Guidelines for repackaging and labelling of medicines

1.1 Legal Basis ..................................................................................... 3

1.2 Interpretation and Abbreviations ....................................................... 3

1.3 Purpose ......................................................................................... 3

1.4 Scope ............................................................................................ 3 2. PREREQUISITES .................................................................................. 4 3. REPACKAGING ..................................................................................... 5

3.1 Packaging material .......................................................................... 5

3.2 Bulk products.................................................................................. 5

3.3 Repackaging process........................................................................ 6

3.4 Establishing an expiry date ............................................................... 6

3.5 Assigning beyond-use-date (BUD)...................................................... 7

3.6 Repackaging of specific medicines ...................................................... 8 4. LABELLING OF MEDICINES .................................................................. 8 5. RE-LABELLING................................................................................... 10 6. RETENTION OF SAMPLES FOR REPACKAGED MEDICINES .................. 11 7. FINAL PROVISIONS ........................................................................... 12 8. REFERENCES .................................................................................... 12 9. DOCUMENT HISTORY ....................................................................... 12 MCA-GL-101, version 2 – 15 April 2020 Page 2 of 12 Guideline for Repackaging and Labelling of Medicines MCA The Gambia 1. INTRODUCTION

1.1 Legal Basis

1.1.1. The regulation of medicines in The Gambia is governed by the provisions and requirements of the Medicines and Related Products Act, 2014 (“Act”), by which the Medicines Control Agency (MCA) was established as the regulatory body for medicines and related products.

1.1.2. Part II, Section 4 (b) of the Act requires that the Agency regulates the manufacture, labelling, marking or identification of medicines.

1.1.3. The Medicines and Related Products Regulations, 2019 (“Regulations”) details the legal requirements.

1.1.4. The Agency charges non-refundable fees for repackaging as specified in the MCA Fee Schedule.

1.2 Interpretation and Abbreviations Interpretations and abbreviations contained in the MCA Glossary can be found on the MCA Website: www.mca.gm

1.3 Purpose 1 . 3 . 1 . In pursuance of the law this document provides guidance on the repackaging of medicines. Inappropriate packaging can lead to product mix-up, loss of product identity, contamination, cross-contamination and lack of stability data to support expiry dates. 1 . 3 . 2 . It provides also guidance on the content and format of the information on the label essential for identifying product, minimising medication errors and enabling customers and health professionals to select the correct medicine and its safe use.

1.4 Scope

1.4.1. This guideline applies to medicines as defined in the Act and the Regulations except of any radioactive medicines.

1.4.2. It applies to persons or entities engaged in repackaging and/or re-labelling of medicines (re-packager) and to manufacturers, marketing authorisation holders and importers of medicines.

1.4.3. It provides information to any person who removes medicines from their original manufacturer’s container-closure system and repacks them in a different container–closure system for resale or distribution. Note: It does not apply to health professionals who pack medicines for the direct supply to an individual customer.

1.4.4. Usually medicines are distributed in their original package provided and labelled by the manufacturer. In some instances, the manufacturer supplies medicines as bulk product and the medicines need to be repackaged for distribution. Other reasons may also necessitate the need for repackaging and/or labelling such as:  for convenience for the practitioner; MCA-GL-101, version 2 – 15 April 2020 Page 3 of 12 Guideline for Repackaging and Labelling of Medicines MCA The Gambia  to reduce waste and conserve drug supplies;  and in some cases to reduce costs. 2. PREREQUISITES

2.1. Repackaging and labelling of medicines are manufacturing processes which must be conducted in accordance with applicable Good Manufacturing Practice (GMP) requirements.

2.2. Repackaging and labelling are beyond the regular practices of a pharmacist. A person or entity conducting repackaging (re-packager) is required to register with the MCA by submitting an application form (MCA- F-403/01) to the Agency to receive a license for repackaging. The application form is available on the MCA website: www.mca.gm.

2.3. All packaging/repackaging operations are subject to the holding of a valid licence issued by MCA.

2.4. The environmental conditions during the packaging operation and storage should comply with the storage requirements as directed by the manufacturer, especially if the medicine requires storage at special temperature and/or humid conditions (see MCA Guideline for Storage and Distribution of Medicines and Related Products).

