Safety features for packages

The safety features consist of two parts:

• An anti-tampering device that makes it possible to see if the package has been opened.
• A two-dimensional bar code (2D code) that is unique for every single pack. The 2D code contains the following elements, a product code, expiry date and batch number and a code unique for each individual package. This unique code is contained in the national database and verification of each package should be made when the medicinal product is dispensed to the customer/patient.

The person that is dispensing a medical product to a patient, for example at a pharmacy, should verify that the anti-tampering device has not been broken and that the package is included in the database. When the package has been supplied to the patient the unique identifier should be decommissioned in the database.

If the package is not included in the database, this might be an indication of falsification. This must be investigated before the package can be supplied to the patient.

Packages released before February 9^th 2019 can be marketed without being required to have safety features.

European Medicines Verification Organisation (EMVO) is working with safety features in Europe whereas in Sweden it is e-VIS.

e-VIS is a non-profit association that runs the national database Swedish Medicines Verification System (SMVS).

EMVO is a non-profit association that through the European Medicines Verification System (EMVS) on a European level works for the implementation of the safety features. EMVO follows the regulation and ensures the realization of a functional, secure, compatible and cost-effective system in Europe.

There are regulations for the design and update of safety features.

The safety features consist of a unique identifier as a two-dimensional code (2D code) and an anti-tampering device.

In section 17 and 18 of the labelling texts for outer package it should be stated whether the unique identifier should be on the package or not. This does not apply for medical products that do not have a labelling text, for example parallel imported medical products.

1. The unique identifier is placed on the outer package of the medical product together with other labelling.
2. The unique identifier is printed directly on the outer package, and not on a separate label attached to the package. Exemptions from this rule can be granted by the Swedish Medical Products Agency, only for well justified cases, in order to secure the supply for a medicinal product when no other technical solutions exist.
3. In case the medicinal product doesn't have an outer package and it's not technically feasible to print the unique identifier directly on the primary package (e.g. on a bottle) the unique identifier can be printed on a label which is permanently attached to the primary package.
4. The product code and the serial number must be preceded by the headers/prefixes specified in the labelling text document, i.e. "PC" for the product code and "SN" for the serial number. The format of the product code ("GTIN" or "NTIN) is not accepted as header/prefix for the product code.
5. The 2D barcode may contain other information than product code, serial number, batch number and expiry date if the Swedish Medical Products Agency approves it. Current EAN code can still be printed on the package. Please note, however, that the EAN code must match with the human readable codes and the 2D barcode.
6. Packages with the safety features shall not be labelled with any other visible 2D barcode other than the 2D barcode carrying the unique identifier for the purpose of their identification and verification of their authenticity.
7. Since a few years back the Ministry of Commerce and Industry of India has required that all packages of medicinal products that are manufactured in India and exported from India must bear a unique identifier as a 2D code. Since 9th of February 2019 these Indian codes are no longer accepted on packages for human medicinal products that are released in Sweden. Please note that the Indian code cannot be accepted on packages for human medicinal products for which safety features are not required either, e.g. most medicinal products not subject to prescription. Packages from India may be exported to Sweden without bearing the Indian code.

1. When an anti-tampering device is required it should be placed on the outer package. In case the medicinal product does not have an outer package, the anti-tampering device is placed on the primary package.
2. The anti-tampering device must not impair readability, cover any information or damage the labelling when broken. The anti-tampering device should be designed so that it can be seen if the package has been tampered with, without removing for example a lid.
3. The readability of the batch number and the expiry date should normally not be affected by the breaking of the anti-tampering device, but if the 2D code only include product code, serial number, batch number and expiry date it can be acceptable that the readability for the human eye of product code and serial number are affected by opening of the package. Batch number and expiry date in the human readable form should not be affected by the breaking of the anti-tampering device.
4. In case no visual changes has been made on the mock-ups at the introduction of anti-tampering device there is no need to submit mock-ups to the Swedish MPA, neither for approval nor for information. This could be the case when the anti-tampering device consists of a gluing, a sticker or an adhesive tape. The sticker or tape must not contain any text, logotype or other images.
5. If the introduction of dotted lines (marking out perforations) is the only change made there is no need to submit mock-ups to the Swedish Medical Products Agency neither for approval nor for information. This is given that the dotted lines are not placed over current text or images. At the next submission of revised mock-ups for approval or for information the dotted lines marking out perforations should be included. If there is any informative text or symbol to the perforation, mock-ups should be submitted for approval.

