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Author(s)

Kirsten Lykke Vorbeck

Why was it done?

When preparing treatments for blinded clinical trials it is very important to make sure that it is not possible to distinguish between the active and the placebo dose, as this may lead to unblinding of the treatment and thus jeopardise the results of the trial.

What was done?

The purpose was to find solutions for how to handle active and placebo drugs in the production system CATO to ensure they would end up being identical when prepared.

How was it done?

Before preparing a drug using CATO the drug must be registered in the system with all of its data. It is not possible to have two different sets of data for one drug. CATO records detailed documentation of what is being done during preparation and it is not possible to pretend to pick one drug and then grab another instead. Also, the label is printed automatically so it will show exactly what was prepared. We decide on a common name for the active/placebo and register both of these in the system under that name so that they will be prepared in exactly the same way and appear identical on the label but are still distinguishable in the batch documentation. We name the drug ‘Protocol name Active substance/placebo’ and register the stock of both active drug and the sodium chloride solution that is used as placebo under that name. We will also stock vials of NaCl for this purpose next to the drug it is being placebo for, and NaCl can be prepared pretending it has the density of the drug. CATO will think they are the same drug but they have been registered with their very different batch numbers, maybe with a NaCl after the number of that, so it is always possible to see what was actually being prepared.

What has been achieved?

Our doses of active and placebo are indistinguishable. Labels are the same and, for example, withdrawal into a syringe and insertion of a needle into the port of the infusion bag will be done in the same way.

What next?

These very simple routines can be used anywhere for the preparation with CATO and possibly also with other systems.

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Author(s)

Katrine Bødker Rubach-Larsen, Anne Rungø, Anette Eskildsen, Lone Skovhauge

Why was it done?

A research team at the MR Centre (MRC2) wished to set up the production of Pharmacy Kits, but had no prior experience of, or licence to, manufacture drugs. Thus, the hospital pharmacy was asked to participate in the development of such production.

What was done?

A new MR-scanning technology, hyperpolarisation, for the quantification of metabolic processes with an extremely high sensitivity enables physicians early detection of treatment effects in, for example, cancer and diabetes. A so-called Pharmacy Kit is used in the hyperpolarisation process and consists of a specially designed packaging with tubes, vessels and filters containing the contrast agent and buffer solutions. The objective for the hospital pharmacy1 was to manufacture Pharmacy Kits complying with Good Manufacturing Practice (GMP), though neither packaging nor two of the raw materials conformed to European standards.

How was it done?

The MRC research team presented the hospital pharmacy with the desired combination of compounds and the packaging required for Pharmacy Kit production. The task for the hospital pharmacy was then to set up a manufacturing process that met these requirements and complied with the guidelines for GMP. A production complying with GMP was developed in close collaboration with the MRC and an ongoing contact with the Danish Medicines Agency. During the process the hospital pharmacy carried out its own microbiology test in order to determine if, and for how long, the non-CE-marked packaging could store the contrast agent and buffer solutions. Risk assessment of the raw materials not found in the European Pharmacopeia were conducted. The method investigated by the MRC already takes place at a few other places in and outside of Europe. Experiences from these production sites were implemented and expanded with process optimisation, and specially designed equipment for the production.

What has been achieved?

Due to a strong inter-professional collaboration between the MRC and the hospital pharmacy and due to qualified risk assessments, it was possible to set up a production of Pharmacy Kits according to GMP.

What next?

When researchers contact hospital pharmacies with new ideas, we have to be willing to work with GMP in a different way by applying knowhow and risk assessments in order to ensure developments within the healthcare system.
1. Hospital Pharmacy Central Region, Production, Aarhus, Denmark.
2. MR Centre, Aarhus University Hospital, 8200 Aarhus N, Denmark

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Author(s)

Stefanie Sauer, Michael Ober, Jürgen Backhaus, Torsten Hoppe-Tichy

Why was it done?