2.5. In all circumstances, repackaging must not have an adverse effect on the original conditions of the product.

2.6. The re-packager is responsible for ensuring the quality and stability of the repackaged medicine.

2.7. The re-packager has to ensure that an adequate control system is in place.

2.8. The re-packager is expected to ensure that appropriate analytical testing for all pertinent specifications, such as identity and strength of each active ingredient and the finished product tests were done and to maintain those records on a batch by batch basis for the repackaged product.

2.9. If the re-packager does not use a container–closure system equivalent to the manufacturer’s approved package system, the re-packager must generate stability data for the medicine in the new container–closure system to justify the expiry date assigned (see Section 3.4).

2.10. If the re-packager performs stability tests for the repackaged product records of such analysis on a batch by batch basis must be maintained.

2.11. Any alteration or manipulation of the repackaging process should be documented.

2.12. The concept of adverse effects on the original condition of the product as stated in Section 4.1.5 refers to the condition of the product inside the packaging. It is accepted that the condition of the product is not adversely affected when repackaging affects only the secondary packaging, leaving the primary packaging intact. On the other hand the original condition of the product inside the packaging might be indirectly affected where, for example:  The secondary packaging of the repackaged product, or a new set of user instructions or information, omits certain important information or MCA-GL-101, version 2 – 15 April 2020 Page 4 of 12 Guideline for Repackaging and Labelling of Medicines MCA The Gambia gives inaccurate information concerning the nature, composition, effect, use or storage of the product, or  An extra article is inserted into the packaging by the re-packager designed for the ingestion and dosage of the product that does not comply with the method of use and the doses envisaged by the manufacturer.

2.13. Since it is in the trade mark owner's interest that the consumer should not be led to believe that the owner is responsible for the repackaging, an indication must be clearly and legibly shown on the secondary packaging of who repackaged the product. 3. REPACKAGING

3.1 Packaging material

3.1.1. In accordance with the methods of use and administration of medicines, packaging materials, closures and containers vary a great deal and have to meet a wide variety of different requirements.

3.1.2. The manufacturer should include in the product information supplied to the re-packager specifications about the packaging materials as approved in the original application including its oxygen and light transmission characteristics in order to enable the re-packager to properly select an equivalent container–closure system.

3.1.3. A re-packager may or may not use the same container-closure system as the manufacturer.

3.1.4. If the container-closure system is different, the re-packager should use a container–closure system that is at least as protective as, or more protective than, the original container–closure system in terms of moisture vapour transmission rate (MVTR), oxygen transmission, light transmission, and compatibility of the container–closure system with the medicine (equivalent container-closure system).

3.1.5. System equivalency extends to any special protective materials, such as for light transmission, seals, or desiccants associated with the original container–closure system.

3.1.6. These values may be determined by the re-packager, or they may be obtained from the container–closure vendor for the specific container– closure system under consideration.

3.2 Bulk products The following criteria should be considered by the re-packager upon receipt of bulk prior to repackaging:

3.2.1. The bulk product should be distributed to the re-packager by the manufacturer in accordance with MCA regulatory requirements and accompanied by appropriate labelling, batch numbers and valid expiry date. The re-packager should also receive Material Safety Datasheet, Certificate of Analysis, and sample market labelling including product information inserts from the medicine manufacturer.

3.2.2. The bulk product should be received intact and undamaged and in appropriately labelled containers. MCA-GL-101, version 2 – 15 April 2020 Page 5 of 12 Guideline for Repackaging and Labelling of Medicines MCA The Gambia

3.2.3. The bulk product should undergo definitive organoleptic evaluations to confirm its identity (e.g. physical appearance, marking/s, colour, and odour) to confirm the labelling as described by the manufacturer.

3.2.4. Records should be maintained to verify the identity and quantity of each shipment received and to verify the batch number and bar coded information for each article shipment received. These records should also include the name of the manufacturer or supplier and the date of receipt.

3.2.5. The re-packager should store and maintain the bulk under storage conditions specified by the manufacturer.

3.3 Repackaging process The following criteria should be observed:

3.3.1. The re-packager operations should be conducted under specified storage conditions as instructed by manufacturer and that includes maintenance of required temperature in areas where repackaging is conducted.

3.3.2. It is acceptable to remove blister packs, flasks, vials, ampoules or inhalers from their original secondary packaging and place them into a new secondary packaging without affecting the original condition of the product inside the primary packaging.

