More Medicines for Minors

Transkript

1 More Medicines for Minors Arzneimittelzulassung für Kinder und Jugendliche verbessern Birka Lehmann

2 More Medicines for Minors! Kinder sind keine kleinen Erwachsenen! Ziel der Verodnung (EG) Nr 1901/2006 Verbesserung der Gesundheit der Kinder in Europa durch die Entwicklung und die Zugänglichkeit von Arzneimitteln zur Verwendung bei der pädiatrischen Bevölkerungsgruppe zu erleichtern, zu gewährleisten, dass die zur Behandlung der pädiatrischen Bevölkerungsgruppe verwendeten Arzneimittel im Rahmen ethisch vertretbarer und qualitativ hochwertiger Forschungsarbeiten entwickelt und eigens für die pädiatrische Verwendung genehmigt werden, sowie die über die Verwendung von Arzneimitteln bei den verschiedenen pädiatrischen Bevölkerungsgruppen verfügbaren Informationen zu verbessern. Diese Ziele sollten verwirklicht werden, ohne die pädiatrische Bevölkerungsgruppe unnötigen klinischen Prüfungen zu unterziehen und ohne die Genehmigung eines Arzneimittels für andere Altersgruppen zu Kearns et al 2003 n verzögern. engl j med 349;12 september 18,

3 Arzneimittel für Kinder Studien Studien Studien Studien 3

4 Verordnung (EG) Nr. 1901/2006 Anreize & Bonusse Artikel 7 (alle) neue(n) Arzneimittel Artikel 8 patentgeschützte Arzneimittel bei Anträgen auf Zulassung, - neue Indikation - neue Darreichungsform - neuen Verabreichungsweg Verlängerung der Patentschutzzeit (Schutzzertifikat) um 6 Monate ( Orphan Drugs ) Verlängerung der Marktexklusivität von 10 auf 12 Jahre

5 Verordnung (EG) Nr. 1901/2006 Anreize & Bonusse Artikel 30 Paediatric Use Marketing Authorisation (PUMA) Genehmigung für die pädiatrische Verwendung 10 Jahre Schutz für Daten und Inverkehrbringen für die Kinderindikation & entsprechender Darreichungsform

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7 Opinions on paediatric investigations plans and waivers Overall Paediatric investigations plans = 381 Waivers = 188 7

8 3.8 Paediatric clinical trials by year of authorisation (or, if not available, by year of protocol upload into EudraCT). Overall Trials (children & adolescents included): 1542 Trials paediatrics only: 963 8

9 3.8 Number of children planned to be enrolled in clinical trials, by age by year of authorisation (or, if not available, by year of protocol upload into EudraCT). 9

10 EMA Auskunft: Arzneimittelzulassungen mit Pädiatrischer Information Zulassungen Mit pädiatrischer Indikation: Mit pädiatrischer Indikation (variation or line extension): Informationen in der Fachinformation= aktualisierte Zulassungen: 26 Freistellungen 27 Rückstellungen 124 Änderungen 10

11 3.9. Paediatric use marketing authorisation In the past year, the CHMP granted a paediatric use marketing authorisation (PUMA) for Hemangiol for the treatment of proliferating infantile haemangioma, which are benign tumours of blood vessels. PUMAs can be granted for medicines which are already authorised but no longer under patent or supplementary certificate protection, and that have been developed specifically for children. As an incentive to stimulate the development of existing medicines for the treatment of children, PUMA medicines are granted ten years of market protection. This is the second PUMA authorised since the beginning of the Paediatric Regulation. 11

