List of shortcuts

List of shortcuts

AR

Authorised Representative

ATD

Anti-tempering Device

CEO

Chief Executive Officer

CER

Certificate

CFO

Chief Financial Officer

CIO

Chief Information Officer

CMO

Contract Manufacturing Organisation

CSR

Certificate Signing Request

DR

Delegated Regulation

EAEPC

European Association of Euro-Pharmaceutical Companies

EFPIA

European Federation of Pharmaceutical Industries and Associations

EMVO

European Medicines Verification Organisation

EMVS

European Medicines Verification System

EU Hub

European Hub

FMD

Falsified Medicines Directive

GIRP

European Healthcare Distribution Association

IQE

Integrated Quality Environment

ITE

Integrated Test Environment

MAH

Marketing Authorisation Holder

NDA

Non-Disclosure Agreement

NMVO

National Medicines Verification Organisation

NMVS

National Medicines Verification System

OBP

On-boarding Partner

OBP Portal

On-boarding Partner Portal

PA

Participation Agreement

PD

Parallel Distributor

PGEU

Pharmaceutical Group of the European Union

PLMVS

Polish Medicines Verification System

PoD

Point of Dispense

PRD

Production Environment

RR

Registration Requester

SDK

Software Development Kit

SPOC

Single Point of Contact

UI

Unique Identifier

General questions

What are the safety features?

The safety features consist of two elements placed on the packaging of a medicinal product:

  • a unique identifier, a unique sequence carried by a two-dimensional barcode allowing the identification and authentication of the individual pack on which it is printed; and
  • a device allowing the verification of whether the packaging of the medicinal product has been tampered with (anti-tampering device). 
When do the rules on the safety features apply?

They apply as of 9th February 2019. Belgium, Greece and Italy have the option of deferring the application of the rules by an additional period of up to 6 years.

Do the safety features need to be applied on all medicinal products for human use?

No. The safety features should only be applied on the packaging of the following medicinal products for human use:

  • medicinal products subject to prescription which are not included in the list set out in Annex I to of Regulation (EU) No 2016/161;
  • medicinal products not subject to prescription included in the list set out in Annex II of Regulation (EU) No 2016/161;
  • medicinal products to which Member States have extended the scope of the unique identifier or the anti-tampering device to in accordance with Article 54a(5) of Directive 2001/83/EC.
Are there exceptions from the requirements for certainmedicinal products to bear or not the safety features?

Yes. The list of categories of medicinal products subject to prescription which shall not bear the safety features are set out in Annex I of Regulation (EU) No 2016/161, while the list of medicinal products not subject to prescription which shall bear the safety features are set out in Annex II of the same Regulation.

Do the rules on the safety features also apply to veterinary medicinal products?

No. The rules apply only to medicinal products for human use.

Do the rules on the safety features apply to medicinal products intended for research and development trials?

Medicinal products intended for research and development trials and not yet granted a marketing authorisation are excluded from the rules on the safety features. Authorised medicinal products have to fulfil the requirements of Directive 2001/83/EC and Regulation (EU) No 2016/161 up to the moment it becomes known which batch/unit will be used for research and development trials. In practice, a batch of an authorised investigational medicinal product or an authorised auxiliary medicinal product is excluded from the rules on the safety features if it is known at the time of manufacture that the whole batch is manufactured for use in clinical trials.

In addition, unique identifiers on authorised investigational medicinal products and authorised auxiliary medicinal products bearing the safety features should be decommissioned in accordance with Articles 16 and 25(4)(c) of Regulation (EU) No 2016/161.

Are the safety features required where the medicinal product manufactured in the EU is destined for exportation only?

No.

In the case of a medicinal product bearing the safety features is brought into the territory of a Member State in accordance with Article 5(1) of Directive 2001/83/EC, do the rules on the safety features apply?

When a medicinal product is brought into the territory of a Member State in accordance with Article 5(1) of Directive 2001/83/EC, the rules on the safety features in principle do not apply, unless there is applicable national legislation requiring otherwise. Member States can however use national legislation to regulate which provisions of Directive 2001/83/EC or of Regulation (EU) No 2016/16 apply to Article 5(1) products brought into their territory. Member States can, for example, require the mandatory verification/decommissioning of Article 5(1) products in accordance with Regulation (EU) No 2016/16.

In the absence of national legislation requiring otherwise, the rules on the safety features do not apply. The "importer" of a medicinal product brought into the territory of a Member State in accordance with Article 5(1) is not required, for example, to (re)place the safety features on its packaging (e.g. through labelling/relabelling operations). The verification of the safety features and decommissioning of the unique identifiers of Article 5(1) products already bearing the safety features are also not mandatory. Pharmacies, healthcare institutions and other relevant stakeholders in that Member State are nevertheless strongly encouraged to verify the authenticity of and decommission the medicinal product before supplying it to the public.

Does an obligation to bear "the safety features" imply an obligation to bear both a unique identifier and an anti-tampering device?

Yes.

Once Regulation (EU) No 2016/161 applies, can manufacturers place the safety features, on a voluntary basis, on medicinal products not required to bear the safety features?

No. Once Regulation (EU) No 2016/161 applies, manufacturers cannot place the safety features on medicinal products not required to bear the safety features, unless the Member States have extended the scope of application of the unique identifier or of the anti-tampering device to those medicinal products in accordance with Article 54a(5) of Directive 2001/83/EC.

Certain medicinal products are currently bearing an antitampering device on a voluntary basis. Are those products allowed to maintain the anti-tampering device once Regulation (EU) No 2016/161 applies, if they are not required to bear the safety features?

Once Regulation (EU) No 2016/161 applies, medicinal products can only bear an anti-tampering device if they are in the scope of Article 54a(1) of Directive 2001/83/EC (i.e. if they are medicinal products subject to prescription or medicinal products listed in Annex II of Regulation (EU) No 2016/161) or if the Member State(s) where they are placed on the market extended the scope of the anti-tampering device to those medicinal products.

Would it be possible to place a unique identifier on the packaging of a medicinal product during the 3 years period between the publication of Regulation (EU) No 2016/161 and its application?

Yes, on a voluntary basis. It is recommended that, whenever possible, unique identifiers are placed on the packaging only once a functional national/supranational repository allowing the storage, verification of the authenticity and decommissioning of those identifiers is in place. Unique identifiers which are placed on medicinal products before such repository is in place are expected to be uploaded in the repository as soon as it becomes operational.

Will the mandatory changes to the packaging due to the placing of the unique identifier and of the anti-tampering device require the submission of variations to marketing authorisations?

The regulatory requirements to be followed to notify the EMA of the placing of the unique identifier and/or the anti-tampering device on centrally authorised products are detailed in an implementation plan developed by the EMA and the European Commission and published in the "product information templates" section of the EMA website:

http://www.ema.europa.eu/docs/en_GB/document_library/Other/2016/02/WC500...

