Biosimilars in the French and Polish System: Chosen Aspects of Reimbursement and Access

The EU approved the first biosimilar drug in 2006. By 2017, the EU had authorized the highest number of biosimilars worldwide, acquiring considerable experience in their use and safety. In May 2019, the European Medicines Agency (EMA) search engine showed 54 authorized biosimilars. Biosimilars reduce public expenditure; however, the discussion about their potential disadvantages is still ongoing. Each country adopts different regulations on the interchangeability, switching, and substitution of a reference medicine by its biosimilar, since the EMA does not regulate this issue. Additionally, each nation has a unique reimbursement system, which results in significant differences in patients’ access to biosimilars. The importance of securing a higher availability of these cheaper versions of biological drugs is well-recognized. The better the access to these biosimilars is, the lower the overall drug expenditure and need for rationing would be, and therefore the better treatment results. The aim of this paper is to compare selected aspects of reimbursement and access to the EMA authorized biosimilar medicines in two countries – France and Poland. The stated drug policy goal of both countries is to significantly improve biosimilar implementation in the coming years. The research is based on an analysis of four main sources: the EMA biosimilars database, the Polish reimbursement list published by the Polish Ministry of Health, and two French reimbursement databases published by the French Ministry of Health. An additional literature review was conducted. The expected results concentrate on differences in the number of reimbursed biosimilars, the average time between EMA authorization and country reimbursement decision date, and the availability of biosimilars registered outside of the centralized (EMA) procedure. These findings could identify areas of improvement and help with discussions on how to optimize the reach of biosimilars, as well as improve French-Polish collaboration on this matter.

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The Biosimilar Landscape: An Overview of Regulatory Approvals by the EMA and FDA

Pharmaceutics ◽

10.3390/pharmaceutics13010048 ◽

2020 ◽

Vol 13 (1) ◽

pp. 48

Author(s):

Ioana Gherghescu ◽

M. Begoña Delgado-Charro

Keyword(s):

Drug Administration ◽

Action Plan ◽

European Medicines Agency ◽

Patient Access ◽

Clinical Evaluations ◽

The Past ◽

The Us ◽

Improve Patient ◽

The Eu

Biosimilar medicines expand the biotherapeutic market and improve patient access. This work looked into the landscape of the European and US biosimilar products, their regulatory authorization, market availability, and clinical evaluation undergone prior to the regulatory approval. European Medicines Agency (EMEA, currently EMA) and Food and Drug Administration (FDA) repositories were searched to identify all biosimilar medicines approved before December 2019. Adalimumab biosimilars, and particularly their clinical evaluations, were used as a case study. In the past 13 years, the EMA has received 65 marketing authorization applications for biosimilar medicines with 55 approved biosimilars available in the EU market. Since the first biosimilar approval in 2015, the FDA has granted 26 approvals for biosimilars with only 11 being currently on the US market. Five adalimumab biosimilars have been approved in the EU and commercialized as eight different medicines through duplicate marketing authorizations. Whilst three of these are FDA-approved, the first adalimumab biosimilar will not be marketed in the US until 2023 due to Humira’s exclusivity period. The EU biosimilar market has developed faster than its US counterpart, as the latter is probably challenged by a series of patents and exclusivity periods protecting the bio-originator medicines, an issue addressed by the US’s latest ‘Biosimilar Action Plan’.

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A Follow-On Biological Drug is not a Biogeneric: Lessons from Omnitrope and Valtropin

Journal of Generic Medicines The Business Journal for the Generic Medicines Sector ◽

10.1057/jgm.2009.8 ◽

2009 ◽

Vol 6 (3) ◽

pp. 237-245 ◽

Cited By ~ 2

Author(s):

Robert I. Roth ◽

Nicholas M. Fleischer

Keyword(s):

United States ◽

Therapeutic Proteins ◽

Cost Savings ◽

The United States ◽

Substantial Cost ◽

Biological Drugs ◽

Biological Drug ◽

Therapeutic Properties ◽

Drug Developer ◽

The Eu

Recent years have seen the approvals, more so in the EU than the United States, of follow-on biological drugs. These products have been new formulations of recombinant therapeutic proteins, developed to compete with the marketed originator products. Intended to closely mimic the originator products in terms of chemistry and therapeutic properties, these so-called ‘biosimilar’ products were initially conceived to be developed according to abbreviated development programmes, presumably at a substantial cost savings to both the drug developer and the consumer. With several such products now recently approved, however, it has become clear that their development programmes have been quite extensive and not particularly abbreviated. Accordingly, cost savings to consumers appear to be relatively modest.