Patients of the Children’s Hospital at the Heidelberg University Hospital are regularly supplied with extratemporaneous medicines from the hospital pharmacy. This often leads to issues in continuity of care in the outpatient setting as patients are required to access ongoing treatment through local pharmacies, which in turn must develop the formulations and procure the necessary raw materials. Therefore, it is not uncommon for interruptions in patients’ therapy to occur.

What was done?

The aim was to improve continuity of care by discussing the medication with the responsible pharmacy before the patient was discharged. Allowing missing raw materials to be procured and clarify any uncertainty about the prescription.

How was it done?

We designed a document that is available on the Intranet. While the child is still on the ward the discharge medication should be noted. The parents had the opportunity to indicate a retail pharmacy of their choice, preferably near the place of residence. This document could be sent to the hospital pharmacy. A hospital pharmacist contacted the specified pharmacy to discuss the extemporaneous medications before the child was discharged. If necessary, the pharmacist can forward the hospital pharmacy manufacturing instructions. Furthermore, the compositions plus further information were then made available on the homepage of the pharmacy in an area to which only experts have access. A telephone number on the hospital pharmacy homepage is available for queries, including those about the formulations.

What has been achieved?

In the discussions with the retail pharmacies, the colleagues were very pleased and grateful about the service provided by the hospital pharmacy. They saved time in preparing patients’ prescriptions. Concerns or doubts were cleared up at an earlier stage of the discharge process, leading to the patient receiving their medicine on time.

What next?

Provision of the document and manufacturing instructions on the homepage serve as a valuable aid for ensuring that the outpatient therapy functions smoothly. It is important that the information is kept current. In the future, further information will be linked to the homepage in the hope of reducing the number of incoming telephone enquiries.

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Author(s)

Jemos Costantino, Martina Milani, Mariantonietta Piccoli, Mara Provenzi, Paola Paochi, Ilaria Clerici, Cinzia Lucia Ursini, Claudio Colosio, Fabrizio Mastrilli, Emanuela Omodeo Salè

Why was it done?

In outpatient setting, WT between medical visits and administration is strongly conditioned by time needed for preparation. We needed to reduce our WT caused by the use of an automated system by ensuring the same standards of quality control checks and traceability, not achievable with manual preparation.

What was done?

We introduced an assisted system for chemotherapy preparation, with a gravimetric and barcode verification. We started to switch part of preparations previously prepared by an automated system to this assisted system. We performed an analysis to measure the impact of a different strategy in preparing chemotherapy on patients WT.

How was it done?

Time needed for preparation was monitored in the first trimester of 2016, where drugs were prepared using an automated system or manually, and compared to the first trimester in 2017, when we introduced the assisted system.
In the first period we used a “WT optimization” criteria in selecting the preparing technology, while in the second period we decide to use a “risk based” criteria.
Risk based criteria consists of selecting the automated system for cytotoxics, assisted system for antibodies and low risk drugs and manual procedure when no other options are available.
In order to evaluate bias introduced by the risk based selection of different drugs, we performed a contest comparing preparation times of a defined sequence of representative preparations typologies. Three technicians are involved in order to reduce human factor impact.

What has been achieved?

Average WT (AWT) in the first period was 1h36m and median WT (MWT) was 1h22m (sample = 2365 preparations in 3 months). AWT in the second period (sample = 3437 preparations in 3 months) was 1h17m (-19,79%) and MWT 1h1m (-25,61%). The percentage of therapies dispensed after 2 hours waiting decreased by 55,69%. WT was stratified by preparation technology (assisted system: AWT =50m; MWT=44m – automated system: AWT=1h26m; MWT=1h07m).
The contest results were (average of three series) : manual preparation 15m19s; assisted 26m42s; automated 1h14m3s.

What next?

Assisted systems are able to guarantee quality standards for patients similar to automated ones, but with an important reduction in WT when compared with an automated one and an improvement in traceability compared to the manual procedure.

Author(s)

Ismail Bennani, Amine Cheikh, Hafid Mefetah, Mustapha Bouatia

Why was it done?

