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Pharmaceutical residues can harm the environment. Therefore any Marketing Authorisation Application (MAA) for a medicinal product for human use shall be accompanied by an "indication of any potential risks presented by the medicinal product for the environment" according to Article 8(3)(g) of the Directive 2001/83/EC. Since 2006 a guideline document from the European Medicines Agency (EMA, formerly EMEA) is available for this task, which is now called the "Environmental Risk Assessment" (ERA). Recently the EMA released a draft revision of an updated ERA guideline. The present paper provides a summary of the intended innovation. A number of options have been discontinued, but some of them cannot be easily recognised, even though they are potentially affecting the MAA and its costs in a relevant way. A new specifically tailored experimental testing course for antibiotics and a secondary poisoning assessment is introduced. The selection of required study types is altered and the environmental fate evaluation is adapted to the scientific progress. In the recent situation it is suggested that marketing authorisation applicants may reconsider the conduct of water/sediment studies for substances not requiring these according to the guideline revision. The new tailored testing approach for antibiotics avoids any vertebrate use, because it demands no fish study, therefore it may be applied henceforth. If the new prescriptions are not yet in force at the point in time of the MAA submission, appropriate waivers should be stated in the ERA. No further HPLC-study types and acute earthworm toxicity tests should be performed, since the guideline update draft does not accept them. In preclinical toxicity and pharmacokinetic studies, additional data gathering on metabolites should be considered in order to avoid unnecessary leaflet warnings. The cost for ERA may change significantly, with a tendency to increase for generic pharmaceutical MAA, but with a possible reduction for substances of low environmental concern. Earlier consideration of ERA in the drug development process is recommended. [ABSTRACT FROM AUTHOR]

New European Union (EU) pharmacovigilance legislation, effective from July 2012, introduced new concepts and procedures to optimise the way medicines are regulated within the Union and provided new channels for public health interventions. Triggered by the EU legislation, the work done by the International Conference on Harmonisation (ICH) has provided a common standard for periodic benefit-risk evaluation reporting within the ICH regions. The present paper provides a review of the concepts behind the use of periodic benefit-risk evaluation reports (PBRER) in supporting safety evaluation and assessment of benefit-risk balance and covers essential points in the documentation of safety information, risk evaluation and benefit-risk assessment. The review incorporates the experience to-date with the PBRER at EU level led by the Pharmacovigilance Risk Assessment Committee of the European Medicines Agency. The scope of the PBRER, the main content topics and the challenges relevant to the different stakeholders are highlighted together with key success factors for the report to deliver its objectives and maximise the use of the regulatory assessment procedure. It is clear that the PBRER extends beyond new ways of data presentation and analysis and reflects a further shift in pharmacovigilance in the EU towards more integrated benefit-risk assessment of marketed medicines. [ABSTRACT FROM AUTHOR]

Purpose: Various incentives are provided by the European Medicines Agency (EMA) to facilitate the development and marketing of orphan drugs. A 10-year period of market exclusivity is reserved to an orphan medicinal product. Sometimes, the sponsor renounces the designation before the expiration of that standard period. Our aim was to focus on these premature withdrawals. Methods: We retrieved all the molecules included in the Community Register of Orphan Medicinal Products for Human Use from 2000 to November 2020. We considered the active substance, therapeutic indication, sponsor, year of designation, year of approval of the corresponding medicinal product, and that of the withdrawal of the orphan designation, if occurred. Results: Overall, 2350 orphan designations were approved from 2000 to November 2020. Of these, 141 have been marketed. Premature withdrawal of orphan designation concerned 23 drugs (20 being antineoplastic agents), corresponding to 16 medicinal products. These withdrawals occurred after almost 2 years (range <1–7 years). Conclusions: A not negligible fraction of marketed orphan medicinal products underwent premature removal of their orphan designation. No motivation is requested by the EMA for this renouncement, although the peculiarity of the orphan medicinal products would need a greater transparency. We can only speculate about possible compensations in support of this decision, for instance in terms of commercial agreements between pharmaceutical companies, giving way to alternative products, as a couple of examples suggest. An open debate on this topic among members of academia, regulatory bodies, price and reimbursements committees, and pharmaceutical industry representatives will be welcome. [ABSTRACT FROM AUTHOR]

Purpose: To review the marketing authorization of biosimilars and provide a critical analysis of the pivotal trials supporting their approval by the European Medicines Agency (EMA). Methods: EMA website to identify the biosimilars approved up to July 2019 and the European Public Assessment Report for information on pivotal trial design, duration, intervention and control, primary outcome, data on immunogenicity, and comparability margins. Results: The EMA has approved 55 biosimilars (62% in 2017–2019) of 16 biologic products, used in several clinical indications. Some biosimilars were licensed as multiple products, with different commercial names, by the same or different companies. The comparability exercise and subsequent approval of 49/55 (89%) biosimilars were based on one or more pivotal phase III trials testing their clinical efficacy. In all, biosimilars were approved on the basis of 55 trials, mostly phase III (42/55, 76%) assessing clinical efficacy; these were mainly equivalence trials (31/55, 56%). The pivotal phase III trials assessed surrogate measures of clinical effect, and 71% reported immunogenicity data. Conclusion: Analysis of the approval of biosimilars in Europe depicts a complex and heterogeneous scenario. The requirement for showing similarity in terms of clinical efficacy and safety provides a robust demonstration of comparable clinical outcomes but lays a burden on biosimilar manufacturers and may delay the introduction of the drugs. The development, licensing, and monitoring of biosimilars would benefit from new strategies to accelerate access to these drugs while reducing uncertainties about their use in practice. [ABSTRACT FROM AUTHOR]

New regulatory guidance documents from the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have recently been finalized or are in draft format outlining new pathways for preclinical safety testing. The US and the European Union appear to be moving in a similar direction focussing and refining preclinical safety data requirements for both radiodiagnostics and radiotherapeutics. We here summarize these recent documents from both the US and European perspective. [ABSTRACT FROM AUTHOR]