The regulatory requirements for nationally authorised products are available on theHMA/CMDh website: http://www.hma.eu/fileadmin/dateien/Human_Medicines/CMD_h_/Falsified_Med...

Are there any mandatory specifications for the anti-tampering device?

In accordance with Article 54(o) of Directive 2001/83/EC and Article 3(2)(2) of Regulation (EU) No 2016/161, an anti-tampering device has to allow the verification of whether the packaging of the medicinal product has been tampered with. There are no other mandatory specifications. The CEN standard EN 16679:2014 "Tamper verification features for medicinal product packaging" is available for manufacturers to consider.

Will the pharmaceutical companies receive any financial support (EU or national) for acquiring the instrumentation for applying the safety features on individual packages?

No, it is not currently foreseen that pharmaceutical companies will receive any financial support (EU or national) for acquiring the instrumentation for applying the safety features on individual packages.

Who shall bear the financial responsibility for the covering the expenses of establishment and implementation of the repository system in the ramp up period?

In accordance with Article 31(1), the repositories system shall be set up and managed by a non-profit legal entity or non-profit legal entities in the Union by manufacturer and marketing authorisation holders. The costs of the system shall be borne by the manufacturer of medicinal products bearing the safety features in accordance with Article 54a(2)(e) of Directive 2001/83/EC.

Are radiopharmaceuticals required to bear the safety features?

No. All pharmaceutical forms and strengths of radiopharmaceuticals (as defined by Article 1(6) of Directive 2001/83/EC), radionuclide generators (as defined by Article 1(7) of Directive 2001/83/EC), radionuclide precursors (as defined by Article 1(9) of Directive 2001/83/EC) and kits (as defined by Article 1(8) of Directive 2001/83/EC) shall not bear safety features.

The wording of Article 54(o) of Directive 2001/83/EC ("medicinal products other than radiopharmaceuticals") excludes radiopharmaceuticals, as defined by Article 1.6 of the said Directive, from the scope of the safety features. Consequently, any medicinal product fulfilling the definition of radiopharmaceutical shall not bear the safety feature. Since radiopharmaceuticals are outside of the scope of the safety features, their addition to Annex I of Regulation (EU) No 2016/161 is unnecessary.

Concerning pandemic-influenza vaccines, the EMA mock-up procedure allows a vaccine to be developed and authorized in advance of a pandemic, containing a strain of flu virus that few people have been exposed to but that could potentially cause a pandemic. These can be modified into pandemic-influenza vaccines in a future pandemic case. After a pandemic has been declared there is an emergency procedure for the final vaccine. Are there exceptions from the requirements for pandemic-influenza vaccines to bear or not the safety features?

No, as pandemic influenza vaccines are not included in Annex I of Regulation (EU) No 2016/161. Pandemic–influenza vaccines authorised via the mock-up procedure should bear the safety features in accordance with the said Regulation.

In case of a bundle of several single packs which is sold as one unit, should the anti-tampering device and unique identifier be placed on the bundle packaging or on each single pack?

Whether a manufacturer needs to place the safety features on the bundle packaging or on each single pack within the bundle depends on how the medicinal product is described in its marketing authorisation dossier – regardless of what is the commercial sellable unit.

If, in the marketing authorisation dossier, the product presentation is described as a "multi-pack", the outer packaging as that of the bundle and the single packs as not for individual sale (the text 'can’t be sold separately' or equivalent is present on the packs), then both the UI and the ATD need to be placed on the bundle packaging. The outer packaging must include, in addition to the unique identifier and ATD, all applicable labelling requirements as laid down in Article 54 of Directive 2001/83/EC.

If, however, the marketing authorisation dossier of the medicinal product describes the product presentation as a single pack and the text 'can’t be sold separately' or equivalent is not present on the packs, then each pack within the bundle needs to be serialised and have an anti-tampering device. In this case, the bundle packaging should not bear a unique identifier, but it may bear an aggregated code containing the information on all unique identifiers within the bundle.

If a pack bearing the safety features is lawfully opened (e.g. by parallel traders/manufacturers replacing the leaflet under the supervision of national competent authorities), can it be resealed (e.g. by applying a new ATD on top of the old, broken ATD)?

In certain circumstances, based on the assessment of the national competent authority in the destination Member State.

Parallel traders/manufacturers that wish to reseal packages must provide the competent authority in the destination Member State with sufficient information to allow an informed assessment of equivalence of the new anti-tampering device (description, explanation, mock-ups, pictures, etc. of both the original and replacement ATD). The newly placed ATD can only be considered equivalent if, inter alia, it is equally effective in enabling the verification of authenticity of the medicinal product and in providing evidence of tampering. 
An anti-tampering device (ATD) placed on top of an older, broken ATD can be considered as effective in providing evidence of tampering as an ATD placed on an intact outer packaging only if:

(a) The new ATD completely seals the pack and covers any visible sign of the original, broken ATD;

(b) The replacement of the ATD is conducted in accordance with applicable good manufacturing practice for medicinal products and is subject to supervision by the competent authority; and

(c) The manufacturer placing the equivalent ATD has verified the authenticity of the unique identifier and the integrity of the ATD on the original pack before breaking the ATD/opening the original pack, in accordance with Article 47a(1)(a) of Directive 2001/83/EC.

Is it possible for manufacturers/wholesales/parallel traders to market/supply medicinal products with a packaging showing visible signs of opening/intrusion, but where the ATD has been replaced by a new ATD in accordance with Article 47a of Directive 2001/83/EC?

No. If the pack has been opened lawfully (see Q&A 1.20), the manufacturer placing an equivalent ATD should ensure the pack is perfectly re-sealed and no signs of the original, broken ATD are visible.

It should be noted that Articles 24 and 30 of Commission Delegated Regulation (EU) 2016/161 prohibit wholesalers and persons authorised or entitled to supply who receive a medicinal products having a packaging showing signs of tampering from supplying that product.

In case of parallel-traded packs, can parallel traders cover or remove the safety features of the original pack?

Parallel traders covering or removing the existing safety features are required to place equivalent safety features in accordance with Article 47a of Directive 2001/83/EC (see also Q&A 1.20).

Furthermore, if the product code, batch number and/or expiry date of the parallel-traded product change compared to the original product, parallel traders must place a new unique identifier after first decommissioning the original one. The new unique identifier should comply with the requirements of the Member State where the medicine is intended to be placed on the market (Article 17 of Commission Delegated Regulation Regulation (EU) 2016/161).