For medicinal products not required to have anti-tampering device it can be introduced on a voluntary basis.

To introduce an anti-tampering device voluntary, a notification should be submitted to the Swedish Medical Products Agency.

Voluntary anti-tampering device applies for:

• Prescription medicinal products or product categories listed in appendix I of the EU regulation.
• Non-prescription medicinal products or product categories that are not listed in appendix II of the EU regulation.

A notification for packages currently not having any anti-tampering device should be submitted before it is introduced on the outer package. In case the anti-tampering device is removed this should be applied for before removing it.

Application form for voluntary anti-tampering device

Application form for voluntary anti-tampering device, in Swedish

Mock-ups only needs to be submitted to the Swedish Medical Products Agency if the readability on the package is affected by applying or removing the anti-tampering device, and in that case as a “for information only” notification in a separate submission and not with the form.

Parallel imported medicinal products

The requirements of safety features for prescription medicines apply also for parallel imported and parallel distributed medicinal products.

Parallel imported medicinal products can either be re-labelled or repacked in new packages. Under certain circumstances it can be allowed to break an anti-tampering device when relabelling and then seal the package with a new equivalent anti-tampering device. An anti-tampering device is regarded as equivalent only if:

• The new anti-tampering device seals the package completely and covers all visible signs of the original broken anti-tampering device
• The exchange of anti-tampering device is made according to good manufacturing practice.
• The re-packer has verified the authenticity for the unique identifier and that the original anti-tampering device is intact before the package is opened.

This is in line with article 47a in Directive 2001/83/EG.

Relabelling and repacking are not clearly regulated, but some regulations are of importance for assessment. In article 18, 24 and 30 of EU regulation 2016/161 it is stated that if a manufacturer, wholesaler or someone authorized or entitled to dispense medical products to the general public have a reason to believe that the package has been tampered with, they are not allowed to release, supply or dispense the product.

The anti-tampering device from the source country should be designed so that it is possible to verify if the package has been broken or tampered with. The anti-tampering device should, when it is broken or tampered with, leave traces on the package that cannot be concealed afterwards. The possibility to re-seal the package with a new anti-tampering device at parallel importation might be limited. To fulfil the requirement that the package should not show any signs of having been opened it might be necessary for the parallel importer to re-pack the medicinal product to a new package with safety features.

This also applies for parallel distributed medicinal products to be supplied on the Swedish market.

The requirements of safety features for prescription medicines apply also for parallel imported and parallel distributed medicinal products.

Parallel imported medicinal products can either be re-labelled or repacked in new packages. Under certain circumstances it can be allowed to break an anti-tampering device when relabelling and then seal the package with a new equivalent anti-tampering device. An anti-tampering device is regarded as equivalent only if:

• The new anti-tampering device seals the package completely and covers all visible signs of the original broken anti-tampering device
• The exchange of anti-tampering device is made according to good manufacturing practice.
• The re-packer has verified the authenticity for the unique identifier and that the original anti-tampering device is intact before the package is opened.

This is in line with article 47a in Directive 2001/83/EG.

Relabelling and repacking are not clearly regulated, but some regulations are of importance for assessment. In article 18, 24 and 30 of EU regulation 2016/161 it is stated that if a manufacturer, wholesaler or someone authorized or entitled to dispense medical products to the general public have a reason to believe that the package has been tampered with, they are not allowed to release, supply or dispense the product.

