Introduction

The European Agency for Safety and Health at Work (EU-OSHA) has established that the handling of hazardous drugs (HD) is one of the most relevant risk factors for the health of healthcare workers¹. The evidence for this is incontrovertible, in that it has been estimated that in Europe more than 12.7 million healthcare workers handle HDs. This figure implies that occu pational exposure may cause an estimated 2,220 new cases of leukaemia leading to 1,467 deaths among these workers in this continent².

The National Institute for Occupational Safety and Health (NIOSH) de fines drugs as hazardous if, in animal or human studies, they demonstrate any of the following characteristics: carcinogenicity, teratogenicity or other developmental toxicity, genotoxicity, reproductive toxicity, organ toxicity at low doses, and drugs with a structure or toxicity profile similar to that of other hazardous drugs³.

Numerous studies have shown that HDs carry chemical risks for the workers who handle them^{4 5 6 7 8 9 10 11 12-13}.

Thus, risk assessment is one of the key points in the HD handling and control process, given that its results support all the measures adopted to guarantee the safety of the process¹⁴. The scientific literature has descri bed several risk assessment models¹⁵. Although each one has its particular characteristics, all of them include the identification of process-associated hazards as an essential first step in their handling.

However, although risk assessment is a legal requirement in Spain¹⁶, and the need for it is recognised, there are few studies on HD risk analysis. In 2009, a French team of hospital pharmacists applied the "hazard analysis and critical control points' methodology to the preparation of anti-cancer drugs in pharmacy services¹⁷. To the best of our knowledge, the American Hazardous Drug Consensus Group is the only group that has proposed a specific methodology for HD risk analysis¹⁸.

Given the foregoing, and on the basis of expert consensus, the objective of this study was to identify the hazards and define the theoretical occupa tional risks arising from the process of handling HDs in hospital pharmacy services.

Methods

Results

The experts had an average of 22 ± 3.17 years of experience (median: 25.50 years; range: 8-28 years). In all cases, the degree of consensus on the objective criteria of choice was 100%. Table 1 shows the characteristics of the experts who comprised the group.

Table 1. Characteristics of the Members of the Expert Group (n = 6) 

Flowchart and HD management chart

Based on the expert consensus, we first designed the general outline of the process (Figure 1), which facilitated the development of the global process (Figure 2). Figure 2 shows all the stages that comprise the HD traceability management procedure in hospital pharmacy services, which would allow its monitoring and reproducibility.

Each stage was represented in a table (Table 2) to systematize and facilitate the understanding of the results. The following variables were coded for each stage of the process: stage, operation and operation number (i.e. the number that appears in each of the operations shown in the flowchart and facilitates their identification in the different documents), potential hazard (i.e. yes/no), type of hazard identified (i.e. chemical and physical), and HD exposure routes (skin and mucous membranes, ingestion, ocular, and injection).

Figure 1. Hazardous drug (hd) handling in hospital pharmacy service. 

Figure 2. Hazardous drugs (HD) handling in hospital pharmacy services - global process (1/2). 

Table 2. Risk management chart by stage 

^†Number that identifies each of the operations in the flowchart and facilitates its identification in the table

^††see flowchart.

¹Operation 10 will only be conducted if the person responsible for transporting the HDs from the general store to the clean rooms did not previously wear PPEs in the storage area; ² Handwashing usually consists of disinfecting them with antiseptic solution when staying in the clean rooms because the work in them has not been completed. If the clean room is vacated, handwashing is done with soap and water; ³ PPEs used for processing will vary depending on the type of HD prepared (sterile or non-sterile); ⁴ Needles are required when preparing pharmaceutical forms from HDs contained in ampoules; ⁵ modify whole solid forms: split, cut, crush tablets, open capsules; ⁶ The removal of PPEs is conducted gradually, while passing through rooms with different degrees of environmental quality, following the standardized work procedure established.BSC, biological safety cabinet; HD, hazardous drug; IM, intramuscular; IT, intrathecal; IV, intravenous; PPE, personal protective equipment; SC, subcutaneous.

In total, 42 operations were established corresponding to the four stages of the handling process conducted in hospital pharmacy services: recep tion and bulk storage (17 operations (40.5%)); preparation (19 operations (45.2%)); drug storage (5 operations (12%)); and dispensing (1 operation (2.4%)).

Discussion

The scientific literature has investigated and discussed in detail the health risks of handling HDs, regarding which there is increasing concern from the point of view of occupational health²³.

