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The European Union (EU) has rulemaking authority in the area of public health. EU law requires that all prescription medicine, including samples, be serialized and tracked from production to end user (patient). To facilitate such tracking, medicinal packages must be furnished with unique identifying information contained in a two-dimensional bar code that can be scanned at each point along the distribution channel.
Medicinal product samples may not be distributed to patients and must be removed from the tracking system (decommissioned) by the supplier of the sample before they are sent to the pharmacist, doctor, or nurse to whom the samples are provided. Medicinal products that qualify as narcotics may not be distributed as samples.
I. The European Union Medicinal Product Regulatory Framework
The European Union Member States have vested rule-making power with the European Union in the area of public health.[1] The European Union has used this rule-making power to adopt regulations and directives pertaining to, among other things, medicines verification systems, the distribution of medicinal product samples, and the tracking of samples.[2]
Regulations are of general application in the Member States.[3] Directives are binding upon the Member States as to the results to be achieved, but require Member States to transpose them into national law,[4] which allows Member States to choose the form and methods to be used to obtain the results.[5] The Commission oversees the Member States’ transposing of directives. If a Member State does not transpose a directive within the time allotted in the directive, the European Commission may bring the Member State before the European Court of Justice.[6]
In addition, the European Commission may receive delegated authority to adopt nonlegislative acts to supplement and amend nonessential elements of a legislative act pursuant to article 290 of the Treaty on the Functioning of the European Union (TFEU).[7] A legislative act containing such delegation of power must explicitly state the conditions for the delegation of power, and the Council and Parliament may revoke the power.[8] The European Commission was given such power in article 54(a)2 of Directive 2001/83/EC and exercised this power when adopting Commission Delegated Regulation (EU) 2016/161, which details the rules for how safety features must appear on packaging of medicinal products within the EU.[9]
Thus, Member States are responsible for transposing the Directive into national law and must also implement rules penalizing violations of the transposed provisions.[10] In 2018, the European Commission conducted a study of the Member States and found that the penalties adopted were satisfactory and efficient throughout the European Union.[11]
II. Tracking of Medicinal Products
A. Legal Requirements of Serialization
In accordance with the Falsified Medicines Directive (2011/62/EU),[12] which amends Directive 2001/83/EC on the Community Code relating to medicinal products for human use[13], EU Member States must put in place a system whereby “Marketing Authorisation Holders” (MAHs) and manufacturers include safety measures on packaging of medicinal products in order for others to be able to verify the authenticity of the medicinal product.[14] The purpose of the uniform EU-wide system is to guarantee the authenticity of a given medicinal product through an “end-to-end verification,”[15] thereby preventing counterfeit products from reaching the patient. This system should have been set up by February 9, 2019,[16] and the commission delegated Regulation 2016/161 (EU) specifies how the serialization takes place.[17] Accordingly, the manufacturers must encode the packaging with a unique identifier (UID), using a two-dimensional (2D) barcode.[18] The UID must be a “sequence of numeric or alphanumeric characters that is unique to a given pack of medicinal product, and consist of
(a) The unique identifier shall be a sequence of numeric or alphanumeric characters that is unique to a given pack of a medicinal product.
(b) The unique identifier shall consist of the following data elements:
(i) a code allowing the identification of at least the name, the common name, the pharmaceutical form, the strength, the pack size and the pack type of the medicinal product bearing the unique identifier (‘product code’);
(ii) a numeric or alphanumeric sequence of maximum 20 characters, generated by a deterministic or a non-deterministic randomisation algorithm (‘serial number’);
(iii) a 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;
(iv) the batch number;
(v) the expiry date.
(c) The probability that the serial number can be guessed shall be negligible and in any case lower than one in ten thousand.
(d) The character sequence resulting from the combination of the product code and the serial number shall be unique to a given pack of a medicinal product until at least one year after the expiry date of the pack or five years after the pack has been released for sale or distribution in accordance with Article 51(3) of Directive 2001/83/EC, whichever is the longer period.
