Medicines, medical devices and blood regulation and safety – guidance

Medicines: packaging, labelling and patient information leaflets

How to package medicines for sale and what information you must provide to consumers and healthcare professionals.

Overview

MHRA approves all packaging and labelling information for medicines sold in the UK including the information that must be provided. Medicines must include a patient information leaflet (PIL) if the label does not contain all the necessary information.

You should read the relevant European and UK legislation before making an assessment submission.

Guidelines on the readability of the label and package leaflet of medicinal products for human use is available on the European Commission website.

Labelling for medicines

Labels must be clear. Healthcare professionals and patients must easily be able to identify the medicine by the label.

You should use the letters CD in an inverted triangle if your product is a controlled drug. This isn’t compulsory but we encourage you to include this mark on your product’s labelling.

All information on packaging for licensed medicines must be printed directly on to the packaging. Over-labelling must not be used.

Sample packs must have ‘Free medical sample – not for resale’ or similar wording on the outer packaging. Over-labelling must not be used.

To register a common pack (a pack that can be supplied in more than 1 member state) in the UK and another member state, the licence details for the product must be almost identical. This does not apply to marketing authorisation (MA) numbers and addresses. If you need to update the packaging to include an MA number it should be submitted as a notification.

Safety features legislation

The European Parliament and Council has approved and published a Delegated Regulation (EU2016/161) in the Official Journal of the European Union. This supplements the Falsified Medicines Directive (FMD) and introduces two mandatory safety features that will allow medicines to be verified and authenticated.

These safety features are:

  • a unique identifier (a 2D data matrix code and human readable information) which will be placed on medical products that can be scanned at fixed points along the supply chain
  • tamper evident features on the pack

The unique identifier comprises:

  • a product code which allows the identification of at least the name of the medicine, the common name, the pharmaceutical form, the strength, the pack size, and the pack type
  • a serial number which is a numeric or alphanumeric sequence of a maximum of 20 characters randomly generated
  • a batch number
  • an expiry date

If the member state to which the medicine is being supplied requires it, the unique identifier will also need to include the national reimbursement number. The unique identifier must be printed on the pack in a 2D data-matrix code and be printed in a way in which the information can be read by the human eye.

The Delegated Regulation does not specify which tamper-evident feature should be used. The choice of tamper-evident feature to be used will be for the marketing authorisation holder (MAH) to decide. A European Standard is available which gives guidance on the types of tamper-evident features which could be considered by MAHs. This is titled ‘Tamper verification features for medicinal product packaging EN 16679:2014’.

The delegated regulation comes into force in the UK in 2019. MAHs will be required to place the safety features on the packaging of medicines which fall within the remit of the delegated regulation no later than 9 February 2019.

We are already receiving enquiries about how MAHs can tell us that they have taken the necessary steps to introduce the safety features on the packs of medicines impacted by the FMD. The European Commission has published advice to MAHs.

An implementation plan has been agreed and published for centrally authorised medicines on the website of the European Medicines Agency. A similar plan has been agreed by all member states for decentralised and mutual recognition marketing authorisations.

For nationally authorised medicines the MHRA will operate a similar scheme.

MHRA’s implementation plan

For new marketing authorisations submitted from April 2016 the revised QRD template should be used and will include reference to the placement of the unique identifier on the packaging. If the tamper evident features are included on outer packaging you do not need to include any information about this in the dossier. However, if the tamper-evident feature is added to immediate packaging and it affects the container-closure system you will need to include information in sections 3.2.P.2.4 and/or 3.2.P.7 of the Notice to Applicants Volume 2B. The term “new marketing authorisation” applies to abridged applications, change of ownership, line extensions and to new active substance applications.

For marketing authorisation applications already under assessment you should update the dossier during the procedure and before the application is granted.

For existing marketing authorisations granted before the publication of the Delegated Regulation you must update your dossier before 9 February 2019. Any regulatory submission which affects the product information can be used to tell us that you will be complying with the provisions of the FMD by the due date.

Submissions which affect the product information include renewal, variation type II, variation type IB, variation type IA, national 61(3) applications and BROMI 61(3) notifications. Normal fee arrangements will apply.

You can introduce the safety features at any time between approval of these submissions and the 9 February 2019.

