Performance Challenges in a Newly Established Clean Room at Omid Hospital, Isfahan, Iran: A Descriptive Study

ABSTRACT

Objective:

This study aimed to comprehensively assess the challenges faced by a newly established clean room in the oncology center of Omid Hospital, Isfahan, Iran, one of the first of its kind in the country. The research also sought to identify the underlying causes of these challenges and propose potential solutions to address them.

Methods:

A 6-month cross-sectional study was conducted from December 2021 to May 2022. International guidelines such as British Columbia Cancer Agencies’ guideline of hazardous drugs, the National Institute for Occupational Safety and Health guideline for working with hazardous drugs, and United States pharmacopeia related to cleanroom performance were studied, translated, and summarized into a checklist. The staff performance in Omid Hospital’s clean room was compared to the data collection form, and all medication errors were documented and analyzed. The study also explained the underlying causes of these challenges and proposed potential solutions.

Findings:

Among 1005 chemotherapy regimens, 836 errors were detected, stemming from issues such as engineering and construction challenges, lack of human resources and essential equipment, and budgetary constraints.

Conclusion:

Despite the involvement of a trained oncology clinical pharmacist, Omid Hospital’s cleanroom faces significant challenges within the medical and hospital system, leading to non-standard challenges. The study recommends multidisciplinary approaches in the hospital to mitigate these challenges and improve cleanroom performance.

INTRODUCTION

The concept of a “clean room” is defined in various ways, with different standards providing specific criteria for its construction and operation. The United States Federal Standard defines a clean room as a highly efficient room designed to minimize the generation and retention of airborne particles, controlling airborne particles and typically including one or more clean areas. The International Organization for Standardization (ISO) standard ISO 14644-1 defines a clean room as a controlled environment where the concentration of airborne particles is regulated, focusing on minimizing the introduction, generation, and retention of particles. Temperature, humidity, and pressure are also controlled as needed.[1]

Cleanrooms are used in various industries for purposes such as medical devices, sterile compounding, semiconductors, microelectronics, pharmaceuticals, food processing, and protection against hazardous substances.[2]

The concept of cleanrooms originated in the 1880s, initially in health-care settings, driven by the efforts of scientists and surgeons such as Joseph Lister, William Cain, and Gustav Neuber. Over time, cleanrooms expanded into other industries, such as aerospace and electronics. They recognized the importance of maintaining a clean environment in hospitals and played a crucial role in constructing early cleanrooms.[3]

The need to control infections during surgical procedures drove early contamination control techniques, and the invention of “laminar flow” ventilation in the 1960s revolutionized cleanroom design. This innovation revolutionized the design of cleanrooms, particularly in the context of cytotoxic cleanrooms, and has remained a cornerstone of cleanroom technology to this day.[3]

Cleanrooms are classified based on permissible size and quantity of particles per volume of air. In the United States, Federal Standard 209E (FS 209E) was commonly used for cleanroom classification until ISO 14644-1 replaced it in 1992. ISO 14644-1 introduced a classification system from ISO 1 to ISO 9, with ISO 1 being the cleanest.[3] Both FS 209E and ISO 14644-1 provide specific guidelines to determine the cleanliness level of a cleanroom or clean area which can be seen in Table 1.[4]

Table 1.

Clean room classification standards

Cleanroom class	ISO 14644-1	Federal standard 209E	Number of particles per cubic meter by micrometer size
			0.1 µm	0.2 µm	0.3 µm	0.5 µm	1 µm	5 µm
ISO 1	≤10	-	10	2
ISO 2	≤100	-	100	24	10	4
ISO 3	≤1000	Class 1	1000	237	102	35	8
ISO 4	≤10,000	Class 10	10,000	23,700	1020	352	83
ISO 5	≤100,000	Class 100	100,000	23,700	10,200	3520	832	29
ISO 6	≤1,000,000	Class 1000	1,000,000		102,000	35,200	8320	293
ISO 7	-	Class 10,000				352,000	83,200	2930
ISO 8	-	Class 100,000				3,520,000	832,000	29,300
ISO 9	-					35,200,000	8,320,000	293,000

Grade A=ISO 5 (100), Grade B=ISO 5 (100) (at rest), Grade C=ISO 7 (10,000), Grade D=ISO 8 (100,000). ISO=The International Organization for Standardization

Cytotoxic cleanrooms are designed for compounding drugs, particularly cytotoxic and hazardous drugs used in chemotherapy. These cleanrooms are critical for ensuring the safety and integrity of compounded products and protecting health-care personnel. Cytotoxic agents used in chemotherapy are hazardous and require strict precautions to minimize risks.

