Falsified Medical Directive (FMD) and updated QRD template released February 2016

Falsified medicines are fake medicines that are designed to mimic real medicines. Due to the increase of falsified medicines on the market the EU has a strong legal framework for licensing, manufacturing and distribution of medicines. In July 2011 DIRECTIVE 2011/62/EU (http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2011:174:0074:0087:EN:PDF ) came into force; this directive aims to prevent falsified medicines entering the legal supply chain and thus reaching patients. One of the Directive’s measures is the introduction of safety features on medicines.

 

Update on Safety Features on Medicines:

On February 9th 2016 the EC published an implementation plan for the introduction of the safety features on the packaging of nationally authorised medicinal products for human use:

http://www.hma.eu/fileadmin/dateien/Human_Medicines/CMD_h_/Falsified_Medicines/CMDh_345_2016_Rev00_02_2016_1.pdf

In conjunction, a Regulation was also published laying down detailed rules for the safety features appearing on the packaging of medicinal products for human use:

http://ec.europa.eu/health/files/eudralex/vol-1/reg_2016_161/reg_2016_161_en.pdf

 

What do you need to do?:

The Delegated Regulation will apply in all European countries from the 9th February 2019 (3 years after its publication). Belgium, Greece and Italy have the option of deferring the application of the rules by an additional period of up to 6 years.

There are two safety features to be placed on the packaging of most prescription medicines and certain non-prescription medicines no later than 9 February 2019.

-1). a unique identifier (a 2-dimension barcode) and

-2). an anti-tampering device (ATD).

 

How does this affect your medicinal products and applications?

 New MAAs submitted from April 2016:

  • QRD:
    • Revised QRD template.
  • Revised dossier sections:
    • In the case of medicinal products where the ATD is placed on the immediate packaging because there is no outer packaging and the ATD affects the container and its closure system(s), applicants are required to include information on the ATD and how the ATD affects the container and its closure system(s) (sections 3.2.P.2.4 and/or 3.2.P.7 of the Notice to Applicants Volume 2B)

 Ongoing MAAs

  • QRD:
    • CHMP opinion in March 2016 advised to comply Revised QRD template
    • CHMP opinion from April 2016 onwards, applicants must comply with the revised QRD template
  • Revised dossier sections:
    • As per new MAAs

 Existing MAs

  • QRD:
    • Revised QRD template within 3 years – Can be implemented in Type IA, Type IB, Type II, Renewals, Line extension etc. where the submission affects the product information (PI). Approval of submissions must be no later than the 9th February 2019. If no regulatory procedure occurs within the required timeframe a notification is requested to be submitted pursuant to article 61(3).
  • Revised dossier sections:
    • If the ATD is placed on the immediate packaging and the ATD affects the container and its closure system(s), applicants are required to submit the appropriate variations to include the information on the ATD and how the ATD affects the container and its closure system(s) (see section B.II.e of the Variation Guidelines).
    • If the ATD does not affect the container and its closure system, or is placed on the outer packaging, no regulatory procedure is necessary. However, if the addition of the ATD has an impact on the readability of the packaging information, MAHs are requested to submit mock-ups as per http://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2009/10/WC500004891.pdf

Medicinal product no longer needs to bear safety features

  • QRD:
    • Regulatory procedure to remove the standard statements regarding the unique identifier and ATD.
  • Revised dossier sections:
    • ATD on immediate packaging: Regulatory procedure to remove the statements regarding the ATD in the dossier. ATD on outer packaging – no regulatory procedure necessary.

Change of Legal Status

  • QRD:
    • Non-prescription to prescription following a MAH switch application: MAH should use the regulatory procedure to comply with the revised QRD and regulations. Non-prescription to prescription following a Commission referral or a PSUR assessment, the Commission Decision will cover, inter alia, the regulatory requirements to implement the safety features.
  • Revised dossier sections:
    • Non-prescription to prescription: MAH should use the regulatory procedure to include the information on the ATD and how the ATD affects the container and its closure system(s)

 

What does the new QRD template now include?

The new QRD template includes the following sections in: Particulars to appear on <the outer packaging> <and> <the Immediate packaging:

  1. UNIQUE IDENTIFIER – 2D BARCODE
  1. UNIQUE IDENTIFIER – HUMAN READABLE DATA

Updated QRD template in track changes is available here:

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2009/12/WC500029823.pdf

 

Are any medicinal products exempt from the above?