When placing an equivalent unique identifier, parallel traders are required to fulfil, inter alia, the obligations laid down in Articles 33, 40 and 42 of Commission Delegated Regulation (EU) 2016/161 concerning the uploading and keeping up to date of the information on the new unique identifier into the repositories system.

Is it possible to place a transparent sticker used as an ATD over the human readable codes or the 2D Data Matrix, even if opening the pack might lead to the human-readable data and/or 2D bar code being damaged and unreadable?

It is acceptable to place a transparent sticker, used as an ATD, over the 2D data matrix, provided that it does not impact its readability (for example if the sticker is reflective), and the data matrix does not contain information intended for the patient or included in accordance with the recommendation in Q&A 2.12 (e.g. content previously included in a QR code).

Concerning the human-readable code, the human-readable batch number and expiry date are relevant information for the patient and should remain readable after the pack is opened. Hence, it is not acceptable to place a transparent sticker, used as an ATD, over the human-readable batch number and expiry date if it risks damaging this information when the pack is opened.

TECHNICAL SPECIFICATIONS OF THE UNIQUE IDENTIFIER

Does Regulation (EU) No 2016/161 limit the length of the unique identifier to 50 characters?

No. Only the length of the product code, one of the data elements of the unique identifier, is limited to 50 characters.

Would it be possible to include, on a voluntary basis, a twodimensional barcode on the packaging of medicinal products for human use not having to bear the safety features if the information carried by the barcode does not serve the purposes of identification and authentication of the medicinal product and does not include a unique identifier?

Yes, provided that the relevant labelling provisions of Title V of Directive 2001/83/EC are complied with. Examples may include two-dimensional barcodes encoding price indications, reimbursement conditions, etc.

Is it possible to include one-dimensional barcodes on the packaging of medicinal products for human use having to bear the safety features, in addition to the two-dimensional barcode carrying the unique identifier?

Yes, provided that the inclusion of both barcodes does not negatively impact the legibility of the outer packaging.

Is a printing quality of 1.5 according to ISO/IEC 15415 mandatory?

No. Manufacturers are required to use a printing quality which ensures the accurate readability of the Data Matrix throughout the supply chain 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. The use of a printing quality of 1.5 or higher gives a presumption of conformity, i.e. manufactures using a printing quality of 1.5 or higher will be presumed to have fulfilled the requirement mentioned in the first paragraph without need to prove that it is actually the case. If a printing quality lower than 1.5 is used, manufacturers may be asked to prove that requirements mentioned in the first paragraph are met.

Can manufacturers, on a voluntary basis, place the human readable code on medicinal products with packaging having the sum of the two longest dimensions equal or less than 10 centimetres?

Yes.

Are medicinal products with packaging having the sum of the two longest dimensions equal or less than 10 centimetres exempted from bearing the two-dimensional barcode carrying the unique identifier?

No, Article 7(2) only provides for an exemption from bearing the unique identifier in human readable format. The unique identifier in machine-readable format – the 2D barcode – is still required.

Is it compulsory to print the national reimbursement number in human-readable format?

The national reimbursement number or other national number should be printed in human readable format only if required by the national competent authorities of the relevant Member State and not printed elsewhere on the packaging. It should be printed adjacent to the two-dimensional barcode if the dimensions of the packaging allow it.

Is it compulsory for the human-readable data elements of the unique identifier to be placed adjacent to the two-dimensional barcode?

Yes, whenever the dimensions of the packaging allow it.

What is the smallest font size that can be used to print the unique identifier in human-readable format?

The font size of the unique identifier should be in accordance with the "Guideline on the readability of the labelling and package leaflet of medicinal products for human use" published in Eudralex – Notice to Applicants - Volume 2C (http://ec.europa.eu/health/files/eudralex/vol-2/c/2009_01_12_readability...).

Should the data elements of the unique identifier in humanreadable format be printed on the packaging (product code, serial number and, where applicable, national reimbursement number) in an established order?

Yes. The order of printing is set out in the QRD template and is the same as set out in Regulation (EU) No 2016/161: Product code, Serial number, National number or other national number identifying the medicinal product (where required).

Regulation (EU) No 2016/161 does not mention batch number and expiry date as mandatory components of the human readable code. Is it mandatory to print the batch number and the expiry date in a human-readable format and adjacent to the two dimensional barcode?

Batch number and expiry date are mandatory components of the labelling of all medicinal products – regardless of whether they bear the safety features – and should be printed on the packaging in accordance with Article 54 (h) and (m) of Directive 2001/83/EC. There is no obligation to place batch number and expiry date adjacent to the two dimensional barcode.

Is it allowed to place a QR code on the packaging of a medicinal product bearing the safety features?

Regulation (EU) No 2016/161 does not prohibit the placing of a QR code as far as it is not used for the purposes of identification and authentication of medicinal products.

Marketing authorisation holders are however encouraged, wherever technically feasible, to exploit the residual storage capacity of the Data Matrix to include the information they would otherwise include in the QR code. This would minimise the number of visible barcodes on the packaging and reduce the risk of confusion as regard the barcode to be scanned for verifying the authenticity of the medicinal product.

Where on the packaging should the unique identifier be placed?

The delegated Regulation does not specify where on the outer packaging the safety features should be placed. The placement of the safety features is therefore to be supervised by competent authorities in accordance with current practice for labelling requirements.

Can the graphics on the containers of the medicinal products be printed separately and the Data Matrix added at the final packaging stage - or are there digital printing technologies where all packaging graphics and the UI can be printed in one step?

The Delegated Regulation does not specify how the safety features should be applied to the outer packaging. The placement of the safety features is therefore to be supervised by competent authorities in accordance with current practice for labelling requirements. The specifics of the technologies used to apply the UI will be for the individual manufacturer to decide and for them to select the most appropriate model suitable for their needs.

Upon the medicinal product being supplied to the public, the UI is decommissioned and the package is no longer active in the repository. However, the 2D Data Matrix can still be read-out, for example by a consumer using a smartphone application. Will the possibility to verify the authenticity of the product via the Data Matrix be extended to the end-user (patient)?

The Delegated Regulation does not provide for verification of the authenticity of the product by the end user. Nevertheless, the verification conducted by the person authorised to supply to the public guarantees that the product is not falsified.

After the UI data has been encoded, can any residual storage capacity in the Data Matrix be used to store other information?

The delegated Regulation states in Article 8 that manufacturers may include information additional to the information contained within the unique identifier in the two-dimensional barcode, where permitted by the competent authority in accordance with article 62 of Title V of the Directive2001/83/EC. That information should be consistent with the summary of product characteristics, useful for the patient and may not contain promotional elements. The amount of residual storage capacity of the Data Matrix after the UI data has been encoded will depend upon the size of the Data Matrix as selected by the individual manufacturers responsible for the placing of the UI on the packaging.

