1. No category

27/05/2015
ellaOnevägen till receptfritt för ett centralt godkänt läkemedel
Receptfritt – en klass för sig 2 juni 2015
Victoria Inestam
Regulatory Affairs Manager, Takeda Pharma AB
[email protected]
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Takeda - a research based company with a global
presence
#15
700+
products
Precence in
70+
Largest
global
pharma
company
countries
#1
Pharma company
Japan/Asia*
100+
approx
Research
partnerships
30,000
#7
employees in
the world
largest pipeline
pharmaceuticals
*IMS Health 2013, ϯCiteline Pharma R&D Annual Review 2012
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HRA Pharma France - MAH
Products sold in 80+ countries Innovation oriented
9 products in women’s health
& endocrinology
Leader in emergency contraception in Europe
7 subsidiaries and many partners
(Takeda in Nordics)
70m€
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What is ellaOne
 30 mg ulipristal acetate, tablet
 Contraception within 120 hours (5 days) of unprotected
sexual intercourse or contraceptive failure
 Approved in Europe as Rx through centralized
procedure (2009)
 Marketed in 72 countries
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What were the initial challenges
• Not been widespread used for five years, in medicinal products
subjected to a medical prescription
• Pending Follow-Up Measures at time of application
• Pharmacy practice varying across Europe
• Controversial area
• Need for educational material?
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What were the initial challenges
Identification of areas of concerns
• Need for clinical data to address items such as:
– efficacy / safety study in adolescents
– PD / safety repeat use study
– safety in pregnancy: pan-European pregnancy registry to facilitate webbased reporting of pregnancy cases
• Benefit – Risk model
– Switch guidance only looking at risk considerations…
– Brass model useful tool to get and defend Company’s position on a global
overview of benefits vs. risks of transition to OTC
• In depth investigation to understand national procedures post-EC
decision
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A shift in thinking from:
”Pharmaceuticals for the Consumer”
Towards:
Consumer products about health & wellnes
…applying patient/sufferer based thinking and
involving the whole organisation
R&D, regulatory, production, logistics
Ims: OTC Conference 2013
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…and our strenghts
• Indication already non-Rx in 21 (+2) countries
• Clear demonstrated benefits
1. Need of rapid access for best effectiveness
2. Superior efficacy vs. existing option
3. Strong public health rationale
• Single use indication
• Very good safety data
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Rx-to-OTC switch of ellaOne - objectives
• 4th compound approved as OTC through central procedure
(after pantoprazole, orlistat, esomeprazole)
• 1st hormonal product as OTC
• 1st time switch from Rx to OTC via type II-variation
- same strength
- same pack size
- same indication
- same name
ellaOne Rx
ellaOne non-Rx
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Key steps of ellaOne switch
2010/11
2012
• Gap analysis against EU guidance
• Additional studies launch
• Assessment of options for regulatory pathway
• Meetings with EMA, Rapporteurs and 8 National Agencies (Spain, Ireland, UK, Estonia, France, CZ, Portugal, Belgium)
2013
• Submission of switch application (Feb)
• RfSI #1 (Apr), MAH response (Sept), RfSI#2 (Nov)
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Key steps of ellaOne swithc cont.
2014
• Procedure on hold during referral on impact of weight on efficacy of emergency contraceptives (Jan‐Jul)
• MAH response (Sept), oral explanation & CHMP positive opinion (Nov)
2015
• EC Decision Jan 2015
11 ellaOne - vägen till receptfritt för ett centralt godkänt läkemedel | 2015-06-02
QR code = Patient Information Leaflet
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Objectives reached?
YES!!
and additionally…
• 1 year data exclusivity
– Exclusivity starts at time of switch
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Switch of ellaOne in key figures
23
months of procedure (after many more of preparation!)
CHMP opinion granted
1
5
years after Rx launch
year of data exclusivity granted
>3
>65,000
million doses used at time of switch
unwanted pregnancies
expected to be prevented each year
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Lessons learned from our experience
THINK AHEAD!!
• Have in mind a possible request for an OTC switch during Rx
development program
• Consider possibility to request OTC switch when deciding for initial
regulatory strategy
• Allocate resources
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Lessons learned from our experience
THINK OUT OF THE BOX
• Ex: 5 years: no definitive rule
– Many MS ready to grant switch after 4 years
…and be prepared for anything!