(e) Where the national reimbursement number or other national number identifying the medicinal product is contained in the product code, it is not required to be repeated within the unique identifier.[19]
In addition, the UID must continue to be unique for one year longer than the expiry date listed on the package or five year from the release, whichever is longer.[20] The code must also be encoded in a two-dimensional barcode.[21] Further details on the specific configuration of the UID is specified in article 5 of Delegated Regulation (EU) 2016/161.[22] Member States may also include additional nonmandatory information in the UID.[23]
According to the European Commission, a UID that also complies with the ISO standard requirements contains a product code (such as (01) 09876543210982) followed by serial number (such as (21) 12345AZRQF1234567890) followed by batch number (such as (10) A1C2E3G4I5) followed by an expiry date (such as (17)180531), [24] and carries a 2D barcode (Data Matrix ECC200).[25] Note that a package may contain multiple UIDs if the product is sold using “multi-language packs” that sell in more than one Member Country.[26] However, the European Commission recommends the use of only one 2D bar code.[27]
The deadline for serialization was February 9, 2019, a deadline certain countries have reportedly struggled with.[28] Because the Directive only applies to medicines released prior to February 9, 2019, it is estimated that patients will continue to encounter medicines without these markers for up to five years (until 2024).
B. How the Serialization System Operates
The serialization system works through the use of both a National Medicines Verification Systems (NMVS) and the European Medicines Verification System (EMVS), which is controlled by the European Medicines Verification Organisation (EMVO).[29] As of March 2019, all EU Member States, except Greece and Italy who had both been given an extension until February 9, 2025,[30] had set up an NMVS.[31] The NMVS looks different in all Member States.[32] The main purposes of an NMVS are as follows:
- Holding the relevant product serialization data for the national market.
- Receiving revised/new product serialization data from the EU-Hub.
- Serving as the verification platform for pharmacies or other registered parties such as wholesalers and hospitals to certify the authenticity of a product.
- Serving as the platform for wholesalers in the case of member states application of Art. 23 DR, to mark a product pack as decommissioned prior to handing it over the patient.
- Serving as the platform for wholesalers to mark a product pack as “decommissioned” e.g. ‘exported out of EU’[33]
The EMVS describes the process of serialization as the pharmaceutical manufacturer produces the medicine and assigns each package containing information on a unique serialization with random numbers; that number is then uploaded, together with a product code, an S/N code, a batch number, and an expiry number, to the NMVS.[34] Before placing the product on the market the wholesaler checks the number against the verification system throughout the supply chain process (transport, etc.); the pharmacist, doctor, or nurse who dispenses the medicine then verifies the information before dispensing it to the patient.[35] The system is set up and governed by the MAHs and other stakeholders, but is overseen by competent authorities.[36] Each NMVS[37] must then connect to the EMVS via the “European HUB” (EU Hub), a central database and router for the EMVS.[38]
Member States are charged with supervising the national repository system and enforcing the requirements of the delegated regulation (including the use of the UIDs).[39] Any reports on the supervision of the work of the NMVS must be shared with the EMA and the European Commission.[40]
III. Regulation of Distribution of Medicinal Product Samples
In accordance with European Union law, medicinal product samples may only be provided very restrictively. Article 96 of Directive 2001/83/EC on the Community Code relating to medicinal products for human use, states that free samples of “psychotropic or narcotic substances” may not be provided under any circumstances.[41] Moreover, free samples may only be provided in exceptional cases and only to persons qualified to prescribe such products (i.e., doctors, dentists, nurses, pharmacists) if the following conditions are met:
1. . . .