Do human-readable headers (PC, SN, Lot, EXP, NN) have to be placed adjacent to the respective data elements, on the same line, or is some flexibility possible?

Human-readable headers are not required to be placed adjacent/on the same line as the respective data element. Headers can be placed in any position which allows the unequivocal identification of the human-readable data element.

For products bearing the human-readable code, is it acceptable to place data elements in multiple locations across the packaging?

It depends on the data elements and dimensions of the packaging. The product code and serial number should be placed on the same surface, where space allows, so to facilitate manual decommissioning of the unique identifier. Concerning the other data elements, an effort should be made to place them on the same surface as the product code and serial number. Should the packaging dimensions not allow it, however, it is acceptable to place the other data elements as close to the product code and serial number as possible (e.g. adjacent sides).

Is it acceptable to use a 2D Data Matrix which is rectangular (rather than square) or printed white on black (rather than black on white)?

Yes. Manufactures can chose to encode the unique identifier in a 2D Data Matrix which is rectangular and/or printed white on black, provided that it fulfils the technical requirement laid down in Article 5 of Regulation (EU) No 2016/161.

Is it mandatory to include Application/Data Identifiers as part of the human-readable headers or data elements?

No. Manufacturers can choose whether to include the Application/Data Identifiers as part of the human-readable headers/data elements.

Is it acceptable to use stickers to place the unique identifier on the outer/immediate packaging?

The unique identifier should be printed on the packaging along with all other information required under article 54 of Directive 2001/83/EC, in accordance with Article 5(3) of Commission Delegated Regulation (EU) 2016/161.
Placing the unique identifier by means of stickers can be accepted in the following circumstances:

  • No legal and/or technically feasible alternative exists (e.g. safeguard of trademark rights; glass/plastic immediate packaging without outer packaging; etc.); or
  • Competent national authorities authorise it due to the marketing authorisation, including for parallel import, or to safeguard public health and ensure continued supply.

 In cases where placing the unique identifier by means of stickers is authorised by competent national authorities under the circumstances mentioned above, the following conditions should be met:

  • The sticker on which the unique identifier is printed should become one with the outer packaging/immediate packaging, i.e. the sticker should be tamper-evident and it should not be possible to remove it without damaging the packaging or the sticker itself or leaving visible signs;
  • The sticker on which the unique identifier is printed should be placed by a manufacturer under GMP conditions; and
  • The outer/immediate packaging on which the sticker is placed includes, in addition to the unique identifier, all applicable labelling requirements as laid down in Article 54 of Directive 2001/83/EC.

 Notwithstanding the above, placing the unique identifier by means of stickers should never be allowed when:

  • It impairs readability. Article 56 of Directive 2001/83/EC  requires that “the particulars referred to in article 54, 55 and 62 shall be easily legible, clearly comprehensible and indelible”; or
  • The sticker on which the unique identifier is printed can be detached from the packaging without damaging the packaging or the sticker itself or leaving visible signs; or - The sticker on which the unique identifier is printed is intended to be placed on top of an existing sticker, as this could engender confusion and suspicions of tampering.

GENERAL PROVISION ON THE VERIFICATION AND DECOMMISSIONING OF THE SAFETY FEATURES

How should the unique identifier be decommissioned if the two-dimensional barcode is unreadable or deteriorated?

The unique identifier in human readable format should be recorded by any suitable method allowing the subsequent manual querying of the repository system in order to verify and decommission the unique identifier.

Where the barcode carrying the unique identifier cannot be read, or in case the verification of the unique identifier is temporarily impeded, is it possible to supply the medicinal product to the public?

Article 30 of Regulation (EU) No 2016/161 prohibits supply to the public if there is reason to believe that the packaging of the medicinal product has been tampered with, or the verification of the safety features of the medicinal product indicates that the product may not be authentic. In all other cases, the supply of medicinal products to the public is regulated by national legislation. Without prejudice to national legislation, in the case where it is permanently impossible to read the unique identifier and verify the authenticity of the medicinal product, for example because both the data matrix and the human readable code are damaged, it is recommended that the medicinal product is not supplied to the public.

Can a medicinal product which cannot be authenticated be returned, and to whom? Who should pay for the return?

Regulation (EU) No 2016/161 does not change the national provisions in place regulating returns of medicines from pharmacies and hospitals. The regulation of returns of medicinal products, including their financial aspects, remains a national competence.

Is the use of aggregated codes to simultaneously verify the authenticity of or decommission multiple unique identifiers permitted?

Recital 20 of the Delegated Regulation gives the possibility of giving aggregated codes allowing the simultaneous verification of multiple Unique Identifiers, provided that the requirements of Regulation (EU) No 2016/161 are complied with. However, since aggregation is not regulated in the Delegated Regulation any action in that sense from manufacturers/wholesalers/parallel traders (or any actor in the supply chain, for the matter) is only voluntary and needs to be agreed upon by the stakeholders.

Is it possible to reverse the decommissioned status of a medicinal product that has been physically exported to third countries, when such product is brought back into the EU?

No. When a medicinal product is physically exported outside of the EU, its unique identifier must be decommissioned in accordance with Article 22(a) of Commission Delegated Regulation (EU) 2016/161. If the exported product is subsequently reimported onto the EU territory (e.g. because it is returned), it is considered an "import" and must be imported by a manufacturing import authorisation (MIA) holder (not a wholesaler) and is subject to the import requirements laid down in Article 51 of Directive 2001/83/EC (batch testing, batch release, etc.). The imported medicinal product should also be given a new unique identifier containing a new batch number and expiry date, if applicable, before it is released for sale and distribution in the EU.

VERIFICATION OF THE SAFETY FEATURES AND DECOMMISSIONING OF THE UNIQUE IDENTIFIER BY MANUFACTURERS

Do the records referred to in Article 15 of Regulation (EU) No 2016/161 have to be stored in the repositories system?

No. The manufacturers can decide how and where to keep the records of every operation he performs with or on the unique identifier.

Article 18 requires that, in case of suspected falsification or tampering, the manufacturer should inform the competent authorities. Should he also inform the holder of the marketing authorization for the medicinal product?

Yes, Article 46 of Directive 2001/83/EC requires manufacturers to inform the competent authority and the marketing authorisation holder immediately if they obtain information that medicinal products which come under the scope of their manufacturing authorisation are, or are suspected of being, falsified.

Articles 18, 24 and 30 of Commission Delegated Regulation (EU) 2016/161 require that manufacturers, wholesalers and persons authorised or entitled to supply medicinal products to the public immediately inform national competent authorities in case of suspected falsification of medicinal products. How should this information be notified by manufacturers?

It is recommended that manufacturers contact national competent authorities, since the procedure to follow for such notification is a national competence. If they exist, national guidelines should be followed.

