Understanding quality assessments for UK manufactured Specials

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 medicinal form (sterile, aseptically prepared, non-sterile, solid dose, liquid etc.). The sections below explain what information to request, why it is required and how it can be interpreted. Our quality information checklist for UK manufactured 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 manufacturer information

In the UK, Specials may be manufactured only by the holder of a Specials Manufacturing Authorisation (MS) from the MHRA. MS holders are inspected by the MHRA, but the medicines that they make are not evaluated by the MHRA. This is legally the responsibility of the purchaser and prescriber.

The assessment of pharmaceutical quality is based on knowledge of the manufacturer and details about the medicine itself.

The supplier should provide the manufacturer’s name, address and MS licence number. This enables the purchaser to check on the MHRA’s website that the manufacturer has a Specials licence that covers the type of product to be purchased.

The supplier of the medicine may not be the manufacturer, but the supplier should always be able to provide information about the manufacturer to the purchaser.

Evaluating product information

Specials manufacturers should be able to provide a finished product specification that provides the information required to assess the suitability of the medicine. Additional information may need to be requested. The information available from importers will depend on the status of the medicine in the country of origin.

Description

This should include all the critical information about the medicine:

• generic name of active ingredients
• pharmaceutical form
• strength and/or concentration
• quantity or volume per container
• the route of administration for which it is formulated

All excipients should be stated and the final presentation described so the purchaser can check that the medicine matches the purchasing requirement and is suitable for the patient.

If there is a BP Monograph, the medicine should comply with the Monograph.

Packaging, labelling and leaflets

The labelling of the UK manufactured Special should always be reviewed to identify any risks in use. As with all medicines, they should be labelled with all the critical information shown above, and they should bear the MS licence number of the manufacturer, a batch number and the expiry date as minimum.

Owing to the nature of the products, UK Specials may be relatively poorly differentiated from each other by their labels so additional steps may need to be taken to prevent errors in use. NHS England has produced guidance for the NHS about the labelling and packaging of Specials which, although not mandatory for commercial manufacturers, is best practice.

In some cases the manufacturer may agree to customer-specific labelling or to amend the label in the interest of patient safety.

UK manufactured Specials do not have SmPCs and cannot be marketed with any claim to treat specific conditions, so the supply of PILs is unusual. If patient advice leaflets are needed these are usually provided by the prescribing clinic.

Method of manufacture

Understanding how a product is made helps the purchaser understand the risks associated with purchasing a particular UK manufactured Special. For example

• an oral liquid may be made as a single item/pack from crushed solid dose forms, or in bulk from a raw active pharmaceutical grade ingredient with testing of samples for dose uniformity before filling the batch. In this example, batch preparation provides a higher assurance of dose uniformity and so is generally preferable.
• An injectable medicine may be prepared aseptically from sterile starting materials, or it may be made from separate ingredients and then terminally sterilised in its final container (for example by heat). Where thermal stability allows, a terminally sterilised medicine is usually preferred, as this gives the highest degree of assurance of sterility when administered to patients.

Shelf life and justification for the shelf life

The manufacturer should be able to provide a stability statement explaining the rationale for the assigned shelf life. This should be specific to the formulation and presentation of the medicine to be supplied, and is applicable to both bespoke, patient-specific medicines and those made in large batches.

Additional information about requirements placed on Specials manufacturers is in Section 3.6 of  Guidance for ‘specials’ manufacturers.

Product approval

Understanding arrangements for testing and approval of the final product before release for sale also helps the purchaser understand the risks associated with purchasing a particular Special.

These arrangements may be documented in the product specification, might take the form of a Certificate of Analysis that states all the release requirements, or may be part of a SOP, policy or a batch manufacturing record.

Some UK manufactured Specials are tested for conformity to the specification before release. In general, this is applicable for batched products with shelf lives beyond 89 days. The MHRA’s expectations about this are detailed in Section 3.6 of  Guidance for ‘specials’ manufacturers. Purchasers should check that the manufacturer’s arrangements for testing the product are compliant with the guidance.

Certification

UK manufactured Specials are usually provided with a Certificate of Conformity (CoC) or Certificate of Analysis (CoA). This may be a hard copy, or a web link may be provided.

Certificates of Analysis should be available for all batches of medicines that have undergone finished product testing. Each should state the acceptance criteria, the results, a pass/fail conclusion and should be signed by the Head of Quality or their delegate. A certificate without stated acceptance criteria should be challenged.

For medicines that do not undergo finished product testing the manufacturer should be able to provide a batch-specific Certificate of Conformity. This confirms that the batch has been made in accordance with its specification, under the manufacturer’s MS licence, and provides evidence that the batch has been released by the Head of Quality or their delegate.

In both cases the signature may have been added electronically.

Sample certificates provided for the quality assessment should be retained so that every subsequent batch specific certificate can be compared with it to ensure that there have been no changes.

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 the principles for their use.

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