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State Aid Rules and Public Financing of Infrastructure. The Case of Autostrada Wielkopolska S.A.

TalTech Journal of European Studies ◽

10.1515/bjes-2020-0005 ◽

2020 ◽

Vol 10 (1) ◽

pp. 77-96

Author(s):

Paulina Kubera

Keyword(s):

Public Expenditure ◽

State Aid ◽

Public Financing ◽

The Road ◽

Playing Field ◽

Toll Road ◽

Legal Provisions ◽

Concession Contract ◽

The Eu ◽

Made In

Abstract The operation of a toll road typically involves an economic activity for which State aid rules apply. However, if the construction and operation of the road infrastructure is bundled and they are tendered out together, they usually fall outside the State aid regime. The reason for it lies in the fact that the use of competitive procurement procedures aim to increase the efficiency of public expenditure and to ensure a level playing field for private operators to compete for public contracts. Nevertheless, based on the European Commission’s decisional practice, it transpires that an economic advantage for a concession holder cannot be ruled out automatically, in particular when there are amendments made to the original agreement. On the example of the Autostrada Wielkopolska S.A. case, critical State aid issues are discussed, among others, the application of State aid rules to public financing of infrastructure, the amendments made to a concession contract in the light of the risk assignment problem, as well as the existence of State aid in the form of overcompensation for a concession holder. The considerations are carried out on the canvas of a concrete case; however, they are enriched by the analysis of relevant legal provisions as well as conclusions from the EU courts and the European Commission decisions made in similar cases.

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Differences between the European and Eurasian Good Pharmacovigilance Practices

Safety and Risk of Pharmacotherapy ◽

10.30895/2312-7821-2021-9-2-75-84 ◽

2021 ◽

Vol 9 (2) ◽

pp. 75-84

Author(s):

A. V. Matveev ◽

A. E. Krasheninnikov ◽

E. A. Matveeva ◽

B. K. Romanov

Keyword(s):

Marketing Authorisation ◽

European Medicines Agency ◽

The European Union ◽

Current Version ◽

Eurasian Economic Union ◽

Expert Analysis ◽

The Russian Federation ◽

Economic Union ◽

Systems Effectiveness ◽

The Eu

Good pharmacovigilance practices (GVP) of the Eurasian Economic Union (EAEU) were prepared based on the GVP of the European Medicines Agency that have been in force in the European Union (EU) since 2012. The EAEU GVP have been in force in the Russian Federation and the other EAEU member states since 2016. It is important to identify potential diﬀerences between the current regulations in order to harmonise requirements for the pharmacovigilance systems in the EU and EAEU. The aim of the study was to analyse and compare GVP requirements in the EU and EAEU. The analysis helped to identify diﬀerences in the structure and contents of GVP sections, the deﬁnitions of terms (EU GVP deﬁnitions are more detailed and supported by examples, subsections, and references to other documents). Moreover, supplements and annexes to the EU GVP contain ﬁgures, templates, examples, algorithms, and tables, which are missing in the EAEU GVP. Expert analysis of these diﬀerences as applied to assessment of the pharmacovigilance systems’ eﬀectiveness, and practical activities of marketing authorisation holders, medicine developers, and regulatory authorities, demonstrated that the two GVPs are suﬃciently harmonised and have very few diﬀerences. However, the number of diﬀerences between the documents increases, as changes are made to the EU GVP. A more comprehensive harmonisation of the EAEU GVP with the current version of the EU GVP will make it possible to develop and use uniform pharmacovigilance documents in the EU and EAEU, and will facilitate the introduction of EAEU medicines into the global pharmaceutical market.

