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  1. Mohd Sani N, Aziz Z, Kamarulzaman A
    Ther Innov Regul Sci, 2021 05;55(3):490-502.
    PMID: 33231863 DOI: 10.1007/s43441-020-00243-y
    INTRODUCTION: Biosimilars are a cost-effective alternative to original biologic medicines that allow patients access to biologic therapies for various chronic diseases. Our paper aims to provide an overview of biosimilars in Malaysia with emphasis on the comparison of Malaysian guidelines with guidelines from well-established regulatory agencies, a review of biosimilars' market approval and their reported adverse effects (AEs) as well as clinical trials conducted in Malaysia.

    METHODS: We searched the official websites of the National Pharmaceutical Regulatory Agency (NPRA) Malaysia and three other well-established agencies, online databases of Medline® and EMBASE for guidelines on legislation and regulations of biosimilars. Meanwhile, we extracted the reports of AEs involving biosimilars in Malaysia from the NPRA database and for global AEs from the World Health Organisation VigyLize database. The ClinicalTrials.gov Website by the U.S. National Library of Medicines was the source for data on clinical trials.

    RESULTS: Malaysia followed the principles of the European Medicines Agency biosimilar regulations and issued their guideline in 2008. Since then, NPRA has approved 24 biosimilar products and recorded 499 AE reports, of which 43 (8.6%) were serious. NPRA has also approved ten Phase III clinical trials in Malaysia with four trials still ongoing.

    CONCLUSION: Malaysia follows a stringent regulatory pathway for the approval of biosimilars enacted by well-established regulatory agencies to maintain the quality, efficacy and safety of biosimilars. Introducing biosimilars to the Malaysian market would improve patients' accessibility to biologic therapies.

    Matched MeSH terms: Biosimilar Pharmaceuticals*
  2. Godman B, Fadare J, Kwon HY, Dias CZ, Kurdi A, Dias Godói IP, et al.
    J Comp Eff Res, 2021 Aug;10(12):1019-1052.
    PMID: 34241546 DOI: 10.2217/cer-2020-0273
    Aim: Global expenditure on medicines is rising up to 6% per year driven by increasing prevalence of non-communicable diseases (NCDs) and new premium priced medicines for cancer, orphan diseases and other complex areas. This is difficult to sustain without reforms. Methods: Extensive narrative review of published papers and contextualizing the findings to provide future guidance. Results: New models are being introduced to improve the managed entry of new medicines including managed entry agreements, fair pricing approaches and monitoring prescribing against agreed guidance. Multiple measures have also successfully been introduced to improve the prescribing of established medicines. This includes encouraging greater prescribing of generics and biosimilars versus originators and patented medicines in a class to conserve resources without compromising care. In addition, reducing inappropriate antibiotic utilization. Typically, multiple measures are the most effective. Conclusion: Multiple measures will be needed to attain and retain universal healthcare.
    Matched MeSH terms: Biosimilar Pharmaceuticals*
  3. Sani NM, McAuslane N, Kasbon SH, Ahmad R, Yusof FAM, Patel P
    Ther Innov Regul Sci, 2020 Sep;54(5):1215-1224.
    PMID: 32865804 DOI: 10.1007/s43441-020-00140-4
    INTRODUCTION: The National Pharmaceutical Regulatory Agency (NPRA) embarked on a regulatory-strengthening program and is evaluating its processes. Optimising Efficiencies in Regulatory Agencies (OpERA) is a regulatory-strengthening program that provides benchmarking data that can define performance targets and focus performance improvement. The objective of this study was to use OpERA methodology to determine where time is spent in the NPRA approval process and to form a baseline to measure the performance improvements.

    METHODS: The OpERA tool was used to collect specific milestone data that identify time periods, review stages, and data points for new active substances and biosimilars approved by NPRA in 2017.

    RESULTS: In 2017, 25 new active substances and 1 biosimilar were approved by NPRA in a median of 515 days, representing both agency and applicant time. The median time between dossier receipt and the initiation of NPRA scientific assessment was 135 days, but there was a wide variation in queuing time. The median total assessment time was 279 days (agency and applicant timing). NPRA took a median of 166 days; applicants took a median of 131 days to respond to deficiency questions, with up to 6 cycles of review required for approval and 65% of applications requiring 4-5 cycles to provide satisfactory responses.

    CONCLUSIONS: As a result of these data, NPRA proposes three improvements: target start for scientific assessment 100 days after file acceptance, a maximum of 5 review cycles, and applicant response time limited to 6 months. These results will serve as a baseline for further assessment.