These precautions include using personal protective equipment (PPE) and specialized engineering controls, such as biological safety cabinets. Properly designed and classified cytotoxic cleanrooms help minimize contamination and ensure safety.

The first cytotoxic cleanroom in Iran was established in 2013, at the Imam Khomeini Cancer Institute in Tehran, and similar cleanrooms were developed in hospitals across the country. Recognizing the importance of compounding hazardous drugs in a controlled environment, the decision to construct a cleanroom at Omid Hospital in Isfahan, Iran, was made in 2018 and became operational in 2019. Initially, the cleanroom operation was limited to the outpatient chemotherapy department. However, it later expanded to include the preparation of chemotherapy regimens for both outpatient and inpatient settings, under the supervision of a general pharmacist and a clinical pharmacist.

Given that the cleanroom department is a recent addition and still evolving within the country, it is unsurprising that the personnel within this department might not yet have received sufficient training and become fully acquainted with the precise protocols required for effective operation. To mitigate performance errors, it was crucial to implement a monitoring process for the performance of cleanroom staff. This involved developing an observation plan to identify, record, and report deficiencies or shortcomings in their practical knowledge and skills. The results obtained from these observations should be carefully reviewed and compared against correct international guidelines. The purpose of this study is to provide a scientific and reliable explanation of these challenges and their impact on preventing the staff performance in the cleanroom from meeting international standards at the newly established clean room of Omid Hospital, Isfahan, Iran.

METHODS

This study was a descriptive-analytical and cross-sectional study conducted over a period of 6 months, from December 2021 to May 2022, at Omid Hospital in Isfahan, Iran. Omid Hospital is a specialized reference hospital for treating patients with hematology malignancies, solid tumors, and related conditions in Isfahan Province, Iran. Patients receiving chemotherapy regimens visit the hospital’s outpatient center and are hospitalized for a short period. These regimens contain various hazardous drugs that must be accurately compounded and prepared in the cytotoxic cleanroom.

The objective of this study was to observe and evaluate the performance of the cleanroom staff, including nurses, technicians, and established general pharmacists, in adhering to the cleanroom work procedures based on updated international standard guidelines. Different aspects were assessed, including hand and clothing hygiene, proper use of biological safety cabinets, preparation methods, handling leaks, and cleaning processes. The study also investigated the cooperation between nurses, the general pharmacist in the clean room, and the clinical pharmacist of the hospital in terms of error correction and addressing inconsistencies.

The sample size was determined to estimate the prevalence of various types of pharmaceutical errors while preparing chemotherapy regimens in a clean room. Using a formula with a 5% error level, a 95% confidence level, and a P = 0.05 based on similar studies examining the overall prevalence of errors related to chemotherapy drug preparation, a sample size of 1825 was calculated. Considering a dropout rate within the statistical population, the final sample size was estimated to be 2007 samples (observations of the preparation of 2007 intravenous drugs).

Due to the large sample size and the limited timeframe for data collection, a convenient sampling method was employed, resulting in a total of 1005 samples. Convenient sampling was chosen as it allowed for the efficient collection of data within the given time constraints.

During the 6-month period, the researcher collaborated with the staff team to gather information on all of the staff working in the cleanroom. They were provided with an overview of the general rules and structure of the cleanroom. The collection of information on eligible cytotoxic regimens was done continuously and randomly in relation to the cleanroom of the corresponding outpatient department. To obtain the necessary data for the project, the researcher reviewed and translated relevant sources and the latest international guidelines, including British Columbia Cancer Agencies’ policy for hazardous drugs, National Institute for Occupational Safety and Health guidelines for working with hazardous drugs and the United States pharmacopeia related to cleanroom performance.[5,6,7] Subsequently, the student prepared a data collection form under the project supervisors’ supervision.

In the data collection form, the researcher initially collected demographic information about the staff, including age, gender, marital status, presence or absence of children, work experience in the hospital, and the number of working hours per week.

Furthermore, the work criteria specific to the cleanroom were translated from international guidelines and organized into seven general sections and sixteen subsections. These sections and sub-sections were designed to assess various aspects of cleanroom work comprehensively.

A list of cleanroom staff was compiled after the data collection form was prepared. The study’s statistical population was determined to be the number of cytotoxic regimen prescriptions. During a total of 64 working days spent in the cleanroom, on each designated working day, the requested daily regimens to be prepared in the cleanroom were randomly selected. This random selection was facilitated by generating random numbers using Excel software. The researcher accompanied this process and observed the performance of all cleanroom staff in a maximum hidden way. Simultaneously, a reference questionnaire was administered, including two parts; the first part gathered demographic information about the staff, and the second focused on recording and measuring staff errors.

