From 09 February 2019, medicines subject to verification may only be released for sale or distribution if they have the new security features, on the one hand the unique identifier and on the other a device on the packaging against manipulation (“anti-tampering device”). With the introduction of the new security features, the identity and authenticity of each individual drug is to be checked in order to identify counterfeit products from the legal supply chain. In this context, the basic conditions for the approval departments are also changing.

Legal basis

The Counterfeiting Directive from 2011 has been extended by technical and organizational details regarding the security features. On February 9, 2016, Regulation (EU) 2016/161 was published in the Official Journal of the European Union and must be implemented by all pharmaceutical companies within three years of that date. In addition, regulations on safety features in the German Medicines Act § 10 Paragraph 1c and in Article 54a of Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use were amended.

The unique identifier

In future, an individual Data Matrix code will have to be printed on each outer packaging for machine reading. This will ensure that the medicinal product comes from the lawful manufacturer. The barcode shall include at least the product code (GTIN/NTIN/PPN), the serial number, the batch number, the expiry date and, if required, the national reimbursement number or another national number in accordance with Article 4 of the delegated Regulation. The manufacturer may also include further information in the barcode if the competent authority so permits. In order not to create confusion as to which barcode is to be read for the purposes of authentication and identification, only one two-dimensional barcode is allowed on each package. In addition to the barcode, the product number, serial number and, if required, the national reimbursement number or other national number shall be indicated in plain text on the packaging.
Due to the additional identifying features on the outer packaging, the EMA has added points 17 (“Individual identifier – 2D barcode”) and 18 (“Individual identifier – human readable format”) to the Labelling section of the QRD template for product information texts. Pharmaceutical companies are thus obliged to report their updates to the authorities in accordance with the new QRD template. This change can be submitted with any regulatory process (variation regarding information texts, renewal or extension). If no suitable regulatory process is pending, the template update will be requested from the competent authority in accordance with Article 61(3) 2001/83/EC. It is important that the competent authorities are informed before 09 February 2019. Furthermore, the submission of the template update is not dependent on the actual attachment of the security features to the packaging or vice versa. The submission itself is only a kind of declaration of intent that the application of the security features will be implemented by 09 February 2019. In addition, it should be noted that the product information for medicinal products that are not subject to verification must also be adjusted by points 17 and 18, whereby only the reference “not applicable” is included in both sections. However, the transitional period is irrelevant for these medicinal products, as it does not result in any changes to the labelling.

The anti-tampering device

With the device on the outer casing, everyone should be able to see whether it has been opened or changed since manufacture. The definition of features for checking manipulations is regulated in the CEN standard DIN EN 166679: 2015-03.
Different methods are available for this purpose. The folding box could, for example, be closed with perforation, a film wrapping, blisters, cuffs or sealing labels or tapes.

If the device against manipulation does not impair the container and its sealing system or is placed on the outer packaging, no regulatory procedure is necessary.

Which medicines need the safety features?

Article 54a(1) of Directive 2001/83/EC requires that prescription-only medicinal products must bear the safety features, while non-prescription medicinal products must not bear the safety features (unless they appear on the list with a risk of counterfeiting, see Article 54a(2)(b) of Directive 2001/83/EC). As regards samples of medicinal products, Article 41 of the delegated Regulation (EU) 2016/161 supplementing Directive 2001/83/EC contains the following information: A marketing authorisation holder intending to supply as a free sample in accordance with Article 96 of Directive 2001/83/EC one of his medicinal products bearing the safety features shall mark that medicinal product in the data storage and retrieval system as a free sample and ensure that the individual identifier is deactivated before the medicinal product is supplied to persons authorised to prescribe it.

What happens to medicines without security features already on the market?

According to Article 48 of Regulation (EU) 2016/161, all released medicinal products placed on the market before 09.02.2019 may be released to the public until their expiry date.

Technical implementation with the verification system

A National Medicine Verification Organisation (NMVO) is set up in each EU member state, which is responsible for the system handling of authentication. In Germany, this is done by securPharm e.V. with its technical verification system of the same name for authentication. The serial numbers are transmitted to the verification system and stored there before they are placed on the market. Before being released to the public, the barcode is scanned onto the pharmaceutical packaging and checked in the national verification system. The system indicates whether it is the original or a counterfeit. When the original is delivered, it is cleared from the system.