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An analysis of characteristics of post-authorisation studies registered on the ENCePP EU PAS Register

F1000Research ◽

10.12688/f1000research.12198.1 ◽

2017 ◽

Vol 6 ◽

pp. 1447 ◽

Cited By ~ 5

Author(s):

Robert Carroll ◽

Sreeram V. Ramagopalan ◽

Javier Cid-Ruzafa ◽

Dimitra Lambrelli ◽

Laura McDonald

Keyword(s):

Risk Assessment ◽

Chart Review ◽

Drug Utilisation ◽

Data Capture ◽

Primary Data ◽

European Medicines Agency ◽

Therapeutic Area ◽

The European Union ◽

Study Designs ◽

The Eu

Background: The objective of this study was to investigate the study design characteristics of Post-Authorisation Studies (PAS) requested by the European Medicines Agency which were recorded on the European Union (EU) PAS Register held by the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP). Methods: We undertook a cross-sectional descriptive analysis of all studies registered on the EU PAS Register as of 18th October 2016. Results: We identified a total of 314 studies on the EU PAS Register, including 81 (26%) finalised, 160 (51%) ongoing and 73 (23%) planned. Of those studies identified, 205 (65%) included risk assessment in their scope, 133 (42%) included drug utilisation and 94 (30%) included effectiveness evaluation. Just over half of the studies (175; 56%) used primary data capture, 135 (43%) used secondary data and 4 (1%) used a hybrid design combining both approaches. Risk assessment and effectiveness studies were more likely to use primary data capture (60% and 85% respectively as compared to 39% and 14% respectively for secondary). The converse was true for drug utilisation studies where 59% were secondary vs. 39% for primary. For type 2 diabetes mellitus, database studies were more commonly used (80% vs 3% chart review, 3% hybrid and 13% primary data capture study designs) whereas for studies in oncology, primary data capture were more likely to be used (85% vs 4% chart review, and 11% database study designs). Conclusions: Results of this analysis show that study objectives and therapeutic area influence PAS design in terms of type of data capture used.

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Trends in the costs of drugs launched in the UK between 1981 and 2015: an analysis of the launch price of drugs in five disease areas

BMJ Open ◽

10.1136/bmjopen-2018-027625 ◽

2019 ◽

Vol 9 (5) ◽

pp. e027625 ◽

Cited By ~ 1

Author(s):

Derek J Ward ◽

Lucy Doos ◽

Andrew Stevens

Keyword(s):

Colorectal Cancer ◽

Cross Sectional Study ◽

New Drugs ◽

Regulatory Agencies ◽

European Medicines Agency ◽

Biological Drugs ◽

Cross Sectional ◽

Medical Benefits ◽

Using Data ◽

The Uk

ObjectivesTo investigate the trend in the launch price of new drugs for five common health conditions.DesignCross-sectional study using data on new drugs launched in the UK between 1981 and 2015 for hypertension, asthma, rheumatoid arthritis, schizophrenia and colorectal cancer.Data and sourcesAll drugs marketed in the UK between 1981 and 2015 (inclusive), and licensed specifically for the treatment of one of the five chosen conditions were included in the study. Newly launched medicines and their launch prices were identified by hand-searching all editions of the British National Formulary in addition to searching the websites of relevant regulatory agencies (European Medicines Agency and Medicines and Healthcare products Regulatory Agency). The launch price in UK pounds for a 28-day supply of each medicine at a typical or usual maintenance dose was adjusted for the effects of general inflation using the gross domestic product deflator series.Results104 drugs were included in our study with a mean inflation-adjusted 28-day launch price of £288 (SD £678). The launch price of new drugs varied significantly across the five conditions, with drugs for hypertension having the lowest mean price (£27) and drugs for colorectal cancer having the highest mean price (£1590) (p<0.001). There were large increases in launch prices across the study period, but the magnitude and pattern was markedly different between therapeutic areas. Biological drugs represented 13.5% of all included drugs and had a significantly higher launch price than non- biological drugs (£1233 vs £141, p<0.001). 22.1% of included drugs were first-of-kind and had a significantly higher launch price than follow-on drugs (£768 vs £151) (p<0.0001).ConclusionDrugs prices continue to increase across different therapeutic areas. This has some association with novelty, but, it is not clear if this increase in price is associated with medical benefits.

