This article is Part 2 of a 2-part series on creating cleaning practices that are compliant with USP <800> requirements. Part 1 discussed elements of a USP <800> compliant cleaning program, including:
- FDA guidance on cleaning
- USP definitions of cleaning
- Objectives of a compliant cleaning program
- The four steps required for cleaning compliance
Part 2 shares tips for ensuring the success of a cleaning program, including:
- Specific elements of USP <800> compliance
- Assessing the efficacy of cleaning through wipe sampling
To read Part 1 of this series, Elements of a USP <800> Compliance Cleaning Program, go to pppmag.com/MassoomiCleaning.
An effective cleaning program supports safe hazardous drug (HD) handling, eliminates transference of HD residue throughout the facility, and helps ensure staff and patient safety. A robust cleaning program should include clearly delineated standard operating procedures (SOPs), staff training, and follow-up monitoring to ensure best practices are maintained over time. The following tips will help ensure an effective cleaning program.
- The specific names of the defined chemicals used in each of the four-step cleaning process; the SOP should note that if cleaning solution residue is present, a fifth step is required
- Dilutions of solutions used
- Assigned expiration dates for commercially available solutions that are opened for use
- Assigned expiration dates for solutions that are diluted and prepared onsite
- Cleaning frequency based on USP standards
- Required personal protective equipment (PPE) while handling cleaning solutions
- Required dwell times (ie, wet surface time) to achieve desirable -cidal effect
- Clearly defined surfaces that must be cleaned with cleaning tools/technique (wipe vs mop), cleaning agent, cleaning frequency, and whether or not rinsing is required
- Correct technique for how to use the cleaning agents with the cleaning supplies
- Proper hygiene technique for minimizing cross-contamination of surfaces
(ie, cleanest to dirtiest; wipe and lift technique)
- Monitoring for cleaning solution residues, including corresponding residue-removal procedures with sterile water
- Monitoring for discoloration, rouging, or pitting of surfaces, which may indicate cleaning solution reactions with those surfaces
- Required documentation steps
Utilize the Four-Step Cleaning Process
- Deactivation renders any HD surface
contamination inert or inactive
- Decontamination focuses on inactivating, neutralizing, and physically removing surface contamination/HD residue with a deactivation agent and transferring it to sterile, lint-free, absorbent, disposable materials
- Cleaning focuses on removing contaminants from surfaces using water, detergents, surfactants, and solvents or other chemicals
- Disinfection, which is intended to inhibit or destroy microorganisms, must occur in areas that are required to be sterile
The four USP <800> cleaning steps must be employed in all locations where HDs are handled. Detailed information on the four steps is included in Part 1 of this series, available at: pppmag.com/MassoomiCleaning.
Image courtesy of Acute Care Pharmaceuticals
Cleaning is considered a hazardous process that requires formal staff education, demonstrated competency, and proper documentation. Sites must clearly define what PPE is required when handling cleaning solutions, as cleaning solutions can be caustic to skin and may elicit respiratory reactions. Do not assume that HD-rated PPE is suitable for all cleaning solutions; all PPE must be vetted to ensure it is resistant to the cleaning solutions used.
To begin, review the accompanying literature for the PPE and consider requiring the use of two pairs of HD gloves rated to ASTM D6978 as well as impermeable disposable gowns rated to ASTM F739 for cleaning activities. Because there is a potential for splashes to occur during the cleaning process, sites should strongly consider the use of tight-fitting eye protection or face shields.
Some solutions may require the addition of respiratory protection beyond a paper mask. In this case, consider employing a fitted N-95 mask. Furthermore, when handling solutions with nauseating odors, it is possible to utilize an R-95 mask that incorporates carbon or charcoal to filter out nuisance smells when cleaning areas exposed to drugs such as carmustine, cyclophosphamide, cisplatin, etoposide, and 5-fluorouricil.1 Note that this is not a complete list of drugs that have the potential to vaporize at room temperature, but represents a group of drugs that have been tested.
Additional information about respirators is available in the July 2018 PP&P article, Choosing Proper Hazardous Drug PPE for USP <800>: Part 2, at pppmag.com/MassoomiRespirator.
