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Bevan Exemplar Cohort 8 Projects

Batch manufacture of OPAT products by Pharmacy Technical Services

Chris Goodwin

Betsi Cadwaladr University Health Board

OPAT is Outpatient Parenteral Antimicrobial Therapy; this is the provision of intravenous antibiotics to patients in their home through the use of elastomeric ambulatory infusion devices. These treatments are offered to patients requiring long term antibiotic therapies for a range of indications.

Within Wrexham, OPAT is being carried out on a small number of suitable patients, approximately 2 per month. The devices required are sourced from an external manufacturer at great cost and the logistical implication that once a suitable patient is identified the manufacturer must be notified before 12:00 PM for a 48-hour delivery (Monday – Friday), pay a significant fee for next day delivery or face a delay in the start of this treatment. This is a limiting factor in the expansion and wider adoption of the OPAT model within YMW and across BCUHB.

This project looks to bring the production of OPAT devices in house to Pharmacy Technical Services. Where the latest aseptic manufacturing technologies will be used to develop and produce a high volume batch manufactured product.

By manufacturing these products in-house, the following benefits will be realised:

•           Elimination of the minimum 24-hour lead-time

•           Cost reduction

•           Enhanced patient experience

•           Improved patient flow

•           Efficient production

Once this initial product is in place, the OPAT programme can be expanded to a wider range of patients and indications leading to a paradigm shift in the way antimicrobial therapies are offered by BCUHB.

Poster Presentations

We presented at the Quality Assurance Symposium in September 2023 and the Clinical Pharmacy Congress in November 2023. Take a look at the poster presentations below.

Summer 2023 Update

A very busy summer in lab with staff holidays, retirements and illness has meant that it has not be possible to provide monthly updates but that doesn’t mean we haven’t been hard at work trying to bring the OPAT project to life!

The HPLC method has now been successfully validated and has been shown to be stability indicating across the range of flucloxacillin products we may look to expand into in the future. Developing this method will enable us to carry out a stability study on the devices we make and potentially enable us to extend the shelf life from the manufacturer stated 2 weeks, up to 4 weeks (or even longer). This will be beneficial for the Technical Services and Pharmacy as it will enable the finished products to be kept as stock items within the pharmacy reducing the lead time to treatment further.

Discussions with elastomeric device suppliers have been fruitful with much interest gathered in the project and a robust supply chain for the elastomeric devices set up. This is essential for the longevity of the project and puts us in a good place (if and) when the service goes live and is scaled up.

All of this has meant that we now in a position to produce our test batches within the laboratory. We will be 6 batches in the next week to enter into our stability study which will also serve as a manufacturing validation. These batches will be produced in a range of elastomeric containers and across a range of temperatures that the products will encounter throughout their lifecycle and use:

  • 4oC – refrigerated storage
  • 25oC – ambient temperature, during transport and use
  • 32oC – elevated temperatures experienced during use

Within BCUHB the project has started to generate interest with the other hospital sites in North Wales now interested in becoming involved in the service and its use in the Winter contingency is being explored. Whilst the update may seem short, a lot of the ground work has now been completed to set up a robust, efficient and prudent service going forward.

If anyone is in Newport and attending the NHS QA Symposium at the end of September, we will be showing off the work that we have been doing over the past 6 months with a poster in the exhibition hall where we will be more than happy to talk your ear off about how brilliant OPAT and Technical Services are!

May 2023 Update

Another busy month with the project picking up a lot of momentum and good progress being made. A few key milestones of the process have been reached, these include:

1. Sourcing of materials – suppliers of all of the ingredients and consumables needed to produce the OPAT devices have been identified and the materials bought in. This proved somewhat trickier than initially anticipated but now trial batches of the OPAT devices can be manufactured and tested in the laboratory.

2. Determination of a production method – using the automated systems available to us a production method have been generated. Even in these early stages, the benefits of automation can be seen with the taken to produce four devices being approximately 20 minutes. This does not include the preliminary spray and wipe stages currently being used, but is a significant improvement in the current 5-hour manufacture time!

3. Analytical method development – an important part of this project is the improvement in the shelf life of the products being produced. In order to do this, stability studies will need to be carried out by the QC department. A key piece of equipment within the laboratory that will enable us to do this is the High Performance Liquid Chromatography (HPLC) machines, which require bespoke methods based on the molecules being studied. A stability indicating method has been devised and is now under-going validation.

With these 3 milestones being reached, we are in a promising position to move forward with the process validation stage of the project throughout June and July.