The strict control of medicines cold chain is linked to a triple risk for a hospital: a risk for the patient through the efficiency and safety of the drug, a financial risk, and a regulatory risk.

What was done?

Our study aimed to map the process of management of medicines requiring a strict cold chain control at a referral pediatric hospital and to identify the critical points associated to this process in order to realize a risk analysis using the FMEA method

How was it done?

The method used is FMEA for a priori inductive risk analysis which aims to identify potential system failures. These failures are analyzed to determine their criticality by establishing an index for each failure that will be scored and calculated using the formula: Criticality index = frequency × severity × detectability.
The rating of each criterion is based on predetermined rating tables.

What has been achieved?

Process Mapping: The mapping of the process allowed identify 7 major actors: the supplier, the general store, the logistics platform for product reception, the transportation, the logistics department of hospital, the pharmacy and the patient.
Identification of the critical points: All failures modes that were ranked between 201 and 504 on criticality index are considered as main critical points:

Problem of breakdown of electricity and its management: 504
Respect of the cold chain at the level of the care services until administration: 448
Temperature indicators at the level of care services: 384
Conditions of transportation: 315
Temperature monitoring at pharmacy level: means and management: 245
Logistics agents transport time management: 210

Implementation of improvement actions: Corrective and preventive improvement measures have been defined and implemented, such as: setting up alternatives to power outages, periodic temperature assessments at all critical levels, and integration of remote control and monitoring computer devices.

What next?

The continuous improvement of the medicines’ cold chain remains an important topic for the institutions in view of the overall risks associated with the quality of these medicines, therefore to the medical treatment of the patient.

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Author(s)

Janne Jensen, Solvej Wandy Pedersen, Susanne Nørregaard, Karin Herkell, Anne Thestrup Nielsen, Anita Gorm Pedersen

Why was it done?

A group of hospital pharmacists representing all hospital pharmacies in Denmark have in a previous study identified and slimmed a national portfolio of extemporaneous pharmaceutical preparations used by Danish hospitals from a total of 2,754 preparations down to approximately 750 preparations being considered of clinical importance. Without a common overview of the national portfolio there will be initiated production of duplicates and almost identical products resulting in a large and inconsistent portfolio.
The purpose of this GPI was to make the national portfolio of extemporaneous pharmaceutical preparations accessible to all hospital pharmacists in Denmark and to implement a common procedure to evaluate preparations before adding them to the national portfolio to avoid duplets and obsolete products.

What was done?

A common national procedure for adding new preparations to the national portfolio was developed and implemented to avoid duplets and to ensure a uniform quality and appropriate risk assessment of the preparations.

How was it done?

A national database was developed and tested. Each hospital pharmacy entered their own extemporaneous pharmaceutical preparations in the database. Also, the extemporaneous pharmaceutical preparations manufactured by community pharmacies and used in the hospitals were entered in the database.
One hospital pharmacist in each of the five regions in Denmark was appointed as gatekeeper for the national portfolio. A template for an application form for new preparations was developed. When a physician requests a new preparation the application form will be completed by the clinical pharmacist. It is forwarded to the gatekeeper who will evaluate the preparation before approving it as a candidate for the national portfolio.

What has been achieved?

430 extemporaneous pharmaceutical preparations from the hospital pharmacies are entered and quality approved in the database. 255 extemporaneous pharmaceutical preparations manufactured by community pharmacies were entered in the database.
A national group of five gatekeepers was formed, and the workflow for both the group and the individual gatekeeper was described and implemented at all Danish hospital pharmacies.

What next?

The GPI provides an easy-accessible overview of the national portfolio of extemporaneous pharmaceutical preparations, releasing production time and resources at the manufacturing pharmacies.

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Author(s)

A Elsheashaey, A Elshishiny, A Orabi, A Almutairi, A Aboulwafa, H Alobaid, F Dashti, D Saeed, R Yassin, M Salama

Why was it done?