After completing observations for all of the staff in the cleanroom and reaching the desired statistical population from the received copies, the total errors were measured, and the type and number of errors were recorded and quantitatively analyzed.

In the subsequent stage, the study analyzed the demographic information of the cleanroom staff and the error rate they encountered. The study addressed the primary challenges confronted by the cleanroom staff, which were responsible for hindering their efficiency and productivity. However, it is essential to emphasize that this review is limited to a report specifically for the relevant hospital and does not encompass advanced analyses.

It should be noted that to minimize the study’s Hawthorne effect, the researcher took measures to ensure unbiased observations. Random days were selected to visit the cleanroom, and different staff members were observed during random regimen preparations, determined using random numbers from Excel software. In addition, the cleanroom staff were not informed of the true purpose of the researcher’s presence to prevent any potential alteration in their behavior due to awareness of being observed. These steps aimed to enhance the objectivity and accuracy of the study’s findings.

Following the comprehensive data collection process described above, our next objective was to discern any discernible correlations between the demographic characteristics of the nursing staff and the occurrence and frequency of errors. This critical analysis was carried out systematically to illuminate potential patterns and connections. An independent samples t-test was used to compare baseline parameters across the two treatment groups for continuous variables, and the Chi-square test was used to compare categorical variables. For the association between demographic information and the sort of errors occurring in the dataset, Pearson Chi-square and Spearman’s correlation tests were applied. All data were analyzed using SPSS (version 26; IBM, Armonk, NY, USA). All statistical tests were performed at the two-tailed 5% significance level; therefore, P ≤ 0.05 were considered statistically significant.

RESULTS

The demographic information of staff working in the clean room and the findings of common detected errors are reported in Tables 2 and 3, respectively. During the preparation of 1005 combined regimens, which served as our statistical population, 836 errors were identified. Among these errors, 556 were related to the compounding of drugs in the serum. The specific breakdown of these errors includes improper insertion of the syringe needle into the vial (200 errors), failure to adhere to the negative pressure rule (159 errors), neglect to disinfect critical sites and the body of the solution bag (101 errors), air removal errors (60 errors), and mistakes in needle replacement (12 errors). Furthermore, there were 127 errors related to working with biological safety cabinets. These errors encompassed issues such as improper cabinet disinfection (15 errors), inadequate disinfection of the supply tray (13 errors), incorrect placement of vials in the cabinets (99 errors), and incorrect placement of the cabinets themselves.

Table 2.

Demographic information of clean room staff and correlation with number of errors

Variables	Staff (n=11)	P	P values for correlation with sort of error
Age (years)	39.63±9.4	0.87	0.1
Gender (male), n (%)	5 (45.45)	0.67	0.008
Marital status (married), n (%)	9 (81.8)	0.65	0.78
Work shifts (morning), n (%)	9 (81.8)	0.67	0.94
Work experience (years)	18.36±10.84	0.41	0.00
Work hours (h/week)	44.72±4	0.12	0.16
Having children, n (%)	8 (72.72)	0.21	0.03

Table 3.

Common errors in the preparation of anticancer regimens by cleanroom staff

Error type	Number of errors (%)
Personal equipment errors	72 (8.61)
Having a heavy makeup	56 (6.7)
Wearing jewelry and hand watch	1 (0.12)
Not wearing reasonable masks	5 (0.6)
Wrong way of cleanroom gowning	10 (1.2)
Hand hygiene errors	15 (1.79)
Hand wash errors	56 (6.7)
Outer glove replacement errors	10 (1.2)
Disinfection of outer glove errors	5 (0.6)
Improper working with biological safety cabinets	127 (15.19)
Cabinet disinfecting errors	15 (1.79)
Supply tray disinfecting errors	13 (1.56)
Wrong placement of vials in cabinets	99 (11.84)
Wrong placement of cabinets	Construction error
Improper drug compounding	556 (66.51)
Improper inserting of syringe needle into the vial	200 out of 556
Not using negative pressure rule	159 out of 556
Not disinfecting the critical side of the solution bag	101 out of 556
Improper ventilating of the solution bag	32 out of 556
Improper syringe needle capping and ventilation	28 out of 556
Improper needle changes	12 out of 556
Improper control of leakage and contamination	0
	No leakage was detected during observation
Biological safety cabinet cleaning errors	66 (7.89)
Lack of sufficient equipment and disinfectants	33 (3.95)
Wrong order of cleaning the cabinets	33 (3.95)