Can a manufacturer use an outer packaging carrying a unique identifier which has been placed by another (contracted) manufacturer?

Yes. Art. 14 of Regulation (EU) No 2016/161 requires that the manufacturer placing the safety features on the medicinal product verifies that the two-dimensional barcode carrying the unique identifier complies with Articles 5 and 6 of the said Regulation, is readable and contains the correct information. Where pre-printed cartons are used, the manufacturer using the pre-printed carton has the obligation to verify the 2D barcode complies with Articles 5 and 6 of the above Regulation, is readable and contains the correct information before releasing the medicinal product for sale and distribution.

In agreement with Chapter 7 of Part I of the EU GMP Guidelines, a written agreement has to be signed among the parties establishing the corresponding responsibilities. The manufacturer releasing the product for sale and distribution (see Q&A 7.13) should verify the capacity of the contracted manufacturer to perform the task in accordance with the requirements of the Regulation and in compliance with applicable GMP. The contracted manufacturer needs to be included in the marketing authorisation.

VERIFICATION OF THE SAFETY FEATURES AND DECOMMISSIONING OF THE UNIQUE IDENTIFIER BY WHOLESALERS

How should the expression "the same legal entity" referred to in Articles 21(b) and 26(3) of Regulation (EU) No 2016/161 be interpreted?

This expression should be interpreted in accordance with national legislation. As general guidance, and without prejudice to national legislation, a legal entity may be considered the same when, for example, it has the same registration number in the national company registry or, if no national registration is required, the same number for tax purposes (i.e. VAT number).

Member States may hold stocks of certain medicinal products for the purpose of public health protection. How should the unique identifiers on those products be verified and decommissioned?

In accordance with Article 23(f) of the delegated Regulation No 2016/161, Member States may request wholesalers to verify the safety features of and decommission the unique identifier of medicinal products which are supplied to governmental institutions maintaining stocks of medicinal products for the purposes of civil protection and disaster control.

Articles 18, 24 and 30 of Commission Delegated Regulation (EU) 2016/161 require that manufacturers, wholesalers and persons authorised or entitled to supply medicinal products to the public immediately inform national competent authorities in case of suspected falsification of medicinal products. How should this information be notified by wholesalers?

It is recommended that wholesalers contact national competent authorities, since the procedure to follow for such notification is a national competence. If they exist, national guidelines should be followed.

Articles 20, 21 and 22 require wholesalers to verify the authenticity and/or decommission the unique identifier only. Do wholesalers need to verify the integrity of the anti-tampering device when complying with those Articles?

No, wholesalers do not need (but can) to verify the integrity of the antitampering device when complying with Articles 20, 21 and 22.

Article 22(a) requires a wholesaler to verify the authenticity of and decommission the unique identifier of all medicinal products he intends to distribute outside of the Union. Is it necessary to decommission the unique identifier if the medicinal product is sold to a party established outside the EU but that product does not physically leave the wholesaler's premises in the EU?

No. The purpose of Article 22(a) is to ensure the decommissioning of unique identifiers on packs which leave the EU territory, in order to avoid that those active codes may be harvested by traffickers. In case the medicinal product is sold to a party established outside the EU but physically remains in the wholesaler's premises in the EU, the unique identifier on the product should not be decommissioned. If that medicinal product is subsequently imported (while physically remaining in the EU) by a holder of a manufacturing and import authorisation (a wholesaler cannot import medicinal products), no action from the wholesaler physically holding the product is required with regard to the safety features.

Do wholesalers have the obligation to decommissioning the unique identifier of a medicinal product when they sell the product “business-to-business” to a company which buys it for the purpose of research?

Article 23(g) allows the decommissioning by wholesalers of medicinal products supplied for the purpose of research, except when supplied to healthcare institutions. Although the Article does not explicitly mention that it applies to the supply of products for the purpose of research to companies which are not universities or other higher education establishments, it is desirable to include such a case in the scope of this Article (provided that those companies are not healthcare institutions) in order to guarantee the decommissioning of the unique identifiers on those products.

Is wholesale distribution of medicinal products with a damaged/unreadable 2D Data Matrix code allowed, if there is no suspicion of falsification?

It depends. If the verification of the authenticity of the unique identifier (UI) can be performed by using the human readable code, the products can be further distributed.

If the verification of the authenticity of the UI cannot be performed (because the human readable code is damaged or absent), then two scenarios can be envisaged:

1. The wholesaler is subject to the obligation to verify the authenticity of the medicinal product in accordance with Article 20 of the DR (because the products are either returns or have been supplied by a wholesaler who is not the manufacturer not the MAH not a designated wholesaler). In this case, the wholesaler cannot further distribute the products with the unreadable codes as doing so would mean to breach Article 20 of Regulation No 2016/161.

2. The wholesaler does not have an obligation to verify (because, for example, s/he procured the products from the manufacturer or the MAH or a designated wholesaler). In this case, Regulation No 2016/161 does not explicitly prohibit further distribution (the wholesaler may not notice the codes are damaged/unreadable as s/he has no obligation to verify the UI).  Even if the distribution of products with unreadable codes may be legal in certain circumstances, it is certainly not desirable, as the authenticity of those products cannot be verified. In addition, distributing those products further would be pointless, as the products would never reach their final users: they would be blocked further down the supply chain by other distributors/pharmacies/hospitals unable to fulfil their verification/decommissioning obligations under Regulation No 2016/161. 

Can a wholesaler request another wholesaler to verify the authenticity and decommission the unique identifiers for medicinal products they intend to distribute outside the EU on their behalf?

No. According to Article 22(a), the wholesaler who intends to distribute medicinal products outside the EU must verify their authenticity and decommission the unique identifiers. This obligation cannot be delegated to another wholesaler.

VERIFICATION OF THE SAFETY FEATURES AND DECOMMISSIONING OF THE UNIQUE IDENTIFIER BY PERSONS AUTHORISED OR ENTITLED TO SUPPLY MEDICINAL

In-patients in a hospital may be administered medicinal products during their stay, the costs of which may be charged to their insurer, which constitutes a sale. In this case, would the hospital (or any other healthcare institution) be allowed to verify the safety features and decommission the unique identifier of those products earlier than the time of supply to the public, in accordance with Article 25(2)?

Yes. In the case described, the charging of the medicinal products costs to the patient's insurer happens as a consequence of the administration of that product to the patient (regardless of whether the sale takes place before or after the actual administration). Consequently, it is considered that the charging of the cost of the medicinal product to the patient's insurer (or to the patient himself, for the matter) does not preclude hospitals from applying the derogation provided for in Article 25(2).

How should the expression "the same legal entity" referred to in Articles 21(b) and 26(3) of Regulation (EU) No 2016/161 be interpreted?

