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Published on 23 July 2018

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Implications of licensed standardised chemotherapy doses and their potential impact

Chemotherapy is the single biggest service area-spend within NHS England specialised commissioning. In 2016/17, NHS England spent approximately £1.7 billion on the routine commissioning of chemotherapy, with drug costs accounting for the largest proportion (80%).1
In 2015 Lord Carter published a report2 on productivity and efficiency in the NHS, identifying £5bn of efficiency opportunities resulting from unwarranted variation. The report outlined that potential savings could be made within the NHS, by improving workflow systems. The hospital pharmacy and medicines optimisation programme (HopMOp) was initiated following the recommendations of Lord Carter and it has undertaken various projects to be able to deliver the efficiency targets as set out in the report. Since 2016, NHS Trusts in England have seen the introduction of chemotherapy dose standardisation through dose banding.
Dose banding is the process by which calculated drug doses are grouped and set to a pre-defined dose. Each series of consecutive doses is the ‘band’ and the dose that they are rounded towards is the ‘banded dose’.3 Dose banding was launched for an initial 19 commonly used chemotherapy drugs to help the NHS achieve value through the ability to purchase standard off-the-shelf products.1 The NHS Pharmaceutical Quality Assurance Committee and the British Oncology Pharmacy Association (BOPA) have published a guide on sourcing ready to administer chemotherapy.3
NHS England has now published the first set of product specifications to support the production and supply of ready-made chemotherapy.4The addition of the dose-banded chemotherapy standardised product specifications means that hospitals should be purchasing exactly the same products from licensed suppliers, with no variation. Previously, each pharmacy department or regional purchasing team negotiated their own product specifications with the suppliers and there were variations across different areas in terms of the final product. Examples of variation include syringe sizes selected as final product storage, that is, should volumes between 25ml and 30ml be stored in 30ml or 50ml syringes, whether to remove the same volume of a fluid bag to match the amount of active drug being added, and what volume to state on the final product label.
These variations and others have led to a large product catalogue being present across suppliers to NHS hospitals. With a known capacity issue for specials manufacturing in both commercial and NHS facilities, removing variation helps to free up capacity by limiting the number of different items or presentations that need to be manufactured. Decreasing the variation and having set product specifications for dose-banded products helps to increase the need for those specific products and doses. This is needed if we are to take the next logical step of trying to get some of these products licensed. For there to be a financially viable product for pharmaceutical companies to consider investing in licensing, there first needs to be a market and sufficient need or usage to make it a worthwhile investment. National dose banding implementation and the production of product specifications information by NHS England are all initiatives that are hoped will encourage the development of licensed ready-made standardised chemotherapy doses. Table 1 outlines some of the advantages of dose banding for chemotherapy.
Table 1: Advantages of dose banding of chemotherapy

Benefits of licensed standardised doses

The benefits of having licensed standardised chemotherapy doses (LSCDs) are wide ranging. Unlicensed medicinal products are, by their nature, high risk. All injectable medicines must undergo a risk assessment to determine the level of risk (high–low) associated with the preparation of the injectable medicines. This allows for targeting of high-risk injectable medicines to be manufactured within pharmacy aseptic units.5 Cytotoxic injectable medicines are high risk in nature. NHS hospital aseptic units that are not licensed for manufacturing are operating under section 10 exemption of the Medicines Act 1968; this requires them to manufacture chemotherapy under the supervision of a pharmacist for all medications prepared.
Only patient-specific doses of chemotherapy in response to a signed prescription must be prepared and there is a maximum expiry of seven days for any product. The injectable cytotoxic and monoclonal antibodies prepared in hospital aseptic units therefore tend to be bespoke, have a fast turnaround, a short expiry, and fewer doses. This leads to a relatively high cost per dose manufactured, whereas in contrast standard dose and formulation, batch manufacture with a long expiry and high volume either by a ‘specials’ manufacturer or as a LSCD would lead to lower costs per dose manufactured.
By law, before a medicine can be placed on the market, it must be given a marketing authorisation (product licence) by a medicines regulator (the Medicines and Healthcare products Regulatory Agency in the UK).6 This process guarantees that all those involved in bringing products to market are accountable for their actions, ensure that processes, supplies and quality can be thoroughly monitored, and enable swift corrective action to be taken when needed. LSCDs would also have to undergo the rigorous process of obtaining a marketing authorisation.
Where LSCDs doses are used in accordance with their Summary of Product Characteristics, the liability would lie with the manufacturer. The introduction of LSCDs removes the need for managing the quality of unlicensed medications on receipt and it ensures that the product can be used as soon as it has arrived rather than having to go through local quality assurance process prior to release for general use.
Increasing the number of agents available as LSCDs frees up capacity through the supply chain. At a local individual hospital aseptic unit, this could free-up capacity to concentrate on the bespoke and highly specific items that are not suitable for licensing. It could potentially provide capacity to either start or expand a centralised intravenous additive service (CIVAS) within the hospital to improve quality of care in therapy areas other than cancer. With an increased number of new advanced therapy medicinal products coming to market, this will allow aseptic units to focus on these newer treatments, which tend to be high cost, highly complex, and having a short shelf life. It could also release time to be put into clinical trials and research, particularly with the recent national tender for seven genomic sites;7 this released capacity for units would greatly advantageous.
The Carter report states, “Overall, the standardisation of doses should reduce costs for providers, while releasing capacity within local units to support other activities and, in particular, clinical trial and research.”2 A greater number of licensed products would help to achieve this.
If many of the dose-banded items currently supplied within the commercial ‘specials’ sector were no longer needed (by the introduction of LSCDs), this would free up their capacity at a time when there is a struggle to meet the required demand. Initial finding from the recent NHS Improvement pharmacy aseptic service review7 revealed that the dose banded items outsourced to them in England tend to have low profit margins and are not allowing companies to invest in future investments and capital projects. Removing these would allow commercial suppliers to look at diversifying what they offer and providing different services to the NHS as required.
With licensed products should come less waste and longer times for use because they would have a much longer shelf life then items made in an unlicensed hospital pharmacy aseptic unit or a specials unit. In the event of a dose not being used for a particular patient, the LSCD could be returned to local stock holding and re-assigned to another patient.
Currently for the majority of dose-banded items outsourced to specials manufacturers, a minimum quantity (five of one particular drug and strength) has to be ordered. With licensed products, it is likely that minimum orders would not be needed. LSCDs could become part of a normal delivery from a wholesaler. Often orders placed to wholesalers are available the next day rather than the usual five-day turnaround from specials; this would allow a smaller stock holding as fewer items could be ordered (but more frequently) to meet the local need.
LSCDs would have product branding and design incorporated into their marketing authorisation applications. This process ensures that product licence holders ensure a risk reduction in their labelling and identification of different product strengths, and which would reduce the chance of picking errors within the pharmacy as the majority of products from a single specials supplier would usually look the same and might only be differentiated by reading the label for drug and dose.
At present, there is an individual licensed ready-made chemotherapy agent – Sun Pharmaceuticals’ gemcitabine – available on the market.8The product was introduced to the market in line with national dose bands. Doses currently range from 1200mg to 2200mg and each individual dose of gemcitabine (1200mg/120ml; 1600mg/160ml; 1800mg/180ml; 2000mg/200ml; 2200mg/220ml; a 1400mg dose will be available in Summer 2018) is presented in a different coloured outer box.