Yes, the medicinal products exempt from the above are listed in Annex I of the Regulation located here:

http://ec.europa.eu/health/files/eudralex/vol-1/reg_2016_161/reg_2016_161_en.pdf

 

Are any medicinal products not subject to prescription but that should include the safety features above?

Yes, the medicinal products not subject to prescription that shall bear the safety features, referred to in Article 45(2) are listed in Annex II of the Regulation located here:

http://ec.europa.eu/health/files/eudralex/vol-1/reg_2016_161/reg_2016_161_en.pdf

If you have any queries on the above, if you would like any help with complying with the new regulation or if you have any other queries please contact us .

Written by Emily Fletcher.

EF photo

Points to note on the eAF

General

The eAF is mandatory for all procedures from 01/01/2016 (CP, MR, DC, National in eCTD/NeeS/Paper). However, Presubmission Meeting Requests, Article 61(3) & MAT forms remain the outside scope and can be submitted as paper or PDFs.

Please contact us if you require any assistance with any of the forms or any advice on any of the above procedures. For your convenience, the following is a summary of the important aspects of using the eAF.

  • Always check the e-submission website for the latest version of the eAF (http://esubmission.ema.europa.eu/eaf/)
    • Word versions will be removed from Notice to Applicants in January 2016
    • After 11/01/2016 only version 1.19 will be acceptable for new procedures
    • eAF should be printed for Paper submissions
    • Version 1.20 is planned for April 2016 (unless hotfixes are required before then)
    • It is important to note, and welcome news, that there is no need to update to a newer version of the eAF in the middle of a procedure
    • See the guidelines (update planned in January 2016) and release notes (lists the changes made to newer versions) for further information
    • In line with the proposed move towards a Single Submission Portal (SSP) in place of CESP and the EMA Gateway, there are plans to reformat the eAF into a data capture system that can be submitted directly through CESP. This is in a very preliminary stage.
  • Technical queries should be sent to EMA Service Desk via IT service portal (login)
    • Q&A documents should be consulted first
    • Fast web view warning in the dossier validation report for the eAF can be ignored
  • Procedural queries should be directed to the National Competent Authority (NCA) (and response sent to EMA Service Desk). Complicated queries should be sent to both parties.
  • Webinars are available for the NCAs (to try to reduce the requests for MS specific national requirements)

 

Using the eAF

  • Technical Validation of the form (internal):
    • Once signature is added and form validated, it is now locked. Locked forms cannot be amended. Therefore, the signature should be the last thing added to the form.
    • Always keep a copy of the unlocked form so that amendments can be made (e.g. during preparation or for requests from NCA for updated forms during a procedure)
    • Do not use bookmarks as these may cause invalidation issues
  • Annexes to the form should be filed separately in module 1.2 (do not use the PDF function to insert them into the eAF)
    • Form should be named; cc-form-eaf-var
    • Annex should be named; cc-form-annex-var (e.g. cc-form-5-19 or cc-form-proofpayment)
  • Electronic signature can be an image of a real signature (e.g. jpeg file – a scanned copy of wet signature. This however is not an electronic signature and is only used to close/lock the form) or can also be a line of text which states that signature is on file internally (e.g. “This form was authorised following company policies by Majella Ryan, Regulatory Affairs Manager of Ivowen with authorisation to sign. The signature is on file”)
    • The eAF does not accommodate multiple signatures at present. A separate annex should be provided if multiple signatures are mandatory for a particular NCA. Multiple name sections will be incorporated into version 2.0 but no mention of whether multiple signatures will also be accommodated.
    • The signature should be provided by the responsible MAH or can be provided by any authorised deputy
    • Please also check national requirements for signatures.
    • See Q&A guidance for further information
  • Workaround solutions (e.g. Annex B for multiple MAH or Product names) should always be mentioned in your cover letter
    • Some unforeseen variations (category z) are not adequately accounted for yet. Details of such changes should be outlined in the scope section of form and in the cover letter.
    • Duplicate sections only if products differ with regard to API or Pharmaceutical Form
    • Annex A or Annex B can be used for multiple MAH or Product names. Click on Annex A/B button in form and add the annex as a separate file in Module 1.2
    • Detailed instructions on how to use workaround solutions is available in the eAF Q&A document and the eAF Technical Guidance documents – both are published on the eAF webpage – if you need more advice contact EMA Service Desk.
  • No translations of the eAF are available, nor should they be requested.
  • Drug substances can be entered from controlled vocabulary lists or free text, and these each have different EV codes.
    • The focus should be on using substance, product, organisation and referential (SPOR)
  • Request for New Terms:
  • Strikethrough text function is not available in eAF but text can be copied and pasted (with text struck through) from Word or Outlook
  • In MRP/DCP one common application form is highly recommended, one per pharmaceutical form or strength for all member states in case of new MAA and one eAF for all involved products for all member states in case of variations and renewals.