If you do not have any other regulatory submissions taking place which will conclude by 9 February 2019 and which impact on the product information you will need to make a separate submission to the MHRA under Article 61(3) of Council Directive 2001/83/EC. Normal fee arrangements will apply.

MHRA, the Department of Health and the Devolved Administrations will continue to work with the European Commission and other member states on implementation plans for the new regulation. We will also be working with stakeholders throughout the supply chain to secure implementation within the three years.

Further guidance will be published as it becomes available.

Patient information leaflets (PILs)

Unless all the information is on the pack, all medicines must include a PIL, regardless of how patients get them. PILs must:

  • be easy to understand
  • not contain personal information that can identify an individual, including names of staff members or digital signatures

Each product authorised under a marketing authorisation must have its own leaflet as explained in our best practice guidance on patient information leaflets. Also see MHRA guidance document always read the leaflet - getting the best information with every medicine (PDF, 588KB, 173 pages) .

Our assessment of PILs includes a review of the font, colours, text size and layout of the information to assure the accessibility and readability of the statutory information.

We also have guidance on information in the PIL to address areas of potential misuse or abuse of over the counter (OTC) antihistamine sleep aid and laxative medicines.

Warnings on labels and leaflets for medicines

Labels must include warnings for safe use of the medicine. All products that contain paracetamol must include statutory warnings.

Additional warning statements must be included on the packaging of specified medicines.

You must also follow the guidance on the development of artwork for medicines for codeine and dihydrocodeine if applicable.

You should include these warnings when making an application to register labelling and/or leaflets with us. Deviations from the proposed wording must be fully justified in your submission.

Braille on labelling and in PILs

All medicines must have the name of the medicine displayed in Braille on the labelling.

You must make you PILs available for blind and partially-sighted patients.

Braille can appear on more than one side of a product’s carton. You must not use abbreviated Braille. Braille can appear on printed areas of the carton, as long as the underlying text is clear and visible.

You can submit changes to Braille on the labelling through a notification.

Guidance

We accept 2 Braille alphabets, both approved by the Royal National Institute for the Blind.

You must use the same Braille format for all your products.

Guidance concerning the braille requirements for labelling and the package leaflet

The British Standards Institute has guidance on the application of braille to the labelling of medicines.

Child-resistant packaging for medicines

Child-resistant packaging is used to make it difficult for young children to open medicines but easy for adults to use.

Packaging must be child-resistant if the medicine contains:

  • aspirin
  • paracetamol
  • more than 24mg of elemental iron

You don’t need to provide child-resistant packaging if your product is:

  • effervescent
  • in single dose units

An MA or variation must demonstrate that child-resistant packaging meets international standards for reclosable or non-reclosable containers:

  • reclosable packaging consists of container-closure systems that, when the closure is removed, permit access to more than 1 dosage unit and can be reassembled to form a child-resistant pack; reclosable containers must comply with international standard BS EN ISO 8317

  • non-reclosable containers are container-closure systems that once opened can’t be reassembled to form a child-resistant package such as blister packs; such non-reclosable packs must must comply with international standard BS EN 14375

The British Standards Institute has published a consumer’s guide to the standards for child resistant packaging.

If aspects of the packaging system change, it may be necessary to vary the MA and include additional evidence that the new packaging system has been shown to comply with relevant international standards.

Factors that can affect the child resistant properties of a container-closure system include:

  • change in foil material
  • change in blister material
  • change in adhesive
  • different orientation of blister pockets
  • different wadding materials in closures
  • inclusion of a liquid medicine in a container-closure system previously used for solid dosage forms

Submit information for full assessment

Product information which needs a submission for full assessment and approval must include change codes on the application form.

P1

First approval of mock-ups following a granting of a MA where only text-only versions were submitted and approved as part of the MA application.

P2

Changes to PILs which include significant changes to content and/or design and layout and must show continued compliance with user testing or bridging data. Changes to the leaflet in line with article 62 (allowing a MA holder to include extra statutory information on the label and in the PIL) also fall into this category.

P3

Changes to pack design must always be submitted for full assessment. Changes include either layout of the information or changes to graphics on the pack, or both. If a third party has pre-approved the changes they will be assessed in 30 days.

