Drug development: EU paediatric legislation, the European Medicines Agency and its Paediatric Committee-adolescents’ melanoma as a paradigm

2014 ◽  
Vol 13 (4) ◽  
pp. 211-213 ◽  
Author(s):  
Klaus Rose ◽  
Stephen Senn
Keyword(s):  
Drug Development ◽  
European Medicines Agency ◽  
Paediatric Committee

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

2014 ◽  
Vol 20 (10) ◽  
pp. 1282-1287 ◽  
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.

scholarly journals Concept and utility of population pharmacokinetic and pharmacokinetic/pharmacodynamic models in drug development and clinical practice

2021 ◽  
Vol 71 (4) ◽  
pp. 336-353
Author(s):  
Maša Roganović ◽  
Ana Homšek ◽  
Marija Jovanović ◽  
Valentina Topić-Vučenović ◽  
Milica Ćulafić ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Drug Development ◽  
Current Knowledge ◽  
European Medicines Agency ◽  
Population Pharmacokinetic ◽  
Population Modelling ◽  
Dose Individualisation ◽  
Regulatory Bodies ◽  
Development Phases ◽  
Modelling Approach

Due to frequent clinical trial failures and consequently fewer new drug approvals, the need for improvement in drug development has, to a certain extent, been met using model-based drug development. Pharmacometrics is a part of pharmacology that quantifies drug behaviour, treatment response and disease progression based on different models (pharmacokinetic - PK, pharmacodynamic - PD, PK/PD models, etc.) and simulations. Regulatory bodies (European Medicines Agency, Food and Drug Administration) encourage the use of modelling and simulations to facilitate decision-making throughout all drug development phases. Moreover, the identification of factors that contribute to variability provides a basis for dose individualisation in routine clinical practice. This review summarises current knowledge regarding the application of pharmacometrics in drug development and clinical practice with emphasis on the population modelling approach.

scholarly journals Preclinical biomarker qualification

2017 ◽  
Vol 243 (3) ◽  
pp. 222-227 ◽  
Author(s):  
John-Michael Sauer ◽  
Amy C Porter ◽  
Keyword(s):  
Drug Development ◽  
Drug Administration ◽  
Medical Devices ◽  
Food And Drug Administration ◽  
European Medicines Agency ◽  
Clinical Biomarkers ◽  
New Information ◽  
History Of ◽  
Novel Biomarkers ◽  
Novel Approaches

Biomarkers are ubiquitously used within drug development programs in both nonclinical species and in humans to assess safety and efficacy of novel compounds. To routinely apply such novel biomarkers with certainty, a well-defined data package is necessary for review and endorsement by regulatory agencies including the US Food and Drug Administration, European Medicines Agency, and Japanese Pharmaceuticals and Medical Devices Agency. This type of endorsement is known as regulatory qualification. Novel approaches are being applied to speed the process, lower the resource intensity, and increase the accessibility of biomarker qualification data and it is likely that consortia will continue to play a fundamental role in the qualification process by bringing together like-minded stakeholders focused on specific tools to accelerate drug development. This article will focus on learnings from the previous three nonclinical biomarker qualification projects, as well as discuss the progression of preclinical biomarker projects into the clinical qualification space and the current strategy for the use of nonclinical biomarker data in the translational qualification of clinical biomarkers; much like nonclinical information is used in the approval of drug development candidates. Impact statement This minireview provides an overview of the history of preclinical biomarker qualification by summarizing the three examples of this type of qualification with US Food and Drug Administration, European Medicines Agency, and Japanese Pharmaceuticals and Medical Devices Agency. In addition, an overview of the biomarker qualification process is included to educate key stakeholders with links to relevant white papers that provide information on current evidentiary considerations. The manuscript also provides new information on the evolution of the role that preclinical qualification plays in clinical qualification of biomarkers and the novel approaches that are being utilized to improve the process.

scholarly journals First Regulatory Qualification of a Novel Digital Endpoint in Duchenne Muscular Dystrophy: A Multi-Stakeholder Perspective on the Impact for Patients and for Drug Development in Neuromuscular Diseases

2021 ◽  
pp. 183-190
Author(s):  
Laurent Servais ◽  
Eric Camino ◽  
Aude Clement ◽  
Craig M. McDonald ◽  
Jacek Lukawy ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Drug Development ◽  
Neuromuscular Diseases ◽  
European Medicines Agency ◽  
Motor Abilities ◽  
Stakeholder Perspective ◽  
Functional Outcome Measures ◽  
Multi Stakeholder ◽  
The Impact