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P23 Accelerating and de-risking the production of paediatric oral formulations

Archives of Disease in Childhood ◽

10.1136/archdischild-2020-nppg.32 ◽

2020 ◽

Vol 105 (9) ◽

pp. e18.1-e18

Author(s):

Dilawar Khan ◽

Daniel Kirby ◽

Simon Bryson ◽

Maryam Shah ◽

Mohammed Afzal

Keyword(s):

Paediatric Population ◽

European Medicines Agency ◽

List Type ◽

Scanning Calorimetry ◽

Glycopyrronium Bromide ◽

Paediatric Regulation ◽

Age Appropriate ◽

Screening Platform ◽

The Eu ◽

Paediatric Medicines

Background & AimAs part of the EU paediatric regulation, the paediatric use marketing authorisation (PUMA) was introduced, with an aim to stimulate research in existing compounds that are off-patent and/or to help transform known off-label use into authorised use.1 However, success has been limited, with only a few products gaining a PUMA, such as Sialanar 320 micrograms/mL glycopyrronium (equivalent to 400 micrograms/mL glycopyrronium bromide). A distinct challenge to overcome in this area is the development of more ‘age appropriate formulations’, particularly with an excipient composition and load that is suitable for paediatric patients. This project aims to establish an excipient screening platform, supplemented with analytical characterisation of materials, which will act as a decision making tool to accelerate and de-risk the production of age appropriate paediatric medicines.MethodTo develop this excipient screening platform, a list of drugs that require an age appropriate formulation was produced using the ‘needs for paediatric medicines’ documents provided by the European medicines agency (EMA),2whilst common problematic excipients in paediatrics were identified using an EMA reflection paper.3 Literature and prescribing data were also reviewed to ensure drugs selected would benefit from an age appropriate formulation. Differential scanning calorimetry (DSC) to determine compatibility of selected drugs with widely used excipients was carried out using a TA DSCQ200 instrument (TA Instruments, New Castle, DE) with TA Instruments Universal Analysis 2000 software. Data was collected under nitrogen atmosphere (50 mL min−1) using pierced flat-bottomed TZero aluminium pans (sample mass about 2 mg) and heating rate of 10 °C min−1 in the range from 50 to 400°C. For samples containing both the drug and an excipient, 1 mg of each was measured out and gently mixed with a spatula for one minute.ResultsThe most common class of drugs identified as requiring age appropriate formulations were related to cardiovascular disorders and neurology, whilst the majority of drugs identified also exhibit poor aqueous solubilities. Some identified problematic excipients include ethanol, sodium benzoate and sorbitol; however, these excipients may still be used in paediatric formulations, as long as they are below certain concentrations (for example, ethanol concentration should not exceed 0.5% w/v for under 6 years old). Two drugs identified through the initial screening, carvedilol and nifedipine, were analysed by DSC, alone and then alongside starch from corn and starch 1500; the resulting DSC curves showed no changes in peak size, position (peak onset temperatures for nifedipine and carvedilol were observed at 173.2°C and 117.3°C, respectively) and shape, as well as no additional peaks, therefore suggesting compatibility between the tested samples.ConclusionThis first phase of the development of an excipient screening platform will continue to scan several different excipients with selected active pharmaceutical ingredients (APIs) in order to create compatibility profiles. The excipient screening platform generated will accelerate and de-risk the production of age appropriate formulations, as it would allow screening for potential incompatibilities and acceptability, alongside informing formulation of appropriate oral paediatric dosage forms.ReferencesEuropean Commission. State of Paediatric Medicines in the EU. 10 years of the EU Paediatric Regulation. COM (2017) 626. Available at: https://ec.europa.eu/health/sites/health/files/files/paediatrics/docs/2017_childrensmedicines_report_en.pdfNeeds for paediatric medicines - European Medicines Agency [Internet]. 2019 [cited 28 June 2019]. Available from: https://www.ema.europa.eu/en/human-regulatory/research-development/paediatric-medicines/needs-paediatric-medicinesReflection paper: formulations of choice for the paediatric population [Internet]. European Medicines Agency. 2019 [cited 28 June 2019]. Available from: https://www.ema.europa.eu/en/documents/scientific-guideline/reflection-paper-formulations-choice-paediatric-population_en.pdf