Kuwait Cancer Control Center (KCCC) is the only oncology hospital in Kuwait. Chemotherapy Preparation Unit (CTPU) was unable to meet the increased orders; causing delivery delay and more patients’ waiting time. Moreover; rework and more waste due to defective and faulty processes of current workflow resulting in frequent incident reports of wrong final products dispatched.

What was done?

Shifting to a systematic multi-step production workflow to increase compounding capacity, minimize risk of errors, reduce processing time, and maximize utilization of integrated technological resources.

How was it done?

Using multiple PDSA cycles, a comprehensive educational and practical training was conducted, proceeded by staff rotation with newly trained team. Every three weeks a new pharmacist trained and assigned to CTPU. Raw materials stores were rearranged for better accessibility and diminishing unnecessary staff movement. A staging step as the first independent double-check before the start of compounding, and for assembly of raw materials and supplies required for compounding. A verification Step as the second independent double-check upon compounding, using bar-code scanners, touchscreens and cross-checking with the chemotherapy order to assure the quality and integrity of the finished product. Production workload were restructured over three parallel line of manual stations and one automated preparation unit. Pharmacy Information System (PIS) screens were customized to give a first and second audio-visual alarms after 30 and 45 minutes of transcription time respectively. Chemotherapy sessions appointment system were established to assess the daily chemotherapy compounding needs from CTPU in advance with an incremental increase of production capacity to reach 100~120 patients/day or 180~200 preparations/day.

What has been achieved?

Number of preparation compounded by CTPU was increase by 8%, where more than 43% of preparations were validated to release in less than 30 minutes and approximately 88% of preparations were delivered in less than 45 minutes. Number of preparation by automation was increased by 82%, Furthermore, all production incidences has been completely eliminated after full implementation of final verification and validation step.

What next?

The new workflow has increase the workload capacity with less production errors and zero incident reports. Patient experience was improved by comparable preparation time to other international Pharmacy Workload Unit and average time required per patient visit.

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Why was it done?

Individual total parenteral nutrition (TPN) for neonates was originally compounded by nursing staff on the respective wards. This process of TPN compounding was error-prone. Documentation and traceability was inadequate. Clean room conditions were absent. By transferring the compounding of TPN from the ward to the pharmacy level, several aims were accomplished. Time of nursing staff was released and the highest quality standards for compounding were implemented. By doing so, several types of errors (e.g. overdosing, wrong additives) were eliminated.

What was done?

Development and implementation of nutrition support protocols by using an electronic prescribing and compounding software (catoPAN™) to address the special needs of neonates and ensure a high level of individualized care.

How was it done?

In cooperation with neonatologists, nutrition protocols were developed. Furthermore, a TPN compounding process was implemented and validated, including the validation of catoPAN™ software and compounding pumps. An integrated risk analysis was performed, stability data to allow TPN supply for weekends were generated and fail-safe procedures were determined. To finally succeed, various process and organizational changes concerning the wards, the production and the QC department of the hospital pharmacy were required.

What has been achieved?

Compounding of individualized nutrition solutions within defined standards, predetermined specifications and quality attributes is implemented. The production process is continuously monitored, including complete traceability. A strong interprofessional collaboration between physicians, nurses and pharmacists was established, ultimately leading to a high level of confidence among all members. Workload of nurses in terms of compounding medicines was dramatically reduced.
Currently, we provide nutrition bags for four wards (24 ICU- and 30 intermediate care beds), equaling an average production of 50 bags per day. In 2016, a total of 11.126 bags were supplied, implying an increase of 75% compared to 2015. We expect an increase of around 30% in 2017 due to rising demand.

What next?

With the expansion of TPN compounding to further pediatric wards, new nutrition protocols addressing other requirements have to be developed. Process changes are likely to follow. Further support can be provided by pharmacy-based IV admixture service. Additionally, due to current software updates, the prescribing and compounding software catoPAN™ must continually be revalidated.

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Author(s)

María Lourdes Recio Blázquez, Alberto Pérez Morales

Why was it done?

It was necessary to establish a quality control of this pharmaceutical process.

What was done?

A computer method of gravimetric quality control of the tablet splitting process was designed.