(a) the number of samples for each medicinal product each year on prescription shall be limited;
(b) any supply of samples shall be in response to a written request, signed and dated, from the prescribing agent;
(c) those supplying samples shall maintain an adequate system of control and accountability;
(d) each sample shall be identical with the smallest presentation on the market;
(e) each sample shall be marked ‘free medical sample’ – ‘not for sale’ or shall show some other wording having the same meaning;
(f) each sample shall be accompanied by a copy of the summary of product characteristics;
(g) no samples of medicinal products containing psychotropic or narcotic substances within the meaning of international conventions, such as the United Nations Conventions of 1961 and 1971, may be supplied.
2. Member States may also place further restrictions on the distribution of samples of certain medicinal products.[42]
As stipulated in the preamble of the Directive, the purpose of the use of samples is, “within certain restrictive conditions to provide samples of medicinal products free of charge to persons qualified to prescribe or supply them so that they can familiarize themselves with new products and acquire experience in dealing with them.”[43] As noted in the preamble, the “distribution of samples free of charge to the general public for promotional ends must be prohibited.”[44]
IV. Tracking of Medicinal Product Samples
As discussed in Part II, above, in 2016, the European Commission, through a delegation regulation, published accompanying provisions to Directive 2001/83 requiring that all medicinal products, including free samples, be fashioned with safety features, specifically requiring both a unique code as well as a safety features that enable users to see whether or not the product has been tampered with.[45] Thus, it requires serialization of medicinal products. Nonprescription medicinal products are generally exempt, whereas only a limited number of designated prescription medicines are exempt.[46] In addition, Member States may also optionally require that also otherwise exempted medicinal products bear the safety features.[47]
The handling of samples is specifically regulated in the delegation regulation. Article 41 of Commission Delegated Regulation (EU) 2016/161 requires that a marketing authorization holder that intends to supply any of its medicinal products as a free sample must, where that product bears the safety features, indicate that it is a free sample in the repositories system and ensure the decommissioning of its unique identifier before providing it to the persons qualified to prescribe it.[48] Consequently, free samples are covered by the delegation regulation and have to bear the safety features.[49] Moreover, the decommissioning of the unique identifier means that the sample is taken out of circulation, and not intended to be given to a patient as the end user. By decommissioning the number and by marking the sample with a logo that designates it at a sample, the sample is more likely to be recognized as a sample before erroneously being transferred to a patient.[50] When decommissioning the sample the category code “sample” must be used in the EU Hub system.[51]
V. Funding Serialization
The industry itself bears the cost of the serialization and does not receive funding from the European Union.[52] The funding structure and the fees associated with participating in the NMVS vary between Member Countries, with most assigning a combination of fees and six countries (Estonia, Malta, Portugal, Slovakia, Slovenia, and Sweden) not assigning any fee, or not reporting the fee.[53] The fees assigned typically include both a one-time “entrance fee” to gain access to the verification system and an annual fee collected from either corporations or the MAHs.[54] There appears to be no cost to pharmacists, doctors, or nurses for using the system.[55]
VI. National Guidelines
Some Member States have produced national guidelines that explain the EU obligations. For example, in 2019, the Health Products Regulatory Authority of Ireland issued a report titled Good Distribution Practice of Medicinal Products for Human Use.[56] It provides that “samples of medicinal products that may be given to, or administered to, patients must be stored and transported to the end customer in accordance with GDP [good distribution practice].”[57] In addition, “[s]ales representatives may not hold or supply free medicinal samples unless there are systems in place to guarantee that those samples are not given to, or administered to, patients.”[58]
The EMVS published pack coding guidelines in 2017, in anticipation of the 2019 serialization.[59] It noted that manufacturers appear to prefer the GTIN (Global Trade Item Number) but that the European Hub supports both the use of GTINs, NTINs (National Trade Item Numbers), and PPNs (Pharmacy Product Numbers).[60] Examples of numbering systems used in 2017 in Europe include the following:
- France 3400 + CIP/ACL Code + check digit (France)
- 4150 + 8-digit PZN + check digit (Germany)
- 704626 + Nordic Drug Code issued by Nordic Number office + check digit (Nordic Countries Denmark, Finland, Iceland, Norway, and Sweden)[61]
Elin Hofverberg
Legal Research Specialist
September 2019
[1] Treaty on the Functioning of the European Union (TFEU) art. 168, 2012 O.J. (C 326) 1 (consolidated version), https://perma.cc/3TQA-U2VX.