The anti-tampering device from the source country should be designed so that it is possible to verify if the package has been broken or tampered with. The anti-tampering device should, when it is broken or tampered with, leave traces on the package that cannot be concealed afterwards. The possibility to re-seal the package with a new anti-tampering device at parallel importation might be limited. To fulfil the requirement that the package should not show any signs of having been opened it might be necessary for the parallel importer to re-pack the medicinal product to a new package with safety features.

This also applies for parallel distributed medicinal products to be supplied on the Swedish market.

• Mock-ups for information only should be sent to the Swedish Medical Products Agency by email. Please clearly specify the case.
• If the changes on the mock-ups are not fulfilling the requirements to be sent for information only they should be submitted separately for assessment and approval or as a variation of parallel import.

More information about mock-ups can be found on the webpage Submission of product information.

Questions about mock-ups for ongoing procedures are sent by email to

RIC@lakemedelsverket.se

General questions about mock-ups are sent by email to

registrator@lakemedelsverket.se

References to appendixes, articles and the EU-regulation in the answers below refer to Commission delegated regulation (EU) 2016/161.

Regulation

What is the purpose of regulation?

The system that has been introduced in the entire EU, is intended to make an already safe distribution of medicinal products even more safe. It is required that almost all medicinal products for prescription and some non-prescription medicines should have an anti-tampering device so that it can be verified that the package has not been opened and a 2D code as a unique identifier. All 2D codes should be included in a national database. All pharmacies are connected to the national database and all national databases in the EU are linked to a central hub.

What does this mean for the individual patient?

Patients will have safe medicinal products just as before. If a package cannot be found in the data base at the pharmacy this needs to be investigated to ensure that the medicinal product is not a falsification. During this investigation time the pharmacy cannot sell the medicinal product.

Are there many falsified medicines on the Swedish market today?

No, only at a few occasions there has been suspected falsifications of medicinal products in Swedish pharmacies and the healthcare system. However, it is an increasing problem worldwide. To prevent the risk of falsified medicines on the European market the European countries have decided to introduce this system.

What is the responsibility of the Swedish Medical Products Agency regarding safety features?

The Swedish Medical Products Agency (Swedish MPA) approves almost all medicinal products and their packages. The medicinal products not approved by the Swedish MPA are approved by the EU commission. The Swedish MPA will assess the safety features for medicinal products. The Swedish MPA also supervises manufacturing, distribution and pharmacies. By this responsibility the authority makes sure that everyone fulfils the requirement of control and decommissioning etc.

Which medicinal products should have safety features?

Only medicinal products intended for humans are affected by the regulation. Safety features should be included for prescription medicinal products not included in Annex I and non-prescription medicinal products included in Annex II.

Medicinal products released before 9^th February 2019 do not need to have safety features even if they are sold after 9^th February 2019.

Decommissioning

If the medicinal product is supplied by a healthcare facility, who should decommission the medicinal product?

As a general rule it is the healthcare facility that should decommission the package. It is though possible for an outpatient pharmacy or a wholesaler to decommission the package in the name of the healthcare facility. To be able to do that there should be a written agreement between the health care facility and the one who is making the decommissioning and there must be no sale of the medicinal product after it has been decommissioned. In the agreement the responsibilities for those involved should be clearly stated.

If it is an outpatient pharmacy or a wholesaler that decommissions the medicinal product the pharmacy/wholesaler should document the information regarding who it has been sold to, and information about the medicinal product through the unique identifier to fulfil the requirements enabling traceability.

What applies if the healthcare providers are going to use the medicinal product for production of extemporaneous products?