<b><i>Background:</i></b> Functional outcome measures used to assess efficacy in clinical trials of investigational treatments for rare neuromuscular diseases like Duchenne muscular dystrophy (DMD) are performance-based tasks completed by the patient during hospital visits. These are prone to bias and may not reflect motor abilities in real-world settings. Digital tools, such as wearable devices and other remote sensors, provide the opportunity for continuous, objective, and sensitive measurements of functional ability during daily life. Maintaining ambulation is of key importance to individuals with DMD. Stride velocity 95th centile (SV95C) is the first wearable acquired digital endpoint to receive qualification from the European Medicines Agency (EMA) to quantify the ambulation ability of ambulant DMD patients aged ≥5 years in drug therapeutic studies; it is also currently under review for the US Food and Drug Administration (FDA) qualification. <b><i>Summary:</i></b> Focusing on SV95C as a key example, we describe perspectives of multiple stakeholders on the promise of novel digital endpoints in neuromuscular disease drug development.

scholarly journals P84 Pediatric oncology studies triggered by the united states (US) food and drug administration (FDA) and the european union (EU) european medicines agency (EMA) aim at labels, not at improved treatment. Some harm young patients by exposing them to substandard monotherapy instead of combination treatment

2019 ◽  
Vol 104 (6) ◽  
pp. e52.1-e52
Author(s):  
K Rose
Keyword(s):  
Drug Development ◽  
Childhood Cancer ◽  
Pediatric Oncology ◽  
Combination Treatment ◽  
Cytotoxic Agents ◽  
European Medicines Agency ◽  
Status Report ◽  
Pediatric Drug ◽  
Drug Labeling ◽  
Age Limits

BackgroundBoth FDA and EMA reward/demand pediatric oncology studies. Do they advance pediatric cancer care?MethodsWe analysed publications of FDA representatives,1–3 FDA-triggered pediatric oncology studies in the literature and in www.clinicaltrials.gov,4 and FDA/EMA pediatric reports.5–6ResultsFDA authors express two key assumptions: (1) children, defined as < 17y, need separate proof of efficacy;1–3 (2) with the exception of chronic myelogenous leukema, the biology of cancer in children is different from adult cancer.1 FDA-triggered studies investigated single cytoxics agents in heavily pretreated refractory/relapsed patients < 21y.2 4 In these days, combination treatment with up to 13 cytotoxic agents was standard of care.7 Another round of treatment with a single chemotherapy agent did not increase survival, but rewarded companies with patent extension, researchers with publications, the FDA with labeled information. The EU expanded the definition of children to < 18y and demands ‘pediatric investigation plans’ (PIPs) also for rare diseases. One FDA-triggered package investigated ipilimumab in ‘pediatric’ melanoma; 13 EMA PIPs demand ‘pediatric’ studies in solid tumors including melanoma; two ‘pediatric’ monotherapy studies with ipilimumab and vemurafenib, respectively, were terminated in 2016, five others continue recruiting.3 4 8DiscussionFDA/EMA-requested/demanded ‘paediatric’ oncology studies focus on labels in administratively defined ‘children’. FDA/EMA-used age limits are not physiological. FDA assumptions about different biology of ‘pediatric’ malignancies are incorrect.3 4 8 9 FDA/EMA reports list regulatory, not therapeutic achievements.5–6 Some EU researchers perform predominantly PIP-demanded oncology studies. In a cartel-like cooperation, the EMA demands such studies, threatening non-approval of life-saving drugs. Researchers and EMA representatives co-author lauding reports.10ConclusionFDA representatives augmented the flawed ‘therapeutic orphans’ concept by additional wrong assumptions about ‘paediatric’ malignancies´ biology.1–4 The EMA further expanded the ‘Paediatric Imperative’. Also PIPs do not advance treatment. Ethics committees should be alerted to re-analyze ongoing ‘pediatric’ studies, suspend questionable ones, and reject new ones. US+EU pediatric laws need revision.ReferencesSnyder KM, et al. The impact of the written request process on drug development in childhood cancer Pediatr Blood Cancer. 2013;60:531–537.Wharton GT, et al. Impact of pediatric exclusivity on drug labeling and demonstrations of efficacy Pediatrics. 2014;134(2):e512–e518.Roberts R, et al. Pediatric Drug Labeling. Improving the Safety and Efficacy of Pediatric Therapies JAMA. 2003;290(7):905–911.Rose K, Grant-Kels JM. Pediatric Melanoma - The Whole (Conflicts Of Interest) Story Int J Womens Dermatol 2018FDA. Best Pharmaceuticals for Children Act and Pediatric Research Equity Act. July 2016. Status Report to Congress Department of Health and Human Services.EMA. 10-year Report to the European Commission. General report on the experience acquired as a result of the application of the Paediatric Regulation.Norris RE, Adamson PC. Challenges and opportunities in childhood cancer drug development Nat Rev Cancer. 2012 Nov;12(11):776–82.Rose K, Walson PD. Are Regulatory Age Limits in Pediatric Melanoma Justified?Curr Ther Res Clin Exp. 2019Pappo AS. Pediatric melanoma: the whole (genome) story. Am Soc Clin Oncol Educ Book. 2014:e432–5.Ruperto N et al. A European Network of Paediatric Research at the European Medicines Agency (Enpr-EMA). Arch Dis Child. 2012 Mar;97(3):185–8.Disclosure(s)The author has worked for more than 20 years in research & development/medical affairs in pharma¬ceutical industry and is now an independent consultant, advising pharmaceutical companies and academic institutions in all aspects of pediatric drug development, organizing scientific conferences, publishing, & more. The author´s elder daughter is severely handicapped with a rare syndrom, which has biased him against empty governmental promises.

