The importance of testing “specials” and the process required
The production of special-order medication must be an efficient and fairly rapid process to get this form of personalised medicine to the patient as quickly as possible … and to keep costs down.
Here, Broughton’s Operations Manager, Beccy Bell, and Emmet Tilley, Quality Manager, explore manufacturing a “special” and the testing required for this type of prescription.
A special-order medicine or “special” is an unlicensed medicinal product that the Medicines and Healthcare products Regulatory Agency (MHRA) or a similar regulatory body only recommends to be prescribed if existing approved medications are unsuitable for a patient.
A “special could be a dosage form of an existing medicine that has not been approved for the market, a bespoke formulation of an existing medicine or a specially imported drug from another country that has not been approved for use in the UK.
According to the NHS Business Services Authority, it was expected that manufacturers would pay up to £1600 in the first quarter of 2023 for a set of ingredients for a special-order medicine prescription (before packaging, testing and the initial production process).
When would a special be prescribed?
A special is prescribed when an existing medication is not suitable for the patient. A good example of this is a paediatric drug; the licensed medicine might need to be at a lower dosage than has been tested and approved for adult use.
This means that the efficacy and effects of a lower dosage are unknown as the medication has not been licensed for use in this way. A special is required to meet the medical requirements of an individual or small group of patients.
Specials may also be required when a medication cannot be taken in the dosage form that it has been manufactured and licensed for. For example, a patient with a feeding tube or swallowing issues would be unable to take an oral solid dosage form and would require the formulation to be adapted to a liquid.
Changing the method of administration of the licensed medication can alter its efficacy and safety profile, so it must be manufactured and tested following the guidelines to produce a special.
If a patient is allergic to an ingredient in the licensed medication, then a bespoke formulation may be required. Adding or removing ingredients can alter how the drug is absorbed, distributed, metabolised and excreted (ADME) and, potentially, alter interactions between the drug excipients.
This new set of conditions would not have previously been tested, so must be reviewed before the patient who requires this personalised formulation is treated.
Requirements when manufacturing specials
As specials are unlicensed, any adverse reactions that the patient experiences would be the responsibility of the prescriber, reinforcing the importance of rigorously testing these medicines. A company may only manufacture a special if it holds a manufacturing license granted by the MHRA.
This guarantees that the sourcing of the ingredients, the product development, packaging, labelling, manufacturing and supply process all meet regulatory standards. The facility at which the manufacturing occurs must also hold a good manufacturing practice (GMP) certificate, demonstrating that appropriately qualified individuals supervise and oversee the manufacturing process.
Specials are usually manufactured for an individual or a very small group of people and, as such, do not go through the same testing and approval procedures as medicines for general population use.
To be licensed as a new drug, a medicine must gain approval through a five-step process: concept, preclinical research, clinical research, regulatory review and, after authorisation, post-market safety monitoring.
This is a lengthy process that can take years to complete. However, when prescribing a special, the patient usually needs the prescription as quickly as possible.
To undergo clinical trials, drugs must be tested on a minimum quota of test subjects — something a specials prescription would not meet because of the bespoke nature of the prescription.
With this being said, specials must still meet specific quality standards to be issued to a patient.
Once a special has been manufactured to meet the individual patient’s requirements, it must undergo testing procedures for quality control. The precise tests should be recommended by the prescriber, at which point manufacturers can reach out to a contract research organisation (CRO), such as Broughton, that will advise on the testing strategy and then conduct the relevant assays.
For mass-produced medicines, there will be a bank of historical data that analytical scientists can use as a reference point when reviewing test results for an approved medicine. For specials, however, this is not the case as they are usually created in small batches or as a “one-off.”
Testing request documentation provided by the prescriber will outline dosage, methodology and expected test results. Analytical scientists at the CRO must then identify these parameters through analytical testing, ensuring that the drug is safe for patient use.
To identify the active pharmaceutical ingredient (API), scientists will perform a high-performance liquid chromatography (HPLC) test to separate the ingredients. Analytical scientists will use known concentrations of the ingredients, outlined by the manufacturer, and compare this with the special formulation.
This allows for the test to verify the presence of the ingredient and the concentration. If this aligns with the parameters set in the testing request document, the drug can be prescribed to the patient.
Specials often have a shorter shelf-life than mass-produced medicines … and patients often already require the medication when the manufacturing process begins.
This makes it vitally important that the production and testing of these specials is done quickly, and that manufacturers and the testing facilities prioritise them compared with other products.
It is important that communication between the prescriber, manufacturer and the testing facility is clear and efficient. The prescriber and manufacturer should remain informed of the testing being done by the CRO and the time frame for result delivery.
If results do not meet the parameters set out in the testing document, it is important to determine how these deviations occurred and whether the formulation needs to be adapted to rectify the issues.
Special-order medicines or specials are a vital enhancement to our healthcare system and ensure that patients get the most suitable treatment for their individual requirements.
By collaborating with an experienced high-quality testing laboratory, drug manufacturers and healthcare providers can deliver these specialised treatments safely and to the same high-quality standards as licensed medicines.