Information on changing the secondary packaging of a medicinal product

The need to change the secondary packaging of a medicine may arise in the following cases:

1. Parallel import of medicinal product
2. Correction of certain quality defects of a medicinal product
3. Allowing the release of individual batches of a medicinal product in foreign language packaging (foreign language batch)
4. Medicinal products in a specific therapeutic programme
5. Repackaging of a medicinal product due to specific marketing authorisation changes (e.g., changes requiring the recall of batches of the medicinal product manufactured before the change, extension of the shelf life, safety changes)

In the above cases, it is acceptable to breach the original packaging of the medicinal product, remove the original secondary packaging, and insert the product in a new secondary packaging or add information to the original packaging in the form of a reprint or stickers that are required and approved by SÚKL. This process may also include, if necessary, the replacement of the package leaflet of the medicinal product. The above steps may only be carried out by manufacturers of medicinal products with a manufacturing authorisation at least within the scope of 1.5.2 ‘secondary packaging’, under Section 62(2) of Act No 378/2007 Coll., on Pharmaceuticals and on Amendments to Some Related Acts (the Act on Pharmaceuticals), as amended (hereinafter referred to as the Act on Pharmaceuticals) and have to be carried out following the principles of good manufacturing practice (GMP). When repackaging, particular emphasis is placed on compliance with the following GMP principles:

• Creation of specifications for new printed materials.
• Initial inspection of printed materials against specification.
• Establish written instructions for repackaging, including the method of handling the medicinal product from the removal of secondary packaging until the time of new adjustment and its identification during all manufacturing operations.
• Creating a new batch number for a repackaged product, e.g. by adding a prefix or suffix to the original batch number.
• Documenting the inspection of the condition (cleanliness) of work areas and production lines before the start of packaging (absence of materials unrelated to the repackaging of a given batch).
• Application of continuous production controls.
• Minimising the risk of product mix-ups through appropriate procedures and controls (e.g. using validated computer systems) and appropriate training of staff involved in repackaging.
• Keeping sufficiently detailed records of repackaging production activities with emphasis on material balance.
• Collection of retention samples of the repackaged medicinal product in accordance with Appendix 19 of the European Commission’s Good Manufacturing Practice Guidelines (in Czech language only)
• Determination how a qualified person certifies a repackaged batch of a medicinal product.

1. Parallel import of a medicinal product

A list of manufacturers involved in the repackaging carried out with the parallel imported medicinal products is included in the application for a parallel import authorization. For these manufacturers, the applicant shall provide evidence of the authorization to manufacture medicinal products or evidence of compliance with GMP requirements (post-inspection certificate issued following the Compilation of Union procedures on inspections and exchange of Information, as amended). Following Section 45(7)(b) of the Act on Pharmaceuticals, the holder of a parallel import authorization is obliged to label the repackaged medicinal product and to use only the services of the manufacturers of the medicinal products for repackaging and to notify the Institute in advance of any changes to these manufacturers (Section 45(7)(b) of the Act on Pharmaceuticals). The qualified person of the manufacturer who repackages a medicinal product in the context of a parallel import shall certify, following the provisions of Section 66(3) of the Act on Pharmaceuticals, that each batch of the repackaged medicinal product has been manufactured following GMP principles and corresponds to the manufacturing documentation of the parallel imported medicinal product.  The name and address of the manufacturer who repackaged a particular batch of the medicinal product shall be indicated in the package leaflet. Manufacturers carrying out repackaging in the case of parallel imports shall comply with the requirements of Article 64 and the Act on Pharmaceuticals.