With the new legal requirements for counterfeit protection, a good starting condition has been created for combating drug counterfeiting. The challenge now lies with the pharmaceutical companies and all those involved to meet the requirements of the Anti-Counterfeiting Directive and the Delegated Ordinance on time, especially with regard to regulations. The fact is that as of February 9, 2019, no drugs requiring verification may be placed on the market without an individual identifier and tamper protection. This process is also a major hurdle for the approval authorities, as they have to deal with the flood of mass applications without endangering the supply of medicines in the European Union.

Since June 2003, approval officers have been able to submit approval documents to European authorities in paper form (CTD) as well as electronically (eCTD). This option will soon no longer be available. Electronic submission in eCTD format has been mandatory for new registration applications in the decentralised procedure since July 2015. From 01.01.2017, it will also be mandatory to submit new applications for approval in the MRP procedure in eCTD format. From 2018, the eCTD obligation will then apply to all processes in CP, DCP, MRP and national procedures. The eCTD format is becoming the standard throughout Europe. It is high time for authorisation holders to switch to the eCTD format.

Tip 1: Integrate into project planning at an early stage

The change to the eCTD format can be made in any product life cycle, whether at the time of new approval or later with a variation (notification of change) or a renewal. In addition to the acquisition and integration of the corresponding eCTD software, the additional time required for document transfer to the eCTD, the adaptation of internal company processes and the necessary employee training must also be taken into account. It is important that once the data has been transmitted in eCTD format, everything else must also be submitted via eCTD.

Tip 2: Adapting work processes

In the meantime, many pharmaceutical companies have largely converted their approval processes to electronic processes. The documents are no longer submitted via the laborious process of creating several hundred folders and sending them by post, but on CD/DVD or on the computer via the CESP portal (Common European Submission Platform).

For the eCTD submission, the registration documents are prepared as an eCTD sequence using special software. When purchasing software, you should choose one that meets the needs of your company. This question will be difficult to answer if you have no experience with the new format. In this case it makes sense to use an eCTD-experienced service provider. The purchase costs for the software as well as the maintenance costs and training requirements are thus eliminated.

The structure of the eCTD is based on the CTD structure. The individual files are equally stored as Word or PDF documents in a predefined folder structure. The naming of the individual documents and folders as well as the formatting rules are precisely specified in the eCTD specification. Finally, the eCTD software generates an XML file for each sequence, which serves as a table of contents. In this way, users can access the relevant information in seconds. We recommend that you always create an eCTD baseline when converting to the eCTD format, despite the high workload. This is the only way to create a solid basis for effective life cycle management in which the marketing authorisation officer can quickly call up the current consolidated version of the dossier at any time with a click. In cooperation with an experienced service company, it is possible to integrate a baseline into the eCTD software in a relatively short time. The service provider creates the complete baseline and finally transfers it back to the company.

Tip 3: Integrate external support

There are enormous costs to purchase and integrate the eCTD software. Admissions staff need separate training to be able to use the new system properly. Small and medium-sized pharmaceutical companies in particular have start-up difficulties because they simply have difficulty in assessing the actual extent of the changeover to eCTD. On the other hand, eCTD-experienced service providers know exactly when a changeover makes sense and in what steps to take. They also have the necessary software systems and know-how to make the approval documents eCTD-compliant. This begins with the correct data preparation up to the professional creation of the eCTD dossier based on the applicable eCTD specifications. The current regulations for electronic submission in accordance with the EMA’s eSubmission Roadmap must always be taken into account.

Tip 4: Submit new applications via eCTD

The time for the Europe-wide eCTD obligation is approaching. We recommend that you create the next new applications in eCTD format if possible. Acting with foresight is more promising than reacting at short notice.

B.A. Sonja Friedsam

Marketing Project Manager

pharmadocs GmbH & Co. KG

eCTD wird Pflicht – 4 Tipps für eine reibungslose Umstellung.pdf