Transcript Document

Falsified Medicines Directive
Where are we now?
WQPF 7th November 2013
This presentation is the opinion and expression of Pharmallaney Ltd
and does not in any way represent that of other organisations or aim
to detract from legislative requirements. Individual websites and
references should be reviewed for accuracy..
Agenda
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Recent examples
European transposition
UK transposition/ MHRA expectations
Adopted activities
Pending Activities
Worldwide activities
Related legislation updates
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Recent Examples
• Sept 2013
– Symbicort inhaler, UK wholesaler,
legitimate B. No.
– WHO notified of suspected drug
intoxications involving 11 paediatric
patients in Paraguay (2-9yrs)
Dextromethorphan contaminated with
Levomethorphan
http://www.mhra.gov.uk/PrintPreview/DefaultSplashPP/CON149803?ResultCount=10&D
ynamicListQuery=&DynamicListSortBy=xCreationDate&DynamicListSortOrder=Desc&
DynamicListTitle=&PageNumber=1&Title=Counterfeit%20medicine%20recalls%20and
%20previously%20seen%20counterfeits
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European Implementation
Type
Activity
Target Date
Status
Delegated act
GMP AS
2013
Closed
Implementing act
AS assessment
criteria
2013
Adopted
3rd country listing
On-going
Guideline
GDP for AS
2013
Consultation Feb
2013
Guideline
GMP excipients
2013
Consultation Feb
2013
Guideline
Brokering
2013
Adopted
Delegated Act
Safety features
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2014
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On-going
UK Transposition
• 20 August 2013 - The Falsified Medicines
Directive is transposed through The
Human Medicines (Amendment)
Regulations 2013 [SI 2013/1855].
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MHRA Expectations
• Active substances systems in place to
demonstrate
– manufactured in accordance with GMP
and distributed in accordance with GDP.
– Evidence of audits at the sites of
manufacturers, importers and/or
distributors of active substances to
verify compliance with GMP and GDP.
http://www.rpharms.com/events-presentations-pdfs/qp-2013---mhra--approach.pdf
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MHRA Expectations
• Excipients
– risk assessment/risk management
procedure is incorporated in the Quality
Management System.
– There is an on-going program of work
to determine the appropriate level of
GMP for the excipients being used and
that application of those standards can
be demonstrated.
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MHRA Expectations
• Manufacturers, importers and
distributors of active substances
already operating before 2 January
2013 should have applied for
registration before 2 March 2013.
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Registration
• Existing holders of current MIA
– Have to register as a manufacturer or
importers of active substances.
• Existing holders of current WL and
WDL that also import API
– have to register separately as
Importers and/or distributors of active
substances.
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Registration - API
• Register
– API Nr
– Company Name
– Address
– Manufacture/ import/ distribute
http://www.mhra.gov.uk/home/groups/commsic/documents/websiteresources/con326473.pdf
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Registration Brokers
• All activities in relation to the sale or
purchase of medicinal products,
except for wholesale distribution, that
do not include physical handling
• Eight registered thus far
– Registration number BRKR 11111
– Date authorised
– Name
– Address
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Brokers
(2013/C 68/01) Sept 2013 Chapter 10
• QMS
• Personnel
• Documentation
– Complaints/ recall
– Falsified medicines notification
– Recall
– Checking MA status
– Supply chain
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Wholesaling
• (2013/C 68/01) GDP Sept 2013
• Includes the requirements for
–Supply chain
–Identification of falsified medicines
–Reporting of falsified medicines
–Export to third countries
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Active Substances
• Active substances
– White list
– Written confirmation
– Waiver
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Active Substances
• Assessment of manufacturing
standards in the EU for active
substances are those of the
‘International Conference for
Harmonisation’ – ICH Q7.
• White list for equivalent GMP and
inspection capabilities.
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Slide 15
Active Substance White List
– Switzerland 23 Nov 12
– Australia 25 Apr 13
– Japan 5 Jun 13
– USA 21 Jun 13
– Singapore – no listing
– Israel- contacts on going
– On-going - Brazil, New Zealand
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Written Confirmation
• Issued by the Regulatory Authority
• Based on the plant
• each imported consignment has to be
accompanied by written confirmation; a
copy is permitted
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Written Confirmation
Independent of
• site inspection by an EU Member State or
by the European Directorate for the
Quality of Medicines (EDQM) of the
Council of Europe
• MRA
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India 15 July 2013
• India’s Central Drugs Standard Control
Organization (CDSCO) posted a list of granted
written confirmations
• 57 active API manufacturing sites have been
confirmed by the CDSCO
• based on Certificate of Pharmaceutical
Product, WHO GMP guidelines, US FDA or
EDQM or TGA inspection certificates.
• If a company does not have prior inspections
or certificates, the CDSCO will conduct an
inspection.
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http://www.cdsco.nic.in/WC%20List.%20(2)17.7.2013%20(1).xls
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Slide 19
Others
• Some countries (Korea, South Africa,
Ukraine) have started to issue
confirmations
• others have confirmed that they will
(Canada & Taiwan).
• Some countries (Mexico) have agreed
to provide confirmations but will later
apply for listing.
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Slide 20
Waiver
• Exceptionally and where necessary to
ensure the availability of medicinal
products, following inspections by an
EU Member State, a Member State
may decide to waive the need for a
written confirmation for a period not
exceeding the validity of the GMP
certificate.
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Slide 21
Pending Activities
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GMP for excipients
GDP for AS
Sales at a distance
Safety features
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Slide 22
Excipients
• Draft guidance issued in Feb 2013
– Embraces ICHQ9
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Type of excipient – quality/ safety/ function
Identity of appropriate GMP – QMS focus
Confirmation – supplier review
EXiPACT – has anyone used this route?
