Information

2012/13

Falsified Medicines Directive

Update 24-Oct-2013

A further meeting between the European Commission and industry representatives was held on 18-Oct-2013 at which the current status of ‘white list’ applications and ‘written confirmation’ issues was shared.

The on-site audit relating to Brazil’s ‘white list’ application has taken place and some remediation work is required before they can be regarded as equivalent to EU GMP.  It is likely to take 6 – 12 months to address the points raised, after which a re-inspection is likely.  In the meantime, Brazil will issue written confirmations.

India and China continue to issue written confirmations.  Copies of Indian documents are available via the CDSCO website (see link under 23-Jun-2013 update below).  Chinese documents are not so readily available. but there are apparently over 300 issued, covering over 500 APIs by nearly 200 different manufacturers.

No drug shortages arising from the FMD implementation have been reported to date, but there remain concerns that this is due to contingency stockpiling; a significant number of companies are still missing written confirmations that would support future imports.  At least one case of the use of ‘waiver 2’ was reported. 

There is concern about processes for the renewal of written confirmations with some that have been issued to date having expiry dates at the end of 2013 or early in 2014.

There is also concern that there have been some cases of non-compliances reported by Third Countries or Member States which have impacted the status of previously issued written confirmations.  However, these  GMP non-compliances are not considered public information and there is reliance on the impacted Third Country API manufacturers to notify their customers.  It was requested that the Commission evaluate making public the suspension of written confirmations in a similar manner to suspended/withdrawn CEPs being notified via the EDQM website.  Expanded use of the EudraGMDP database to make public non-compliances arising from EU Authority inspections is planned.

Update 23-Aug-2013

MHRA have announced that the FMD has been transposed into UK legislation with effect from 20-Aug-2013. (via The Human Medicines (Amendment) Regulations 2013 [SI 2013/1855], for those of you wishing to impress in your QP viva!).

Furthermore, they have created a specific website on FMD which may be found at http://www.mhra.gov.uk/Howweregulate/Medicines/Overviewofmedicineslegislationandguidance/TheFalsifiedMedicinesDirective/index.htm
Well worth a look.

Update: 02-Jul-2013

Today is implementation day for the active substance importation requirements!
MHRA have posted an announcement which is well worth reading at http://www.mhra.gov.uk/Howweregulate/Medicines/Medicinesregulatorynews/CON295440
This includes a link to the Heads of Medicines Agencies (HMA) website where there is a document outlining a process “intended to facilitate a common approach” across the EU to importation without a written confirmation in the early days post-implementation.
There are also links to the EC website listing the ‘white listed’ countries and to the MHRA process for requesting a waiver.
There is some key information applicable to any importation via Germany where the import requirements are being applied at the border (rather than MHRA’s approach of inspection of manufacturers (and possibly, dependent on risk, of AS importers and distributors)).

Update: 23-Jun-2013

The US’s white listing has now been confirmed.  See http://ec.europa.eu/health/human-use/quality/index_en.htm

The Indian CDSCO’s list of issued written confirmations is now up to134.  See http://cdsco.nic.in/wc.htm

Update: 10-Jun-2013

Japan white listing has now been confirmed. 

Update: 20-May-2013

MHRA have just posted an announcement regarding its “contingency plans that would allow the Agency, in cases where there is an overriding need to ensure continued supply of specific ASs after 2 July 2013, to provide an opinion on the importation of the AS to permit manufacture, QP certification and supply of finished medicinal products”.

See http://www.mhra.gov.uk/Howweregulate/Medicines/Medicinesregulatorynews/CON273746 for details.

Update: 25-Apr-2013

Australia’s white listing has just been posted on the Commission website.

Brazil’s application for white listing has now entered the assessment stage, though they will not be white listed before 02-Jul-2013.  They should be issuing written confirmations in the interim.

MHRA stated at the GMP/GDP consultative committee meeting on 19-Apr-2013 that there have been delays in transposition of the Directive into UK legislation and this may not now be in place by 02-Jul.  This does NOT change the obligation to comply with the primary (EU) legislation from that date.

MHRA shared with Industry representatives a contingency proposal that they have developed to ensure ongoing supplies in the event of issues with written confirmations/white listing as of 02-Jul.  They are taking this to the Heads of EU Medicines Agencies (HMA) meeting this week, where it will be discussed with any other ideas brought by other representatives.  It is recognised that an EU-wide solution is needed and that time is short.  Outcome will be shared as soon as possible.

Note that any contingency arrangements will be time limited and that we should continue to pursue written confirmations for our imported active substances by first intent.  If you have not yet made all your suppliers aware of the requirements and encouraged them to engage with their regulatory agency, then please do so as soon as possible.

You may be interested to know that Rx360 have produced a table on the implementation of the FMD in different Member States.

Update 16-Apr-2013

The Commission’s Q&As document is now at version 4.1 and may be accessed via the European Commission website.  This version replaces a version 4.0 which was issued briefly and included a Q&A relating to atypical actives over which some further Member State discussions are required.

India’s procedures for the issue of written confirmations have now been issued (10-Apr) and are accessible via the link provided with the 10-Mar update.

Update 02-Apr-2013

The European Commission’s Pharmaceutical Committee has issued an update, dated 27-Mar-2013, on ‘the state of play’ with regard to the top 18 countries for API exports to the EU, plus South Africa and Ukraine.  There are also some additional Q&As.  Read it here.

Update: 12-Mar-2013

The EC white list table has been updated.  Singapore have NOT been white listed at this time due to the fact that their GMP certification scheme is non-mandatory.  However, they will issue written confirmations.

Update: 10-Mar-2013

The Indian Central Drugs Standard Control Organisation (CDSCO), which has been nominated as the competent authority for the issue of written confirmations for active substances manufactured in India, has recently issued a series of guidelines detailing how it will comply with the relevant FMD requirements.  These may be found at http://cdsco.nic.in/API%20WC2013.htm

Update: 25-Feb-2013

China have now formally announced that SFDA will issue written confirmations.  However, no details of guidelines or process to be followed have yet been issued.

Update: 08-Feb-2013

Public consultation guideline documents for risk assessment of excipients and good distribution practices for active substances were published by the Commission on 06-Feb and may be found HERE

Update: 29-Jan-2013

New versions of the Commission’s Q&A document (v3) and written confirmation template (v2) were published yesterday and are now accessible via the Commission website link above.  You will also see that the USA have now applied for white listing and are undergoing assessment (17-Jan).

The MHRA held a stakeholder meeting on the Falsified Medicines Directive (FMD) on June 11th 2012 and the presentation and Q&A session documents issued from that meeting are listed below:

MHRA Presentation on Falsified Medicines status

Questions and answer session

A further meeting with Industry representatives was held on 15-Nov-2012, with the primary focus being on active substance requirements.  Notes from this meeting are linked below.  PQG were thanked for providing several questions which will form the basis of a new Q&A page on MHRA’s website.

Notes from MHRA meeting with Industry representatives on FMD active substance requirements, 15-Nov-2012

If you are wanting to keep track of applications and approvals for ‘white listing’, then keep an eye on this European Commission website and scroll to the bottom of the page.