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Older people are often affected by impaired organ and bodily functions resulting in multimorbidity and polypharmacy, turning them into the main user group of many medicines. Very often, medicines have not specifically been developed for older people, causing practical medication problems for them like limited availability of easy to swallow formulations, easy to open packaging and dosing instructions for enteral administration. In 2020, the European Medicines Agency (EMA) published a reflection paper 'Pharmaceutical development of medicines for use in the older population', which discusses how the emerging needs of an ageing European population can be addressed by medicines regulation. The paper intends to help industry to better consider the needs of older people during pharmaceutical/clinical medicines development by summarising data on the most relevant topics, providing early suggestions on how to move forward and prompting expert discussions and studies into knowledge gaps. Topics include patient acceptability, (dis)advantages of an administration route, formulation, dosage form, packaging, dosing device and user instruction. While the paper is directed at older people and the pharmaceutical industry, the reflections are also relevant to younger patients with similar disease‐related needs and of value to other stakeholders parties, e.g., healthcare professionals, academics, patients and caregivers, as the paper makes clear what can be expected from industry and where collaborative work is needed. This commentary provides an overview of the different steps in the development of the reflection paper, discusses points considered most controversial and/or subject to (multidisciplinary) expert discussions and indicates their value for real world clinical practice. [ABSTRACT FROM AUTHOR]

The recent benefit–risk framework (BRF) developed by the Food and Drug Administration (FDA) is intended to improve the clarity and consistency in communicating the reasoning behind the FDA's decisions, acting as an important advancement in US drug regulation. In the PDUFA VI implementation plan, the FDA states that it will continue to explore more structured or quantitative decision analysis approaches; however, it restricts their use within the current BRF that is purely qualitative. By contrast, European regulators and researchers have been long exploring the use of quantitative decision analysis approaches for evaluating drug benefit–risk balance. In this paper, we show how quantitative modelling, backed by decision theory, could complement and extend the FDA's BRF to better support the appraisal of evidence and improve decision outcomes. After providing relevant scientific definitions for benefit–risk assessment and describing the FDA and European Medicines Agency (EMA) frameworks, we explain the components of and differences between qualitative and quantitative approaches. We present lessons learned from the EMA experience with the use of quantitative modelling and we provide evidence of its benefits, illustrated by a real case study that helped to resolve differences of judgements among EMA regulators. [ABSTRACT FROM AUTHOR]

Therapeutic use of an unauthorised drug (or of an authorised drug for an unauthorised indication) for patients with a life-threating disease is permitted outside a clinical trial as an Expanded Access Programme (EAP).The regulations regarding EAPs is not the same all over the world. For example, the recommendation of the European Medicines Agency (EMA) in EU countries also includes within EAPs patients who have been treated in a clinical trial and who wish to continue the treatment. Nevertheless, the patients treated in a clinical trial could have the option of continuing treatment for an extended period in an Open-label Extension study, aimed to generate long-term data on efficacy, safety, tolerability and administration.The aims of this paper - based on the difficulties and incoherence encountered by an Italian Ethic Committee (EC) during the authorisation process of EAPs - are: understanding the origin of this misclassification by analysing differences and similarities among USA, European and Italian regulations concerning EAPs; and showing difficulties in classifying international study protocols as a consequence of the lack of harmonisation of definitions.We performed a critical review of the current USA, European and Italian regulations and we analysed some practical cases by retrieving protocols from Clinicaltrials.gov and the Italian Clinical Trials Registry (OsSC) containing in the title the keywords 'Expanded Access Programme', "'Expanded Access', 'Open-label Extension study' or 'Early Access'.We observed that the Food and Drug Administration ( FDA) definition of EAP is very clear while the EMA definition is similar to that of an Open-label Extension study. This lack of a clear definition generates misclassification and it is possible to find an EAP with an efficacy or safety endpoint; or an EAP managed as a clinical trial; or an EAP classified in Clinical Trials Registries as a phase II, III or IV clinical trial.The internationalisation of the studies requires a harmonisation on a global level of legislation and definitions to eliminate misclassification of protocols. For this reason, the authors suggest that: a) the EMA definition should be harmonised with the FDA definition of EAPs, b) European regulation, even if optional, should be adopted in a compulsory way by national regulations. Moreover, separate registries for both EAPs and clinical trials should be organised. [ABSTRACT FROM AUTHOR]

The development of specific drug therapy for children was a paradigm‐changing event that transformed paediatric medical practice. However, a series of tragedies involving drug treatment for children resulted in a gap developing between drug regulation and practice, with the majority of drugs used in child healthcare being used off‐label, rendering children therapeutic orphans. Over the past two decades changes in drug regulation led by the US Food and Drug Administration and followed by the European Union's European Medicines Agency have led to substantial changes in how new drugs with potential use in children are studied and labelled. While these changes have substantially improved labelling for new drugs, there has been much less progress with older drugs. Although the unique challenges of conducting clinical research in children have been addressed by novel clinical trial designs, many of these innovations have not been translated into approaches accepted for the drug approval process. The regulations applying to the need for paediatric studies currently are only applicable in the United States and the European Union, and there is less impetus for paediatric labelling in other jurisdictions. This impacts on a number of issues beyond labelling, including the availability of child‐friendly formulations. Finally, the impact of Brexit on paediatric drug studies in the UK remains unclear and is subject to ongoing negotiations between the UK government and the European Union. [ABSTRACT FROM AUTHOR]

Chinese herbal medicines (CHMs) have unique advantages in the prevention and treatment of diseases, which are widely recognized in the world. More and more CHMs are becoming increasingly popular in the international markets. However, the quality control of CHMs is a significant issue for their acceptance and recognition in the international market. This review mainly focuses on the quality requirements for CHMs to enter the European Union (EU) market. Both Chinese and European regulations and quality controls are compared. Firstly, the EU medicinal regulatory system and relevant regulations were reviewed. Secondly, the key factors of the quality control of CHMs, including Chinese herbal drugs, extracts and products were compared with those of European herbal medicines in the EU market. Subsequently, three main registration routes for herbal medicinal products including Chinese herbal medicinal products entering the EU were introduced. Furthermore, the legal status of traditional Chinese medicine granules in the EU was also discussed. Through the comparison of the key quality factors for CHMs in China and the EU, the similarities and differences in terms of quality requirements and regulations are addressed, which provides a reference for the development of CHMs into the EU market. [ABSTRACT FROM AUTHOR]

Scientific advice (SA) is an important tool offered by regulators to help developers generate robust evidence on a medicine's benefits and risks. Drawing on accumulated experience and looking at the SA provided by the European Medicines Agency in 2018 to advanced therapy medicinal products originally developed by public bodies, we discuss most commonly raised issues and the complexity and timings of the questions posed. Earlier and more frequent SA could help advanced therapy medicinal product developers to pre‐empt delays at the marketing authorisation stage. Carefully addressing quality and nonclinical issues before entering the pivotal phase of development will clear the path for a smooth clinical development and successful marketing authorisation. [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]