The Price and Market Share Evolution of the Original Biologics and Their Biosimilars in Finland

Background Biological drugs are generally expensive and produce a continuously growing share of drug costs. Yet they are essential in the treatment of many chronic diseases. Biosimilars, clinically equivalent to biological originator products, are expected to restrain drug costs in the biological market. Objective This study aimed to examine the impact of the biosimilar market entry on the prices of the reference products in outpatient care in Finland, investigate the impact of biosimilar market entries on price competition among biological medicinal products, and examine how the prices and market shares of outpatient biosimilars have developed in Finland during 2009-2020. Methods This retrospective register study applied data from IQVIA covering national community pharmacy wholesale data between 1 January, 2009, and 31 August, 2020, for somatropin, epoetin, filgrastim, follitropin, insulin glargine, insulin lispro, etanercept, pegfilgrastim, adalimumab, teriparatide, and enoxaparin biosimilars and their reference products, in addition to two relevant insulin products. We determined the monthly wholesale amounts in defined daily doses and wholesale weighted average prices (excluding value-added tax) per defined daily dose for each product. We analyzed the evolution of the price and market shares. We performed a linear segmented regression analysis to examine the impact of the market entry of biosimilars on the prices of reference products. Results The prices of the reference products mainly decreased after the biosimilar entered the market. If the reference product price was not reduced, it was no longer reimbursable after evaluation under the Health Insurance Act, leading to marginal market shares. The changes in the prices of biosimilars were not as remarkable as the changes in the prices of reference products after the biosimilar market entry. For most active substances, biosimilar prices were stable or decreased. The utilization of biosimilars varied widely between different active substances at the end of the observation period. Conclusions Changes in pricing policy and the public reimbursement scheme related to the market entry of biosimilars were the main reasons for the decrease in the prices of reference products. Therefore, biosimilars did not generate genuine price competition between biological products. In many of the drug groups examined, the market shares of biosimilars have growth potential in the future.Peer reviewe

Organisation of cross-sector collaboration and its influence on crisis management effectiveness among pharmaceutical supply chain stakeholders during the COVID-19 pandemic

Objectives: To investigate the organisation of cross-sector collaboration and how it influenced crisis management effectiveness among pharmaceutical supply chain stakeholders in Finland during the COVID-19 pandemic. Study design: Qualitative semi-structured interview study. Methods: Purposeful selection was used to obtain the study sample consisting of leaders and specialists from the pharmaceutical industry and wholesalers (n = 9), community pharmacy owners (n = 9), hospital pharmacy heads (n = 6), government agency directors and officials (n = 5) and advocacy organisation representatives (n = 2). Inductive content analysis was performed to examine the data from the semi-structured individual (n = 29) and paired (n = 2) interviews in March–May 2021. Results: A new conceptual model was developed to describe the organisation of collaborative crisis management. Without a predefined crisis management organisation, cross-sector collaboration was organised based on previous collaboration structures, channels and relationships and through the establishment of issue-specific groups by government agencies as per legal mandates. Crisis dynamics and related issues guided the group formation and meeting frequency. Advocacy organisations and government agencies acted in bridging role between stakeholders. Shared knowledge among pharmaceutical supply chain stakeholders enabled anticipation and preparedness during crisis; shared resources fostered maintenance of core functions; and shared problem-solving facilitated cross-sectoral solutions. Conclusion: This was the first study exploring cross-sector collaboration among pharmaceutical supply chain stakeholders during a crisis. Sharing knowledge, resources and problem-solving increased the crisis management effectiveness. The study presented a new illustration of organising for collaborative crisis management and added knowledge about private-third sector collaboration and issue-specific groups to the cross-sector collaboration and crisis management literature

Simulating atomic force microscopy imaging of the ideal and defected TiO2 (110) surface

In this study we simulate noncontact atomic force microscopy imaging of the TiO2 (110) surface using first-principles and atomistic methods. We use three different tip models to investigate the tip-surface interaction on the ideal surface, and find that agreement with experiment is found for either a silicon tip or a tip with a net positive electrostatic potential from the apex. Both predict bright contrast over the bridging oxygen rows. We then study the interaction of this tip with a bridging oxygen vacancy on the surface, and find that the much weaker interaction observed would result in vacancies appearing as dark contrast along the bright rows in images.Peer reviewe

Difficulties in administration of oral medication formulations to pet cats: an e-survey of cat owners

The purpose here was to determine the problems cat owners encounter in medicating their cats with orally administered drugs at home. The study was carried out as an open e-questionnaire survey addressed to cat owners in which the authors focused on the oral administration route. A total of 46 completed questionnaires were included in the survey. In the study, 46 cats received 67 orally administered drugs. Approximately half of the drugs were registered for use in cats by the European Medicines Agency (54 per cent), and there were also off-label drugs registered for human (36 per cent) and canine medication (7.4 per cent) and an ex tempore drug (3.0 per cent). The owners were unable to give the doses as prescribed for their cats for one-fourth of the medications (16/67). Drugs that were registered for feline medication were significantly more palatable than drugs registered for other species (odds ratio (OR) 4.9), and liquid formulations were significantly more palatable than solid formulations (OR 4.8). However, most of the owners (22/38) preferred a solid dosage form, while few (4/38) chose a liquid formulation. The results indicate that there is still a need for more palatable and easily administered oral drugs for cats.Peer reviewe

An inventory of collaborative medication reviews for older adults-evolution of practices