Personal Protective Equipment (PPE) and hand hygiene errors were also detected, totaling 72 errors each. Examples of PPE-related errors included wearing excessive makeup among cleanroom staff, which occurred 56 times. Other PPE errors involved wearing jewelry and hand watches (1 error, corrected orally), failure to use appropriate masks during work (5 errors), incorrect cleanroom gowning techniques (10 errors, corrected orally), errors in hand washing (56 errors), mistakes in outer glove replacement (10 errors), and errors in the disinfection of outer gloves (5 errors). Finally, cleaning errors were observed, totaling 66 errors. These errors encompassed issues such as insufficient equipment and disinfectants for cleaning cabinets and the cleanroom itself (33 errors) and errors in the sequence of cleaning the cabinets (33 errors). Figure 1 and Table 3 show a more comprehensive understanding of the results.

Figure 1.

Percentage of errors detected in preparation of chemotherapy regimens in cleanroom

The results of Chi-square tests consistently indicate a statistically significant association between gender and hand hygiene errors in the dataset (P < 0.008). Based on the Chi-squared tests, no substantial evidence suggests that marital status is associated with the likelihood of errors in this dataset. The data indicate that, on average, individuals with children tend to have a higher mean number of hand hygiene errors (116) compared to those without children (68.67) (P < 0.03). Furthermore, there appears to be a statistically significant difference between individuals with and without children. Specifically, the group with children tends to have more errors. There is a significant positive correlation between the number of years working and the number of errors, suggesting that as employees accumulate more years of experience, they tend to make more errors (P < 0.00). However, neither the number of work hours nor years working significantly correlates with the other variables in this dataset. There are no statistically significant differences between other demographic variables and the presence of errors [Table 2].

DISCUSSION

Among the significant challenges that hinder optimal work efficiency in the cleanroom, adhering to international standards, the following can be highlighted:

1. Cleanroom Engineering and Construction Challenges: Cleanrooms are specifically designed to maintain low levels of particles and biological impurities. These rooms are categorized based on their application, such as cleanrooms in industrial factories, hospital cleanrooms, and laboratory cleanrooms. The lower the number associated with the cleanroom classification, indicating the number of particles per cubic foot of air, the cleaner the room. Constructing these facilities involves complex and specialized components, including air filters, air generators, and interconnected air channels with hoods. The technical features required for the design and construction of cleanrooms necessitate the involvement of experts from various construction fields. This includes building engineers, construction workers, independent and general contractors, construction management specialists, construction material manufacturers and distributors, hospital ward supervisors, and construction safety experts.

   A similar study conducted in Canada regarding cleanroom construction observed that achieving compliance with all construction factors necessitates establishing contracts involving multiple competent individuals. These contracts come in various types and entail different economic and management complexities. As a result, comprehensive cooperation between the hospital management system and engineering teams is required.

   The study further revealed numerous complications, such as unforeseen spatial limitations and other factors, that pose challenges in attaining 100% compliance with construction standards outlined in international guidelines.[8]

   Regarding the cleanroom at Omid Hospital, these challenges have also resulted in structural problems in the building. As the cleanroom needed to be installed in the outpatient chemotherapy department, the area with the highest volume of chemotherapy drug preparation, the available space for the cleanroom project was limited within the original hospital structure. Consequently, the cleanroom at the hospital faces structural and engineering weaknesses, including inadequate space for changing basic clothes, changing shoes, and the anteroom. In addition, while the overall cleanroom space is large and sufficient, the standard distance of one meter between the hoods inside the cleanroom has yet to be maintained.

2. Lack of Personnel Challenge: The sensitivity of the cleanroom environment demands that only essential staff enter these areas. To effectively manage the cleanroom, the relevant center must ensure the presence of well-trained and qualified staff. However, due to the nature of the cleanroom being designed to prepare anticancer and cytotoxic drugs, nurses may be concerned about potential adverse effects on their health, such as cancer, infertility, malignancy, and more. As a result, there needs to be more support among some staff to work in this center. Addressing these concerns and providing comprehensive training and support is crucial to attracting and retaining qualified cleanroom facility staff.