How was it done?

The procedure consists on a precision scale connected to a computer in which, according to the uniformity of mass assay of the European Pharmacopoeia, the weights of 20% of a batch of whole tablets destined to be split are automatically recorded in a spreadsheet, carrying out the following formulas:
=AVERAGE: provides the average weight of the sample of whole tablets.
=MAX and =MIN: selects respectively the largest and the smallest of the weights.
=STDEV: calculates the standard deviation of the sample weights.
With the average weight of the whole tablets, the theoretical weight of the half-tablets is calculated, establishing a maximum and a minimum admissible limit with the following formulas:
=AVERAGE(whole tablets)/2: determines the theoretical average weight of each half-tablet.
=AVERAGE(whole tablets)/2 ± 7.5%: establishes upper and lower gravimetric limits that cannot be exceeded by any half-tablet.
All the half-tablets need to be weighted, as the tablet-splitting process is carried out tablet-by-tablet and this modus operandi is not reproducible enough. In case of non-compliance with maximum and minimum weight criteria, the half-tablet must be discarded.
Conditional functions were established such that the spreadsheet itself reflects the half-tablet acceptance/rejection decision.
Basic technical computer skills, training in the technique of tablet splitting, appropriate clothing and environmental measures to avoid risks to the operator and the medications are required.

What has been achieved?

Since 2015, two different medicinal products were subjected to the tablet splitting technique. A total of 10,536 halves of suitable tablets were obtained, which permitted safe dosing at lower doses than commercialized, and also generated a financial asset of 101,724 Euros. 566 halves were discarded. The splitting efficiency was of 94.9%.

What next?

This quality control procedure is applicable to all divisible solid oral dosage forms. The standardization of the technique and the quality controls will allow to extend it to other medicinal products with dosing and economic purposes.

Author(s)

MERCEDES GIMENO-GRACIA, TRANSITO SALVADOR-GOMEZ, ROSA MARECA, JOSE IGNACIO GARCIA-MONTERO, MIGUEL ANGEL SALVO, PILAR ABAD, BEATRIZ ABAD, CESAR VELASCO

Why was it done?

The Spanish Agency of Medicines and Health Products (AEMPS) issues drug and health product-related alerts to the health centres through each region’s Department of Health. The means through which said alerts reach the health professional is not always adequate. The procedures for alert dissemination in our hospital hadn’t been standardized yet: some professionals were alerted more tan once while others weren’t alerted at all. Furthermore, there was no record of these alerts

What was done?

We developed a safety alert management and dissemination system implementation in a hospital setting.

How was it done?

In April 2014, a multidisciplinary workgroup was established (3 members of the Preventive Medicine Service, 2 pharmacists, 2 members of the Supplies Service, 2 computer technicians and 2 members of the hospital’s Management) to analyse management and dissemination of alerts within the hospital at that time. Safety alerts can attain to different elements: drugs, medical devices and public health. Throughout 2015 new circuits and actions were established and in 2016 their implementation was initiated.

What has been achieved?

The workgroup held 7 meetings from April 2014 to June 2016. The project started focusing on drug-related alerts. An algorithm was designed to handle them, in which a pharmacist filtered the alerts (via e-mail) and assessed which had to be spread, and among which professionals. Additionally, the pharmacist managed the alert. The dissemination worked as follows: from the Pharmacy Service to Medical or Nursing Directors, who spread the message to the different units recommended by pharmacist, specifically to their respective Manager, Tutor of Residents and Quality Manager. All alerts were recorded in a database, along with how they were handled.
From January to June of 2016, a total of 235 drug-related alerts were sent from AEMPS. The dissemination was as follows: 44.3% (104) were spread among pharmacists, 36.6% among doctors, 5.5% among nurses and 9.4% to other professionals. The types of drug-alert received were classified as: supply problems (84.7%), use recommendations (7.2%), quality alerts (7.7%) and others (0.5%).

What next?

Next step is implantation of this alert management system with medical devices alerts and public health alerts.