12 05 /09/

13 5-Jahresbericht der Europäischen Kommission zu Umsetzung der Verordnung (EU) Nr. 1901/ The PUMA concept: a disappointment Thus, the main goal of the PUMA concept is to stimulate research in The Paediatric Regulation existing introduced products. a new This type scheme of marketing has been authorisation supported the by Paediatric EU funding Use Marketing Authorisation (PUMA). As an incentive to carry out research into the potential paediatric use of off-patent through medicinal the products EU Framework that have been Programmes authorised for adults, for Research this marketing and Technological authorisation offers 8 years of data and 10 years of market Development exclusivity to any new off-patent product developed exclusively for use in the paediatric population. Thus, the main goal of the PUMA concept is to stimulate research in existing products. This scheme has been supported by EU funding through the EU Framework Programmes for Research and Technological Development. However, to date only one PUMA has been granted, with a few more projects currently in the pipeline. Neither industry nor academic networks have embraced this opportunity as fully as the Regulation intended. It would seem that the incentive of data and market exclusivity does not work for these products, or at least that the market opportunities in this sector are currently considered insufficient to outweigh the inherent economic risks of pharmaceutical development. Researchers are not engaging in trials with medicines that have been on the market for years. Companies seem to fear that market exclusivity will not prevent physicians from continuing to use competitor products with the same active ingredient off-label, at lower costs, or that substitution for cheaper adult forms takes place at the level of pharmacies. Moreover, national pricing and reimbursement rules in Member States often do not allow for the additional research needed to obtain the PUMA to be rewarded in price negotiations. Against this background the PUMA concept has failed so far to fulfil the initial expectations. The EMA will in future accept paediatric investigation plans for a PUMA that cover only certain age groups and not the entire paediatric population. This may offset some of the reservations that currently hamper better endorsement of the PUMA concept. 13

14 European Research networks supported by the European Commission Funding is provided through the European Union Framework Programmes for the development of medicines, with a view to the submission of a PUMA. The European Medicines Agency's Paediatric Committee (PDCO) adopted a priority list of off-patent medicinal products for which studies are required. Preparations for Horizon 2020, are underway. As a result, the Agency adopted a revised provisional priority list in July 2013 after a public consultation.

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16 BfArM Beteiligung an Europäisch geförderten Studien für bekannte Arzneimittel (Abtl. 5) Examples: TINN 1 and TINN2 Ciprofloxacin Azithromycin Fluconazole

17 5-Jahresbericht der Europäischen Kommission zu Umsetzung der Verordnung (EU) Nr. 1901/ The PUMA concept: a disappointment The Paediatric Regulation introduced a new type of marketing authorisation the Paediatric Use Marketing Authorisation (PUMA). As an incentive to carry out research into the potential paediatric use of off-patent medicinal products that have been authorised for adults, this marketing authorisation offers 8 years of data and 10 years of market exclusivity to any new off-patent product developed exclusively for use in the paediatric population. Thus, the main goal of the PUMA concept is to stimulate research in existing products. This scheme has been supported by EU funding through the EU Framework The Programmes EMA will for in Research future and accept Technological paediatric Development. investigation However, plans to date for only a one PUMA that has been cover granted, only with certain a few more age projects groups currently in the pipeline. Neither industry nor academic networks have embraced this opportunity as fully as the Regulation intended. and It would not seem the that entire the incentive paediatric of data population. and market exclusivity This does may not work for these products, offset or at some least that of the the market reservations opportunities that in this sector currently are currently hamper considered insufficient to outweigh the inherent economic risks of pharmaceutical development. Researchers are not engaging in trials with medicines better that endorsement have been on the of market the for PUMA years. Companies concept seem to fear that market exclusivity will not prevent physicians from continuing to use competitor products with the same active ingredient off-label, at lower costs, or that substitution for cheaper adult forms takes place at the level of pharmacies. Moreover, national pricing and reimbursement rules in Member States often do not allow for the additional research needed to obtain the PUMA to be rewarded in price negotiations. Against this background the PUMA concept has failed so far to fulfil the initial expectations. The EMA will in future accept paediatric investigation plans for a PUMA that cover only certain age groups and not the entire paediatric population. This may offset some of the reservations that currently hamper better endorsement of the PUMA concept. 17

18 Modification der Leitlinie für die Antragstellung Pädiatrische Prüfpläne OJ INFORMATION FROM EUROPEAN UNION INSTITUTIONS, BODIES, OFFICES AND AGENCIES EUROPEAN COMMISSION COMMUNICATION FROM THE COMMISSION Guideline on the format and content of applications for agreement or modification of a paediatric investigation plan and requests for waivers or deferrals and concerning the operation of the compliance check and on criteria for assessing significant studies Paediatric population Applications subject to the requirements of Article 7 or 8 of the Paediatric Regulation should cover all subsets of the paediatric population (1) unless there are grounds for a waiver. The paediatric population encompasses several subsets, as defined e.g. in international guidelines (2): pre-term and term neonates from 0 to 27 days; infants (or toddlers) from 1 month to 23 months; children from 2 years to 11 years; and adolescents from 12 up to 18 years. However, when it is considered more appropriate to use different subsets (e.g. based on gender or stage of pubertal development), this may be acceptable, but the choice of subsets should be explained and justified. A PIP application intended to support a future paediatric use marketing authorisation (PUMA) may be limited to certain paediatric subsets; it is not required to address all subsets. 18

