Quality Assurance in Hospital Pharmacy Compounding Units is a Multi Player Game

The hospital pharmacist is responsible for the quality of drug products and medical devices used in the wards. In the pharmaceutical technology units where drugs are compounded the issue is complex as it is multiform. Many parameters need to be mastered and monitored to ensure the quality of the products. In fact, the direct environment of the preparations should be controlled (quality of air, chemical and microbiological contaminations) and the skills of the workers should be assessed. Many quality controls are also implemented during the process and on the final products to ensure their quality; for example on chemotherapeutics - see a review published in our journal earlier this year [1]. As stated in another editorial, the pharmacist is the key person for the quality of drug products in the hospital [2]. Our journal has published many papers on this subject, showing in issues after issues and articles after articles the complexity of the pharmacist’s job, especially in the compounding units. In this issue we included a few more examples of the technical questions the pharmacist is facing.

The first paper published by the Canadian team from Hospital Sainte Justine in Montreal, Canada, describes the evaluation of four cleaning solutions and two types of cleaning mops on the chemical decontamination of floors initially contaminated by cyclophosphamide. The choice of this chemical tracer is smart because it is mainly used in every chemotherapy compounding unit and it is volatile; thus the drug is very often responsible for surface contamination in the production area. The detection of the drug was performed by UPLC-MS-MS, allowing the quantification of low concentrations of cyclophosphamide. Sodium hypochlorite, hydrogen peroxide, quaternary ammonium and a detergent (action 3^®) applied with a disposable or a non-disposable mop were efficient to eliminate approximately 99 % of cyclophosphamide on the floor tiles. However, no cleaning strategy was able to completely remove cyclophosphamide. This study is a good example of how far the pharmacist has to go to ensure the quality and security of the compounding process. The validation of the cleaning procedure is one of the corner stones of the ensemble of techniques used to avoid cross contamination of batches with chemical entities and to ensure the security of the personnel closely involved in the preparation process. Monitoring chemical contamination over the years is also a good way to follow the quality of cleaning procedures over time, as described before in our journal [3].

The second paper describes a method for process monitoring of an automated multichannel pump used to prepare parenteral nutrition. The study was performed by the pharmacy team of Mainz University Hospital in Germany. This work describes precisely a performance qualification test. The work performed on simulated prepared infusions showed that the maximum deviation of the automated pump was lower than 3 %. However, for some compounds some results were derived from the specification. The performance of the device was improved by resetting the flow factors for those compounds. This study highlights the importance of on-site performance qualification of the devices used to produce pharmaceutical preparations. Especially in the case of parenteral nutrition, the pump delivers some volume and thus the dose of the ingredients. Volumes errors can be harmful to the patients. If the volume error is made with an ingredient of a negligible quantity in comparison to the full preparation (i. e. a few milliliters for a 500 mL bag) it may not be detected on the mix check performed by gravimetry control with a balance. Validating every channel of the pumps for every possible ingredient is thus of primary importance. This is once again another example of the role of the pharmacist to ensure the quality of the final product. Pump qualification was subject of one of the first papers [4] published in PTHP and is really a critical point to address in sterile compounding units.

Analytical control is one of the main themes of our journal and papers in this field are included in every issue. In this one, we have a survey of the use of UV-Raman after 18 months of routine use. The study was performed in Hospital Trousseau (APHP, Paris, France). A few months ago the same team described the implementation of UV-Raman spectroscopy in chemotherapy compounding units for pediatric patients [5]. This technique allows the use of samples of limited volumes, which is very important in the case of low volume pediatric preparations. The follow-up performed along 18 months under real-life conditions demonstrates that UV-Raman quality control is feasible under routine conditions. The rate of conformity was found to be between 74.7 % and 97.2 %. The lowest conformity rates were obtained with low soluble drugs. This highlights the issue of homogenization before the control. Moreover those techniques are still related to sampling, which can cause chemical contamination of the bench [1]. A pure Raman analysis can be performed through the drug container but is limited to a few drugs [6].

The next paper comes from the same team at Hospital Trousseau. This study is an evaluation of disinfection protocols of the vials used to prepare parenteral nutrition. The study was launched after the discovery of positive microbiological controls (bacillus presence) performed on prepared infusion bags. The team tested 5 protocols, namely hydrogen peroxide (H2O2) and sodium hypochlorite (both by immersion or spray), and ethanol by immersion. At the end of the study, considering practical use and the performance of the tested protocols, immersion in hydrogen peroxide was preferred. The question of disinfection of raw materials entering the controlled area in parenteral nutrition compounding units is of primary importance and has been raised and discussed in the newly edited fifth edition of UK standards on quality assurance on aseptic preparation services (QAAPS) published in 2016 by the royal pharmaceutical society (see chapter 12 of the document downloadable at https://www.rpharms.com/resources/professional-standards/quality-assurance-of-aseptic-preparation-services).

Finally this issue ends with an opinion paper on the European Council’s resolution on good reconstitution practices in health care establishments for medicinal products CM/Res(2016)2 over the Centralised Intra Venous Additive Services (CIVAS). Those services dedicated to the preparation of batches of sterile products have been implemented a few decades ago in the UK and in some European countries. The resolution is a guide to decide where the preparation of injectables should be performed (ward or pharmacy facilities) in function of a risk assessment study. The author of this paper, Dr Sandy Vrignaud, hospital pharmacist from Angers University Hospital in France, discusses the challenges and opportunities of CIVAS in the view of this new resolution. The paper also explores the reasons and the limits for CIVAS implementation.

In summary, this issue shows, once again, how broad the missions of pharmacists are to ensure the quality of prepared drug products in hospitals. This is why it is of primary importance to communicate the results of the studies performed in different locations in order to help the profession to move forward. This is the reason why this journal was born and we are strongly in need of communications reflecting the expertise of all pharmacists in the form of opinion papers, original research studies and review papers. We hope to receive many submissions from all countries in the next weeks to make this journal a new, stronger exchange platform in the field of pharmaceutical technology in hospitals.