Images courtesy of 3M
Ensure Staff Safety During Cleaning
A report from the World Health Organization (WHO) identifies hospital cleaning solutions as a potential cause of respiratory (Chronic Obstructive Pulmonary Disease [COPD]) and reproductive disorders, eye and skin irritation, central nervous system impairment, cancers, and other human health effects.2,3 Under the US Occupational Safety and Health Administration’s (OSHA) Hazard Communication Standard (HCS) (29 CFR 1910.1200(g)), chemical manufacturers, distributors, or importers must provide safety data sheets (SDSs) (formerly known as material safety data sheets or MSDS) to communicate the dangers of hazardous chemical products. SDSs include the properties of each chemical; its physical, health, and environmental health hazards; required protective measures to employ when using the solution; and safety precautions for handling, storing, and transporting the chemical. To ensure staff is properly educated and protected when using cleaning solutions, organizations must share SDSs with all staff using these chemicals; this is particularly important for those staff members with active airway diseases (eg, asthma, COPD). Documentation that staff has received this information, and that an assessment of risk to exposure has occurred, are required.
Choose Cleaning Equipment Carefully
Cleaning solutions should be applied with equipment specifically designed for cleaning cleanrooms; avoid over-the-counter or commercially available equipment that may react or melt from repeated exposure. The cleaning equipment itself should be placed on a routine cleaning schedule, and be sure to determine when equipment must be replaced due to wear and tear and risk of contamination.
Cleaning solutions should be poured onto sterile, disposable, low-linting wipes, rather than sprayed, due to the risk of aerosolization of the solution(s) as well as the potential to aerosolize moistened HD residue. All cleaning materials and PPE must be considered contaminated and disposed of according to state and facility policies for hazardous materials.
Decontaminate Drug Vials
Several published articles have starkly demonstrated that measurable HD residue exists on the outside of vials, the accompanying package inserts, and the outer shipping boxes of vials received from manufacturers.4 USP <800> states that sites can reduce contamination by wiping down vials prior to placing them on any surfaces (eg, preparation tables, staging bins, primary engineering controls). Be sure that the cleaning solutions used for decontaminating drug vials do not impact the readability of the label.
Clean C-PECs Thoroughly
Containment primary engineering controls (C-PECs) must be cleaned at least daily and the compounding surfaces of the C-PECs must be decontaminated between the compounding of each unique drug to prevent any potential cross-contamination of products. This process is clearly supported by the 2018 FDA Guidance Document on Insanitary Conditions.5 Consider that case reports have demonstrated cross-contamination of Bacillus of Calmette and Guerin (BCG) to compounded sterile preparations subsequently prepared, leading to patient harm and deaths.6
In the event of a spill, deactivation, decontamination, and cleaning should occur immediately; if the spill occurs on a compounding surface, disinfection must also occur. To minimize HD exposure for maintenance and certifying personnel, surfaces should be cleaned prior to any servicing by personnel outside of the department.
C-PECs are designed to circulate ISO 5-classified air in a unidirectional pattern. To accomplish this process, their design may include areas under the compounding work surface trays. These under-spaces assist with moving air through vents located near the compounding surface to move contaminants away from the compounding surface. However, these areas may accumulate HD residue and items dropped during compounding (eg, vial caps, syringe packaging, pens, alcohol swabs).
PHOTOS 1-4 demonstrate items and HD residue contaminating the area under the compounding work surface trays. USP <800> clearly states that the under-spaces must be cleaned using the four-step process on a monthly basis to reduce contamination build-up.
It should be noted that accessing the under-space can be challenging, so staff may require assistance lifting and holding the upper work surface in place during cleaning. In addition, cleaning this surface disrupts the C-PEC’s protected airflow, and should be classified as a hazardous process requiring additional PPE and specialized training. Sites are encouraged to check the manufacturer’s maintenance information on the proper process for accessing the C-PEC under-spaces.
See TABLE 1 for a list of companies that supply cleaning products.
Conduct Wipe Sampling
USP <800> recommends routinely conducting surface sampling for HD residue, including an initial wipe analysis to establish a baseline. To establish a true baseline, wipe sampling ideally should be conducted prior to beginning the process of redesigning and reconfiguring work spaces to meet USP <800> standards.
