Industry Perspective of Turkey from the Outside

PDA: A Global
Association
Industry Perspective of
Turkey from the Outside
2014 PDA Europe Conference Parenteral Manufacturing
Istanbul, June 24-25, 2014
Ursula Busse, PhD MBA
Group Quality External Relations
Novartis
June 24, 2014
© 2014 Novartis AG
Disclaimer
• The information contained in this document
belongs to Novartis and/or its affiliates. Novartis
does not make and expressly disclaims: (a) any
representation or warranty (express or implied)
with respect to the information shown in this
presentation; and (b) any liability relating to the
accuracy or completeness of the information.
• The views and opinions expressed in this
presentation are those of the author and do not
necessarily reflect the official policy or position of
Novartis or any of its officers.
2
Thanks to my colleagues
Regulatory CMC
Lily J. Lee
Quality Control
Yeliz Turgut
Pharma Supply Chain
Muhammed Percin
Manufacturing
Cenk Eden
External Relations
Georges France
3
Novartis
• One of 25 largest companies by market capitalization
• Global presence in over 140 countries with
approximately 133,000 employees
• Leading through science-based innovation (NIBR)
• Six (6) divisions: Pharma, Sandoz, Alcon, Vaccines,
Consumer Health and Animal Health
• Headquarters in Basel, Switzerland
4
Novartis in Turkey
 Headquarters in Istanbul
 Operating in the health services and pharmaceutical
sectors with 2200 employees
 4 manufacturing sites, including an API plant
 Products exported to approximately 100 countries from
Turkey. In 2013, a value of over 150 mio USD was
exported
 Accounting for 25% of all pharmaceutical R&D
investment in Turkey by foreign investors
 Partnered with Istanbul University to launch a
Pharmaceutical Research Unit in 2011
5
Turkey's Opportunities
•
•
•
•
•
•
Unique geograhic location
Free trade agreement with EU
Highly qualified personnel
Low operating cost
Industry associations (AIFD, IEIS)
Recent healthcare reform
– Full healthcare coverage
6
Turkey's Opportunities
• Adheres to European Pharmacopoeia
• Regulations aligned with EU regulations
– Falsified Medicines Directive
• Serialization & product tracking already fully implemented
On-line Coding:
•
law in place
Serialization & Product Tracking
•
law in place
•
law emerging
7
Turkey's Challenges
Regulatory/GMP requirements
•
•
•
•
Product registration / approval
GMP inspections (imported products)
Post-approval changes
Manufacturing requirements for certain
product categories
• Re-testing of medicines exported from Turkey
Pricing pressure
8
Product registration/approval
Unique data / document requirements
• Some examples
Module 1
–
–
Module 2:
Summary
–
–
Module 3:
Quality
Module 4: Nonclinical
Module 5:
Clinical
CTD
–
–
–
Manually
signed
Original copies
Manually signed CoAs, Testing
Monographs, composition of DP
Certificate of Analysis of 1 batch of each
packaging material, DS Raw materials &
intermediates
Chromatograms for test method validation
parameters, for assay and degradation
products for all registration stability batches
(long term conditions) (time-points: 0, 6, 12,
24, 36 months)
• For biologics
–
–
Original
copies
Detailed data
Cold chain validation for DP shipment
Detailed descriptions of
manufacturing/validation USP and DSP
Confirmation that plant-derived raw
materials are non-GMO
Manually signed CoA of WCB, MCB, BH,
ECB/ECPB
Raw data on analytical validation reports
for sterile products
9
Product registration/approval
Some European countries (e.g. Italy)
Registration process
Launch
Manufacturing
Reimbursement
Patient
GMP Inspection
Most of the European countries
Reimbursement
Registration process
Launch
Manufacturing
Patient
GMP Inspection
GMP Inspection
(MoH)
time
Registration process
(MoH)
Reimbursement
(SGK)
Patient
Turkey (as is)
Launch
Manufacturing
(MoH: Ministry of Health; SGK: Sosyal Güvenlik Kurumu-Social Security Institution)
Adapted from Stephan Rönninger , 2011
10
GMP Inspections
• Since Dec 2009, all
foreign sites
importing
medicines to
Turkey must be
inspected by the
Turkish MoH
• Steady increase in
average duration
for both completed
and pending
applications
Recent
requirement
Line/product
based
certification
• General GMP
Inspection not
pursued
• Many sites to be
inspected
• Approved and
pending
applications
Biologics API
site inspection
Mean time to GMP
certification is 677 days
11
Timelines for new products
EU new MAA
submisson
- 18
- 12
-6
0
TMoH GMP
certificate required
for MA submission
6
12
EU and/or US approval
required for final MA
approval by TMoH
18
30
months
MOH:
dossier
review
Application
for GMP
inspection
GMP
inspection
ca. 2 years
•
•
Turkey new
MA
submission
Inspectorate:
waiting queue
Turkish
GMP
certificate
Turkey
MA
Approval
if no/minor
findings!
