Medicines without a product licence must be treated differently at all stages of the supply chain. Recent RPS guidance puts the prescribing of specials back under the microscope.

 

Unlicensed medicines have an important niche in healthcare and have different manufacturing, prescribing and dispensing requirements to those products with a licence. Guidance and regulations from professional and regulatory bodies reflect these requirements.

The latest guidance for prescribers of specials was published by the Royal Pharmaceutical Society in April. This updated the resource first published in 2011 by the National Prescribing Centre and is intended to be used alongside the RPS ‘Professional guidance for pharmacists on the procurement and supply of specials’, which was published last year.

The updated guidance continues to be based around five principles that should be used to guide prescribing decisions (see panel) but now contains case studies that illustrate the challenges to be met in ensuring that patients receive optimal treatment.

The importance of ensuring that patients and prescribers are aware of the complexities and risks associated with transferring the prescribing and supply of specials across settings is given more emphasis in this latest guidance. Communication between prescribers and pharmacy colleagues is also emphasised.

Additional precautions for specials prescribing are highlighted in the case studies, and include: 

• Prescribers must be satisfied that there is sufficient evidence or experience of using the unlicensed medicine to demonstrate its safety and efficacy
• Specials have not been assessed by the regulatory authorities for safety, quality and efficacy in the same way as licensed medicines and they have no summary of product characteristics (SPC) outlining the dose, contraindications, storage conditions and side-effect profile
• Patient information leaflets are not routinely available for specials
• Specials can be obtained from a range of sources and are not all manufactured in the same way, so their quality, bioavailability and consistency can vary even where the same product is prescribed
• It can be difficult to identify a special at the point of prescribing
• When responsibility transfers from one prescriber to another, ensuring a safe and timely supply can present additional challenges for the prescriber and the supplying pharmacist. In cases where patient care is transferred between different settings and prescribing responsibility changes, potential risks increase, so there must be a planned transfer of information that ensures a safe, consistent and timely supply is maintained.

 

 

Although the new guidance is more comprehensive than the previous version, it should not be used in isolation, says the Association of Pharmaceutical Specials Manufacturers. While the advice references the MHRA’s Guidance Note 14 (a major regulatory standard for specials), it omits some of the detail.

For example, GN14’s hierarchy of risk sets out a preferential order for product choice, moving from UK licensed, to UK licensed off-label, to non-UK licensed, then UK-manufactured special (or other, but not stating what this is). The APSM would like to see this risk hierarchy re-introduced to the guidelines.

GN14 does not make provision or recommendations around dosage manipulation, or crushing tablets. The risks of crushing tablets are widely accepted within the sector and by regulators, although it is still sometimes recommended. The APSM does not believe that dosage manipulation should be encouraged.

Shared roles and responsibilities

All APSM member companies have customer services helpline teams and pharmaceutically trained specialists. Their role is to provide advice and support to pharmacists on all aspects of supply and manufacture. For example, a specials supplier may recommend an alternative formulation, or advise if a licensed product is available.

Although most pharmacists are confident in the support offered by manufacturers, many prescribing doctors are unaware of manufacturers’ role in helping to ensure the appropriate formulation is provided, says APSM chair Sharon Griffiths.

 

 

“Our members deal with up to 500 different formulation requests a day and we are uniquely qualified to advise prescribers and dispensers on many aspects of specials – sometimes that means changing a formulation or even recommending that a special is not appropriate. Our primary concern is the patient’s best interest.”

The APSM announced in September that it was broadening its membership criteria to include importers as well as virtual specials manufacturing organisations that own the rights to, and act as the first supplier of, a specials medicine in the UK. Its decision reflected the changing shape of the specials market, particularly over the past five years following the introduction of the Specials Tariff and a developing regulatory framework and professional guidance around specials.

“The decisions and actions we take now have implications for the entire supply chain and we need to give other organisations who have an interest in this market an opportunity to contribute to those decisions,” says Griffiths. “Our ultimate goal is to maintain a sustainable specials sector that provides high quality, safe medicines to patients. We are looking forward to working with more organisations who share this vision.”

 

Talking on the telephone

The General Pharmaceutical Council announced earlier this year that it had been contacted by the MHRA regarding the ordering of specials from manufacturers. The agency had received reports from firms that some pharmacists were not confirming telephone orders in writing which, it believes, increased the risk of atranscription error and therefore the wrong product being supplied to the pharmacy.

To avoid such errors, the MHRA requires specials manufacturers to get confirmation of orders in writing, for example by email, fax, or via an online ordering system provided by the manufacturer. RPS guidance on specials supply also recommends that, where necessary, the agreed formulation should be confirmed to the manufacturer in writing.

The APSM says most orders are not received in written form because pharmacists don’t work in this way, preferring to talk to a customer services representative/formulation expert for formulation guidance and immediate confirmation of acceptance of the order.

As soon as the order is confirmed, the manufacturer has to begin preparation in order to deliver within the expected timeframe, which is usually 24 hours. Mandatory written confirmation could lead to delays.

Most requests are for easily identifiable items that are unlikely to be mistaken for anything else, according to the APSM, and its members train their customer services teams to ensure that special clinical needs are understood and correctly identified.

“The effectiveness of this part of the quality system of each member company can be, and often is, verified during regulatory inspection,” says Griffiths. “Therefore, in most cases, a written request is not essential. While APSM members are happy to receive orders in written form, the expectation from our customers is that telephone orders are the preferred method because this has proved to be the most efficient and satisfactory service.”