    Matched MeSH terms: Biosimilar Pharmaceuticals*
  4. Kang HN, Thorpe R, Knezevic I, Casas Levano M, Chilufya MB, Chirachanakul P, et al.
    Ann N Y Acad Sci, 2021 05;1491(1):42-59.
    PMID: 33222245 DOI: 10.1111/nyas.14522
    The World Health Organization (WHO) issued guidelines for the regulatory evaluation of biosimilars in 2009 and has provided considerable effort toward helping member states implement the evaluation principles in the guidelines into their regulatory practices. Despite this effort, a recent WHO survey (conducted in 2019-2020) has revealed four main remaining challenges: unavailable/insufficient reference products in the country; lack of resources; problems with the quality of some biosimilars (and even more with noninnovator products); and difficulties with the practice of interchangeability and naming of biosimilars. The following have been identified as opportunities/solutions for regulatory authorities to deal with the existing challenges: (1) exchange of information on products with other regulatory authorities and accepting foreign licensed and sourced reference products, hence avoiding conducting unnecessary (duplicate) bridging studies; (2) use of a "reliance" concept and/or joint review for the assessment and approval of biosimilars; (3) review and reassessment of the products already approved before the establishment of a regulatory framework for biosimilar approval; and (4) setting appropriate regulatory oversight for good pharmacovigilance, which is essential for the identification of problems with products and establishing the safety and efficacy of interchangeability of biosimilars.
    Matched MeSH terms: Biosimilar Pharmaceuticals/standards*
  5. Azizam NA, Hussain M, Nauenberg E, Ang WC, Azzeri A, Smith J
    PLoS One, 2024;19(9):e0307234.
    PMID: 39240834 DOI: 10.1371/journal.pone.0307234
    OBJECTIVE: In Malaysia, there is now a dearth of recommendations pertaining to the priority of biologic treatments for the effective management of psoriasis, given the multitude of available therapeutic alternatives. Present analysis reports results of a cost-effectiveness model that determines the most optimal arrangement of biologic treatments, with a particular focus of adding biosimilars to the existing treatment pathway for psoriasis in Malaysia.

    METHODS: A Markov model was developed to compare the cost effectiveness of various biologic sequential treatments in a hypothetical cohort of moderate to severe psoriasis patient in Malaysia over a lifetime horizon. The model simulated the progression of patients through three lines of active biologic therapy, before transitioning to best supportive care. Costs and effects were discounted annually at a rate of 3%.

    RESULTS: First line secukinumab has produced lowest incremental cost effectiveness ratios (ICERs) when compared to first line systemic [ICERs value; US$152,474 (first set analysis) and US$110,572 (second set analysis)] and first line phototherapy [ICERs value; US$147,057 (first set analysis) and US$107,616 (second set analysis)]. However, these values were slightly higher than the Malaysian based threshold of three times gross domestic product per capita, US$104,337. A 40% reduction in the unit costs of reference biologics renders most of the evaluated treatment sequences cost-effective.

    CONCLUSION: Adding biosimilar to the current treatment sequence could achieve cost savings ranging from 4.3% to 10.8% without significant loss of effectiveness. Given the significant impact of comorbidities and the resulting decline in quality of life among individuals with psoriasis, it may be justifiable to establish a threshold of up to US$184,000 per quality-adjusted life year (QALY) for the provision of therapies in the context of Malaysia.

    Matched MeSH terms: Biosimilar Pharmaceuticals/economics; Biosimilar Pharmaceuticals/therapeutic use
  6. Shakeel S, Hassali MA, Rehman H, Rehman AU, Muneswarao J
    Int J Gen Med, 2020;13:1075-1082.
    PMID: 33204142 DOI: 10.2147/IJGM.S266545
    Background: Pharmacists being the drug experts need to be well aware of the applied handling of biosimilar medicines (BSMs). They are an integral educator, trailblazer, and advocate of biosimilar integration across all clinical settings. Therefore, the current study was conducted to assess the pharmacists' knowledge, attitude, and practices of integrating BSMs into clinical practice.

    Methods: The cross-sectional study was conducted from August 2019 to November 2019. The community pharmacies, clinical and academic settings in Karachi were approached for gathering the responses of pharmacists towards BSMs and interchangeable products using a 30-item survey form. Pearson correlation and independent sample t-test were used to identify the relationship among independent variables and the responses, considering p values <0.05 as statistically significant.