This expression should be interpreted in accordance with national legislation. As general guidance, and without prejudice to national legislation, a legal entity may be considered the same when, for example, it has the same registration number in the national company registry or, if no national registration is required, the same number for tax purposes (i.e. VAT number).

Many hospitals and other healthcare institutions supply the contents of packages of a medicinal product to more than one patient. Where only part of a pack of a medicinal product is supplied, when should the decommissioning of the unique identifier be performed?

The unique identifier should be decommissioned when the packaging is opened for the first time, as required by Article 28 of Regulation (EU) No 2016/161.

Does automated dose dispensing require the placing of new safety features on the individual patient doses/packs?

No. Automated dose dispensing falls in the scope of Article 28 of Regulation (EU) No 2016/161. Consequently, it is not necessary to place new safety features on the individual patient's dose/pack.

Is it possible for the wholesaler to scan the unique identifiers (UI) in a consignment before shipping the consignment to a hospital, store the UI information and then, once the hospital received the consignment, decommission the UIs using the stored information following an explicit request by the hospital?

No, the above process is not in line with the provisions of Regulation (EU) No 2016/161:

- Since the decommissioning would happen through the wholesaler's computer using the wholesaler's log-in ID, the decommissioning operation would be recorded in the system and in the audit trail as an operation performed by the wholesaler, and not by the hospital. This is not acceptable as the audit trail would not reflect the reality of the supply chain, as required by Article 35(1)(g) of the Regulation. - Articles 23 and 26 of Regulation (EU) No 2016/161 are explicit about those cases where wholesalers are entitled to decommission the safety features on behalf of hospitals. Decommissioning on behalf of hospitals under other circumstances is therefore not allowed.

Is it acceptable for hospitals/hospital pharmacies to subcontract their decommissioning obligations to wholesalers?

No. However, there are possible scenarios, compatible with Commission Delegated Regulation (EU) 2016/161, where wholesalers (including manufactures supplying their own products by wholesale) could facilitate the decommissioning operation of hospitals (illustrative examples only, list not exhaustive):

  • Wholesalers could scan the packs in the hospital consignment to acquire the information on the UIs and encode such information into an aggregated code. Decommissioning would then be performed by the hospital by scanning the aggregated code. The only equipment needed for this operation would be a hand-held scanner and a computer (connected to the national repository).
  • Wholesalers could acquire the information on the UIs in the hospital consignment and make this information available to the hospital, by secure means. The hospital would then use such information to perform the decommissioning (without having to physically scan the packs).
Articles 18, 24 and 30 of Commission Delegated Regulation (EU) 2016/161 require that manufacturers, wholesalers and persons authorised or entitled to supply medicinal products to the public immediately inform national competent authorities in case of suspected falsification of medicinal products. How should this information be notified by persons authorised or entitled to supply medicinal products to the public?

It is recommended that persons authorised or entitled to supply medicinal products to the public contact national competent authorities, since the procedure to follow for such notification is a national competence. If they exist, national guidelines should be followed.

For persons authorised or entitled to supply medicinal products to the public operating within a healthcare institution, must the verification of the integrity of the anti-tampering device be done at the same time as the verification and decommissioning of the unique identifier?

No. Article 25(2) of Commission Delegated Regulation (EU) 2016/161 outlines that verification of the safety features can be done at any time a medicine is in the physical possession of a healthcare institution as long as no sale takes place between delivery to the healthcare institution and supply to the public. Therefore, decommissioning of the UI and verification of the ATD can be done separately before supply to the public.

ESTABLISHMENT, MANAGEMENT AND ACCESSIBILITY OF THE REPOSITORIES SYSTEM.

How should the expression "manufacturers of medicinal products bearing the safety features", as used in Regulation (EU) No 2016/161, be interpreted?

For the purposes of Regulation (EU) No 2016/161, "manufacturer" means the holder of a manufacturing authorisation in accordance with Article 40 of Directive 2001/83/EC. The expression "manufacturers of medicinal products bearing the safety features" encompasses any holder of the said authorisation performing partial or total manufacture of a medicinal product bearing the safety features.

Article 31 of Regulation (EU) No 2016/161 allows wholesalers and persons authorised or entitled to supply medicinal products to the public to participate in the legal entity/ies setting up and managing the repositories system, at no costs. Can the terms of such participation be regulated by stakeholders, for examples through the statutes of establishment or incorporation of the legal entity/ies?

Yes, it is possible, provided that the terms do not contradict what is enshrined in legislation. In case of discrepancy, the provisions of Regulation (EU) No 2016/161 and Directive 2001/83/EC prevail.

What is a supranational repository?

In practice, a repository serving as "national" repository for more than one Member State.

How should the expressions "application programming interface" or "graphical user interface" referred to in Articles 32(4) and 35(1) of Regulation (EU) No 2016/161 be interpreted?

The expression "application programming interface" refers to a software/software interface consisting of a set of programming instructions and standards used by a piece of software to ask another piece of software to perform a task. The programming instructions and standards are set by the software being called upon. In the context of Regulation (EU) No 2016/161, the expression refers to the programming instructions and standards allowing the software of persons authorised or entitled to supply medicines to the public, wholesalers and national competent authorities to query the repository system. The expression "graphical user interface" (GUI) refers to a human/computer interface that allows users to interact with software or a database through graphical icons and visual indicators without the need of using complex programming language. Article 35(1)(i) limits the use of the GUI by wholesalers and persons authorised/entitled to supply medicines to the public to the very specific case of failure of their own software. In practice, it can be considered that:

  • wholesalers and persons authorised or entitled to supply medicines to the public are expected to use their own software to connect to their national repository and verify the authenticity of/decommission the unique identifier; and
  • they should use the GUI for the above purposes exclusively when their software fails.
Article 33(1), second subparagraph, requires that information referred to in paragraphs 2(a) to 2(d) of that article, with the exception of the serial number, is stored in the hub. Does this mean that the serial number cannot be uploaded to the hub?

No, the provision only regulates which information is to be stored in the hub.

Articles 34(4), 35(4) and 36(n) refer to the linking of the information on unique identifiers removed or covered to the information on the equivalent unique identifiers placed for the purposes of complying with Article 47a of Directive 2001/83/EC. Is the linking required to be at the level of individual unique identifiers? How does the linking work in practice?

No, it is not necessary to link individual unique identifiers. The link can be made at batch level by linking the list of decommissioned unique identifiers in the "old" batch (the batch to be repacked/relabelled) and the list of new unique identifiers placed on packs in the "new" batch (the repacked batch). The provision does not require the linking to be done at the level of individual unique identifiers, since the number of packs in the batch to be repacked/relabelled (and consequently the number of unique identifiers in that batch) may not correspond to the number of packs (and of unique identifiers) in the new batch – making a one-to-one link between unique identifiers impossible.