19 Paediatric use marketing authorisation (PUMA-Zulassung) Die europäische IST-Situation 19

20 Die europäische IST-Situation PUMAS: Zugelassene Arzneimittel: Buccolam (midazolam, oromucosal use) Indikation Treatment of convulsive seizures Hemangiol (propanolol, oral use) Treatment of proliferating infantile haemangioma Rücknahme im Zulassungsverfahren: Fluad (influenza vaccine) Treatment of influenza Im Zulassungsverfahren: Sialanar (glycopyrronium bromide, oral use) Treatment of sialorrhoea 20

21 Die europäische IST-Situation Pädiatrische Studienpläne mit Bezug zu einer späteren PUMA Zulassung: Entscheidungen des Pädiatrieausschusses: 22 positive Entscheidungen 6 sind in der Bewertung 13 Anträge wurden zurückgenommen 21

22 Beispiel: Enalapril Paediatric Investigation Plan Indication(s) targeted by the PIP Treatment of hypertension. Subset(s) of the paediatric population concerned by the paediatric development: From birth to less than 18 years of age. Pharmaceutical form(s) Tablet for oral suspension and Orodispersible film Opinion: 22

23 Beispiel: Enalapril Paediatric Investigation Plan Indication(s) targeted by the PIP Treatment of heart failure Subset(s) of the paediatric population concerned by the paediatric development : From birth to less than 18 years of age. Pharmaceutical form(s): Solution for oral use. Opinion: 23

24 PUMA (Padiatric Use Markeitng Authorisation) Studien Studien Definierte Altersgruppen Studien Studien 24

25 5-Jahresbericht der Europäischen Kommission zu Umsetzung der Verordnung (EU) Nr. 1901/ The PUMA concept: a disappointment It would seem that the incentive of data and market exclusivity does not work for these products, or at least that the market opportunities in this sector are currently considered insufficient to outweigh the inherent economic risks of pharmaceutical development. Researchers are not engaging in trials with medicines that have been on the market for years. Companies seem to fear that market exclusivity will not prevent physicians from continuing to use competitor products with the same active ingredient off-label, at lower costs, or that substitution for cheaper adult forms takes place at the level of pharmacies. Moreover, national pricing and reimbursement rules in Member States often do not allow for the additional research needed to obtain the PUMA to be rewarded in price The Paediatric Regulation introduced a new type of marketing authorisation the Paediatric Use Marketing Authorisation (PUMA). As an incentive to carry out research into the potential paediatric use of off-patent medicinal products that have been authorised for adults, this marketing authorisation offers 8 years of data and 10 years of market exclusivity to any new off-patent product developed exclusively for use in the paediatric population. Thus, the main goal of the PUMA concept is to stimulate research in existing products. This scheme has been supported by EU funding through the EU Framework Programmes for Research and Technological Development. However, to date only one PUMA has been granted, with a few more projects currently in the pipeline. Neither industry nor academic networks have embraced this opportunity as fully as the Regulation intended. It would seem that the incentive of data and market exclusivity does not work for these products, or at least that the market opportunities in this sector are currently considered insufficient to outweigh the inherent economic risks of pharmaceutical development. Researchers are not engaging in trials with medicines that have been on the market for years. Companies seem to fear that market exclusivity will not prevent physicians from continuing negotiations. to use competitor products with the same active ingredient off-label, at lower costs, or that substitution for cheaper adult forms takes place at the level of pharmacies. Moreover, national pricing and reimbursement rules in Member States often do not allow for the additional research needed to obtain the PUMA to be rewarded in price negotiations20. Against this background the PUMA concept has failed so far to fulfil the initial expectations. The EMA will in future accept paediatric investigation plans for a PUMA that cover only certain age groups and not the entire paediatric population. This may offset some of the reservations that currently hamper better endorsement of the PUMA concept. 25

26 Herzlichen Dank für Ihre Aufmerksamkeit