A number of HD wipe sampling test kits are available, including traditional wipe analysis kits that quantify defined HD residues, as well as a newly introduced quick test system that detects the presence of defined residues without quantifying the amount present. Note that these new quick test systems identify only a few HDs; as such, non-detectable results from a specific analysis do not guarantee complete absence of HD residue. Result assessment from wipe sampling is complicated by the fact that there are currently no standards for acceptable limits of residues; however, the goal should be a zero tolerance of measurable residue(s).
Image courtesy of Fred Massoomi
Many facilities have yet to fully embrace the concept of conducting HD wipe analysis. This was illustrated in PP&P’s 2018 State of Pharmacy Compounding annual compliance survey. Just 25% of sites have ever conducted an environmental wipe sampling test for HD residue, and only 20% of that group continues to conduct wipe sampling on a semiannual basis.7
As part of a best practice HD safety program, incorporate wipe analysis practices that extend beyond simply defining the state of residue at a single point in time; an effective approach provides continuous validation of HD processes. Consider conducting immediate wipe tests of sterile and non-sterile compounding locations to confirm the surfaces are clean and ready for use prior to beginning compounding. This approach provides the information necessary to help minimize the transfer of residue from surface to surface, or from surface to products destined for patient administration. A recent study demonstrated that the use of frequent wipe sampling to assess contaminated locations improves the cleaning process, significantly reducing positive samples.8
The HD Check Analyzer checks for the presence of the drug without quantifying the amounts present (see FIGURE 1). Nonetheless, the presence of residue results in the same response to a quantified sample: recleaning and reassessment to baseline. A variety of vendors provide HD wipe sampling test kits (see FIGURE 2 and TABLE 1). These traditional tests cover a wider variety of HD compounds.
Conducting wipe analysis to identify HD residue helps sites validate their comprehensive HD handling practices. Without this validation, facilities may blindly assume that their cleaning programs are adequate and that they are immune to the widely established pattern of environmental contamination. Regular wipe studies identify the site’s active risk, allowing the facility to either improve practices or praise staff for following SOPs. Thereafter, a well-defined, systematic program for routine sampling assists in monitoring staff’s diligence at following SOPs.
Consider Integrated Cleaning Systems
A variety of integrated cleaning systems are commercially available in the US. These systems are intended to reduce the complexity and increase the ease of HD cleaning.
Some systems employ the use of pre-saturated cleaning solution wipes for each step of the cleaning process. Note that some systems may not address each of the four steps, thus requiring sites to supplement with an additional product. Conversely, some vendors have enhanced their testing to validate that a single product can be used for multiple steps of the four-step cleaning process.
The manufacturer of any commercially available cleaning system must provide validation that demonstrates the product’s desired result. In addition, organizations should collaborate with their infection control, employee health, safety, and environmental services departments in selecting products, training staff, and monitoring the use of these products.
- Kiffmeyer TK, et al. Pharm J. 2002;268:331-337.
- European Lung Foundation. Nurses’ Regular Use of Disinfectants Is Associated with Developing COPD. ScienceDaily. www.sciencedaily.com/releases/2017/09/170910232514.htm. Accessed January 24, 2019.
- World Health Organization. Chronic Respiratory Diseases: Causes of COPD.
www.who.int/respiratory/copd/causes/en/. Accessed January 24, 2019.
- Power LA, et al. Hosp Pharm. 2014;49(4):355-362.
- US FDA CDER Office of Compliance. Compounding and Related Documents, Revision 1: Insanitary Conditions at Compounding Facilities Guidance for Industry. www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm514666.pdf. Accessed November 27, 2018.
- Bacillus of Calmette and Guerin (BCG) [package insert]. Whitehouse Station, NJ: Merck & Co, Inc; 2018.
- Hazardous Drug Handling Supplement to Pharm Purch Prod. July 2018; S14, S16.
- Crul M, et al. J Oncol Pharm Pract. 2018;24(7):483-489.
Fred Massoomi, RPh, PharmD, FASHP, is a senior director of hospital and health-system pharmacy for Visante, Inc. He received his doctorate from the University of Kansas School of Pharmacy. Fred is a member of PP&P’s Editorial Board.
Part 1 of a 2-Part Series: Elements of a USP <800> Compliant Cleaning Program
Conduct a Drug Diversion Investigation
Special PP&P Buyer's Guide: Temperature Monitoring
Develop a Pneumococcal Vaccination Program
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