[2] Directive 2011/62/EU, 2011 O.J. (L 174) 74), https://perma.cc/3AJF-T9BY, amending Directive 2001/83/EC, 2001 O.J. (L 311) 67, https://perma.cc/89R8-H46S. The legal power to adopt these directives is found in TFEU arts. 114 and 168.4C, and in art. 95 of the Treaty Establishing the European Community, 1997 O.J. (C 340) 173 (consolidated version), https://perma.cc/Y7MT-TTNE.
[3] TFEU, supra note 1, art. 88.
[4] Id. art. 288.
[5] Id.
[6] Id. art. 258.
[7] Id. art. 290.
[8] Id. art. 290(2)(a).
[9] Directive 2001/83/EC, supra note 2, art. 54a(2);Commission Delegated Regulation (EU) 2016/161, 2016 O.J. (L 32) 1, https://perma.cc/MF3K-ACP4.
[10] Directive 2001/83/EU, supra note 2, art. 118a.
[11] European Commission, Report on the Commission to the European Parliament and the Council on the Member States’ transposition of Article 118a of Directive 2001/83/EC of the European Parliament and the Council of 6 November 2001 on the Community code relating to medicinal products for human use as amended by Directive 2011/62/EU of the European Parliament and of the Council of 8 June 2011 at 8 (Jan. 26, 2018), https://perma.cc/Z8BC-L4QT; European Commission, Study on the Transposition Measures of Member States in Relation to the Pharmaceutical Legislation (Art. 118a of Directive 2001/83/EC): Final Report (2018), https://perma.cc/2M6A-GDZH .
[12] Directive 2011/62/EU, supra note 2.
[13] Directive 2001/83/EC, supra note 2.
[14] Id. art. 54.
[15] Commission Delegated Regulation (EU) 2016/161, supra note 9, pmbl., para. 15; see also European Medicines Verification System (EMVS), https://perma.cc/4SG8-BRWM.
[16] Three years after the delegation regulation was published in the Official Journal of the European Union. See Commission Delegated Regulation (EU) 2016/161, supra note 9.
[17] Id. Note that this Delegated Regulation applies to all EEA countries, i.e. all EU Member Countries as well as Lichtenstein, Norway, and Switzerland.
[18] Id. art. 5.
[19] Id. art. 4 (a).
[20] Id. art. 4 (d).
[21] Id. art. 5 (1).
[22] Id. art. 5.
[23] Id. art. 8.
[24] Patizia Tosetti, DG Sante & European Commission, Medicines Verification in Europe: What to Expect 9 (Stakeholders’ Workshop, Feb. 26, 2016), https://perma.cc/BAA9-FVXR.
[25] Id. at 10.
[26] Id. at 11. See also EFPIA, Multi-Market Pack Coding Requirements EFPIA Position, Medicines and Healthcare products Regulatory Agency (July 2017), https://perma.cc/VWK8-FECK.
[27] Commission Delegated Regulation (EU) 2016/161, supra note 9, pmbl., para. 14.
[28] Sean Milmo, Meeting the EU Serialization Deadline, 42(6) PharmTech (June 1, 2018), https://perma.cc/JQ29-8DC5.
[29] Commission Delegated Regulation (EU) 2016/161, supra note 9, arts. 31-37; see also EMVS, supra note 15.
[30] European Commission Directorate-General for Health and Food Safety, Safety Features for Medicinal Products for Human Use, Questions and Answers – Version 10 3 (Discussion Draft, July 2018), https://perma.cc/VN2P-R8ND.