3.3.3. The new secondary packaging must be fully compliant with the MCA requirements.

3.3.4. The re-packager must ensure that all information provided by the manufacturer has been affixed on the secondary packaging.

3.3.5. Written procedures should be in place and maintained to ensure that correct packaging materials are used for the repacked medicines and required conditions are met.

3.4 Establishing an expiry date

3.4.1. To establish the expiry date, stability studies are to be performed on the medicine in the original manufacturer’s package system. When a medicine is repackaged into a different container, the product’s expiry date may be altered or interrupted.

3.4.2. The re-packager may perform stability studies on the repacked products to establish an expiry date for the repackaged product based on scientific evaluation of the medicine in the equivalent container–closure system and complies with criteria established for equivalency. Establish equivalence means

3.4.3. The requirements stated in this guideline are met.

3.4.4. Specifications such as light transmission, seals or desiccants associated with the original container–closure system, or special protective materials in which the medicine is marketed, are the same. Comparison of container–closure systems may be done through stress testing of the product after storage under exaggerated conditions of temperature and humidity.

3.4.5. A re-packager should not use the equivalent container-closure system criteria to repackage medicines where such products have been identified by the manufacturer to have stability problems or if the manufacturer specifically states that the product should not be repackaged using the MCA-GL-101, version 2 – 15 April 2020 Page 6 of 12 Guideline for Repackaging and Labelling of Medicines MCA The Gambia equivalency container closure-system criteria. For e.g. the medicine is labile (moisture sensitive) and therefore should be dispensed only in the original manufacturer’s container. In this case, a re-packager needs to demonstrate the stability of the medicine in the re- packager’s container closure system.

3.4.6. Establishing the expiry date in the case listed in 5.4.5 is applicable to unit dose containers and multiple unit dose containers.

3.5 Assigning beyond-use-date (BUD)

3.5.1. In the absence of stability data, where a re-packager repackages a product into a unit dose or multiple–unit container without conducting appropriate stability studies to support expiry dates used, the period of use of the product is limited by the Beyond–Use Date for the repackaged product, which must be less than expiry date.

3.5.2. For unit–dose packaging the following criteria should be considered:  The original bulk container of the medicine to be used for repackaging has not been previously opened.  The contents of the original bulk product to be repackaged are repackaged at one time.  The unit-dose container meets testing requirements for either class A or B containers.  The unit dose container meets or exceeds the manufacturer’s specification for light resistance.  The conditions of storage meet the storage specifications as provided by the manufacturer of the bulk product. Where no specific conditions are specified, the product should be maintained at the required manufacturer’s temperature and in a dry place during repackaging.  The BUD used for the repackaged product does not exceed 6 months from date of repackaging.  The BUD does not exceed the manufacturer’s expiry date.  Documentation should be in place to show that the criteria above are met and to show the type of packaging material used. The testing for these materials should also kept on file.  The re-packager may not repackage if the manufacturer specifically states ”Do not Repackage”. However, the re-packager may affix the re- packagers labelling, if it is in accordance with MCA requirements and in agreement with the manufacturer of the product (see Section 6).  The re-packager may not use the expiry date and BUD interchangeably because they imply the presence or absence of stability testing respectively.

3.5.3. For multiple–unit packaging, the following criteria should be considered in assigning BUD:  The original bulk container of the medicine to be used for repackaging has not been previously opened.  The contents of the original bulk product to be repackaged are repackaged at one time.  The conditions of storage meet specifications of the labeling of the manufacturer’s bulk product. Where no specific storage conditions are MCA-GL-101, version 2 – 15 April 2020 Page 7 of 12 Guideline for Repackaging and Labelling of Medicines MCA The Gambia specified, the product should be maintained at the manufacturer’s requirement and in a cool and dry place during repackaging.  The type of container system used for repackaging should be the same type used by the manufacturer for the market container or equivalent.  The container meets or exceeds the test results of the manufacturer’s multiple-unit market container for light transmission.  The container meets or exceeds the manufacture’s container in special protective features, methods used to prevent leaching of container materials or the use of desiccants to maintain low moisture content (NB: desiccants should always be packed on top of drug product).  For all products, if the re-packager uses a container that is equivalent to the manufacture’s container or one that has a higher barrier, then BUD should be 12 months or manufacturer’s expiry date, whichever is less.