Challenges in drug development for central nervous system disorders: a European Medicines Agency perspective

2016 ◽  
Vol 15 (12) ◽  
pp. 813-814 ◽  
Author(s):  
Florence Butlen-Ducuing ◽  
Frank Pétavy ◽  
Lorenzo Guizzaro ◽  
Malgorzata Zienowicz ◽  
Tomas Salmonson ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Drug Development ◽  
European Medicines Agency ◽  
Central Nervous System Disorders

The European Medicines Agency (EMEA) guideline on oncology drug development

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 6636-6636 ◽  
Author(s):  
S. Palmeri ◽  
J. Bergh ◽  
L. Bergmann ◽  
S. W. Hansen ◽  
J. M. Moraleda ◽  
...  
Keyword(s):  
Drug Development ◽  
Primary Endpoint ◽  
Imaging Techniques ◽  
Disease Free Survival ◽  
Phase Iii ◽  
European Medicines Agency ◽  
Individual Compound ◽  
The European Union ◽  
Cytostatic Agents ◽  
Free Survival

6636 Background: The scientific assessment and positive opinion of the EMEA is mandatory for the approval of new oncology drugs in the European Union. One of the tasks of the EMEA is to provide guidance on the conduct of the various tests and trials necessary for approval. The EMEA has recently revised its guideline on the clinical development of new anticancer drugs. The revised version includes specific guidance on the development of non-cytotoxic (i.e., cytostatic) agents ( http://www.emea.europa.eu/pdfs/human/ewp/020595en.pdf ). Specific guidance is given about methodological issues using progression-free survival (PFS) as primary endpoint in confirmatory trials for registration ( http://www.emea.europa.eu/pdfs/human/ewp/26757506en.pdf ). Methods: The key elements of the revised guideline are described with particular reference to requirements for approval. Results: The early stages of clinical drug development have to be tailored according to the assumed pharmacology of the individual compound as defined in non-clinical studies. The integration of information from exploratory (phase I-II) and confirmatory (phase III) studies is of primary importance. In general, phase III trials should be designed with the aim of establishing the benefit risk balance of the drug, in a well-characterized target population. These studies should be randomized controlled and, where possible, blinded or include blinded evaluation. Acceptable primary endpoints include overall survival (OS) and PFS or disease-free survival (DFS). It is acknowledged that there are situations where PFS can be considered as a primary endpoint that measures clinical benefit. Adherence to protocol-defined schedules for tumor assessments, typically by imaging techniques, is important and deviations should be reported. Independent, blinded review and confirmation of best tumor response and progression should be undertaken if PFS is the primary endpoint. Conclusions: The current revision of the EMEA guideline provides useful clinical regulatory guidance for the development of cytostatic agents. When recommended guidelines are considered suboptimal, sponsors are encouraged to seek regulatory scientific advice. No significant financial relationships to disclose.

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