Outside of these milestones, some workshops and engagement sessions were held with the aseptic operators, who will eventually be the ones operating these devices routinely. These provided the team with the chance to use the equipment, provide some insight on how they could work, and get a better understanding of the project-taking place. These were a positive step in generating enthusiasm and awareness for the project in the wider department.

April 2023 Update

April has been a busy month for the project with numerous meetings with suppliers for the elastomeric devices and filling machines, as well as equipment deliveries and installations.

We now have on-site an IMF Medimix compounder and a Grifol’s Gri-Fill 4 filling machine, so development work can begin in earnest on the manufacturing method we will adopt going forward. There are plans that next month demonstrations will be provided to the Aseptics production team to really bring them on board with the project and show the benefits that semi-automation can bring to their workday.

Most excitingly the first doses of OPAT were prepared by technical services in Wrexham!! A course of 8g flucloxacillin was prepared manually for a patient and highlighted the need for automation to ensure the success and feasibility of this project. The following key learning points were taken from this initial production run:

1. Manual preparation takes a long time, a very long time. Close to 5 hours to prepare the 3 devices, including spraying in times and manufacture.

2. There is a lot to spray and wipe! Each 8g device requires 8 individual vials in order to manufacture, 24 vials takes up a lot of space in the limited isolator environment and also takes a lot of time for the operator to do.

3. 24 vials takes a lot of syringes, dilutions and strenuous effort from the operators to dissolve.

At this early stage in the process, we have been able to devise a part way solution to making this easier, which will translate into the final process as well. Through this initial batch and our ambitions for the project we have managed to get Flucloxacillin 2g vials added to the NHS contract in Wales. Whilst these vials have a slightly higher cost to buy, this is much offset by the time savings within the process. Additionally the greater volume reduces the amount of manipulations required during the manufacturing process leading to a much safer product for both the operator to produce and the patient.

Patient Experience

The first doses of OPAT flucloxacillin were actually produced for one of our very own team members! Using their own initiative, they suggested the OPAT service to their doctor and helped to arrange it for themselves. They have now made a full recovery and have been kind enough to provide some insight on their experience of the OPAT service.

“I was admitted to Wrexham Maelor Hospital with suspected septic arthritis, following this I underwent surgery on my knee and was then admitted to Mason ward where I began receiving IV Flucloxacillin treatment. After a few days on the ward, I was feeling more like myself and was given the opportunity to continue my treatment as a part of the Outpatient Parenteral Antibiotic Therapy project. I, of course, agreed to this and was very pleased that I would be going home sooner than I initially thought.

I was briefed by a Pharmacist upon being discharged on how to correctly use the flucloxacillin pump, this gave me confidence to use the pump under my own supervision away from the healthcare setting. The Pharmacist was very thorough when explaining this to me and ensured I was happy with the outcome. I was also given a demonstration by a nurse on the IV suite on how to safely change the pump once it had emptied and briefed on the infection prevention measures I had to adhere to. The information I was given allowed me to continue with the OPAT at home where I was more comfortable and could begin recovering on my own. I was also pleased knowing that I would not be stuck on the ward unnecessarily and that I would be freeing up a space on the ward for a patient that needed it more than myself.

The OPAT service is massively beneficial for those that are able and want to go home whilst also continuing their treatment. In my case, my preferred option was to do this, so I was extremely pleased when given the opportunity to do so. The OPAT service allowed for a quality of life improvement for myself along with my family members that would no longer have to come visit me on the ward, whereas I felt more comfortable being at home where I was able to both continue with my treatment and recover in a more familiar environment. I was also able to speed up the rehabilitation process due to being at home and having more space to carry out the stretches and exercises I was advised to do by the physiotherapy team.

I was very satisfied with the support the OPAT team provided, my care was carried out professionally and efficiently and I was listened to when I had any questions regarding the treatment.

Unfortunately, whilst I was able to return home, I was unable to return to work due to the nature of my job working in aseptic preparation services, where these pumps that are a part of the OPAT service are actually manufactured – It would have been an infection risk for me to return to work.

The only downside I can think of with the OPAT service is how at times I found it  difficult to change the pump with just one hand, however this was made easier with the help of my partner – This may be an issue for those that live alone or are unable to rely on others for assistance.

I would absolutely use the service again, I think it is a fantastic idea with many benefits for both hospital staff and the patients involved – I would, without a doubt recommend the service to those that meet the criteria to receive it. I think the idea of the service is something that should become more mainstream and of common knowledge so that patients may request the service if they are not offered it in the first place.”