2 years on average
MA approval 18 months assumes optimal process flow / no delays; industry average
for originators is usually above 24 months
Timeline estimate is for high priority products
12
Post-approval changes
• Handled in alignment with EU Variations Regulations
– EU Variations Regulations have evolved to “do and tell” concept
(Directive 1234/2008/EC)
From Keith Pugh, PDA/EMA 2012
• TMoH applies Directive 1084/2003/EC
13
Post-approval changes
GMP
inspection
requirements
DP/PP site change
Additional data
&
documentation
requirements
DS manufacturing site
change (no CEP*)
GMP inspection of
Type IB
receiving site
EU: 30 days
TK: 24-36 months
DP CoA
DP comparative batch analysis
DP 6 months stability data
Analytical Methods
changes
Comparative validation results
Statistical test data
* CEP = European Pharmacopoeia Certificate of Suitability
14
Impact on Turkey
• Short-term, these hurdles
– Deny Turkish patients a timely access to innovative
treatments
– Can result in drug shortages, increasing the risk of
falsified medicines entering the market
• Long-term, these hurdles risk to impact foreign
investment
15
Opportunities
• Dialogue with Stakeholders
• Mutual recognition agreements with EU health
authorities
• PIC/S membership application
– Should result in better harmonization of inspection
practices; acceptance of GMP certificates by other
agencies
16
PIC/S
• Pharmaceutical Inspection Co-operation
Scheme
• Collaboration between Inspectorates
–
–
–
–
–
Harmonized GMP requirements
Mutual recognition of inspections
Uniform inspection systems
Training of Inspectors
Mutual trust
• Focus on training & developing guidelines,
exchange of information
17
PIC/S
46 Participating Authorities
Canada HPFBI
US FDA
Austria AGES
Belgium AFPMS
Cyprus CyPHS
Czech SKUL & ISCVBM
Denmark DHMA
Estonia SAM
Finland FIMEA
France ANSM and ANSES
Germany BGM and ZLF
Greece EOF
Hungary NIP
Iceland EMA
Ireland IMB
Italy AIFA
Latvia ZVA
Liechtenstein AG
Lithuania SMCA
Malta MAM
Netherlands IGZ
Norway NOMA
Poland MPI
Portugal Infarmed
Romania NAMMD
Slovakia SIDC
Slowenia JAZMP
Spain AEMPS
Sweden MPA
Switzerland Swissmedic
Ukraine SAUMP
UK MHRA, VMD
Taiwan TFDA
Indonesia NADFA
Malaysia NPCB
Singapore HSA
Japan PMDA, MHLW
South Korea MFDS
Israel ISCP
Argentina INAME
South Africa MCC
Australia TGA
New Zealand Medsafe
PIC/S Partners: EDQM, EMA, UNICEF, WHO
Note: some countries have more than one Government Body in PIC/S
In red: joined in 2014
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What Industry thinks about PIC/S
Harmonization
• Opportunity to use a well-established scheme
promoting both standardization and risk-based
approaches
Excellence
• PIC/S has a rigorous entry process which
underscores the high standards and expertise
that exists within participating authorities
Relief from
inspectional
burden
• Opportunities to reduce the number of
redundant inspections by relying on inspections
conducted by other PIC/S members
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Turkey applied to join PIC/S
• Industry welcomes and supports Turkey’s
application for PIC/S membership
“On 3 May 2013, Turkey's Medicines and Medical
Devices Agency (TMMDA) officially submitted an
application for PIC/S membership. The PIC/S
Committee has nominated a Rapporteur and three CoRapporteurs in charge of the assessment of the
accession application.”
• Lengthy entry process (up to 6 years)
– Consider performing GMP certification in parallel to
MAA review
20
Improving Access to Healthcare
• Too big to solve alone
Industry
Patient
Associations
Governments
• Joint effort
– For the benefit of our patients
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Thank you for your attention!
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