According to Guideline Concerning the Swedish MPA’s Provisions (LVFS 2005:11) on Labelling and Package Leaflets for Medicinal Products, an outpatient pharmacy or a wholesaler can decommission medicinal products that are sent to a health care facility according to article 25.2. This means that the decommissioning is made before delivery to the hospital. It applies irrespective of whether the medicinal product is delivered to a medicinal product supply or if it is to be used for extempore production, as long as the extempore production is made within the health care facility and that there is no sale of the product between decommissioning and extempore production or administration to the patient.

What applies if the healthcare providers are going to dispense the medicinal product by automated dose dispensing in the hospital?

An out-patient pharmacy or a wholesaler can decommission the medicinal products that are delivered to the healthcare facility according to what is stated in article 25.2. This means that the decommissioning is made before delivery to the hospital. It applies irrespective of whether the medicinal product is delivered to a medicinal product supply or if it is to be used for dispensing the medicinal product by automated dose dispensing, as long as this is done within the health care facility and that there is no sale of the product between decommissioning and automated dose dispensing or administration to the patient.

Who can make an agreement about decommissioning if there is a central agreement about purchase of vaccines from a wholesaler/marketing authorization holder (MAH)?

If there is a central agreement to purchase a vaccine the agreement can include decommissioning of the medicinal product in connection with sale. It should be clear which healthcare providers that are utilizing the agreement, both from the perspective of the health care provider and the one inactivating the medicinal products for them. Traceability of the buyer and information about the medicinal product by the unique identifier should always be verifiable. The part that has entered the agreement with the vaccine company must not itself be a healthcare provider.

Which person at the company can make an agreement about inactivation?

This is governed by the civil law legislation, which mean that it can differ between companies. The one who is an authorized signatory is entitled to sign agreements for the company. According to civil law it is possible to delegate the authorized signatory.

Can an agreement about inactivation be made at the local pharmacy or only centrally if a pharmacy chain makes an agreement of inactivation?

The company/pharmacy chain must decide who has the right to make an agreement for the company and if this should be for only a local pharmacy or if it should always include all pharmacies within the company. It is important to remember that the traceability always must be ensured, so that it is clear which pharmacy that has inactivated the medicinal product and for the account of which health care provider.

Special regulations for Sweden

A member state can According to Article 23 introduce regulations stipulating that a wholesaler can inactivate the medical products in connection with sale to a number of recipients. Have these regulations been implemented in Sweden?

To ensure the distribution of medicinal products that are needed for defence or preparedness reasons there has been a regulation in the Swedish MPA’s Provisions (LVFS 2014:8) about wholesale trade with medicinal products. Wholesalers should verify and inactivate medicinal products with safety features before they are delivered to Armed Forces, the police or other state agencies that have stockpiles of medicinal products for civil protection or catastrophic events.

The 2D code

Is there a national cost reimbursement number or other national number that makes it possible to identify the medicinal product (NN in section 18 of the labelling text) in Sweden?

No, NN is not applied in Sweden. NN should not be mixed up with the Nordic Commodity number “Varunummer (Vnr)”

Can the 2D-code contain other information than product code, serial number, expiry date and batch number?

Yes, in addition to the mandatory information that should be included in the unique identifier, information that is currently permitted in grid codes (such as a QR code) may also be included in the 2D code. The information must be approved by the Swedish MPA and be in accordance with the requirements of our regulations on labelling and package leaflets for medicinal products. This means, among other things, that the information must be consistent with what is stated in the SmPC and be of benefit to the patient. Nor must it be of an advertising nature.

The 2D barcode may contain other information than product code, serial number, batch number and expiry date if the Swedish MPA approves it. Current EAN code can still be printed on the package. Please note, however, that the EAN code must match with the human readable codes and the 2D barcode.

Can there be both an EAN code and a 2D code on the same medicinal product package?

Yes. For the time being, both an EAN code and a 2D code may be printed on the same package of medicinal products provided that the EAN code complies with the product code in the physically readable information and the 2D code. As it has been shown that it can sometimes be more difficult to scan the 2D code than the EAN code, the two codes should not be placed next to each other on the packaging.