Our experience and implementation

 

At Milton Keynes University Hospital NHS Foundation Trust, we implemented the use of the licensed ready to administer gemcitabine bags and this has been beneficial in a number of ways. No longer having to manufacture on average 50 doses of gemcitabine per month has freed time to be spent on other activities. For example, our organisation was one of the initial UK NHS Trusts to be involved in the OCEAN clinical trial: a randomised, controlled, open-label study where one of the investigational medicinal products (IMPs), melflufen, required manufacturing under strict conditions owing to its high sensitivity to light and short expiry time.
The difference in time taken per one dose in our unit equates to 24 minutes of time saved (this is primarily on production tasks such as label and worksheet generation, spray and wipe sanitisation and manufacturing). This one product in a medium-sized district general has therefore saved 20 hours per month of staff time to be focused on other tasks. We have found the ordering, supply and use of the product very easy and straightforward. We are able to keep just a few of each strength in stock to limit the space required as we are confident of receiving deliveries at our stated times and there is no need to assess them against a product specification when they are received. Therefore, there is no delay in being able to use the doses. As previously mentioned, the five available strengths come in colour coded boxes to aid in picking the correct strength and in the last 12 months since using the product, there have been no reported picking or dispensing errors.

Conclusions

 

Table 2 lists the key positive implications for the introduction of LSCDs and their potential impact to NHS Trusts. At our facility, we have implemented the use of the licensed ready to administer gemcitabine bags and the benefits are evident.
Table 2: Key implications for the introduction of licensed standardised chemotherapy doses

Key points

  • The introduction of dose banding and the recent publication of product specifications by NHS England have set the ball in motion for the introduction of licensed standardised chemotherapy doses (LSCDs). The introduction of LSCDs  works hand in hand with product specfications and national dose banding.
  • With the introduction of LSCDs, aseptic services units will have increased capacity to expand their services to participate in more clinical research that require complex IMP support. It will also offer the opportunity to explore other activities that can be of benefit to patient services such as a CIVAS service.
  • LSCDs will reduce regional variation on product selection.
  • LSCDs will offer regional procurement centres the ability to negotiate better costs associated with the chemotherapy doses. Better buying power as a region, than an individual Trust.
  • LSCDs are products that patients and healthcare professionals can be assured have undergone the necessary rigorous tests to ensure product safety and stability.

References

1 NHS England Chemotherapy Clinical Reference Group. www.england.nhs.uk/commissioning/spec-services/npc-crg/group-b/b02/ (accessed May 2018).
Operational productivity and performance in English NHS acute hospitals: Unwarranted variations. An independent report for the Department of Health by Lord Carter of Coles. February 2016.
NHS Pharmaceutical Quality Assurance Committee with British Oncology Pharmacy Association. 2016. Guidance on managing the sourcing and supply of ready-to-administer chemotherapy doses for the NHS. A How to guide. Version 1 A.
4 NHS England. Dose banded chemotherapy product specifications. www.england.nhs.uk/commissioning/spec-services/npc-crg/group-b/b02/dose-… (accessed May 2018).
Beaney A. Quality assurance of aseptic preparation services standards. Part A. Chapter 3: Minimising risk with injectable medicines. 5th Edition. Royal Pharmaceutical Society and NHS Pharmaceutical Quality Assurance Committee; 2016.
Medicines and Health products Regulatory Agency. My medicine, marketing authorisation information leaflet. www.mhra.gov.uk/home/groups/comms-ic/documents/websiteresources/con02590… (accessed May 2018).
NHS Improvement. Pharmacy aseptic services review summary of key findings. March 2018. www.sps.nhs.uk/wp-content/uploads/2018/04/NHSI-Aseptic-Summary-and-Findi…(accessed May 2018).
Clinical Trials.gov. OCEAN. A randomised, controlled, open-label, Phase 3 study of melflufen/dexamethasone compared with pomalidomide/dexamethasone for patients with relapsed refractory multiple myeloma who are refractory to lenalidomide. EudraCT number 2016-003517-95. https://clinicaltrials.gov/ct2/show/NCT03151811(accessed May 2018).


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