Information for holders of a parallel import authorisation concerning the protection features can be found at the link provided (in Czech language only):

https://sukl.gov.cz/leciva/upozorneni-pro-drzitele-povoleni-soubezneho-dovozu-tykajici

2. Correction of some quality defects of medicinal products

If the sufficiency and appropriateness of the measures proposed by the marketing authorisation holder of the medicinal product due to a quality defect of the secondary packaging or package leaflet is agreed by the quality defects department (hereinafter referred to as the QD department), the product may be repackaged/repaired if the following conditions are met:

• No change of the marketing authorization has been approved between the certification of the defective packages and the certification of the repaired packages.
• A draft notification of the recall of the defective batch from distributors/healthcare facilities/patients will be sent to the QD department (zavady@sukl.gov.cz ) for approval. This information will then be published by the QD department on the Institute’s website (does not apply to medicinal products that have not yet been placed in circulation).
• The repair may be carried out directly by the medicinal product manufacturer. If this way is impossible, the repair may be carried out by the manufacturer (holder of the manufacturing authorisation for the medicinal product which authorises at least the secondary packaging of medicinal products – the supplier) who has a technical agreement with the manufacturer responsible for certification and release (the commissioner of the repair) following Chapter 7 of the European Commission’s guidelines on good manufacturing practice.
• In the case of the recall of a defective batch, a prefix or suffix, e.g. by placing a letter or number after the slash added to the original batch number, should be added to the original batch number when correcting it, to be able to distinguish between defective and corrected packages.
• The repaired batch will be certified by a qualified person of the manufacturer of the medicinal product (the sponsor of the repair) and a copy of the batch release certificate will be provided to the QD department.

In case the marketing authorization holder is interested in correcting the defective batches, the following documents and information will be sent in advance to the QD department either electronically to zavady@sukl.gov.cz, in writing to the Institute’s mailroom or the Institute’s data box (more here):

• Name of the medicinal product, including batch number and number of packages
• A copy of the quality control document and certificate for the batch concerned
• Description of the quality defect
• Sample of the medicinal product in its pre-repair state
• Proposal for a solution to a quality defect
• Proposal for a repackaged sample of the medicinal product to allow the solution proposed by the marketing authorisation holder to be assessed and agreed by SÚKL
• A contract between manufacturers if the repair will not be carried out by the manufacturer of the medicinal product in question
• Name of the entity that will repair the quality defect

The start of batch repair is possible only after approval by the QD department.

Once the repair is complete, the repaired batch can only be re-released after approval/release by the QD department (zavady@sukl.gov.cz ). Therefore, the marketing authorization holder will send the following to the QD department:

• Sample of the medicinal product after repair
• A copy of the certificate issued by a qualified person of the manufacturer of the medicinal product concerned, including the overall repackaging balance

The QD department will assess the repair and re-release of the repackaged batch. If everything meets the requirements, the batch can be released into circulation. If the batch has been recalled from the market before repackaging, a notice of the re-release of the repackaged batch is published on the Institute’s website.

In the case of medicinal products for which the obligation to affix safety features (SF) to the packaging applies under Commission Delegated Regulation (EU) 2016/161, the following procedure must be followed in accordance with Section 64a of Act No.378/2007 on Medicinal Products and on Amendments to Some Related Acts (the Act on Pharmaceutical):

• In case of use of a new outer packaging of the medicinal product:
• If a new unique identifier (UI) is used for repackaged medicinal product packs, the original UI has to first be verified and then decommissioned from the repository system and the outer packaging provided with the new 2D code and UI data elements. The new UI must be uploaded to the repository system.
  The packaging must be provided with a new anti-tampering device (ATD).
• If the original outer packaging of the medicinal product is used:
• The outer packaging of the medicinal product must (re)place the new 2D code and UI data elements through relabelling operations, first verifying and then removing the original UI from the repository system and uploading the new UI to the repository system. For the placement of the UI via a relabel, the recommendation in the European Commission’s Q&A must be followed
  • If, for example, the package leaflet is changed and the ATD has been broken, the outer packaging must be provided with a new equivalent ATD that overlaps the original ATD. The original UI shall be used. Again, the recommendations in the questions and answers of the European Commission must be followed.