P4

Changes where we inform you about the change, for which a full application is needed. These may include but are not restricted to:

  • approval of artwork for a new own-label supplier not previously known to us
  • approval of artwork following a product name change where the changes proposed to the pack are considered to go beyond being relevant to the changes to the summary of product characteristics (SPC) being applied for
  • introduction of new safety information following consideration by an expert advisory committee
  • amendment of artwork following a complaint relating to patient safety

Changes which do not fall into 1 of the 4 categories above will not be accepted for assessment and will need to be re-submitted as a notification.

Notification scheme registration

You must inform us of all changes to the labelling and PIL of a product if those changes are not part of changes to the SPC.

If the proposed changes don’t need to be submitted for full assessment you must register the changes using the notification scheme.

The notification scheme is based on your declaration that the packaging meets legislative requirements and supporting documentation has been submitted.

Although you need to notify us of the amendment, you are responsible for the information on the packaging and in the PIL.

Fees

Fees for assessment of labels

Make a payment to MHRA

Make a submission or notification

Once you have received approval from us, you must introduce the changes within 3 to 6 months, unless you have been told to introduce the new information early because of safety reasons.

You can submit changes to labels, leaflets and packaging for the same product at the same time using a notification or for full assessment.

A separate application must be submitted for each product name. The submission must also include all affected MAs, particularly when a leaflet may be shared across several MAs.

A number of changes to labels and PILs can be made with each submission or notification using the same notification form or application form. You can also group changes that would have been a notification on their own with changes that need to be submitted for full assessment.

Format of data for submission

For a single MA, all label, leaflet and label-leaflet mock-ups must be submitted as a set of consolidated PDF documents. For a single product there could be 3 documents containing either all of the labels, all of the leaflets or all of the label-leaflets for all pack sizes and presentations of the product.

Where a single MA includes more than 1 product - branded or generic - the associated labels, leaflets and label-leaflet mock-ups for all pack sizes and presentations of each product must be submitted as separate sets of consolidated PDF documents.

To vary a label, leaflet or label-leaflet you must resubmit the entire PDF document which may contain labels, leaflets or label-leaflets that are not part of the variation. The new version of the data should be identified within the document.

The names of the PDF files should be in the format Label-Brand/Generic/Distributor name or Leaflet-Brand/Generic/Distributor name or Label-Leaflet-Brand/Generic/Distributor name. See out guidance on file naming requirements for labels, leaflets and label-leaflets (PDF, 67.1KB, 2 pages) .

The SPC and PIL will be published on GOV.UK so it is essential that any personal information about company employees, printing companies or their employees or any other similar information, is removed from all label, leaflet and label-leaflet mock-ups PDF documents.

Submission forms

Submission of applications must use the application form (MS Word Document, 34KB) in Word format or the portal form in PDF format. This form is not for changes accompanying a variation. See variations guidance.

Guidance is available to help you submit a change.

Submission of notifications for self-certified changes to labels and/or leaflets must use either the notification application form (MS Word Document, 324KB) in Word format or the portal form in PDF format.

If you are submitting electronically you will need to copy over the declaration statement and describe the changes applied for.

We acknowledge notifications within 14 days, after which any changes should be implemented immediately.

Complaints about labels, leaflets or packaging

We investigate complaints about the labelling and packaging of medicines made by patients, healthcare professionals or pharmaceutical companies.

We assess any complaint to decide if there is a safety issue or if there is no case to answer.

If a safety issue is identified the MA holder is required to respond – usually within 7 days.

We may identify other issues of regulatory compliance in addition to that raised in the complaint.

Investigations are usually completed in 30 days. It may take longer if the case requires detailed discussion or statutory action.

The complainant and the MA holder both receive a copy of the outcome report, which details the complaint and any action taken.

We do not reveal the identity of the complainant to the MA holder unless they are a competitor company.

UK and European regulation

UK regulation

The regulations for labelling and patient information leaflets are set out in The Human Medicines Regulation 2012 – Part 13.

European regulation

The regulations for labelling and patient information leaflets are set out in Title V of Council Directive 2001/83/EC which was amended by Council Directive 2004/27/EC and Council Directive 2010/84/EU.

The European Medicines Agency (EMA) has also produced guidance on labels, patient information leaflets and packaging.

Contact

To discuss the content of you application, email patient.information@mhra.gsi.gov.uk.

To discuss submitting your application to us, email Area4-renew-psur-piq-bromi-submission-queries@mhra.gsi.gov.uk.

To request further information, email Area4-renew-psur-piq-bromi-rfi-queries@mhra.gsi.gov.uk.