Can the previous 2D code on medicinal products produced in or exported from India remain on packaging in parallel with the European 2D code?

Since 9 February 2019, packages for human medicinal products with Indian codes are no longer allowed to be released in Sweden or any other EU Member State. The Indian codes are therefore also not accepted on packaging for medicinal products for humans, for which safety features are not a requirement, for example most of the prescription free medicines.

However, packages containing the Indian Code released before 9 February 2019 will be available in pharmacies until the expiry date indicated on the packages and may be sold to customers. There is no distinguish between an Indian 2D code and a European 2D code. Pharmacies can access a list of the medicines concerned via e-VIS.

Expiry date

Can the expiry date in the 2D code differ from the expire date specified in format readable to the human eye?

The information in the 2D code may differ from the information that is readable to the human eye, but the specified date should be the same in both places. In the expiry date in format readable to the human eye, the month is indicated in letters or in two digits ("MM"). The year is given in four digits ("YYYY"). The expiry date is always the last day of the specified month, as shown in the package leaflet. Note that it is not acceptable to enter the last day of the month with two zeros ("00") in the format that is readable to the human eye as this can be misunderstood by users.

Example:
The printed expiry date in formats that are legible to the human eye is expressed as MM-YYYY or month-YYYY.
In the 2D code, the expiry date is expressed as YYMM00 or YYMMDD*

(* DD = last day of the month)

Both formats mean that the medicine in the package can be used until the last day of the month.

Must the date uploaded in the European Hub have to match exactly with the date specified in the 2D code?

Yes - The information uploaded in the European Hub must match exactly with the date specified in the 2D code. If the expiry date is specified in the format YYMM00 in the 2D code, YYMM00 should be uploaded in the hub. If the expiry date is instead specified in the Format YYMMDD in the 2D code, the YYMMDD should be uploaded in the hub.

What happens if the expiry date uploaded in the EU Hub doesn't match the expiry date in the 2D code?

If the information in the hub does not match the expiry date specified in the 2D code, an alarm (an alert) will be triggered when the packaging is scanned by an end user (pharmacy/wholesale/healthcare). That is, the YYMM00 does not match exactly with The YYMMDD and an alarm is triggered. The same applies if the DD in the 2D code is not the same DD that is uploaded in the hub. The information in the hub must be corrected before the package can be dispensed.

Should end-user systems make any interpretation of the format when scanning the 2D code?

No. It is important that end-user scanners, software and IT systems do not make their own interpretation of the expiry date. Exactly what is in the 2D code should be read and sent into the hub. For example, if YYMM00 is specified in the 2D code, this must be exactly what is passed in the call to the hub. If the end-user system makes interpretations of the date before it is submitted, this may cause alarms that mean that the package cannot be dispensed.

Safety seal

Can the package for a prescription-free medicinal product have a safety seal after 9 February 2019?

Yes. A company can choose to voluntarily put on a safety seal on a prescription-free medicinal product, which many of them already have. However, in these cases, a notification of voluntary safety sealing is required to be submitted to the Swedish Medical Products Agency.

The legislation applies only to medicinal products intended for humans, which means that medicines for animals can be provided with safety-sealed packaging without notification to the Swedish Medical Products Agency.

Exemption

Is it possible to apply for an exemption from the Swedish MPA in order to be able to release packages without safety features after 9 February 2019?

As a general rule, all prescription medicinal products for humans must have safety features if they are not listed in Annex I. This possibility could be raised when there is a serious shortage situation and where the need for medicinal products cannot be met by any other medicinal product. Exemption from the requirement can therefore only be granted in the event of extreme emergency.

Does the Swedish MPA have register of product number and serial number for medicinal products affected by the safety features requirements?

No, the Swedish MPA does not keep such a register. However, there is information in VARA on which medicinal products should have safety features. Please note that medicinal products released before 9 February 2019 do not need to have the safety features even if they are sold after 9 February 2019.