Understanding quality assessments of imported Specials

Imported Specials are not evaluated for quality, safety and efficacy by the MHRA, so it is essential that the purchaser takes additional steps to gain assurance that the medicine

• is of appropriate pharmaceutical quality
• meets the purchasing specification and is suitable for the patient
• is labelled and packaged in a way that minimises the risk of medication error

Information to enable local quality assessments should be readily available from the supplier.

Obtaining quality information

The information needed depends on the type and origin of the imported Special. The sections below explain what information to request, why it is required and how it can be interpreted. Our quality information checklist for imported Specials can also be used or locally adapted to assist with this process.

If suppliers are unwilling to provide information consideration should be given to using an alternative supplier.

Evaluating imported Specials

The MHRA requires importers to notify them of the intention to import medicines that are unlicensed in the UK. The MHRA may object to importation if there is no evidence of Special Clinical Need, if there are concerns about the pharmaceutical quality of the medicine, or if there are clinical safety issues.

The MHRA does not approve requests to import and does not undertake a full assessment of quality and suitability, which is the responsibility of the purchaser and prescriber. They may either “not object” or may place conditions on importation.

Assurance of pharmaceutical quality

The first step is to gain assurance that the medicine meets standards of manufacturing that are equivalent to those for licensed medicines. For imported medicines, this means obtaining information about the supplier (importer), and the Marketing Authorisation (licence) of the medicine in another country.

Supplier information

The UK importer is usually unrelated to the manufacturer or Marketing Authorisation Holder (MAH) of the medicine, so as with the supplies of licensed medicines, it is essential to undertake checks on bona fides of the importer.

Importers of unlicensed medicines must have an appropriate MHRA licence, as explained in our article about purchasing Specials. Details of an importer’s licence can be checked on the MHRA’s website:

• For imports from an approved country, the site will be listed on the MHRA’s register of licensed wholesale distribution sites
• For imports from elsewhere the site will be listed on the MHRA’s register of licensed manufacturing sites

Marketing Authorisation information

The supplier (importer) should be able to state:

• The name of the Marketing Authorisation Holder (MAH)
• the country where the medicine has a Marketing Authorisation (licence)
• the Marketing Authorisation (or equivalent) number

This information enables the purchaser to identify whether the medicine is licensed in a “trusted” country, and therefore pharmaceutical quality is assured, or whether additional information is needed to gain assurance of pharmaceutical quality.

Our list of countries and their medicines regulator’s websites may be useful in checking the accuracy of the information provided.

Trusted countries

Trusted countries are:

• the approved countries listed in the Human Medicines Regulations, that is those in the EEA
• the countries with which the EU has a Mutual Recognition Agreement (MRA) (Canada, USA, Australia, New Zealand, Switzerland, Israel and Japan)

Although Great Britain no longer has MRAs with the EU or with any of the countries with which the EU has a MRA, GMP standards are currently aligned. Therefore, medicines licensed in any of these countries are assured to have been manufactured according to GMP standards that are equivalent to those required by the MHRA. These countries are listed on the European Medicines Agency website, together with exclusions for certain dose forms.

Note: Sometimes for multi-national companies, the MAH is based in a different country from that in which the medicine has a Marketing Authorisation. For example, the MAH for a medicine with a licence in Poland may be based in the Netherlands.

Other countries

The MHRA may permit importation from other countries, but additional work is usually required to gain assurance of suitability of the manufacturer and the individual batches.

• A Certificate of GMP Compliance from the competent authority (the equivalent of the MHRA) of a “trusted” country provides assurance that the medicine is made in a GMP compliant facility
• A batch-specific QP certificate or certificate of analysis provides evidence that the medicine meets its finished product specification.

A list of GMP compliance certificates can also be found on the EudraGMP website, and the websites of the competent authorities in the USA and Canada.

Note: Sometimes a medicine may be manufactured in one of the other countries (for example India) but have its Marketing Authorisation in one of the “trusted” countries (for example France). This means that the factory in which it is manufactured has been approved by the MHRA or its equivalent in one of the “trusted” countries.

Medicines not licensed anywhere

Sometimes, importers may be allowed to source and supply medicines that are not licensed anywhere. In general, they should be treated as though they were licensed in an “other” country.

In some cases, MAHs in the EEA countries may produce alternative packs in English livery. These are often referred to as “International”, “Emergency” or, since 2020, “Pandemic” packs. The medicines are identical to the licensed version, but packed in unlicensed packaging. The importer will be able to provide a letter from the manufacturer’s QP to confirm this.

Suitability for the patient

The next step is to check that the medicine is suitable for the patient in terms of formulation and presentation.

Medicine characteristics

If the medicine is licensed in another country, a SPC, PIL or other information leaflet is usually available from the importer or from the website of the relevant Competent Authority and can be found by using the medicine details listed above under “Marketing Authorisation information”.

The leaflets may not be available in English language, so it may be necessary to request a translation if the original leaflet language cannot be understood. If translation is needed the purchaser should use an accredited service and/or take steps to ensure accuracy of translation. There is no regulatory requirement for importers to provide a translation, and they may charge an additional fee for this service.

MHRA no-objection

The MHRA’s “no-objection” letter to the importer may place conditions on the importer, for example to notify the end recipient of specific contraindications to use, especially for active substances that are not licensed as medicines in any form in the UK. Importers will provide the letter, or the relevant wording from the letter, on request.

Packaging and labelling for safety

Medicines licensed in other countries may not be labelled in English, and may have labelling features that are unusual in the UK, which may present a risk in use. Artwork and photographs provided by the manufacturer enable a risk assessment prior to the decision to purchase.

Risks: some common themes

It is impossible to list all potential risks, but there are some common themes.

The most obvious concern is that the pack may not be labelled in English so important information cannot be easily identified.

Often the identity and strength of the medicine is clear despite the rest of the pack not being in English, but this is not always the case:

• The INN may not be used. For example “atracurium besilate” may be labelled as “besilato de atracurio” (Portuguese), or instead of “salbutamol”, products from USA may be labelled as “albuterol”.
• Conversely, the INN may be used instead of the BAN (“norepinephrine” instead of “noradrenaline”).
• Strengths/dose statements may use a comma instead of a decimal point, which may be mis-read. This is especially common on French and Canadian packs.

Even where the identity of the active substance is clear there may be other risks, for example:

• important warnings may not be in English or may not be present at all.
• expiry dates may not easily be understood. For example, German packs use “verwenden bis” (use until) rather than “exp”, and Canadian packs sometimes have a bilingual French and English month abbreviation rather than a month number.

Overlabelling and translations

If possible, imported medicines should be over-labelled in English and provided with a translated Patient Information Leaflet.

Some importers are able to provide this service, or alternatively overlabelling could be undertaken locally, either under Section 10 exemption or in a hospital Specials manufacturing unit licensed to undertake overlabelling.

The NHS Pharmaceutical QA Committee produced guidance on overlabelling and provision of translated information guidance on overlabelling and provision of translated information.

Our article and guidance document on overlabelling small batches of medicines may be useful for hospitals undertaking their own overlabelling under Section 10 exemption.

Concluding the assessment

Once all available information has been received from the supplier and evaluated, a conclusion can be made about the quality of the medicine. In some cases the information may be incomplete and only a partial conclusion can be drawn.

In all cases the conclusion should be documented and made available to inform the purchasing decision and, where necessary, local risk mitigation measures.

The other articles in this series provide more advice about the regulation of unlicensed medicines and governance principles for their use.

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