Background Collaborative medication review (CMR) practices for older adults are evolving in many countries. Development has been under way in Finland for over a decade, but no inventory of evolved practices has been conducted. The aim of this study was to identify and describe CMR practices in Finland after 10 years of developement. Methods An inventory of CMR practices was conducted using a snowballing approach and an open call in the Finnish Medicines Agency's website in 2015. Data were quantitatively analysed using descriptive statistics and qualitatively by inductive thematic content analysis. Clyne et al's medication review typology was applied for evaluating comprehensiveness of the practices. Results In total, 43 practices were identified, of which 22 (51%) were designed for older adults in primary care. The majority (n = 30, 70%) of the practices were clinical CMRs, with 18 (42%) of them being in routine use. A checklist with criteria was used in 19 (44%) of the practices to identify patients with polypharmacy (n = 6), falls (n = 5), and renal dysfunction (n = 5) as the most common criteria for CMR. Patients were involved in 32 (74%) of the practices, mostly as a source of information via interview (n = 27, 63%). A medication care plan was discussed with the patient in 17 practices (40%), and it was established systematically as usual care to all or selected patient groups in 11 (26%) of the practices. All or selected patients' medication lists were reconciled in 15 practices (35%). Nearly half of the practices (n = 19, 44%) lacked explicit methods for following up effects of medication changes. When reported, the effects were followed up as a routine control (n = 9, 21%) or in a follow-up appointment (n = 6, 14%). Conclusions Different MRs in varying settings were available and in routine use, the majority being comprehensive CMRs designed for primary outpatient care and for older adults. Even though practices might benefit from national standardization, flexibility in their customization according to context, medical and patient needs, and available resources is important.Peer reviewe

Void conditions and potential for mould growth in insulated and uninsulated suspended timber ground floors

PURPOSE: Millions of properties have suspended timber ground floors globally, with around ten million in the UK alone. However, it is unknown what the floor void conditions are, nor the effect of insulating such floors. Upgrading floors changes the void conditions, which might increase or decrease moisture build-up and mould and fungal growth. The purpose of this paper is to provide a review of the current global evidence and present the results of in situ monitoring of 15 UK floor voids. DESIGN/METHODOLOGY/APPROACH: An extensive literature review on the moisture behaviour in both uninsulated and insulated suspended timber crawl spaces is supplemented with primary data of a monitoring campaign during different periods between 2012 and 2015. Air temperature and relative humidity sensors were placed in different floor void locations. Where possible, crawl spaces were visually inspected. FINDINGS: Comparison of void conditions to mould growth thresholds highlights that a large number of monitored floor voids might exceed the critical ranges for mould growth, leading to potential occupant health impacts if mould spores transfer into living spaces above. A direct comparison could not be made between insulated and uninsulated floors in the sample due to non-random sampling and because the insulated floors included historically damp floors. The study also highlighted that long-term monitoring over all seasons and high-resolution monitoring and inspection are required; conditions in one location are not representative of conditions in other locations. ORIGINALITY/VALUE: This study presents the largest UK sample of monitored floors, evaluated using a review of current evidence and comparison with literature thresholds

Metabolism of a Bioorthogonal PET Tracer Candidate [F-19/F-18]SiFA-Tetrazine in Mouse Liver Microsomes: Biotransformation Pathways and Defluorination Investigated by UHPLC-HRMS

Organofluorosilicon based F-18-radiolabeling is an efficient method for incorporating fluorine-18 into BF-radiopharmaceuticals for positron emission tomography (PET) by F-19/F-18 isotopic exchange (1E). The first PET radiopharmaceutical, F-18 SiFAlin-TATE, radiolabeled with a silicon-based [F-18]fluoride acceptor (SiFA), namely, a para-substituted di-tert-butyl[F-18]-fluorosilylbenzene, has entered clinical trials, and is paving the way for other potential [F-18]SiFA-labeled radiopharmaceuticals for diagnostic use. In this study, we report the in vitro metabolism of an oxime-linked SiFA tetrazine (SiFA-Tz), a new PET-radiotracer candidate, recently evaluated for pretargeted PET imaging and macromolecule labeling. Metabolism of SiFA-Tz was studied in mouse liver microsomes (MLM) for elucidating its major biotransformation pathways. Nontargeted screening by ultrahigh performance liquid chromatography high-resolution mass spectrometry (UHPLC-HRMS) was utilized for detection of unknown metabolites. The oxime bond between the SiFA and Tz groups forms two geometric (E/Z) isomers, which underwent the same biotransformations, but unexpectedly with different kinetics. In total, nine proposed metabolites of SiFA-Tz from phase I and II reactions were detected, five of which were defluorinated in MLMs, elucidating the metabolic pathway leading to previously reported defluorination of [F-18]SiFA-Tz in vivo. Based on the HRMS studies a biotransformation pathway is proposed: hydroxylation (+O) to tert-butyl group adjacent to the silicon, followed by oxidative defluorination (+OH/-F) cleaving the fluorine off the silicon. Interestingly, eight proposed metabolites of a reduced dihydrotetrazine analogue, SiFA-H,Tz, from phase I and II reactions were additionally detected. To the best of our knowledge, this is the first reported comprehensive investigation of enzyme mediated metabolic pathway of tetrazines and para-substituted di-tertbutylfluorosilylbenzene fluoride acceptors, providing novel structural information on the biotransformation and fragmentation patterns of radiotracers bearing these structural motifs. By investigating the metabolism preceding defluorination, structurally optimized new SiFA compounds can be designed for expanding the portfolio of efficient F-19/F-18 isotopic exchange labeling probes for PET imaging