[31] Tobias Beer, NMVO’s Fee Models Status, 3 (Mar. 8, 2019), https://perma.cc/63LP-HMV4. Certain Member States have adopted a stabilization period during the initial phase (rolled out Feb. 9, 2019), as a result of a larger number of alerts on mismatched information. For instance the Swedish NMVS e-Vis (e-verifikation i Sverige) will end its stabilization process on October 1, 2019.
[32] Id.
[33] EMVS, supra note 15.
[34] Id. For discussion on the nature of the identification numbering see also European Association of Euro-Pharmaceutical Companies et al., Coding & Serialisation Delegated Act on the Detailed Rules for a Unique Identifier for Medicinal Products for Human Use, and Its Verification, Concept Paper Submitted for Public Consultation, Joint Response (EAEPC-EFPIA-GIRP-PGEU) (Apr. 26, 2012), https://perma.cc/W6SR-2X6Y.
[35] EMVS, supra note 15, Product Flow Chart & Responsibilities of the Supply Chain Partners Chart.
[36] Commission Delegated Regulation (EU) 2016/161, supra note 9, art. 31.
[37] For a full list of Member State NMVSs see EMVS, supra note 15. Examples of NMVOs include SecurMed, https://www.securmed.org.uk/ (United Kingdom); DMVO, https://www.dmvo.dk/Pages/Welcome.aspx (Denmark); and e-VIS, https://e-vis.se/ (Sweden).
[38] Commission Delegated Regulation (EU) 2016/161, supra note 9, arts. 32-37.
[39] Id. art. 44.
[40] Id. See also Tosetti, supra note 24, at 26.
[41] Directive 2001/83/EC, supra note 2, art. 96.1(g).
[42] Id. art. 96(1)-(2).
[43] Id. pmbl., para. 51.
[44] Id. pmbl., para. 46.
[45] Commission Delegated Regulation (EU) 2016/161, supra note 9.
[46] Commission Delegated Regulation (EU) 2016/161, supra note 9, Annexes I & II. The nonprescription product omeprazole was also subject to the safety features requirement, because of reported incidents of falsification. Tosetti, supra note 24, at 29). Note that whether a medicinal product is considered a prescription drug or a nonprescription drug may differ between the Member Countries, cf. Delegated Regulation 2016/161, supra note 9, pmbl., para. 40, and thus the same medicinal product may be subject to differing serialization requirements even within the EU.
[47] Directive 2001/83/EC, supra note 2, art. 54a(5).
[48] Commission Delegated Regulation (EU) 2016/161, supra note 9, art. 41; see also id. pmbl., para. 22, which explains the nature of the decommissioning process, and its role in ensuring that a sample does not inadvertently reach a patient.
[49] Id. art. 41.
[50] Id. pmbl., para. 22.
[51] See Q&A, e-VIS, https://perma.cc/3VH5-2EX7 (in Swedish).
[52] See European Commission Directorate-General for Health and Food Safety, supra note 30.
[53] Beer, supra note 31.
[54] Id.
[55] Id.
[56] Health Products Regulatory Authority, Guide to Good Distribution Practice of Medicinal Products for Human Use, IA-G0046-4 (May 9, 2019), https://perma.cc/VS2V-WYNK. For other examples see the United Kingdom, Gov.Uk, Guidance: Implementing the Falsified Medicines Directive: Safety Features (updated July 11, 2019), https://perma.cc/MSW2-LVM5, and Italy, Minsitero della Salute & AIFA, Bollino: The Italian Security Label for Pharmaceutical Products (undated), https://perma.cc/9AJ2-FHW7.
[57] Health Products Regulatory Authority, supra note 56, at 24; see also Good Distribution Practice, European Medicines Agency,https://perma.cc/4LG4-JMYD.
[58] Id.
[59] EMVS, European Pack Coding Guidelines Version 4.0 (July 2017), https://perma.cc/L75E-7GPM.
[60] Id. at 5.
[61] Id. at 6.
Last Updated: 12/30/2020