 

Written by Majella Ryan

MMR photo

Ivowen summarise TOPRA Annual Human Medicines Symposium 2015

Alice D’Alton from Ivowen was delighted to be asked to provide a summary of Session 4 at the recent TOPRA Annual Human Medicines Symposium 2015. The full summary is provided in the following link:

SESSION 4: Globalisation of pharmaceutical regulation – What do agencies discuss behind closed doors?

For further information or if you have any questions on the information provided, or any other question, please feel free to contact us.

Written by Alice D’Alton

AD photo

CESP delivery system updated

The latest CESP system, version 2.0, was officially launched on October 1st 2015 (https://cespportal.hma.eu).

Ivowen has been using this facility regularly and can help to guide you through any aspects that you may be struggling with. There are a few new features which sets it apart from the old version:

  • The delivery file creation, has a new look and layout, with similar drop down menus but in a more user friendly format. The individual member states are now represented by the National Competent Authority logos, as well as their corresponding country flag.
  • The new dashboard feature is easy to find and provides you with real time statistics on what has been uploaded and subsequently delivered.
  • It incorporates a new tracking system which includes the following details:
  1. Delivery Created
  2. Delivery Completed
  3. Data Uploaded
  4. Data Delivered

You will still receive the e-mails confirming delivery, so you can file them.

  • There are also statistics presented in this space (in the form of bar charts) which provide an overview of your CESP activity in 2014 and 2015.
  • You can now also view delivery files which have been created but have not yet been utilised, and these delivery files can now also be re-downloaded but must not be re-used..
  • Furthermore, there is an Integrated delivery file system within CESP, which is very easy to use, but if you wish you can still work with your SFTP (e.g. FileZilla) as before.”

Please contact us if you would like any help with using CESP or have any other inquiries.

Written by Alice D’Alton

AD photo

EMA introduces changes to the QRD templates

The EMA has introduced changes to the QRD templates of the product information that accompany all medicines authorised for use in the EU including package leaflet (PL) and the summary of product characteristics (SmPC). Full details are available here:

Summary of Main Changes:

The changes to Quality Review of Documents (QRD)  templates are detailed in the updated guidance for the pharmaceutical industry. The main modifications are:

  1. the acceptance of combined SmPCs for different strengths of the same pharmaceutical form whereas until now a separate SmPC was required for each strength of the same pharmaceutical form
  2. the dates to be recorded in section 9 of the SmPC (i.e. date of first authorisation and date of latest renewal)
  3. the text to be included in Annex II (for centrally approved products (CAPs) only)
  4. the list of local representatives in the PL may only contain the address of the local representative of the marketing-authorisation holder (MAH) in the Member State where this particular medicine is sold, instead of the contact details of all local representatives in all EU Member States (for CAPs only)

What does this mean for you?

  1. This means that updates to common sections can be managed in one document, instead of multiple documents making life-cycle management much easier and reducing variation preparation time, etc.
  2. These dates only need to go in once, and the only one that will require updating is the renewal date. Since most products ordinarily undergo only one renewal, this date will also only have to be inserted once.
  3. The standard text to be included pertaining to the submission of PSURs has changed. This needs to be updated at the next variation to the your approved QRD text.
  4. This is really good news for all holders of Community Authorisations! (products approved through the Centralised Procedure). Instead of having to list up to 31 local contacts on the printed PIL, it is now permissible to list only the local contacts associated with that particular PIL. For example, for Ireland and UK dual packs, only the Irish and UK local contact need be listed. This will result in serious space savings on individual PILs, and time and efficiency improvements for regulatory affairs departments who need to keep the document life-cycles up to date.

What’s next?

Ivowen have extensive experience with the Centralised Procedure and QRD template changes and maintenance. Please contact us if you would like to discuss any of the above changes or any issues that you might have with your centrally approved products.

Ivowen would also advise that you take this opportunity to check over older approved QRD Annexes and correct any legacy typos, font issues, etc.

Written by Majella Ryan

MMR photo