In Article 35(1)(f), does the upper limit of 300 ms for a repository to respond to queries also apply when multiple repositories are implicated in the query, for example in case of cross-border verification?

300 ms is the maximum response time of an individual repository. When the verification/decommissioning operation requires the querying of multiple repositories in the repositories system, for example in case of cross-border verification, the maximum response time is obtained by multiplying the maximum response time of an individual repository (300 ms) by the number of repositories involved in the query – for example, the maximum response time for a query involving national repository A, the hub, and national repository B would be 900 ms. It should be noted that the system response time does not include the time needed by the query data to move from one repository to the other (which depends from the speed of the internet connection).

How will the identity, role and legitimacy of the users of the repository system be verfied?

It is the responsibility of the legal entity establishing and managing a repository to put in place appropriate security procedures ensuring that only verified users, i.e. users whose identity, role and legitimacy has been verified, are granted access to that repository.

In Article 38(1), does the sentence "with the exception of the information referred to in Article 33(2)" refer to data access only, or also to data ownership?

It refers to data access only.

In Article 38(1), what is the meaning of "information on the status of the unique identifier"?

The information on the status of the unique identifier includes whether the unique identifier is active or decommissioned, and in the latter case, the reasons or the decommissioning.

What is the purpose of the exceptions laid out to in the second sentence of Article 38(1) concerning access to the information referred to in Article 33(2) and the information on the status of a unique identifier?

Article 38 of Regulation 2016/161 regulates the ownership and the access of the data stored in the repositories system. It lays down the general rule and  in exception to that rule. Since the purpose of Article 38 is, inter alia, to protect the confidentiality of data in the repositories system, including commercially confidential data, as required by Article 54a(3)(b) and (c) of Directive 2001/83/EC, the exception should be interpreted narrowly. In particular, the use of the exception should be limited to those cases where access to the data is necessary to perform the verification/decommissioning operations required by the Regulation 2016/161, as explained in recital 38.

Is it possible to have multiple national repositories, multiple supranational repositories or a combination of national and supranational repositories serving the territory of a given Member State?

No. In accordance with Article 32, paragraphs 1 and 2, the territory of a given Member State should be served by the hub and either a national or a supranational repository connected to the hub.

For the purposes of the application of Articles 33 and 48 of Regulation (EU) No 2016/161, what is understood for 'medicinal products that have been released for sale or distribution'?

The text 'medicinal products that have been released for sale or distribution' refer to products which have been batch released in accordance with Article 51 of Directive 2001/83/EC. According to Annex 16 of the EU Guidelines for Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use "Certification by a Qualified Person (QP) and Batch Release", the process of batch release comprises of:  i. The checking of the manufacture and testing of the batch in accordance with defined release procedures.  ii. The certification of the finished product batch performed by a QP signifying that the batch is in compliance with GMP and the requirements of its MA. This represents the quality release of the batch.  iii. The transfer to saleable stock, and/or export of the finished batch of product which should take into account the certification performed by the QP. If this transfer is performed at a site other than that where certification takes place, then the arrangement should be documented in a written agreement between the sites.  Therefore, medicinal products that have been certified for release by a QP without including the safety features in their packaging before the 9th February 2019, may be placed on the market, distributed and supplied to the public until their expiry date.

How should the expression "marketing authorisation holder", as used in Regulation (EU) No 2016/161, be interpreted?

The term "marketing authorisation holder" is used in Regulation (EU) No 2016/161 to indicate holders of marketing authorisations in the sense of Article 6 of DIR 2001/83/EC.

Are parallel importers/distributors required to comply with Article 33 and upload, inter alia, a list of designated wholesalers into the repository system?

Parallel traders are obliged to comply with Article 33 and upload in the repositories system, inter alia, a list of designated wholesalers in the following two cases:

- If they hold a marketing authorisation in the sense of Article 6 of Directive 2001/83/EC.

- If they repack/relabel and place new safety features or replace safety features in accordance with Article 47a of Directive 2001/83/EC on the medicinal products they supply.

Parallel traders who repack/relabel their products and place new safety features or replace safety features in accordance with Article 47a of Directive 2001/83/EC on the medicinal products they supply have to comply with Articles 33, 40 and 42 of Commission Delegated Regulation (EU) 2016/161 as they are considered the "persons responsible for placing those medicinal products on the market" in that Member State.

In accordance with Article 33(1), the information laid down in Article 33(2) must be uploaded in the repositories system before the product is released for sale and distribution. Does this mean that the upload needs to take place before the Qualified Person (QP) performs the batch certification and thus the safety feature information relative to any manufacturing waste should also be uploaded in the system?

No. The information laid down in Article 33(2) of Regulation (EU) No 2016/161 needs to be present in the system at the time the batch is released for sale and distribution (see Q&A 7.13 for what is understood for 'released for sale or distribution'). It is acceptable to upload that information at such a time that the system is not burdened with information relative to manufacturing waste, i.e. (parts of) manufactured batches that have not been certified, provided that the upload takes place before the medicinal product is transferred to saleable stock.

Does Article 37(d) require that a national medicine verification organisation (NMVO) directly alerts the relevant national competent authorities, the EMA and the Commission about a falsification? Is there is a time limit for such alerting?

The use of the term "provide for" in Article 37(d) of Commission Delegated Regulation (EU) 2016/161 means that an NMVO has to ensure that the national competent authorities, the EMA and the Commission are informed. The NMVO can fulfil this obligation either directly or by ensuring this task is performed by someone else.

The NMVO should ensure authorities are informed as soon as it is clear that the alert triggered in accordance with Article 36(b) cannot be explained by technical issues with the repositories system, the data upload, the person performing the verification or similar technical issues.

Does Article 35(1)(i) of Regulation (EU) No 2016/161 prohibit wholesalers and persons authorised or entitled to supply medicinal products to the public from using the national medicine verification system's graphical use interface (GUI) to verify/decommission the unique identifiers on their products when their own software is not broken?

No. The use of the GUI by wholesalers and persons authorised/entitled to supply medicines to the public in circumstances other than the failure of their own software is not prohibited but is subject to the agreement of the national medicine verification organisation owning the GUI (in the absence of entitlement, the agreement of the system owner is necessary). See also Q&A 7.4.

Can a marketing authorisation holder delegate the uploading of the information laid down in Article 33(2) of Regulation (EU) No 2016/161?

Yes. Marketing authorisation holders (MAHs) may delegate the uploading of the information laid down in Article 33(2) to third parties by means of a written agreement between both parties. Please note that the MAHs can subcontract or delegate data uploading only to parties which perform the data upload by means of infrastructures, hardware and software which are physically located in the EEA. The MAH remains legally responsible for these tasks.

