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
Read the full article here.
Join Jim Jorgenson, MS, RPh, FASHP, CEO, as he discusses what should be done to prepare for revised USP Chapter 797 and new USP Chapters 800 and 825.
Beyond USP <800>
Frequent Environmental Monitoring for Hazardous Drugs with BD’s HD Check
Proposed revisions to USP <795>Pharmaceutical Compounding – Non-Sterile Preparations, USP <797>Pharmaceutical Compounding – Sterile Preparations, and, proposed USP <800>Handling Hazardous Drugs in Healthcare Settings each have sections devoted to cleaning and surface sampling. Proposed/revised USP <795> defines Cleaning as “The process of removing soil (e.g., organic and inorganic material) from objects and surfaces, normally accomplished by manually or mechanically using water with detergents or enzymatic products.”[1,2,3] Proposed/revised USP <797> defines a Cleaning Agent as; “An agent for the removal of residues (e.g., dirt, debris, microbes, and residual drugs or chemicals) from surfaces,”and, proposed USP <800> adds complexity to the process by building on the ‘cleaning’ definition under section 14.4 CleaningC-PEC and Other Devices Used for Compounding HDs by adding the additional steps of Deactivation, Decontamination, Cleaning, and, Disinfecting.
Historically, sites compounding medications for patients have customarily used 70% isopropyl alcohol as a ‘cleaning’ agent. However, isopropyl alcohol is not a cleaning agent, it is a disinfectant and does not meet the definitions listed within the noted USP standards as a cleaning agent. The use of isopropyl alcohol as a misunderstood surrogate cleaning agent in non-cGMP compounding locations has been employed without a validation process to support the effectiveness of the agent. As noted, for an agent to be defined as a cleaning agent it must remove dirt, debris, microbes and drug residues. The lack of cleaning-ability of isopropyl alcohol is most evident with hazardous drug compounding.
For more than 30 years, studies have found residues of hazardous drugs present in measurable concentrations throughout the environments where they are handled. We also know that these residues can carry-over throughout the line of handling—from the receipt of the drug at the loading dock, to compounding, to administration, and, to its final disposal. 
Proposed USP <800> recommends conducting surface sampling for hazardous drug (HD) residue ‘routinely.’ The chapter recommends an initial wipe analysis to establish a baseline, followed by additional wipe analyses to occur at least every 6 months or more as determined by the needs of the site. When a facility begins the process of redesigning and reconfiguring work spaces to meet USP <800> standards, the ideal time to conduct a wipe analysis is prior to any drugs being brought into the space, as this provides a true baseline. To assist sites with conducting consistent wipe analysis, commercially available wipe kits are available. It is important to note, these commercial kits only test for a handful of specific hazardous drugs and the results do not represent all drugs. As such, non-detectable results from a specific analysis does not guarantee that no HD residue is present. Result assessment is further complicated by the fact that there are currently no standards for acceptable limits for residues; however, the goal should be a zero tolerance of measurable residue(s).
Sites have not fully embraced the process of conducting hazardous drug wipe analysis. This was illustrated in the 2017 CriticalPoint survey of annual compliance with 454 hospitals reporting and only 13% (N= 59/454) of sites reported ever conducting an environmental wipe sampling for hazardous residue. 
Best practice for a hazardous drug safety program would be to utilize wipe analysis to go beyond defining a historical issue and concurrently validate processes within the hazardous drug continuum. For example, each compounding location (sterile and non-sterile) could conduct an immediate wipe test to confirm surfaces are clean and ready for use. This approach would provide information necessary to help minimize the transfer of residue from surface to surface, or from surface to products destined for patient administration. A recent Danish study demonstrated the use of frequent wipe sampling to assess contaminated locations and improve the cleaning processes to greatly reduce positive samples. 
Becton Dickenson (BD) released in 2018 the HD Check Analyzeras a system to provide results in as little as 10 minutes for the hazardous drug residues.
BD HD Check Analyzer; Assay Cartridge; Collection Kit
Visante consultants are using HD Check Analyzer in the field. The system requires minimal training for results. The HD Check Analyzer is designed to be an intuitive and easy process, with just 8 steps:
- Assemble supplies and don personal protective equipment;
- Identify test surface using the HD Check template;
- Swab test surface;
- Transfer swab to the sampling tube and invert 5 times;
- Squeeze 4 drops from sampling tube onto the methotrexate or doxorubicin drug assay cartridge;
- Allow 5 minutes for drug assay cartridge to develop;
- Turn on the analyzer and place the developed cartridge in system when prompted;
- Read the positive or negative result
At the time of writing, the system was limited to methotrexate and doxorubicin, which is used at most facilities in the US. Unlike the commercially available wipe analysis kits, the HD Check Analyzer checks for the presence of the drug without quantifying the results. The mere presence of residue results in the same response to a quantified sample; recleaning and reassessment to baseline. BD is currently developing a catalog of the most frequently handled hazardous drugs in the US.
Sites should consider the continuum of the hazardous drug handling process and assign routing sampling intervals for assessing for residue.
Hazardous Drug Scope
Due to the immediacy of the results, the HD Check Analyzer can be used: daily to validate cleaning processes; whenever cabinets and surfaces where hazardous drugs are used are cleaned; and, whenever a spill occurs to validate the spill has been fully cleaned. Conducting real-time wipe analysis to identify any hazardous drug residue serves as a tool that can assist sites with validating their entire hazardous drug handling practices.
Without conducting a hazardous drug residue wipe analysis, facilities are blindly assuming they are immune to this widely established pattern of environmental contamination. Conducting regular wipe studies identifies the site’s active risk, allowing the facility to either improve practices or praise staff for following well-defined SOPs. Thereafter, a well-defined, systematic program for routine sampling will assist in monitoring the staff’s diligence at following standard operating procedures.
BD’s HD Check Analyzer brings a Visante Best Practice pearl to sites looking to enhance their safety of their programs beyond USP <800> standards.
As the official implementation date of December 1, 2019 for proposed USP <800> and subsequent revisions to USP <795> and USP <797> compliance. The time for review of USP’s newest and revised chapters is now.
Don’t know where to start with a hazardous drug safety program? Visante offers a full line of consulting activities to clients just starting down the road to compliance to practice sites on the journey and wanting to go beyond minimal practice standards. Contact us today to get started.
 proposed revision, USP General Chapter: USP <795> Pharmaceutical Compounding – Non-sterile Preparations. http://www.usp.org/compounding/general-chapter-795
 proposed revision, USP General Chapter: USP <797> Pharmaceutical Compounding – Sterile Preparations. https://www.usp.org/compounding/general-chapter-797
 proposed, USP General Chapter: USP <800> Hazardous Drugs—Handling in Healthcare Settings
 Sessink PJM, Anzion RB, Van den Broek PHH and Bos RP. Detection of contamination with antineoplastic agents in a hospital pharmacy department. Pharm Weekbl (Sci). 1992; 14:16-22.
 Douglass K, Kastango E. USP <800> Let’s Get Started. Pharmacy Purchasing and Products; December 2017 supplement.
 Crul M, Simons-Sanders K. Carry-over of antineoplastic drug contamination in Dutch hospital pharmacies. J Oncl Pharm Pract. 2018;24(7):483-489.