Serialization is the assigning of a unique serial number (unique identifier) to each pack of medicinal product, which is linked to information about the product’s origin, batch number and expiration date.
9 February 2019 is the deadline for manufacturers of medicinal products to comply with the EU rules on serialisation of medicinal products prescribed by the Regulation (EU) 2016/161[1]. Regulation (EU) 2016/161, Directive 2011/81/EU[2] and Falsified Medicines Directive[3] represent legal framework for prevention of entry into the legal supply chain of falsified medicinal products by requiring the placing of safety features consisting of (i) a unique identifier and (ii) an anti-tampering device on the packaging, for the purposes of allowing their identification and authentication.
The Regulation (EU) 2016/161 details the characteristics of the safety features, how medicine authenticity should be verified and by whom.
A unique identifier is a sequence of numeric or alphanumeric characters that is unique to a given pack of a medicinal product, which consists of a product code, serial number, national reimbursement number or other national number identifying the medicinal product, if required by the Member State where the product is intended to be placed on the market, the batch number and the expiry date. Unique identifier is encoded in a two-dimensional barcode, which is printed on the packaging.
Unique identifiers are stored in the repositories system, which must be set up and managed by a non-profit legal entity(ies) established in the EU by manufacturers and marketing authorisation holders (“MAHs”). Wholesalers are entitled to participate in the repositories system on a voluntary basis, at no cost. The repositories system is composed of (i) a central EU hub – European Medicines Verification System (“EMVS”) and (ii) national repositories or supranational repositories (repositories competent for multiple Member States). Each national or supranational repository exchange data with the EMVS.
Before the medicinal product is released for sale or distribution by the manufacturer, unique identifiers and accompanying information have to be uploaded to the repositories system, by which they are activated. Medicinal product then moves through the supply chain before arriving to healthcare institutions and pharmacies. The verification of the authenticity of a unique identifier is performed by comparing that unique identifier against the unique identifiers stored in a repositories system. Verification is an obligation of all participants in the supply chain of medicinal products. Unique identifier must be decommissioned (changing of the status from active to inactive) by pharmacies or healthcare institutions before supplying the medicine to the public. Therefore, the verification process can take place at any point throughout the supply chain, while decommissioning must be performed before the medication is administered to the patient. Unique identifier is unique to a given pack of a medicinal product until at least one year after the expiry date of that pack or five years after the product has been released for sale or distribution, whichever is the longer period.
Hence, manufacturers placing the safety features must keep records of every operation they perform with or on the unique identifier on a pack of medicinal product for the mentioned time period.
Repository in Croatia is a non-profit organisation Croatian Medicines Verification System (“HOPAL”) established on 20 July 2017 by full members – Pharmaceutical Industry Association at the Croatian Employer’s Association, Wholesale Trade Association at the Croatian Chamber of Economy and the Innovative Pharmaceutical Initiative, and as an active member – Croatian Chamber of Pharmacists. HOPAL is managed by a Board of Directors with six members – three members from manufacturers of medicinal products, two members from wholesalers and one member from the Pharmaceutical Industry Association at the Croatian Employer’s Association.
The costs of the repositories system are borne by the manufacturers of medicinal products bearing the safety features. HOPAL published that the annual cost per MAH for the use of HOPAL amounts to HRK 53,000.00 (approx. EUR 7,100.00). This fee is only a fraction of the total costs manufacturers have to invest (have invested) in their production in order meet the serialisation requirements prescribed by the Regulation (EU) 2016/161. Organization “Medicines for Europe” estimated that implementing serialization updating packaging and production lines will cost the average company EUR 5 million with an additional EUR 2 million annually for running and maintenance costs. According to their calculations, serialization will cost the entire pharma industry EUR 5 billion. Since the verification obligation applies to wholesalers, healthcare institutions and pharmacies, they also have significant costs of implementing IT system enabling them to access the repository system for the purposes of verifying the authenticity of the unique identifiers and of decommissioning them in the repositories system.
In conclusion, all manufacturers of medicinal products must ensure that as of 9 February 2019 all packaging of medicinal products placed on the market have the mentioned safety measures and that data is imported in the EMVS and national repositories. These requirements are mandatory and there will be no extensions. Only three countries – Belgium, Greece and Italy have received derogations to extend the compliance deadline to 9 February 2025, since at the time of entry into force of Directive 2011/62/EU they already had systems in place for the verification of the authenticity of medicinal products and for the identification of individual packs.
[1] 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 use.
[2] 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.
[3] 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.