   On the other hand, staff working in chemotherapy centers may be more inclined to work in the outpatient department rather than in the cleanroom. This preference could be attributed to the more demanding working conditions in the cleanroom environment. For instance, entering the cleanroom requires staff to don specialized PPE, such as chemotherapy gowns, gloves, hair, and shoe covers. In contrast, working in the outpatient department typically involves wearing a standard white lab gown and mask; sometimes, sterile gloves are sufficient. Moreover, the cleanroom’s isolated and simple environment, with minimal communication with the outside, maybe less appealing to some individuals working in it. The cleanroom’s stringent protocols and restricted interaction with the external environment could influence staff preferences for working in other areas of the chemotherapy center. Addressing these challenges and considering the choices and comfort of the staff in the cleanroom environment is essential for creating a conducive and efficient working environment.

   In addition to the challenges mentioned earlier, there is a prevalent shortage of human resources, particularly nursing staff, in government centers and hospitals related to oncology. The demanding and specialized nature of the work in these settings contributes to this scarcity, leading to an acute sense of resource insufficiency. The challenging conditions, including the nature of the work in the cleanroom, may contribute to burnout among nursing staff, causing a lack of motivation to cooperate and inhibiting personal growth and development. This shortage can result in decreased responsiveness and engagement among the nursing staff, affecting the overall efficiency and effectiveness of the cleanroom operations. Addressing this issue requires strategic efforts to mitigate burnout, improve work conditions, and provide opportunities for professional growth and personal improvement among the nursing staff.

   By addressing the challenges related to human resources and fostering a supportive and motivating work environment, hospitals, and oncology centers can work toward enhancing staff retention and performance in the cleanroom and other related areas.

   The introduction of a cleanroom in Isfahan province’s hospital marks the first implementation of its kind in the region. Before this, staff preparing chemotherapy regimens in various hospital departments had their techniques and methods. Consequently, transitioning from their accustomed practices to adopting new techniques posed a significant challenge.

   To address this challenge, consider recruiting new staff for the newly established cleanroom who is receptive to adhering to the required protocols and are open to learning and implementing the latest techniques for chemotherapy drug preparation. By bringing in staff who are not set in their ways and are willing to embrace the new methodologies, the cleanroom can operate more efficiently and by the established guidelines. Creating a team who are receptive to change and adaptable to new techniques will facilitate a smoother transition to the cleanroom’s operation and promote compliance with international standards and best practices for drug preparation.

   Unfortunately, the initial consideration of manpower was overlooked in Omid Hospital, leading to the assignment of experienced staff to prepare chemotherapy regimens in the cleanroom. This decision resulted in several challenges between the clinical pharmacist, who serves as the technical manager of the clean room, and the experienced staff. The lack of alignment in preparation techniques deviated from international guidelines and became a common cause of inconsistency and errors in the cleanroom’s operations. To mitigate these challenges and promote adherence to international guidelines, the hospital administration must recognize the importance of having an appropriately trained and dedicated team in the cleanroom. Allocating staff receptive to adopting new techniques and aligning with international standards can significantly improve the efficiency and accuracy of chemotherapy drug preparation.

   In addition, providing comprehensive training and fostering open communication between the clinical pharmacist and nursing staff can facilitate a more collaborative and cohesive working environment in the cleanroom. By addressing these issues, the cleanroom can ensure a safer and more effective preparation of chemotherapy regimens for patients.

   Experienced staff showed significant reluctance to change their procedures in preparing chemotherapy drugs, mainly when adopting new techniques such as correct dressing, hand hygiene, changing gloves, and using negative pressure when drawing drugs. Despite the hospital’s technical and pharmacist team’s careful efforts to address these issues, many errors continued in the cleanroom. Furthermore, the hospital cleaning crew responsible for maintaining the cleanroom’s hygiene and sanitation must be dedicated and adequately trained, just like other staff in the cleanroom. Regrettably, the cleanroom in this center has been affected by the constant rotation of the cleaning crew within the hospital, resulting in frequent changes in the standard cleaning crew assigned to the cleanroom. This inconsistency in cleaning practices has further compounded the challenges of maintaining a clean and sterile environment within the cleanroom.

   Addressing these challenges necessitates a comprehensive approach, including:

   1. Providing extensive training and educational programs for the nursing staff to familiarize them with and encourage adherence to the correct procedures for preparing chemotherapy drugs
   2. Encouraging open communication and collaboration between the hospital’s technical and pharmacist team and the nursing staff to address concerns and implement best practices
   3. Establishing a dedicated and well-trained cleaning crew that remains consistent in their responsibilities for the cleanroom’s maintenance.

   By implementing these measures, the cleanroom can achieve higher safety, efficiency, and accuracy standards in preparing chemotherapy drugs while minimizing errors.

