Documentation for Unlicensed Medicines: Your Questions Answered

Sourcing and supplying unlicensed medicines is our business. However, we realise that prescriptions for these products only account for approximately one percent of a pharmacy’s dispensing, so maintaining your knowledge of the regulatory requirements can be difficult.

In this edition of the Unlicensed Expert, we keep you up to speed by answering the documentation questions that many hospital pharmacy technicians and procurement staff ask us on a regular basis.

What is the difference between a Certificate of Analysis (CofA) and a Certificate of Conformity (CofC)?

Both the CofA and CofC play a key role in quality assurance. Hospital pharmacists should ensure that the unlicensed medicines they dispense are supplied with the appropriate CofA or CofC. Whether you are ordering a bespoke special or a batch-made product will determine which document you receive:

CofA

If a batch-made special is supplied, then a CofA should accompany the order. The CofA confirms that a sample of the final product has been tested and levels of active ingredients have been retrospectively verified.

A CofA should:

·         Confirm the laboratory / organisation issuing it

·         Be authorised by a suitably qualified person (i.e. Quality Assurance or Quality Control personnel) and include their signature

·         Show the specific batch number that matches the medicine supplied

·         Indicate exactly who performed the tests and the date

·         State the specification against which the tests were performed

·         Give the required test results and the actual results – a result in full or ‘complies’ may be shown

CofC

Bespoke specials, which are individual products produced as a one-off, should come with a CofC. The CofC confirms that the final product conforms to the specification supplied by the pharmacist. It should be signed by a suitably authorised person.

Bespoke specials also come with a batch number which is documented on the CofC. This allows traceability back to the manufacturing record and confirms the product was manufactured under a Manufacturing Specials (MS) license, in accordance with GMP.  

Why can’t I get a CofA with my imported medicine?

Imported medicines are licensed for a defined therapeutic purpose and manufactured under the marketing authorisation (MA) in their country of origin. As a licensed product in the country of origin they do not require a CofA. The MA holder will supply the documentation you would expect with a licensed product i.e. the Patient Information Leaflet (PIL) and the Summary of Product Characteristics (SPC). The importing unlicensed medicine supplier should also provide the batch number and if required the MHRA Import Licence number.

Products with non-English packaging, may be over-labelled by the supplier. Translated labelling and PILs help ensure the medicine is taken correctly by the patient.

The supplier must hold a Wholesale Dealer’s Licence if the medicine is being imported from another European Economic Area (EEA) country, or an MS licence if importing from outside the EEA.

What is a TSE certificate and when is it required?

Measures are in place to minimise the risk of Transmissible Spongiform Encephalopathies (TSE) entering medicines for human use. Importers of certain unlicensed medicines must comply with the TSE guidelines, which are provided by the MHRA.

Medicines aren’t supplied to pharmacies with any TSE documentation, but importers must ensure the manufacturer is compliant and keeps records to that effect.

Many products are acceptable by default:

·         Licensed products from within the European Union (EU) / European Economic Area (EEA)

·         Products manufactured and licensed in non EU/EEA countries with relevant Mutual Recognition Agreements (MRAs) with the EU (for more details see further below)

·         Products with statements of absence of TSE risk

Some products will require additional information if a manufacturer or supplier can’t satisfy a total absence of TSE risk materials in the product. The importer would only proceed to import the product having carried out a full and detailed risk assessment.

What is the difference between a Patient Information Leaflet (PIL) and a Summary of Product Characteristics (SPC)?

Every licensed medicine will come with a PIL in the pack, which is there to help the patient take their medication properly. The PIL is based on the SPC, which is used by healthcare professionals.

The SPC contains the full information about the medicine, including conditions relating to its use, side effects and precautions.

SPCs include:

·         The medicine’s licensed indication

·         Dosage and method of administration

·         The pharmaceutical form

·         Composition of active ingredient(s)

·         Pharmacodynamic and pharmacokinetic properties

·         Interactions, contra-indications and precautions for use

The PIL will be written in a way that makes it easier for the patient to understand why they are taking the medication, how to take it, what the possible side effects are and what to do if they have any concerns.

What are mutual recognition agreements (MRAs), and why are they important in unlicensed medicines?

A MRA is an international agreement between two or more countries to accept each other’s testing or certification (conformity) assessments.

MRAs allow EU member countries easier access to non-EU countries’ conformity assessment bodies (CABs). The MRAs provide lists of laboratories, inspectorates and CABs in the respective countries. This enables each party to ensure they are importing / exporting products that are compliant with the requirements of the country in which they will be used. 

MRAs contribute to quality assurance and patient safety in unlicensed medicines by providing clear information on compliance that helps to minimise risk. Importers of unlicensed medicines should prioritise products that comply most closely with EU requirements.

There are MRAs for EU countries importing from and exporting to Australia, Canada, Israel, Japan, New Zealand, the USA or Switzerland.

The MRAs for Australia, Canada, New Zealand, and Switzerland are complete however the MRAs for Israel, Japan and the USA are not and therefore added due diligence is still required for import from these countries for example TSE for imports from the U.S. For more information, click here.

Do you have a question?

The UL Medicines team is on hand to address any of your unlicensed medicines queries, helping to ensure you and your patients receive safe, high quality products. Call us free on 0800 112 3363 or email info@ulmedicines.co.uk.