3.6 Repackaging of specific medicines

3.6.1. A re-packager is expected to repack highly sensitising products such as Penicillins, in facilities separate from those facilities used for other medicines. Moisture and temperature sensitive products

3.6.2. For products identified by the manufacturer as moisture and temperature sensitive, the re-packager must follow the specifications provided by the manufacturer during repacking and ensure appropriate distribution.

3.6.3. A re-packager may not repackage a moisture or temperature sensitive product if the manufacturer so instructs, except if the re-packager is only altering the labelling in accordance with MCA labelling requirements.

3.6.4. For moisture sensitive products, a higher–barrier container should be used for repackaging.

3.6.5. The re-packager should have proper documentation in place to show the higher–barrier protection of the container used.

3.6.6. The storage and handling of the product should meet the conditions specifically instructed by the manufacturer of the product.

3.6.7. The re-packager should label the container ”contains moisture sensitive products”. 4. LABELLING OF MEDICINES

4.1. The primary or secondary container of every medicine shall bear a clearly and legible written label in English language and include:  the generic name and where applicable the proprietary name of the medicine;  dosage form and strength (if not included in the name);  the approved name of each active ingredient and the quantity contained in a dosage unit, or per suitable mass or volume or unit;  in the case of medicines produced using genetic engineering, the active substance and the name of the genetically modified micro-organism or cell line used in its manufacture; MCA-GL-101, version 2 – 15 April 2020 Page 8 of 12 Guideline for Repackaging and Labelling of Medicines MCA The Gambia  in the case of herbal medicinal products, the identification of the active ingredient(s) given by the Latin botanical name in addition to the common name;  excipients that have a recognised action or effect as determined by the Agency and all excipients, if the medicine is injectable or a topical or eye preparation;  the presentation and pack size expressed in the appropriate unit or volume;  instructions for use prior to intake of the medicine where applicable;  the method, and if necessary route of administration by means of suitable words or abbreviations;  the batch or lot number of the medicine;  the manufacture and expiry date in a clear and visible font size;  the name and address of the manufacturer and marketing authorisation holder;  instructions for the storage with specific reference to the applicable storage temperature and other precautions required for the preservation of the medicine;  special or cautionary warnings as applicable;  nutritional information in case of nutritional supplements;  the words “for animal treatment only” and the species of animal for which the medicine is indicated, as applicable in case of veterinary medicines;  the registration number of the medicine allocated by the Agency (where applicable);  any specified warnings to be provided on the label as a condition of registration determined by the Agency.

4.2. The Agency may in respect of an interchangeable multisource medicine, determine additional information to be provided by the applicant.

4.3. The Agency may authorise the inclusion of any special information on the label of a medicine that is not required by this guideline to be included. Blister packs

4.4. If the primary container is a blister pack the minimum information to be displayed are as follows:  The generic name and where applicable the proprietary name of the medicine;  dosage form and strength (if not included in the name);  name of the marketing authorisation holder;  manufacture and expiry date; and  batch or lot number.

4.4.1. The name and strength of the medicine should appear over each blister or be oriented centrally across the pack. The particulars should remain MCA-GL-101, version 2 – 15 April 2020 Page 9 of 12 Guideline for Repackaging and Labelling of Medicines MCA The Gambia available to the user up to the point at which the last dose is removed from the blister pack.

4.5. The required information listed in section 4.1 should appear on the secondary container. Small containers

4.6. Where the labelling requirements cannot be legibly applied to a small primary container (nominal value of 10 ml or less), the following minimum information should appear:  generic name and where applicable the proprietary name of the medicine;  strength (if not included in the name);  route and method of administration, if necessary;  expiry date;  batch or lot number; and  contents by weight and volume of unit.

4.7. The required information listed in section 4.1 should appear on the secondary container. 5. RE-LABELLING

5.1. A re-packager shall provide appropriate labelling of the product in accordance with this guideline and with the labelling information corresponding to the market label that is used by the manufacturer.

5.2. All repackaged products should be labelled with beyond use date (BUD) in the absence of stability data, or with an expiry date in cases where stability studies have been performed on the product using the re- packager‘s container. The expiry date will ensure that the products meet applicable stability and quality.

5.3. The labels may be used on the secondary packaging as well as on the primary packaging.

5.4. The information being affixed to the package has to be of the permanent type in a tamper proof way e.g. any attempt to remove the label will create permanent damage to the packaging.