OBLIGATIONS OF MARKETING AUTHORISATION HOLDERS, PARALLEL IMPORTERS AND PARALLEL DISTRIBUTORS.

Can marketing authorization holders delegate the performing of their obligations under Articles 40 and 41 to a third party?

Marketing authorisation holders can (but are not obliged to) delegate part of their obligations under Articles 40 and 41 to a third party by means of a  written agreement between both parties. However, marketing authorisation holders remain legally responsible for those tasks. In particular, marketing authorisation holders can delegate the performing of their legal obligation under Article 40(a) and 40(b), as well as the decommissioning task in referred to in Article 41.

Situations arise where, for the same batch of product, competent authorities from different Member States issue different levels of recall, e.g. patient level Vs wholesaler level, or no recall at all. How will Article 40 of Regulation (EU) No 2016/161 work in this type of scenario?

Article 40 of Regulation (EU) No 2016/161 would not apply to recalls at patient level as the scope of the delegated act does not extend beyond the supply of the medicinal product to the end consumer. Where a medicinal product is recalled at pharmacy level in a Member State and at wholesale level in another, the marketing authorisation holder should customise the information he needs to provide in the relevant national/supranational repositories in accordance with Article 40(c).

Certain Member States have national systems managing recalls and withdrawals of medicinal products in place. Would it be possible to interface those national systems with the repositories system for the verification of the safety features?

The delegated Regulation No 2016/161 does not provide for the connection between the national systems for recalls/withdrawal of medicinal product and the repositories system. Such connections may be considered by the legal entities managing  relevant repositories in the repositories system, on a voluntary basis.

Are parallel importers/distributors required to comply with Articles 40 and 42 of Commssion Delegated Regulation (EU) 2016/161?

Parallel traders are obliged to comply with Articles 40 and 42 of Commission Delegated Regulation (EU) 2016/161 in the following two cases:

- If they hold a marketing authorisation in the sense of Article 6 of Directive 2001/83/EC.

- If they repack/relabel and place new safety features or replace safety features in accordance with Article 47a of Directive 2001/83/EC on the medicinal products they supply.

Parallel traders who repack/relabel their products and place new safety features or replace safety features in accordance with Article 47a of Directive 2001/83/EC on the medicinal products they supply have to comply with Articles 33, 40 and 42 of Commission Delegated Regulation (EU) 2016/161 as they are considered the "persons responsible for placing those medicinal products on the market" in that Member State.

In the case of free samples which are obliged by national law to include in their labelling the sentence “Free sample. Not to be sold”, can the obligation to bear the safety features be waived?

No. Article 41 of Regulation (EU) No 2016/161 requires that marketing authorisation holder intending to supply any of his medicinal products as a free sample shall, where that product bears the safety features, indicate it as 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. Consequently, free samples are in the scope of the Regulation and have to bear the safety features. 

Can marketing authorisation holders upload in the repositories system serial numbers that are never actually used as data elements of unique identifiers?

No. The purpose of the repository system is to the information on the safety features is contained. Serial numbers that are not actually used as data elements in unique identifiers should not be uploaded and stores in the repositories system as they represent a security risk for the system.

What are the obligations of operators who supply medicinal products on the ground of Article 126a (Cyprus clause) with regard to the safety features?

The term "marketing authorisation holder" is used in Commission Delegated Regulation (EU) 2016/161 and in Directive 2001/83/EC to indicate holders of marketing authorisations in the sense of Article 6 of the said Directive. Hence, the term does not apply to operators who distribute medicinal products on the ground of Article 126a. However, in order to handle medicinal products, those legal entities have to have a manufacturing authorisation and/or a wholesale distribution authorisation and/or a parallel import license. They are therefore subject to the obligations laid down in Commission Delegated Regulation (EU) 2016/161 for manufacturers and/or wholesale distributors and/or parallel importers/distributors.

In addition, should those operators place or replace the safety features in accordance with Article 47a of Directive 2001/83/EC on the medicinal products they supply, they need to comply with Articles 33, 40 and 42 of Commission Delegated Regulation (EU) 2016/161 as they are the "person responsible for placing those medicinal products on the market" in the Member State for which an authorisations in the sense of Article 126a was granted.

In the case of replacement of the safety features by parallel traders, can the decommissioning of the original unique identifier be carried out by the wholesaler from whom they receive the product?

No. The decommissioning of the original unique identifier must be performed by the parallel trader holding the manufacturing authorisation and replacing the safety features (Article 16 of Commission Delegated Regulation (EU) 2016/161).

LISTS OF DEROGATIONS AND NOTIFICATIONS TO THE COMMISSION.

Can marketing authorisation holders submit their proposals for amendments to Annex I of Regulation (EU) No 2016/161 to the Commission?

Only Member States notifications are taken into account for the purpose of establishing Annex I and II of the delegated Regulation, in accordance with Article 54a(2)(c) of Directive 2001/83/EC. Concerning Annex I, Member States may inform the Commission of medicinal products which they consider not to be at risk of falsification (Article 54a(4) of Directive 2001/83/EC).

TRANSITIONAL MEASURES AND ENTRY INTO FORCE.

For the purposes of the application of Article 48 of Regulation (EU) No 2016/161, what is understood for 'medicinal products that have been released for sale or distribution'?

See answer to question: For the purposes of the application of Articles 33 and 48 of Regulation (EU) No 2016/161, what is understood for 'medicinal products that have been released for sale or distribution'?

ANNEX I

How should the term "Kits" referred to in Annex I to Regulation (EU) No 2016/161 be interpreted?

The term "kit" is defined in Article 1(8) of Directive 2001/83/EC. It refers to "any preparation to be reconstituted or combined with radionuclides in the final radiopharmaceutical, usually prior to its administration".

Are fat emulsions used for parenteral nutrition and having an ATC code beginning with B05BA exempted from bearing the safety features?

Yes. Fat emulsions having an ATC code beginning with B05BA are included in the category "solutions for parenteral nutrition" listed in Annex I to Regulation (EU) No 2016/161. Such emulsions are therefore exempted from the obligation to bear the safety features.

ANNEX II

Are over-the-counter omeprazole products formulated as gastro-resistant tablets in the scope of Annex 2 and therefore required to bear the safety features?

No. Only over-the-counter medicinal products containing omeprazole 20 or 40 mg formulated as hard gastro-resistant capsules have to bear the safety features, as the two reported incidents of falsification that led to certain omeprazole products being added to Annex II concerned that specific pharmaceutical form of omeprazole.

Falsification of medicinal products

In recent years the pharmaceutical market has faced the rapidly growing and dangerous phenomenon of falsification of medicinal products.

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