Digitalisation and advanced therapy

“Don’t allow a situation to develop in which doctors think you have a bad [electronic prescribing] system – negative associations tend to persist”, Steffen Härterich (Pharmacy Department, University Hospital of Hamburg-Eppendorf) advised. Dr Härterich has been responsible for the introduction of electronic prescribing in a hospital that already made use of electronic systems for stock control and patient records and wished to implement systems to deal with prescribing, decision support and medication safety.

“Visit people with working systems – that way you learn a lot more about what works and what does not”, he said. Doctors want a system that is easy to learn, allows rapid prescribing and has some flexibility, nurses want a system that is user-friendly and is quick to use, pharmacists want a system that supports unit dose drug distribution and medication safety measures whereas hospital managers want facilities for efficient reporting and case costing. The system that is built or bought must satisfy all of these needs. There must be a hospital formulary in place at the outset – this is critical for ensuring that prescriptions match, unambiguously, the medicines that are available, and not, for example, “expect a nurse to match a tablet to a mg/kg/hour dose”, said Dr Härterich.

Decision support needs to be clinically relevant and clearly presented. “Less is more – do not clutter the screen with unnecessary information”, he said. It is important not to overload doctors with unhelpful information. Side-effects and dosing information can be presented ‘traffic-lights style’ and other items, such as duplicated prescriptions, can be shown as pop-ups.

It is also important to understand the balance between effectiveness and ‘workability’ for human beings. A ‘scan for safety’ scheme had been introduced in Hamburg, using barcoded unit doses of medication. This allows medication, patient and prescription to be matched by means of barcode scanning. In practice, nurses sometimes feel uncomfortable with such a scheme because of the perceived loss of responsibility, he explained.

Interfaces with other hospital systems such as laboratories and patient administration systems are the norm but integration with other systems needs to be evaluated carefully. The user interface also needs to be considered, for example, when a double click or right click is useful and whether the system should be accessible via smartphones.

User-acceptance is essential for the long-term viability of an electronic prescribing system. “You want people who say “I like working with the prescribing system””. Even the best system will fail if users do not accept it and, on the other hand, users can be satisfied with a bad system. “Performance, user-friendliness and ergonomics are the factors that drive user-acceptance; faster is always better but users prefer to wait once for 30 seconds than five times for five seconds. Reasonable waits are tolerable but not long, cumbersome waits”, he said. To check the degree of intuitive usability, he suggested asking a pharmacy technician to test the system by attempting to prescribe a fentanyl patch for two days. “Problems are always common with staggered doses or unusual intervals”, he said. Small things can have a huge influence on ease of use, such as span of vision. For example, a list that is spread across the whole width of the screen requires more effort to read than the same information organised in two-thirds the width. “This takes five minutes for the programmer but makes a big difference in practice”, he said.

The software will never do everything that you want and there will always be competing interests, for example, between system support, user support and data protection. “Your task is to find a compromise that everyone can sign up to and a good first step is go to the wards and find out what ward staff think and want”, he recommended.

Training and support for staff must not be overlooked but it requires a significant investment of time. “It has a huge influence on the long-term success of the scheme”, emphasised Dr Härterich. Support for staff is needed not only at the outset but also for several months afterwards and must be part of the implementation plan.

When it comes to introducing the system, training should be provided near to the implementation date so that information is not forgotten before the start date. Ongoing support should be comprehensive and readily available. Ideally for this you need friendly, approachable colleagues who understand the process and have nerves of steel.

“This will not necessarily be the IT person whose baby the project is”, he emphasised. Finally, he warned that an electronic prescribing system can take two years to ‘bed in’ properly.

Advanced therapy medicinal products (ATMPs) represent a young and fast-moving field in which regulations tend to follow developments, Lenka Taylor (Head of Clinical Trials, Pharmacy Department, University Hospital of Heidelberg, Germany) told the audience. ATMPs comprise gene therapy (GT) products (often genetically modified organisms (GMOs)), somatic cell therapies (SCTs) and tissue-engineered products (TEPs).

The overall framework for ATMPs is EC Regulation 1394/2007. This has been followed by a number of Directives concerned with, for example, blood products, genetically modified organisms and traceability of materials, she explained. In addition, in 2015, Article 5 of the Regulation called for specific good manufacturing practice (GMP) provisions for ATMPs.

Environmental risk assessments (ERAs) have to carried out for all genetically-modified organisms before a clinical trial certificate can be issued. The ERA must consider all possible damaging effects on people, animals, plants, micro-organisms and the wider environment. In addition the measures for safe handling must be fully specified. For example, a genetically modified measles virus was classified as ‘biological safety level 2‘ (BSL2). This is a higher level than the vaccine strain of measles because the organism has been processed differently, she noted. The ERA document also describes management strategies for risks arising from ‘deliberate release’ – in this case application to patients – of the GMO and how non-patient exposure to the GMO should be handled.

In 2015, a statement from the Federal Institute for Vaccines and Biomedicines in Germany (Paul-Ehrlich Institute) clarified the scope of ‘deliberate release authorisation’ of a GMO in the framework of the clinical trial. It contained important provisions for pharmacists, said Dr Taylor. The statement said that ‘deliberate release authorisation’ covered not only administration of the GMO to a patient but also short-term storage and transport of the material. Consequently, the ERA now has to specify the requirements for short-term storage, reconstitution and preparation, in-house transportation and disposal of waste products. Given the importance of these elements to pharmacists, Dr Taylor, together with other specialist colleagues, had met with the representatives of the Institute to discuss the type of provisions that are feasible and appropriate in hospital pharmacies involved in the use of GMOs.

Three gene therapy products have now been authorised in the EU – a viral vector for lipo-protein lipase deficiency, an oncolytic Herpes simplex virus for treatment of malignant melanoma and genetically modified autologous bone marrow cells for adenosine deaminase deficiency.

Two somatic cell treatments have been authorised in EU. One of these is genetically-modified allogeneic T-cells for treatment for patients with high-risk haematological diseases and the other autologous dendritic cells used for treatment of prostate cancer. (This product was withdrawn in 2015 for unknown reasons.) TEPs contain cells or tissue of human or animal origin that have been ‘substantially manipulated’. Two TEPs have been authorised in the EU. One comprises corneal epithelial (limbal) cells used to treat corneal burns. The other comprises autologous cartilage cells that have been grown in a laboratory and selected for specific protein markers.

In practice, tissue could be collected from a patient in hospital and then manipulated in a factory before being returned to the hospital for aseptic preparation by the pharmacy and administration to a patient. Such products are often packed in ‘dry ice’ and have to be thawed before use. The pharmacy needs to have suitable areas for receiving, storing and thawing these products. It is also important to know how long the thawing process takes and what the final product should look like, said Dr Taylor.

A report in 2015 showed that there were 654 trials of investigational ATMPs (ATIMPs) in progress, comprising 187 TEPs, 160 GTs and 307 SCTs.

Many aspects of the use of ATMPs are being actively discussed in an effort to make these treatments safe and available throughout the EU. In conclusion, Dr Taylor noted the diversity of ATMP products makes regulation complicated. However, the pharmacist can be a competent partner for academic producers of ATMPs. Furthermore, there can be no doubt that ATMPs are medicines and therefore should be supervised by hospital pharmacists.

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