    Results: Overall, there were 305 survey forms used with a response rate of 87.14%. More than 80% of the respondents have good knowledge about the definition, characteristics, safety and efficacy, compatibility, cost issues, and utilization of BSMs. Around half of the respondents (48.9%, [95% CI 46.6-51.2]) were confident in using BSMs in clinical practice. However, they were concerned about the BSM's safety profile (45.2%, [95% CI 42.1-48.3]), quality (30.2%, [95% CI 28.3-32.1]), and efficacy issues (32.3%, [95% CI 31.2-37.5]).

    Conclusion: The findings revealed that pharmacists were well informed about the BSMs. However, some of the responses to the attitude demonstrated a lack of understanding of the application of that knowledge. The respondents persuaded that advanced patterns of diseases, product marketing stipulations, and need for better patient care drives higher demand for developing BSMs and were enthusiastic about gaining more insight to integrate BSMs into routine clinical practice.

    Matched MeSH terms: Biosimilar Pharmaceuticals
  7. Haque M, Islam S, Kamal ZM, Akter F, Jahan I, Rahim MSA, et al.
    Hosp Pract (1995), 2021 Oct;49(4):266-272.
    PMID: 33734004 DOI: 10.1080/21548331.2021.1906083
    BACKGROUND: Prevalence rates of patients with diabetes are growing across countries, and Bangladesh is no exception. Associated costs are also increasing, driven by costs associated with the complications of diabetes including hypoglycemia. Long-acting insulin analogues were developed to reduce hypoglycemia as well as improve patient comfort and adherence. However, they have been appreciably more expensive, reducing their affordability and use. Biosimilars offer a way forward. Consequently, there is a need to document current prescribing and dispensing rates for long-acting insulin analogues across Bangladesh, including current prices and differences, as a result of affordability and other issues.

    METHODS: Mixed method approach including surveying prescribing practices in hospitals coupled with dispensing practices and prices among community pharmacies and drug stores across Bangladesh. This method was adopted since public hospitals only dispense insulins such as soluble insulins free-of-charge until funds run out and all long-acting insulin analogues have to be purchased from community stores.

    RESULTS: There has been growing prescribing and dispensing of long-acting insulins in Bangladesh in recent years, now accounting for over 80% of all insulins dispensed in a minority of stores. This increase has been helped by growing prescribing and dispensing of biosimilar insulin glargine at lower costs than the originator, with this trend likely to continue with envisaged growth in the number of patients. Consequently, Bangladesh can serve as an exemplar to other low- and middle-income countries struggling to fund long-acting insulin analogues for their patients.

    CONCLUSIONS: It was encouraging to see continued growth in the prescribing and dispensing of long-acting insulin analogues in Bangladesh via the increasing availability of biosimilars. This is likely to continue benefitting all key stakeholder groups.

    Matched MeSH terms: Biosimilar Pharmaceuticals/administration & dosage; Biosimilar Pharmaceuticals/economics; Biosimilar Pharmaceuticals/therapeutic use*
  8. Bas TG, Oliu Castillo C
    Biomed Res Int, 2016;2016:5910403.
    PMID: 27213153 DOI: 10.1155/2016/5910403
    The development of biological products has experienced continuous growth over the past three decades. The expiration of patent protection for many biological medicines has led to the development of biosimilars in many countries around the world. This paper reviews the literature on biosimilar drugs and covers their therapeutic status, clinical trials, approved biosimilars, and regulatory guidelines in Japan, South Korea, and Malaysia. The literature suggests that biosimilars are comparable but not identical to the reference product. They are not a generic version of an innovative product and do not ensure therapeutic equivalence. Biosimilars present more challenges than conventional generics and their marketing approval is also much more complicated. Guidelines for biosimilars were published in Japan in July 2009 by the Ministry of Health, Labour and Welfare (MHLW), in South Korea in March 2009 by the Ministry of Food and Drug Safety (MFDS), and in Malaysia in July 2008 by the National Pharmaceutical Control Bureau (NPCB).
    Matched MeSH terms: Biosimilar Pharmaceuticals/therapeutic use*
  9. Godman B, Wladysiuk M, McTaggart S, Kurdi A, Allocati E, Jakovljevic M, et al.
    Biomed Res Int, 2021;2021:9996193.
    PMID: 34676266 DOI: 10.1155/2021/9996193
    BACKGROUND: Diabetes mellitus rates and associated costs continue to rise across Europe enhancing health authority focus on its management. The risk of complications is enhanced by poor glycaemic control, with long-acting insulin analogues developed to reduce hypoglycaemia and improve patient convenience. There are concerns though with their considerably higher costs, but moderated by reductions in complications and associated costs. Biosimilars can help further reduce costs. However, to date, price reductions for biosimilar insulin glargine appear limited. In addition, the originator company has switched promotional efforts to more concentrated patented formulations to reduce the impact of biosimilars. There are also concerns with different devices between the manufacturers. As a result, there is a need to assess current utilisation rates for insulins, especially long-acting insulin analogues and biosimilars, and the rationale for patterns seen, among multiple European countries to provide future direction. Methodology. Health authority databases are examined to assess utilisation and expenditure patterns for insulins, including biosimilar insulin glargine. Explanations for patterns seen were provided by senior-level personnel.