NSF-IPEC 363- American std for those not
wanting ISO standard. Under consultation
http://ec.europa.eu/health/files/gmp/2013-02_guidelines_excipients_cons.pdf
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Slide 23
GDP Active Substances
Under consultation
• Typical requirements of GDP
• Records
• - Identity and address of original manufacturer,
batch number
• Purchase orders
• Bills of lading, transportation and distribution
records
• Receipt documents
• Name or designation of active substance
• Authentic Certificates of Analysis, including those
of the original manufacturer
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Sales at a distance to the public
• Sales of certain medicines are permitted
in the UK but the supplier to be a person
authorised or entitled to supply medicines
to the public.
• The General Pharmaceutical Council holds
a register of pharmacies, including those
that supply of medicines via the internet
• a voluntary logo scheme provides some
assurance to the public that the service
provided is authentic
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Slide 25
Sales at a Distance
• The person selling medicinal products at a distance must
– provide the contact details of the body with which
the service is registered
– Every page of a person’s website displays a common
EU logo
– a hyperlink to the national website of the Member
State in which that person and their business is
established.
• Each national website must
– provide information on the national legislation relevant to
the sale of medicines at a distance,
– the purpose of the national logo,
– a list of suppliers of medicines at a distance in that country,
– information on the risks of purchasing medicines illegally
from the internet
– a link to the website to be established by the European
Medicines Agency.
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Safety Features
• The delegated act expected by 2014.
• Member States will have three years after
adoption of the act to put the
requirements in place
• Concept paper Nov 2011 pending further
information.
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Slide 28
Safety Features
• Consultation Paper
– All prescription products must contain
safety features
– to identify an individual pack of
medicinal products ('unique identifier')
– verify whether the outer packaging has
been tampered with (tamper evidence)
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Slide 29
Safety Features
• Consultation paper
• Non-prescription products do not
require safety features unless:
–They are at risk of being falsified
–The risk arising may be a potential
hazard
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Slide 30
Safety Features
• Assessment of non-prescription
– Price of the product
– Sales volume
– Previous incidents of falsification
– Characteristic of the product
– Seriousness of the condition being treated
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Slide 31
Worldwide Activities
FDA 20th August 2013
• FDA Launches Secure Supply Chain Pilot
Program (SSCPP)
– to assist FDA in preventing the importation of
adulterated, misbranded, or unapproved drugs
• Applicants must
– NDA/ANDA sponsor, or the foreign manufacturer, of
the imported finished drug product or API.
– Foreign drug manufacturers and U.S. establishments
receiving drugs comply with GMP
– have a validated secure supply chain protocol per the
U.S. Customs and Border Protection’s C-TPAT program
as either C-TPAT Tier II or Tier III.
http://www.fda.gov/Drugs/DrugSafety/DrugIntegrityandSupplyChainSecurity/ucm365626.htm
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Slide 33
China
• China will issue written confirmation for
APIs from manufacturing sites that are
under the supervision of its own FDA.
• Serialisation mandatory for some
therapeutic areas
• Falsification introduced into (2010) 237.
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Brazil
• April 2013
• The National System of Drug Control by
ANVISA provides for serialized drug identity
and supply chain-wide drug traceability
• Serialized identification on secondary
packaging (and hospital packs), using a 2D
DataMatrix, which includes ANVISA drug
registration number, unique randomized
serial number, lot number, expiration date.
These combine to form the ANVISA Unique
Identifier of Medicines (IUM).
• ANVISA 11.903 2009
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Argentina
• National Food, Drug and Technology
Administration ANMAT
• National Medicines Traceability System
Regulation 3683/ 2011, Resolution
435/2011
• The traceability system shall consist of the
individually and uniquely identifying each
unit
• Format not specified
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Comparators
• Marketed medicinal products covered by
FMD but not clinical trials.
• MHRA discussion PQG March 2012
– Value obtaining direct from originators
Does anyone have something
they can share with regards
FMD and comparators?
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Slide 37
FMD and GMP updates
Eudralex Vol. 4 Chapter 1
•…use of the correct starting and packaging
materials, the selection and monitoring of
suppliers and for verifying that each delivery
is from the approved supply chain
•PQR - …. review of supply chain traceability
of active substances.
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Slide 38
FMD and GMP updates
Eudralex Vol 4 Chapter 7
•The Contract should describe clearly who
undertakes each step of the outsourced
activity, … supply chain,
•Any records ……complaints or a suspected
defect or to investigating in the case of a
suspected falsified product must be
accessible and specified in the relevant
procedures of the Contract Giver.
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Slide 39
FMD and GMP updates
• Chapter 5 – proposed
• Supplier selection… ‘supervision should
be proportionate to the risks posed by the
individual materials, …. source,
manufacturing process, supply chain
complexity and .. final .. in the medicinal
product.
• approval and maintenance of suppliers of
active substances and excipients………
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Slide 40
FMD and GMP updates
• Chapter 8 – Proposed
• All concerned competent authorities
should be informed in case of a quality
defect (….., detection of falsification..)
• Special attention should be given to
establishing whether a quality defect
relates to falsification
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Slide 41
FMD and GMP updates
Annex 16 –Draft
•The entire supply chain of the medicinal
product ….. is documented and available for
the QP.
•The active substances …..have been
manufactured in accordance with GMP
….and distributed to GDP
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Slide 42
FMD and GMP updates
Annex 16 –Draft
•The excipients ….have been manufactured
… in accordance with the ascertained
manufacturing practice
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Slide 43
Thank you!!