3. A high density of demand in the center: The high density of demand in the medical center is an evident issue, with public centers experiencing more crowding and higher footfall than other facilities. The large number of people visiting these centers increases the demand for drugs and anti-cancer regimens in the outpatient chemotherapy department. Consequently, this surge in workload not only slows down the patient acceptance process but also leads to delays in preparing regimens.

   The heightened workload puts significant mental and physical pressure on the staff, particularly the cleanroom personnel, which can negatively impact their work efficiency. The increased stress and workload also elevate the risk of errors during the preparation of regimens. As nurses and other staff members grapple with this situation, they may become impatient, frustrated, and more prone to restlessness, compounding the overall stress experienced by the department staff.

   These factors combined contribute to a reduction in the accuracy and efficiency of working with anticancer regimens. Addressing this challenge requires careful planning and resource management to ensure the center can efficiently handle the high demand. Implementing strategies to support the staff during peak periods and providing adequate training and support can help mitigate the negative effects of the increased workload and ensure a smoother workflow in the cleanroom and the entire department.

4. Essential equipment challenge: Personnel involved in compounding sterile drugs must use proper PPE to mitigate the risk of microbial and particle contamination from human skin, hair, and clothing. The use of appropriate PPE is essential to maintain a clean and sterile environment, thereby reducing the occurrence of contamination and errors during drug preparation. The cleanroom can only meet the requirements for drug preparation and disposal of low- or medium-risk compounds in a standard environment (as defined by ISO-5) with suitable clothing and PPE. Compliance with the ISO-5 standard is critical for ensuring cleanliness and safety in the cleanroom.

   To tackle this challenge, the hospital must prioritize providing and ensuring the availability of appropriate and well-maintained PPE for all personnel working in the cleanroom. Regular training and reinforcement of correct usage and disposal protocols are also essential to ensure staff adherence to safety measures. By adequately addressing the critical equipment challenge, the cleanroom can operate effectively, meeting the required standards for drug preparation and ensuring the safety and well-being of patients and staff.

   Equipment shortages have been a global issue since the outbreak of COVID-19. In our country, the combination of sanctions, difficulties in importing equipment, and the lack of self-sufficiency in equipment production have contributed to errors in the cleanroom. A similar study in the United States explored solutions to compensate for equipment shortages, including alternative equipment.

   In the United States study, the inability to obtain PPE was identified as the primary challenge. As a result, the pharmaceutical department was forced to replace gowns with alternative garments, such as laboratory coats, that had not been tested explicitly for particulate shedding in a cleanroom environment. This unexpected equipment replacement created additional challenges and uncertainties in maintaining the required level of cleanliness and safety in the cleanroom. Using alternative equipment without proper testing and validation could introduce new risks of contamination and errors in the drug preparation process.

   To address equipment shortages, the hospital administration must explore alternative sources for obtaining PPE and essential cleanroom equipment. In addition, any alternative equipment should be thoroughly evaluated and tested for suitability in the cleanroom environment to ensure it meets the required standards and does not compromise the integrity of drug preparation procedures. By proactively addressing equipment shortages and ensuring the availability of tested and validated equipment, the cleanroom can continue functioning effectively and safely, even during challenging times like the COVID-19 pandemic.

   In a critical environment like the cleanroom, proper PPE is essential for preparing sterile compounds with the required half-life after use and ensuring adequate therapeutic effect.

   When faced with equipment shortages, pharmaceutical and therapeutic departments must adopt various strategies to ensure the availability of PPE for compounding sterile products. Some of these strategies include:

   1. Collaborating with suppliers: Establishing strong partnerships with PPE suppliers can help ensure a steady and reliable supply of essential equipment
   2. Rationing and prioritization: Implementing a rationing system to allocate available PPE based on priority and urgency can help manage the limited supply effectively
   3. Local production and repurposing: Exploring the possibility of locally producing or repurposing certain PPE items can help bridge the gap in supply
   4. Resource sharing: Collaborating with neighboring healthcare facilities to share resources and distribute PPE when needed can be mutually beneficial
   5. Streamlining usage: Implementing efficient usage practices and ensuring proper disposal of PPE can help extend their availability
   6. Researching alternatives: Investigating alternative equipment options that meet cleanroom requirements and conducting appropriate testing and validation can provide viable alternatives
   7. Crisis management plans: Developing comprehensive crisis management plans for equipment shortages can enable the facility to respond swiftly and effectively during challenging situations.

   By implementing these strategies, healthcare facilities can improve their preparedness to handle equipment shortages, maintain a safe and sterile cleanroom environment, and continue providing high-quality patient care.[9]

5. Lack of financial resources is indeed an ongoing challenge for government centers in our country. Omid Hospital in Isfahan, managed by a board of trustees, provides free services to many patients, relying heavily on the budget offered by hospital benefactors for its operations. The consumable equipment required inside the clean room depends on continuous cooperation with the hospital pharmacy for procurement.