3. Allowing the release into circulation of individual batches of a medicinal product in foreign language packaging (foreign language batch)

If the Institute, following Section 38 of the Act on Pharmaceuticals and Section 3(6)(b) of Decree No. 228/2008 Coll, on the marketing authorisation of medicinal products, as amended, permits the releasing on the market of individual batches of a medicinal product in foreign language packaging, the marketing authorisation holder shall ensure that they are supplemented on the outer packaging in an appropriate manner, for example by means of a reprint or sticker, with the essential particulars corresponding to the conditions of marketing authorisation in the Czech Republic (which shall include, in particular, the name of the product, strength, pharmaceutical form, pharmaceutical substance, marketing authorisation holder, storage method and expiry date), if these cannot be deduced from the foreign language text. If there is no outer packaging, all above mention information should be placed on the inner packaging. Information on the method of modification of the outer/inner packaging shall be detailed by the applicant in the application. Any changes to the packaging shall be carried out by the holder of the manufacturing authorisation for the medicinal product at least to the extent of modification of the secondary packaging. In addition, each package shall be provided with approved package leaflet information in the Czech language (e.g. by attaching the leaflet information to the outer packaging with tape or a rubber band). More information can be found here. Information on safety features on the packaging of a medicinal product imported as a foreign language batch can be found here (in Czech language only).

4. Medicinal products in a specific therapeutic programme

The repackaging of the medicinal product shall be the responsibility of and provided by the originator of the specific therapeutic programme. Repackaging shall be carried out by an entity holding a manufacturing authorization for medicinal products at least to the extent of secondary packaging treatment. The Ministry of Health sets out the conditions for the submitter in the specific Decision, usually requiring a marking on the outer packaging of the medicinal product (by printing or sticker) with the text: ‘Přípravek je používán v rámci specifického léčebného programu. / The product is used in the context of a specific therapeutic programme’.  Information on the safety features on the packaging of a medicinal product imported under a specific therapeutic programme can be found here (in Czech language only).

5. Repackaging of the medicine due to some variations in the marketing authorization

The medicinal product may be repackaged in connection with the following changes to the marketing authorisation:

• Variation concerning the change of legal status of the medicinal product
• Variation in marketing authorization as a result of the referral procedure
• Extension or reduction of the shelf life

If the Marketing Authorisation Holder requests the QD department (zavady@sukl.gov.cz) to repackage the secondary packaging/packaging leaflet (or primary packaging) in cases above, this is possible under the following conditions:

• The relevant variation in marketing authorisation did not concern changes in the manufacturing processes of the medicinal product, the composition of the medicinal product, the method of its storage

Repackaging (replacement of the existing secondary packaging and package leaflet with secondary packaging and package leaflet corresponding to the relevant variation in the marketing authorisation, or repair of the primary packaging, as appropriate) may be carried out by the original manufacturer or by an entity which holds a manufacturing authorisation for medicinal products at least to the extent of the secondary packaging and with which the manufacturer of the medicinal product responsible for certification has concluded a technical agreement in accordance with Chapter 7 of the European Commission’s Good Manufacturing Practice Guidelines. In the case of a batch recall, a prefix or suffix shall be added to the original batch number at the time of repackaging, e.g. by placing a letter or number after the slash added to the original batch number, in order to be able to distinguish between the original and the repaired packages. For the first two marketing authorization changes above, the shelf life of the batch will be maintained.

The extension of the shelf life of batches of medicinal products manufactured before the approval of the relevant variation is the responsibility of the marketing authorization holder and may be carried out subject to the following conditions:

• The change of the expiry date has been pre-approved under the variation approval procedure.
• The manufacture of batches of medicinal products for which the shelf life is extended was carried out under the same conditions as for medicinal products for which a long-term stability study was submitted as part of the variation application
• All packages of the medicinal products in question were demonstrably stored in the prescribed manner
• Measures are taken to ensure that packages of the same batch of medicinal product with different expiry dates do not occur in the healthcare field
• The new expiry date is clearly marked on the inner and outer packaging
• The relabelling of all packages of the medicinal product is carried out by the approved manufacturer under the conditions of good manufacturing practice
• the marketing authorisation holder informs the State Institute for Drug Control in writing of the extension of the expiry date for batches of medicinal products manufactured before the approval of the relevant variation in the marketing authorisation (including the batch numbers and number of packages of medicinal products for which the expiry date will be extended)

Written information on the extension of the shelf-life of a medicinal product manufactured before the approval of the variation of the marketing authorization and any questions and initiatives on this issue are received and handled by the QD Department (zavady@sukl.gov.cz ). The procedure and conditions in these cases are similar to those in point 2 above.