A major breakthrough in the context of the newly introduced anti-falsification regulation in the field of pharmaceuticals has already taken place. On 9 February 2019, Commission Delegated Regulation (EU) 2016/161 of 2 October 2015 supplementing Directive 2001/83/EC of the European Parliament and of the Council by laying down detailed rules for the safety features appearing on the packaging of medicinal products for human (hereafter the “Regulation”), came into force. The regulation of the European Union (EU) is directly effective in all member states, which means that no further legal transposition into the Czech legislation is necessary for its effectiveness. All the entities concerned are already obliged to comply with the obligations imposed by this Regulation.
The Regulation is an accompanying legal regulation to an even more fundamental Directive 2011/62/EU of the European Parliament and of the Council of 8 June 2011 amending Directive 2001/83/EC on the Community code relating to medicinal products for human use, as regards the prevention of the entry into the legal supply chain of falsified medicinal products(hereafter the “Directive”), which is also referred to as the Falsified Medicines Directive (FMD), and is intended to address the issue of falsification of medicinal products. The Directive is implemented into the Czech legislation by an amendment to Act No. 378/2007 Coll., on Pharmaceuticals, as amended (hereinafter the “Act on Pharmaceuticals”), the effectiveness of which is expected in the upcoming days.
What obligations does the Regulation bring?
The Regulation provides for manufacturers, distributors, marketing authorization holders and persons authorized to dispense medicinal products (pharmacies) with the obligation to provide medicinal products with safety features.
Safety features will need to have:
- Medicinal products subject to medical prescription, unless they are listed in Annex No. 1 to the Regulation (the so-called White List) and unless they are radiopharmaceuticals exempted from this requirement;
- Non-prescription medicinal products, if listed in Annex No. 2 of the Regulation (on the so-called Black List).
To clarify the above, it is generally the case that by the safety features must be obtained medicinal products on prescription, with the exception of those listed in Annex No. 1 (White List) and with the exception of radiopharmaceuticals, taking into account the provision of Article 54 letter o) Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001on the Community code relating to medicinal products for human use. Non-prescription medicinal products must also be provided with safety features if listed in Annex 2 of the Black List.
According to the Czech State Institute for Drug Control (hereinafter “SIDC”), the White List and the Black List should be published on the SIDC website always the last working day of the month.
What are the safety features?
- Unique Identifier (UI) – serves to verify authenticity and at the same time enables the identification of each individual package by comparing the identification data of the packaging with the records in the repository system. It is a series of numerical and alphanumeric characters unique for each given package of a medicinal product. Its carrier is a two-dimensional bar code that meets the requirements of the Regulation.
The unique identifier carrier cannot be a QR code or an EAN code:
- product code (PC),
- serial number of packing (SN),
- batch number,
- expiry date.
- Anti-tampering device (ATD)– serves to verify whether the packaging of the medicinal product has been tampered with after its manufacture. Verification of its integrity. The Regulation does not state any further specifications for the anti-tampering device. It is not determined how exactly should it look like. The anti-tampering device should be placed on the outer packaging. If the medicinal product has no outer packaging, than the ATD is placed on the immediate packaging.
Verification of safety features and repository system
Verification of safety features means verification of both safety features, i.e. both a unique identifier and anti-tampering device. The unique identifier is verified by comparing the product code and the serial number of the packaging with the data stored in the repository system and by the anti-tampering device is verified its integrity whereas verification of these safety features is carried out by manufacturers, distributors to the extent specified by the Regulation or the pharmacies (for all packages of medicinal products when dispensing them).
It can be stated that if there is reason to believe that anti-tampering device has been tampered with or the unique identifier may not be authentic, then such packaging of the medicinal product cannot (i) be disposed of from the manufacturing, (ii) distributed or (iii) supplied and the competent authorities must be informed immediately. For obligated persons, the possibility should be introduced of the automated reporting of unsuccessful verification through the SIDC web interface and the interactive electronic form.
The Article 48 of the Regulation provides for an exception that the medicinal products that have been released for sale or distribution without the safety features in a member state before the date it becomes applicable (before 9 February 2019), and are not repackaged or relabelled thereafter, may be placed on the market, distributed and supplied to the public until their expiry date.
It is necessary for all affected entities to have functional connections to the repository system in order to fulfil the obligations arising from the Regulation and the Act on Pharmaceuticals, which will contain the data needed for verification purposes, identification of individual packages of medicinal products and exclusion of their unique identifiers.
As far as the repository system is concerned, it consists of a central repository (EU hub) and national repositories of each member states. All repositories shall communicate with each another and allow data to be exchanged and updated continuously. The Czech national repository system, which contains information on the safety features, is operated by the National Organization for Authenticity of Medicines (NOOL). Through it, distributors and persons authorized to supply medicinal products will fulfil their obligations. Manufacturers of medicinal products and marketing authorization holders will have to fulfil their obligations through the EU hub.
What does the exclusion of a unique identifier mean?
As mentioned above, the exclusion is carried out by (i) manufacturer, (ii) distributors to the extent set out in the Regulation, or (iii) pharmacies, which do so for all packages of medicinal products when supplying them. Unique identifiers are uploaded to the repository system with an active status, where in the moment of its exclusion the active status is changed to an excluded (typically a medicinal product supplied to a patient). The exclusion of a unique identifier is carried out, for example, in the case of exports outside the EU, disposal or supply of a part of the packaging or advertising sample.
What are the new obligations for individual affected subjects?
Manufacturers and marketing authorization holders are required to ensure that medicinal products will be provided with legal safety features and uploaded to the common European repository system.
In some cases, distributors will be required to verify the authenticity and carry out the exclusion of an unique identifier, such as in case of intend to export medicinal products outside the EU, disposal or to surrender of the medical product to the authority as a sample. The Distributor cannot delegate his / her obligation to verify and exclude the unique identifier to another entity.
The distributor is newly, pursuant to section 77 paragraph 1 letter r) of the Act on Pharmaceuticals, required to verify the safety features and to carry out the exclusion of the unique identifier in accordance with the Regulation before the medicinal product is delivered to the veterinary surgeons, the army, and in case of delivery of vaccines to doctors for vaccination purposes. Other than these deliveries from distributors directly to healthcare facilities are not possible from the effectiveness of the Regulation. It is clear that the supply and the exclusion of some medicinal products will need to be ensured in another way, probably through pharmacies, in order to verify theirs the authenticity of these medicinal products.
Failure to verify a unique identifier will be flagged as a potential case of falsification, which in itself does not necessarily mean that it is a counterfeit. Failure to verify may reside, for example, in incorrect stating of serial number or in poor quality of 2D code, its blurring, etc.
In conclusion
The new legislation in the context of anti-falsification regulation brings a lot of changes and new obligations. It can be assumed that it will also significantly affect the overall distribution of medicinal products. It also brings higher requirements for technical security enabling verification of safety features. It is a question of time how the newly introduced legislation will evolve in practice and whether it will be successful or will need to be revised due to its shortcomings.
In case of any queries we are at your disposal, please do not hesitate to contact us.
Mgr. Bc. Štěpánka Vajdová, junior lawyer – vajdova@plegal.cz
Mgr. Jakub Málek, partner – malek@plegal.cz
15. 02. 2019