The objective of the present study was to identify and analyse the theoretical hazards and risks of HDs in the HD logistics chain in hospital pharmacy services as the initial phase of a risk assessment. This objective required detailed knowledge of the entire logistics chain and its stages. The development of flowcharts played a key role in achieving this objec tive. As Ramos-Merino et al.²⁴ indicated, flowcharts condense a large amount of information in a small space, visually represent the flow of the activities involved, and facilitate the rapid and efficient understanding of processes.

The main differences of opinion between the experts concerned the reception and bulk storage stage. Although this stage has been less ad dressed in the literature, it is the one in which there is the greatest variability in care practice, mainly due to the limited human resources, materials, and facilities available in each health centre. Nevertheless, after combining the opinions of the experts with the scientific evidence, a 100% consensus level was reached

Detailed study of the general process flowchart showed that almost half of the operations were concentrated in the preparation stage. This observation is unsurprising, given the heterogeneous catalogue of HDs that are currently prepared in pharmacy services (e.g. infusion bags, syringes, infusion pumps, topical forms, solid and liquid oral forms, and eye drops). Furthermore, in recent years, these types of processes have become more complex due to the need to improve the management of critical aspects that influence the safety of health personnel, patients, and the drugs themselves. This aspect explains the multiple control and protection operations during the preparation stage (i.e. operations 19, 23, 24, 25, 26, 28, and 32 (see Table 2 and Figure 2), as well as the use of sophisticated devices and equipment that reduce to the greatest extent possible contamination of the work area and environment, thereby ensuring worker safety.

The main risk inherent to the use of HDs is chemical risk, which is due to their intrinsic characteristics of carcinogenicity, teratogenicity, genotoxicity, reproductive or developmental toxicity, or organ toxicity at low doses. However, physical hazards are also an issue because sharp and pointed objects (e.g. glass recipients containing the HD, needles used in their pre paration) may be handled (i.e. operations 2, 4-7, 11-13, 20, 21, 27, and 29 (see Table 2). No biological hazards were identified, because there is no direct contact with patients or their fluids during the stages of the process conducted in the pharmacy services.

However, although physical injury may occur (e.g. cuts from glass bottles or glass fragments, or puncture wounds from needles), it should be noted that in practice this type of risk has been greatly minimized by the increa sed use of devices and equipment without needles, luer-lock connections, and the widespread use of HD containers made of polyolefin-type plastic. Currently, the use of glass is uncommon and has been relegated to specific situations in which there are incompatibilities between plastics and HDs¹⁴.

Given the magnitude of the problem, it is unsurprising that in recent years several governmental and non-governmental organizations, scientific socie ties, and expert panels have encouraged health organization managers to conduct assessments of the risks associated with the HD circuit^{16,18,23,25 26-27}. In any case, the first step in improving occupational safety is to identify hazards.

Although this study is useful as a basis for future projects, it has several limitations. The first of these is related to the selection of the experts. It would have been desirable and enriching to have had available the opinions of other types of expert, such as occupational risk specialists, preventionists, or occupational health technicians (due to their high level of knowledge in the field), as well as pharmacy nurses or technicians (because they work directly in these areas). However, this could not be achieved due to high workloads and the absence of incentives in the development of this study. Nevertheless, it should be noted that this study represents the initial phase of the identification and description of the process: that is, it is the preliminary phase of a risk analysis which will include the opinions of a wider range of experts. A further limitation is that the description of the process and the identification of hazards was based on the healthcare practices of two hospitals and on theoretical knowledge, concerning which there is a lack of solid evidence. The latter aspect is due to both the lack of published material on adverse events that would allow the identification of hazards, as well as the great heterogenicity of internationally published guidelines¹⁹, thus reducing the external validity and applicability of this study in other settings. However, the model obtained in this study should be highly reproducible given that it was based on the high level of knowledge of the participants in HD handling and the systematic review conducted as a preliminary to the expert consensus. In any case, risk analysis is a dynamic process that has to undergo periodical reassessment based on any nonconformities obtai ned, such that any bias derived from the subjectivity of the participating experts can be corrected in the future.

Based on the foregoing, we suggest that HDs should be integrated within a standardized management system to improve the safety of patients and health workers, while maximizing resource efficiency and minimizing procedural incidents. Such a system would make it possible to establish a global system with fully characterized stages that would guarantee the qua lity and safety of the HD handling process in pharmacy services.

Once hazards have been identified, risk assessment should be imple mented using a systematic and preventive methodology to estimate the risk and severity of any adverse event.