5.5. All information present on labels must be printed, using indelible ink. The stamping with ink is not allowed.

5.6. Labels must be large enough to contain the required information in a large enough font for adequate legibility and occupy a prominent place on the package.

5.7. The font is of great significance to legibility.  Simple fonts are suitable;  Narrow (condensed) or wide fonts should be avoided;  Clear areas around the text improve legibility;  The various text items should not therefore be located too close together; MCA-GL-101, version 2 – 15 April 2020 Page 10 of 12 Guideline for Repackaging and Labelling of Medicines MCA The Gambia  Fonts less than 7 points should be avoided; justification should be provided if smaller fonts are used.

5.8. If coloured text or background is used the greatest possible contrast must be aimed for.

5.9. Labels should not cover any existing information on the packaging, if the information being covered is not being replaced by the information being affixed e.g. batch number, etc.

5.10. The name of the medicine should appear on at least two non-opposing faces of the pack to aid accurate identification of the medicine.

5.11. All relevant information on labels must be in English.

5.12. Where the medicine is not labelled in English, a complete translation of the relevant information should be fixed to the secondary packaging of the product. If this is not possible, the English translation should be inserted in the package.

5.13. Where the patient information leaflet (PIL)/package insert is not in English, English translation should be inserted in the package.

5.14. The labelling information as stated in section 4 is required by the MCA.

5.15. Instead of ‘expiry date’ the ‘before use date’ might be applicable.

5.16. The warnings considered critical and included in the approved labelling following registration are to be included on the label of the repackaged product. 6. RETENTION OF SAMPLES FOR REPACKAGED MEDICINES

6.1. Samples needs to be retained and may be requested at any time by the MCA for e.g. analytical testing.

6.2. Samples may therefore fall into two categories:  Reference sample: a sample of a batch of packaging material and/or finished product which is stored for the purpose of being analysed should the need arise during the shelf life of the batch concerned.  Retention sample: a sample of a fully packaged unit from a batch of finished product. It is stored for identification purposes. For example, presentation, packaging, labelling, summary of product characteristics / patient information leaflet, batch number, expiry date) should the need arise during the shelf life of the batch concerned.

6.3. The reference and/or retention samples serve as a record of the batch of finished product and can be assessed in the event of, for example, a dosage form quality complaint, a query relating to compliance with the marketing authorisation/licence, a labelling packaging query, a Pharmacovigilance report or a stability query.

6.4. Reference and retention samples from each batch of finished product should be retained for at least one year after the expiry date.

6.5. The reference sample should be of sufficient size to permit the carrying out, on two occasions, of the full analytical controls on the batch in accordance with the Marketing Authorisation. MCA-GL-101, version 2 – 15 April 2020 Page 11 of 12 Guideline for Repackaging and Labelling of Medicines MCA The Gambia

6.6. The authorised person of the repackaging entity who releases a batch for distribution should ensure that all relevant reference and retention samples are accessible at all reasonable times.

6.7. Where the packs are not opened, only the packaging material used needs to be retained, as there is no or little risk of product mix up. Where the packages are opened, for example, to replace the carton or patient information leaflet, then one retention sample, per repackaging operation, containing the product should be taken, as there is a risk of product mix- up during the assembly process. It is important to be able to identify quickly who is responsible in the event of a mix-up (original manufacturer or assembler) as it would affect the extent of any resulting recall. 7. FINAL PROVISIONS

7.1. This guideline is the second version published by the MCA and will become effective on 15 April 2020.

7.2. The guideline will be reviewed within 5 years of becoming effective. 8. DOCUMENTS NEEDED FOR THIS GUIDELINES Document No Title (as referenced on the document) MCA-F-403/01 Application for Licensing as a Re-packager of Medicines - Form 9. REFERENCES  Medicines and Related Products Act, 2014  Medicines and Related Products Regulations, 2019  MCA Guideline for Storage and Distribution of Medicines and Related Products, 2017  WHO good manufacturing practices for pharmaceutical products: main principles, Annex 2, WHO Technical Report Series No. 986, 2014 10. DOCUMENT HISTORY Version # Implementation Date Reasons for Change 1 13 December 2017 New document 2 15 April 2020 Editorial changes, reference to the Regulations and labelling for registration included. MCA-GL-101, version 2 – 15 April 2020 Page 12 of 12