falsified medicines directive where are we now? wqpf 7 th november 2013 this presentation is the...

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• Recent examples• European transposition• UK transposition/ MHRA expectations• Adopted activities• Pending Activities• Worldwide activities• Related legislation updates

Copyright © Slide 2

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&DynamicListQuery=&DynamicListSortBy=xCreationDate&DynamicListSortOrder=Desc&DynamicListTitle=&PageNumber=1&Title=Counterfeit%20medicine%20recalls%20and%20previously%20seen%20counterfeits


European ImplementationType 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 2014 On-goingCopyright © Slide 4

UK Transposition

• 20 August 2013 - The Falsified Medicines Directive is transposed through The Human Medicines (Amendment) Regulations 2013 [SI 2013/1855].


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


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.


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.


Registration - API• Register

– API Nr– Company Name– Address– Manufacture/ import/ distribute

http://www.mhra.gov.uk/home/groups/comms-ic/documents/websiteresources/con326473.pdf


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


Brokers(2013/C 68/01) Sept 2013 Chapter 10•QMS•Personnel•Documentation

– Complaints/ recall– Falsified medicines notification– Recall– Checking MA status– Supply chain


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


Active Substances

• Active substances– White list – Written confirmation– Waiver


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.


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


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


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


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.

• http://www.cdsco.nic.in/WC%20List.%20(2)17.7.2013%20(1).xlsCopyright © 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.


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.


Pending Activities

• GMP for excipients• GDP for AS• Sales at a distance• Safety features


Excipients• Draft guidance issued in Feb 2013

– Embraces ICHQ9

• 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


GDP Active SubstancesUnder 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


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


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.Copyright © Slide 26

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.


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)


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


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


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


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.


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


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


Comparators


FMD and GMP updatesEudralex 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.


FMD and GMP updatesEudralex 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.


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………


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


FMD and GMP updatesAnnex 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


FMD and GMP updates

Annex 16 –Draft•The excipients ….have been manufactured … in accordance with the ascertained manufacturing practice


Thank you!!

falsified medicines directive where are we now? wqpf 7 th november 2013 this presentation is the...

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