoinjector (Simponi AI), and certolizumab pegol (CZP) syringe (Cimzia syringe) was switched to CZP autoclicks (Cimzia AC) were asked to answer an originally developed questionnaire (Toyohashi Self-injection Assessment Questionnaire [T-SAQ]; Table 1) before and after switching agents. T-SAQ included 18 questions. A score of 0 indicated “best” and 4 indicated “worst” for each question, with a highest possible score of 72. The patients’ characteristics and T-SAQ scores before and after switching agents were investigated. A statistical analysis of the difference in T-SAQ score between before and after switching was performed using the Wilcoxon signed-rank test. A P value &lt; 0.05 was considered significant.Results:The patients were divided into groups according to the agents they received with switching as follows: switchers from ETN pen to ETN-BS, n = 32; switchers from ADA syringe to ADA pen, n = 28; switchers from GLM syringe to GLM-AI, n = 25; and switchers from CZP syringe to CZP-AC, n = 10. The total T-SAQ scores were as follows, respectively: ETN pen and ETN-BS, 23.5 and 19.0; ADA syringe and ADA pen, 25.8 and 14.9; GLM syringe and GLM-AI, 23.8 and 17.4; and CZP syringe and CZP-AC, 30.6 and 18.8. The total T-SAQ was significantly improved after switching to the pen devices in all the switching groups. In the switchers from ETN pen to ETN-BS, the scores for questions 5, 10, 11, 12, 16, 17, and 18 were significantly improved after switching. The total T-SAQ scores were significantly improved for questions 1, 2, 3, 4, 5, 7, 11, 12, 13, 15, 16, and 17 in the switchers from ADA syringe to ADA pen, for questions 1, 2, 5, 7, 10, 16, and 17 in the switchers from GLM syringe to GLM-AI, and for questions of 1, 2, 3, 4, 5, 7, 11, and 15 in the switchers from CZP syringe to GLM-AC.Conclusion:The pen devices were favorably assessed by the RA patients in whom syringe devices were switched to pen devices for the same agent. The total T-SAQ score improved in the RA patients in whom ETN pen was switched to ETN-BS probably because the thickness of the needle was thinner in the ETN-BS than in the ETN pen. The total T-SAQ score for the ADA pen was lowest probably because the thinnest needle was used (29 gauge) and the amount of drug fluid is smallest (0.4ml). The total T-SAQ score for the CZP syringe was the lowest probably because the thickest needle was used (25 gauge).Disclosure of Interests:None declared

Biosimilars in Dermatology

Biosimilars in Dermatology

Similarity assessment by multivariate statistics method based on the distance between biosimilar and originator

The development of biosimilar products or follow-on biologics has been flourishing in recent years because of their lower price than the originators. In this study, a multivariate data analysis method based on JMP software was proposed to assess the glycosylation pattern similarity of antibody candidates from different conditions in optimization experiments with a reference. A specific distance was generated by this method and indicated the glycoform similarity between the biosimilar and the reference. This method can be applied to analyze the similarity of other physicochemical and functional characteristics between follow-on biologics and originators. Then, the design of experimental methods can be realized to optimize the conditions of cell culture to attain similar antibody candidates. A higher concentration of GlcNAc added to the basal media made the glycan of the antibody more similar to the glycan of the reference in this study.

The Biologics Price Competition and Innovation Act 10--A Stocktaking

On March 23, 2010, President Obama signed into law the Biologics Price Competition and Innovation Act (BPCIA) as part of the Patient Protection and Affordable Care Act (“Obamacare”). The purpose of BPCIA was to create for biologics a regime similar to that of the Drug Price Competition and Patent Term Restoration Act (Hatch–Waxman Act) and, in so doing, to open biologics markets to competition and, subsequently, lower the price of these expensive and increasingly important pharmaceuticals. Using original data, this Essay takes stock of the decade that has passed since the enactment of BPCIA. This Essay surveys the state of competition in United States biologics markets, entry of follow-on biologics into these markets, and the effects such entry has had on biologics prices. This Essay’s main findings are that, as of March 23, 2020—exactly ten years since the signing of BPCIA into law—the FDA has approved a total of 26 follow-on biologics deemed biosimilar to 9 original products (ratio: 2.63 follow-on/original products), with only 16 of these deemed biosimilar to 7 original products (ratio: 1.78 follow- on/original products) actually available on the market. None of these follow-on products have been approved as interchangeable with their reference products, which means that substitution of the 7 original products with one of their 16 approved biosimilars cannot be done automatically. The price of these products was 10%–37% lower than the price of the original biologic, with the average price savings being 24% or 27%. All 35 approved follow-on and reference products are owned by a total of 11 pharmaceutical companies. The number of years of market exclusivity of the 9 original biologics before the approval of the first biosimilar ranged between 13.5–28.92 with an average of 18.27 years or 15.33–29.42 with an average of 19.87 years before the launch of the first competing biosimilar. This Essay further puts forward a new method of measuring comparative levels of competition in drug markets by comparing the ratio of total approved follow-on products per total approved original products at certain critical benchmarks. Using this measurement tool, this Essay compares BPCIA’s track record with the levels of competition in small-molecule drugs before and after the Hatch– Waxman Act, showing that that BPCIA significantly underperforms in comparison and fails to instigate levels of competition that would lead to significant price drops and increase access to biologics in the United States. A short survey of the most likely reasons for BPCIA’s underperformance follows. This Essay concludes by presenting the following question: if BPCIA’s current track record is (still) not enough to convince that it is failing to meet its goals, what more would it take to reach such a conclusion, and how much longer should policymakers wait before it is possible to surmise that BPCIA in its current form has failed to significantly increase access to biologics in the United States?

Biosimilars: is interchangeability the proof of the pudding?

Biosimilars: is interchangeability the proof of the pudding?

Key concepts in biosimilar medicines: What physicians must know.

Biologics’ are a class of medications produced by living cells using recombinant DNA technology. Biologics have had an important impact in many areas of medicine, and in particular in rheumatology and oncology. However, the high cost of these agents is a growing concern, particularly as more products become available and their use for the treatment of immune-mediated inflammatory diseases continues to expand. Biosimilars, also called follow-on biologics, have been viewed as a potential cost-saving alternative to traditional therapies. Currently, a product can be considered biosimilar to a reference product if there are no clinically meaningful differences in terms of safety, purity, and potency. In this review, the most important key concepts about biosimilars were summarized for physicians emphasizing the status in Turkey.

Shifting knowledge and attitudes about biosimilars among rheumatologists.

Shifting knowledge and attitudes about biosimilars among rheumatologists.