An agency of the European Union Medicines for Children: Strategic Considerations Module 1 – Strategic Planning in Regulatory Affairs TOPRA MSc in Regulatory Affairs Presented by Paolo Tomasi MD PhD, on 12 December 2014 Head of Paediatric Medicines – European Medicines Agency – London E14 5EU
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An agency of the European Union
Medicines for Children: Strategic Considerations
Module 1 – Strategic Planning in Regulatory AffairsTOPRA MSc in Regulatory Affairs
Presented by Paolo Tomasi MD PhD, on 12 December 2014
Head of Paediatric Medicines – European Medicines Agency – London E14 5EU
Paediatric development is mandatory in the EU for new medicines
• Unless a product-specific waiver or a class waiver (for a class of medicinal products) is granted by EMAby EMA(waivers apply only for specific medical conditions)
• Deferrals can also be granted (studies in children can be initiated and/or completed after applying for marketing authorisation in other populations or conditions)
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The EU Paediatric Regulation
Regulation:
• Most “powerful” type of EU law
• Immediately applicable in all EU Member States
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Why was there a need for a
EU Paediatric Regulation?
3
=for
EU Paediatric Regulation:obligations versus incentives
Type of MP Obligation Incentive Comments
New# medicinal product
Paediatric Investigation Plan or Waiver
6 months extension of SPC (patent) *
Necessary for validation of application
On-patent and Paediatric Investigation 6 months extension When new indication or new On-patent and authorized medicine
Paediatric Investigation Plan or Waiver
6 months extension of SPC (patent)*
When new indication or new route or new pharmaceutical form:
necessary for validation
Orphan-designated medicine
Paediatric Investigation Plan or Waiver
2 additional years of market exclusivity*
In addition to 10 years
Off-patent medicine
None (voluntary PIP possible for PUMA)
10 years of data protection
Research funds
Paed. Use MA (PUMA)
*if compliance with PIP, information, approval EU-wide#according to GMA concept, and not necessarily a new active substance
Rewards
-> if development is compliant with agreed PIP (compliance statement in MA);
-> if results of studies included in Summary of PC + patient’s leaflet;
-> if product is authorised in all MSs (except for PUMA):
Reward is given for all PIPs correctly completed, but PIPs are “always” required (cfr. US PREA, where: obligation but no reward)
• Non-orphan products: 6-month extension of SPC (patent protection) [not when MAH applied for +1 market protection]
• Orphan medicinal products: + 2 additional years of market exclusivity
• PUMA: 8+2 years of data+market protection
- Product-specific or class waiver does NOT trigger the reward- « negative » PIP results allow reward- Inconclusive studies in PIP do NOT trigger the reward
Differences EU (Paediatric Regulation) / USA (BPCA-
PREA-FDASIA)US BPCA US PREA EU
Development Optional Mandatory Mandatory (optional for off-patent)
Instrument Written Request Paediatric Study Plan Paediatric Investigation Plan
Small increase in total PIP + waiver + modification procedures in the last years
The EMA's role in paediatric medicines11
These are procedures, not products
PIPs, waivers and deferralsPIPs, waivers and deferrals
Medicines for children - strategic aspects12
Paediatric Investigation Plan
• Basis for development and authorisation of a medicinal product for all paediatric population subsets
• Includes details of the timing and the measures proposed, to demonstrate:
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measures proposed, to demonstrate:
– Quality
– Safety
– Efficacy
• To be agreed upon and/or amendedby the PDCO
• Binding on company � compliance check (but modifications possible, at the company’s request)
Marketing
Authorisation
Criteria
Paediatric Investigation Plan
• Contained in a PDCO Opinion with key elements
• Timelines for start and completion of each study
• Opinions cover a condition (relevant for both adult and paed
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Formulation
(quality)
Non-clinical studiesToxicology
Carcinogenicity
Genotox
Juvenile animal studies
Paed clinical trialsPK
PK/PD
Tolerability, safety
Efficacy and safety…
Extrapolation
studiesIncluding
modelling and
simulation
• Opinions cover a condition (relevant for both adult and paed
development), within which one paediatric indication is
selected for development.
Other
measuresRegistries
When is a PIP necessary?
• Pharmaceutical companies need to produce data from paediatric studies, done in accordance with an agreed PIP:
– When applying for a new marketing authorisation;
– in case of an already authorised and “patented” product, when applying for a new indication / route / dosage form
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applying for a new indication / route / dosage form (but not for new strengths, presentations, etc.)
• Alternatively, they need a “total” waiver (for applicable condition[s], in all paediatric subsets), or a deferral.
– If “total” waiver: no PIP
– If deferral[s]: deferral implies a PIP; a deferral is for initiating or completing a study / measure, NOT for agreeing the PIP!
When is a PIP or waiver
not required?
• “Off-patent” products already authorised in the EU (authorised products that do not have a valid Supplementary Protection Certificate (SPC) or a valid patent that qualifies for it.)
• New medicinal products that belong to some specific groups (legal basis):to some specific groups (legal basis):
� Traditional herbal medicinal products� Homeopathic products� Generic products� Hybrid products*� Biosimilar products� When there is a class-waiver:
− For a class of products in a condition
*a PIP can optionally be agreed for future PUMA application
Waivers:
Three types:Three types:
•• ““totaltotal”” (product(product--specific) waiver specific) waiver �������� for all paediatric subsets (in
one or more specific condition[s])
•• partial waiver: partial waiver: one and more subset(s), indication(s), but there is a PIP!PIP!
• Class waiver: for a class of medicinal products in a condition
Legal grounds:
•Lack of efficacy and safety
•Disease or condition occurring only in adults population
•Lack of significant therapeutic benefit
Deferral(s):
Instrument to avoid delaying marketing authorisationInstrument to avoid delaying marketing authorisationin adults.in adults.
““DeferredDeferred”” means: Marketing Authorisation Application for means: Marketing Authorisation Application for adults is possible before completion of one or more adults is possible before completion of one or more adults is possible before completion of one or more adults is possible before completion of one or more studies/measures in the PIP studies/measures in the PIP
•• Given by study/measure Given by study/measure ((cfrcfr. US PREA: . US PREA: ““totaltotal”” deferral)deferral)
•• For initiation and/or completion of study/measure: For initiation and/or completion of study/measure: completion of a clinical trial may be deferred, but initiation may not be!
• Completion dates established in any case
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Application Number Substance(s) PIP completion date
Send a question via our website www.ema.europa.eu/contact
Further information
Follow us on @EMA_News
Backup slides
Medicines for children - strategic aspects41
Backup slides
Weblinks
• Annual EMA Report to the European Commission, May 2013: http://ec.europa.eu/health/files/paediatrics/2012_report_paed_regulation.pdf
• Proceedings from Expert groups at EMA:http://tinyurl.com/PaedExpGroups
• EMA decisions on PIPs and waivers:http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/landing/pip_search.jsp&mid=WC0b01ac058001d129rch.jsp&mid=WC0b01ac058001d129
• EU Clinical Trials Register:https://www.clinicaltrialsregister.eu/