    RESULTS: Typically increasing use of long-acting insulin analogues across Europe including both Western and Central and Eastern European countries reflects perceived patient benefits despite higher prices. However, activities by the originator company to switch patients to more concentrated insulin glargine coupled with lowering prices towards biosimilars have limited biosimilar uptake, with biosimilars not currently launched in a minority of European countries. A number of activities were identified to address this. Enhancing the attractiveness of the biosimilar insulin market is essential to encourage other biosimilar manufacturers to enter the market as more long-acting insulin analogues lose their patents to benefit all key stakeholder groups.

    CONCLUSIONS: There are concerns with the availability and use of insulin glargine biosimilars among European countries despite lower costs. This can be addressed.

    Matched MeSH terms: Biosimilar Pharmaceuticals/economics; Biosimilar Pharmaceuticals/therapeutic use*
  10. Ooi CJ, Hilmi I, Banerjee R, Chuah SW, Ng SC, Wei SC, et al.
    Intest Res, 2019 Jul;17(3):285-310.
    PMID: 31146509 DOI: 10.5217/ir.2019.00026
    The Asia-Pacific Working Group on inflammatory bowel disease (IBD) was established in Cebu, Philippines, under the auspices of the Asian Pacific Association of Gastroenterology with the goal of improving IBD care in Asia. This consensus is carried out in collaboration with Asian Organization for Crohn's and Colitis. With biologic agents and biosimilars becoming more established, it is necessary to conduct a review on existing literature and establish a consensus on when and how to introduce biologic agents and biosimilars in the conjunction with conventional treatments for ulcerative colitis (UC) and Crohn's disease (CD) in Asia. These statements also address how pharmacogenetics influence the treatments of UC and CD and provide guidance on response monitoring and strategies to restore loss of response. Finally, the review includes statements on how to manage treatment alongside possible hepatitis B and tuberculosis infections, both common in Asia. These statements have been prepared and voted upon by members of IBD workgroup employing the modified Delphi process. These statements do not intend to be all-encompassing and future revisions are likely as new data continue to emerge.
    Matched MeSH terms: Biosimilar Pharmaceuticals
  11. Hussein Z, Aziz NA, Dhanaraj E, Brahmachari B, Kothekar M
    Med J Malaysia, 2020 07;75(4):372-378.
    PMID: 32723997
    INTRODUCTION: Biosimilar insulins have the potential to increase access to treatment among patients with diabetes mellitus (DM), reduce treatment costs, and expand market competition. There are no published studies evaluating the performance of biosimilar insulins in routine clinical practice in Asia. This study assessed the safety and effectiveness of biphasic isophane insulin injection in Malaysian DM patients.

    MATERIALS AND METHODS: In this open label, single-arm, observational, post marketing study, patients received biphasic isophane insulin injection as per the Prescribing Information; and were assessed for safety (adverse events including hypoglycaemia), effectiveness (glycosylated haemoglobin [HbA1c]; fasting blood sugar, [FBS]; and patient's condition by patient and physician) over a period of 24 weeks.

    RESULTS: Adult male and female diabetes patients (N=119; type 2 DM, n=117) with a mean (SD) diabetes duration of 13 years were included. No new safety signals have been identified. Significant reduction in HbA1c was observed at weeks 12 and 24 (mean [SD] - baseline: 9.6% [1.9]; Week 12: 9.0% [1.7] and at Week 24: 9.1% [1.7]; p < 0.001). There were 10 serious and 9 non-serious adverse events reported in the study. Expected mild events included hypoglycaemia and injection site pruritus. However, the majority of the adverse events were non-study drug related events. No deaths were reported during the study.

    DISCUSSION: Biphasic isophane insulin injection was well tolerated with no new safety concerns. It was found effective in post- marketing studies conducted in routine clinical settings when administered in DM patients in this study.

    Matched MeSH terms: Biosimilar Pharmaceuticals*
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