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Agencies will become more important in EU governance

Emerald Expert Briefings ◽

10.1108/oxan-db236098 ◽

2018 ◽

Keyword(s):

Policy Development ◽

Regulatory Networks ◽

Limited Resources ◽

Regulatory Agencies ◽

European Medicines Agency ◽

Content Type ◽

Foreign Companies ◽

Eu Governance ◽

European Banking ◽

The Eu

Subject Agencies in the EU. Significance Preparations for Brexit last year prompted the decision to relocate two EU agencies that had been based in London -- the European Banking Authority (EBA), which will move to Paris, and the European Medicines Agency (EMA), which will move to Amsterdam. This shined a spotlight on an aspect of EU governance that rarely attracts much attention outside specialist circles: the EU’s decentralised regulatory agencies. Impacts Delegating regulatory tasks allows the Commission to focus its limited resources more on policy development and enforcement. EU agencies tend to enhance transparency as they incorporate and replace existing, often opaque, regulatory networks and expert committees. The location of agencies can influence foreign companies’ decisions of where to base their EU headquarters.

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Structural and Functional Characterization of Low-molecular-weight Heparins: Impact on the Development of Guidelines for Generic Products

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029609332727 ◽

2009 ◽

Vol 15 (2) ◽

pp. 137-144 ◽

Cited By ~ 8

Author(s):

Cafer Adiguzel ◽

Walter P. Jeske ◽

Debra Hoppensteadt ◽

Jeanine M. Walenga ◽

Vinod Bansal ◽

...

Keyword(s):

Molecular Weight ◽

Functional Characterization ◽

Current Data ◽

European Medicines Agency ◽

Low Molecular Weight ◽

Low Molecular Weight Heparins ◽

Biological Drugs ◽

Biologic Drugs ◽

The Us ◽

Us Fda

Low-molecular-weight heparins (LMWHs) are poly-pharmacologic drugs used to treat thrombotic and cardiovascular disorders. Recently, several generic versions of branded LMWHs have been introduced. Although generic versions of LMWHs exhibit similar profiles, marked differences in their biological and pharmacologic properties have been demonstrated. Several studies have demonstrated differences in terms of anti-Xa activity and tissue factor pathway inhibitor release. The current data emphasize the need to consider multiple functional parameters when defining bioequivalence of biologic drugs and also underscore the importance of further pharmacologic studies involving animal and human clinical trials. The US Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) are currently developing guidelines for the acceptance of complex biological drugs including LMWHs. The US FDA considers these drugs as follow-on agents whereas the EMEA classifies these drugs as biosimilar agents. Until clear guidelines are developed, generic interchange of LMWHs may not be feasible.

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Addressing the regulatory and scientific challenges in multiple sclerosis – a statement from the EU regulators

Multiple Sclerosis Journal ◽

10.1177/1352458514546876 ◽

2014 ◽

Vol 20 (10) ◽

pp. 1282-1287 ◽

Cited By ~ 6

Author(s):

Pavel Balabanov ◽

Manuel Haas ◽

Andre Elferink ◽

Serge Bakchine ◽

Karl Broich

Keyword(s):

Multiple Sclerosis ◽

Drug Development ◽

Guideline Development ◽

New Drugs ◽

European Medicines Agency ◽

Guidance Document ◽

Flexible Approach ◽

Official Position ◽

New Drug Development ◽

The Eu

Improving and facilitating the process of making new drugs available to patients with multiple sclerosis (MS) requires cooperation among the regulators and other stakeholders. This cooperation will also positively contribute towards developing guidelines of the highest quality in medical, regulatory and scientific aspects. This would be beneficial both in areas that require further guideline development, but also in fields where existing guidance should be adapted to take into account evolution in science. Considering the input from all stakeholders, the European Medicines Agency confirmed its intention to update the relevant guideline and apply a flexible approach towards new drug development strategies in MS. This article is the first official position from the EU regulators, presenting the main changes to be expected in the guidance document.

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