   To confront this challenge, the hospital administration must explore additional funding sources or seek partnerships with benefactors or other organizations to secure financial support for the cleanroom’s operations. Efficient budget management and resource allocation are also essential to promptly ensure that the cleanroom receives the required equipment and consumables. Furthermore, implementing a transparent and efficient procurement process can help optimize the utilization of available financial resources and streamline the purchase of essential items for the cleanroom. Collaboration between different departments within the hospital, such as pharmacy and cleanroom staff, is vital in identifying priority needs and ensuring that resources are allocated appropriately.

   By actively addressing the financial resource challenge, Omid Hospital can enhance the smooth functioning of the cleanroom, maintain the necessary standards for drug preparation, and ensure the provision of quality care to patients.

   Due to financial constraints, the pharmacy may need to prioritize equipment purchases, resulting in limitations in providing sufficient facilities to the nursing team inside the clean room when required. This shortage of necessary equipment can hinder the efficiency and effectiveness of drug preparation, potentially leading to errors and delays in patient care.

   This causes errors and noncompliance with the standard rules in the composition of drugs. For example, by the end of preparing any serum product containing chemotherapy drugs, it is necessary to clean the entire equipment with alcohol-soaked sterile gauze. But since buying gauze, even in a non-sterile form, entails a high cost for the pharmacy and hospital, purchasing a sufficient amount of gas is always affected. Regarding the correct use of gloves, buy an adequate number of high-standard gloves, such as nitrile gloves, to ensure the timely replacement of gloves by the nursing team residing in the clean room. Therefore, the limitation of resources is a primary factor in needing to fully comply with the preparation of pharmaceutical products by global guidelines, which has led to a constant challenge between the hospital pharmacy and the clean room of this center.

   Likewise, the limitation of medicine and equipment in recent years has been very problematic in our country. In some periods, even finding any serum itself had become a significant challenge in the country. Therefore, the lack of serum in different sizes caused various problems and errors when preparing chemotherapy drugs. The nurses in the clean room regularly had to reduce the size of serums, which caused many errors under the hood and increased the possibility of contamination in the final serum.

6. Budget challenge (lack of budget): Undoubtedly, the lack of funding in the outpatient chemotherapy department occurs for various reasons, such as the reduction of the overall hospital budget, lack of proper planning of the budget program, other hospital priorities, and high hospital costs. One of the main reasons for the lack of budget can be the stagnant economy, which results from many years of sanctions and lack of 100% self-sufficiency. These two factors reduce the purchase or production of high-quality equipment and drugs, and the possibility of errors and weak performance of employees also increases. Besides, in recent years, the outbreak of the COVID-19 epidemic has taken most of the attention of the medical sector, which has caused the budget to move toward the hospitals of the Corona site, and other departments have consequently had a smaller share of the former budget. The lack of funds for any reason causes a decrease in the hospital’s ability to purchase clean room equipment and supplies, a reduction in staff payment, a lack of hospital drug and equipment reserves, and finally, the efficiency of the clean room performance is far from the standard and ideal value.

7. Failure to pay the right of nurses to increase their motivation: Since the clean room itself is an isolated place where work requires minimal communication with each other and with the outside of the room, it is logical that the staff feel tired and unmotivated after a while. One of the ways to encourage and increase their motivation can be the payment of total salaries and sufficient bonuses to the nurses working in this department. This lack of motivation is added to the daily concerns and problems of the employees’ lives and ultimately leads to inaccuracy and can increase the rate of errors.

8. Absence of clinical pharmacist challenge: Considering that the clinical pharmacist of the hospital is busy at several sites (University of Medical Sciences, pharmacy, and other hospitals), it is natural that she would not be able to continuously attend the outpatient chemotherapy department and especially the clean room. On the other hand, the clinical pharmacist is the only person who participated in the establishment work in the clean room in a completely specialized way and oversees all the rules and instructions necessary for proper assignment. Therefore, the lack of constant presence to guide and correct the employees during work and monitor the overall operation of the clean room can be a reason for the increase in the number of errors. However, a trained general pharmacist works in this room, but her presence is temporary and is daily due to her other responsibilities. Therefore, in addition to providing all financial and human resources and sufficient equipment, the permanent company of a team of trained pharmacists can effectively reduce errors in the clean room.