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Key success factors
 Early start of project
 Identification of areas of concerns  e.g clinical data
 Interactions with regulators
• Identification of supporters and challengers
• Clarification meetings systematically
 Collaboration with pharmacy profession
 Team work – RA, MED, PV, Supply, Marketing
 Knowledgeable of regulations and guidelines
 Use available knowledge – e.g. AESGP, NCA
 Passion and commitment
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National implementation – initial challenges
• Unknown situation for NCA
– No precedent via type II variation
– Difficult to get clarity until Opinion / EC decision
• Grey zone between EMA and NCA responsibilities (ex: validation of blue
box)
• National procedures handled differently by NCAs (ex: publication in official
journal)
• Various rules (most often unwritten) for grace period for Rx packs
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Initial challenges - Sweden
• How and when will the EC-decision be enforced by MPA?
• Immediately?
• Grace period?
• Local switch date?
• Need for recall of Rx-packs?
• Distribution and supply
• Pharmacy launch periods
• Who does what – MPA/e-hälsomyndigheten/distributor…
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…and strengths
• Sweden as MS was supporting the application
• Indication already accepted as OTC
• The MPA a cooperative authority
• Established cross-functional meetings
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Scandinavia – various approaches to implementation
Implementation
grace period
Parallel
distribution
Recall Comment
Finland
6 months
Yes, limited
time period
Yes
Internal decision to
recall after 6 months
Norway
6 months
-
No
Rx may be sold until
launch of OTC
Sweden
No
No
Yes
MPA was expecting
guidance from EMA.
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National switch - objectives
• A smooth transition from Rx to OTC from a patient perspective
• Control of all steps in the various systems
• Agree with the MPA on the implementation date
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Key steps of the national switch
2013
2014
2015
• Initial contacts with the MPA on how to implement
(Sep)
• CHMP positive opinion (Nov)
• Application for new VNR
• Linguistic review and validation of art works (Nov‐Dec)
• EC Decision and Initial talks with MPA (Jan)
• MPA asks EMA for centralised guidance (Jan)
• EPAR published (Feb)
• Web based pregnancy register to be launched
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Key steps of the national switch
2015
2015
• Internal decision on switch date and planning for recall
• Partnership with distributor (Feb)
• Talks with MPA (Inspection, PI, RA, NPL) and e‐
hälsomyndigheten (Feb‐Apr)
• Agreement with MPA on switch date
• Information to customers about planned recall
• Recall executed on the same day as OTC switch (13 April)
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Objectives reached?
 Parallel distribution of Rx and OTC packs not possible.
 Sequential transfer of information between systems does not allow
implementation of change in LVIS/NPL to be effective in pharmacy ITsystems. Consequently, from the switch date it took at least 2 days
before pharmacies could actually order ellaOne.
 Switch date = date for recall of Rx packs from pharmacies
 Date was agreed with the MPA (13 April)
 MPA initiated recall of parallel distributed ellaOne
 General Sales List !!
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Lessons learned from our experience - Sweden
MAPPING, PLANNING… THINK AHEAD
 Initiate dialogue with partners early, especially if no precedential
cases. Consider F2F meetings.
 Investigate alternatives
 Keep track of VNR, national requirements/Blue box etc. and IT
 If recall, to what extent
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Key success factors - Sweden
 Set the objectives
 Be aware of time lines in the procedure
 Regular team meetings and status checks - RA,
Marketing, Medical, Supply, PV
 Dedicated team members
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Tack för er
uppmärksamhet!
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ellaOne
Lästips & länkar
• Förordning 726/2004
• Direktiv 2001/83/EC
• Guideline on changing the classification for the supply of a medicinal
product for human use (EC)
• Guideline on legal status for the supply to the patient of centrally
authorised medicinal products (EC)
• www.lakemedelsverket.se
• www.ema.europa.eu/ema/
• www.aesgp.eu
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Glossary
BTC – behind the counter
EC – European commission
MA – marketing authorisation
MED – medical (department)
MPA – Medical Products Agency (LV)
MS - member state
NCA – national competent authorities
NCE – new chemical entity
OTC – over the counter/without prescription
PD - farmakodynamik
PV – pharmacovigilance
RA – regulatory affairs (department)
RfSI – request for supplementary information
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