More Medicines for Minors

Bundesinstitut für Arzneimittel und Medizinprodukte | Das BfArM ist ein Bundesinstitut im Geschäftsbereich des Bundesministeriums für Gesundheit

More Medicines for Minors Arzneimittelzulassung für Kinder und Jugendliche verbessern

Birka Lehmann


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More Medicines for Minors!

Kinder sind keine kleinen Erwachsenen!

Kearns et al 2003 n engl j med 349;12 www.nejm.org september 18, 2003

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 verzögern.


Arzneimittel für Kinder

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Studien

Studien

Studien

Studien


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

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

Verordnung (EG) Nr. 1901/2006

Anreize & Bonusse


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Opinions on paediatric investigations plans and waivers

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Overall 2011 – 2014 Paediatric investigations plans = 381 Waivers = 188


3.8 Paediatric clinical trials by year of authorisation (or, if not available, by year of protocol upload into EudraCT).

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Overall 2011 – 2014 Trials (children & adolescents included): 1542 Trials paediatrics only: 963


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).

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EMA Auskunft: Arzneimittelzulassungen mit Pädiatrischer Information

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Zulassungen 2012 2013 Mit pädiatrischer Indikation: 10 20 Mit pädiatrischer Indikation (variation or line extension): 14 12 Informationen in der Fachinformation= aktualisierte Zulassungen:

26 Freistellungen 27 Rückstellungen 124 Änderungen


3.9. Paediatric use marketing authorisation

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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.


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05 /09/2013


5.2. 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 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.

5-Jahresbericht der Europäischen Kommission zu Umsetzung der Verordnung (EU) Nr. 1901/2006

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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


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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Ciprofloxacin

Azithromycin

Fluconazole

Examples: TINN 1 and TINN2

BfArM Beteiligung an Europäisch geförderten Studien für bekannte Arzneimittel (Abtl. 5)


5.2. 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 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.


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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


OJ 27.09.2014

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.

Modification der Leitlinie für die Antragstellung ‚Pädiatrische Prüfpläne‘

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• Die europäische IST-Situation

Paediatric use marketing authorisation (PUMA-Zulassung)

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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

Die europäische IST-Situation

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Pädiatrische Studienpläne mit Bezug zu einer späteren PUMA Zulassung: Entscheidungen des Pädiatrieausschusses: • 22 positive Entscheidungen • 6 sind in der Bewertung • 13 Anträge wurden zurückgenommen

Die europäische IST-Situation

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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:

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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:

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PUMA (Padiatric Use Markeitng Authorisation)

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Studien

Studien

Studien

Studien

Definierte Altersgruppen


5.2. 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 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 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.


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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.


Herzlichen Dank für Ihre Aufmerksamkeit

Documents

More Medicines for Minors