9. Insurance system failure: One of the critical problems in the financial affairs of hospitals is the problem that arises from the lack of financial management and accounting in hospitals and imposes costs on the hospital. Aside from the hospital’s underfunding, what makes everything worse is the insurer’s reimbursement, which is usually delayed and charged because the insurance company is obliged to pay part of the health expenses of the insured in the hospital. On the other hand, usually every month, the insurance company, after checking the financial records of the hospitals, deducts amounts under the title of “deductible” from the total amount requested. The primary source of funding for hospitals is the insurance system, but hospitals sometimes have problems with the insurer, and usually, all their debts are not collected.[10] This lack of timely collection or incomplete collection causes problems in hospital payments and eventually leads to issues such as lack of compensation to employees and lack of funds for equipment and supplies which we discussed earlier, will, directly and indirectly, cause much damage to the standard work process in the clean room.

   The challenges in aligning the work of the clean room with international standards, particularly in a newly established center like Omid Hospital, are significant and have resulted in errors among the personnel working in this facility. The study shed light on the weak compliance with international standard guidelines and instructions, which can be attributed to various reasons. One of the main challenges observed is the resistance of clean room nurses to adapt to new ways of working with syringes, vials, and serums. Changing established practices can be difficult, especially for experienced personnel who have become accustomed to their techniques. This resistance to change can lead to errors and inconsistencies in drug preparation.

   Furthermore, the long hours of receiving patients in the outpatient chemotherapy center can reduce efficiency, particularly during the last hours of operation. Fatigue and high workload can contribute to errors and impact the quality of drug preparation. Structural defects in the clean room’s design, such as improper placement of air channels for hoods, can also hinder compliance with international standards. Insufficient facilities and equipment, such as a lack of needles, syringes, work tables, and trays, can further exacerbate the challenges clean room personnel face in maintaining proper standards.

   Despite these challenges, the researcher’s observation and work in the clean room revealed an improvement in the work efficiency of the established nurses and an increase in compliance with verbal and educational reforms. This suggests that proper training, guidance, and hands-on experience can positively influence adherence to international standards and reduce errors.

   To address the challenges identified in the clean room and improve the adherence to international standards, a comprehensive approach of solutions can be implemented:

   1. Continuous training: Conduct regular training sessions with all the responsible nursing teams to review and train the latest recommendations of international guidelines for drug preparation. These sessions can focus on proper techniques, safety measures, and adherence to cleanroom protocols
   2. Employ clinical pharmacists: Ensure the continuous employment of clinical pharmacists in hospital departments to train the medical team and identify drug therapy errors. Pharmacists can play a crucial role in verbally correcting nurses during drug preparation, providing guidance, and monitoring performance improvement after training sessions
   3. Improve budget and facilities: Amend the hospital budget to allocate sufficient resources for the clean room department. Increase the availability of required facilities and equipment, such as needles, syringes, work tables, and trays, to enhance the efficiency and effectiveness of drug preparation
   4. Motivate clean room employees: Ensure timely payment of salaries and consider increasing the wages of clean room employees to boost motivation and encourage dedication to their work. A well-compensated and motivated workforce is more likely to adhere to international standards and maintain high-quality drug preparation
   5. Encourage nurses to work in the clean room: Promote the clean room department as a rewarding and essential area of work within the hospital. Encourage nurses employed in the hospital to consider working in the clean room, emphasizing the significance of their role in patient care
   6. Continuous training of cleaning staff: Provide ongoing training to the cleaning staff responsible for maintaining the cleanroom’s hygiene and sanitation. Their role is crucial in minimizing contamination risks and ensuring a safe working environment
   7. Employ young and receptive staff: Consider employing young and receptive nurses and cleaning staff in the clean room. Younger staff may be more adaptable to new techniques and guidelines, facilitating a smoother transition to compliant practices.

   By implementing these solutions, Omid Hospital can improve the performance of its clean room, reduce errors, and promote a safer and more efficient environment for drug preparation. Regular evaluations and feedback mechanisms can be used to monitor progress and identify areas for further improvement.

AUTHORS’ CONTRIBUTION

M. Vaez, S. Karimi, and A. Moghaddas contributed literature search, translating guidelines, data collection, study design, and data analysis. M. Sharifi and A. Moghaddas were involved in hospital coordination, blinding the study, and teaching the work in the cleanroom to the researcher. All authors have approved the final paper.

Financial support and sponsorship

This study was financially supported by the Vice-Chancellory of research of Isfahan University of Medical Sciences, I. R. Iran through Grant No. 340 0952.

Conflicts of interest

There are no conflicts of interest.