Cleaning Program under the Revised Propositions
The proposed revisions to USP <795>, USP <797>, as well as proposed USP <800>, all include sections devoted to cleaning and surface sampling.
Proposed/Revised USP <795> defines cleaning as: The process of removing soil (eg, organic and inorganic material) from objects and surfaces, normally accomplished by manually or mechanically using water with detergents or enzymatic products
Proposed/Revised USP <797> defines a cleaning agent as: An agent for the removal of residues (eg, dirt, debris, microbes, and residual drugs or chemicals) from surfaces
Proposed USP <800> increases the specificity of the process by building on the cleaning definition under section 14.4, Cleaning C-PEC and Other Devices Used for Compounding HDs, by adding the additional steps: Deactivation, Decontamination, Cleaning, and Disinfecting
Historically, sites compounding medications have used 70% isopropyl alcohol (IPA) as a cleaning agent. However, IPA is not a cleaning agent; it is a disinfectant and does not meet the definitions listed within the noted USP standards of a cleaning agent.5 The use of IPA 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, a correctly defined cleaning agent must remove dirt, debris, microbes, and drug residues. The lack of IPA’s cleaning ability is most evident with HD compounding. Although IPA is commonly used, it is important to understand that IPA does not remove residue or break down, so IPA residues linger.
For more than 30 years, studies have identified HD residue in measurable concentrations in the environments where they are handled. These residues can also be tracked throughout the line of handling—from the receipt of the drug at the loading dock, to compounding, administration, and disposal.6 The objectives of a USP <800> cleaning program include protecting patients, health care workers throughout the continuum of HD handling, and the environment.
Cleaning practices should not be developed in a vacuum; rather, consider the totality of FDA guidance and USP requirements. In order for sites to be compliant with USP <800> cleaning practices, they must also be compliant with the requirements set forth in USP <795> for non-sterile preparations and USP <797> for sterile preparations. USP <800> highlights the importance of cleaning by devoting an entire section to it: Section 15 outlines the four-step process of deactivating, decontaminating, cleaning, and disinfecting, noting that not one single method or cleaning process exists as a universal standard for all HDs. USP <800> provides comprehensive definitions of each of these steps, as well as the reasoning behind each. The goal is to provide a suitable environment that protects personnel and patients by removing HD residue and returning the cleaned location to baseline (ie, no residue or contamination).
The Four USP <800> Cleaning Steps
Defining the separate steps helps staff to understand the purpose of each and facilitates compliance. Deactivation, decontamination, cleaning, and disinfection can be defined as follows:
- Deactivation is intended to render any HD surface contamination inert or inactive. It is important to recognize that in terms of deactivation, there is no single, proven method for inactivating all compounds. EPA-registered oxidizing agents (eg, peroxide formulations, sodium hypochlorite, etc) represent the most widely used option and should be used when possible. However, note that these agents are caustic; products such as sodium hypochlorite will pit or mar stainless steel surfaces if left in contact for too long.
- 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. Chemicals such as sodium thiosulfate can help neutralize chemicals used in the deactivation step to minimize corrosion and pitting of stainless steel. In addition to enhancing the cleaning process, decontamination should be strongly considered for each drug vial that may arrive from the manufacturer already contaminated. Applying this step to vials can reduce contamination introduced into sterile compounding primary engineering controls (ie, hoods). Note that it is important to ensure that the solvent used for wiping vials does not alter the product label.
- Cleaning focuses on removing contaminants from surfaces using water, detergents, surfactants, and solvents or other chemicals. The cleaning section in Chapter <797> is appropriate for both hazardous and nonhazardous drugs. It is critical to ensure that any products used for cleaning do not introduce microbial contamination.
Facilities should examine all product material specifications to ensure products chosen are EPA-registered to meet the five “-cidal” criteria: bactericidal, fungicidal, virucidal, tuberculocidal, and sporicidal. Remember that if an agent states that it “kills spores” or that it kills a specific type of spore, this is not equivalent to being labeled a sporicidal agent. If a product in use is not clearly labeled as sporicidal, a sporicidal-labeled agent should be added to the cleaning regimen.
Another important consideration for choosing cleaning agents is the required contact time of an agent with a surface to induce the specific -cidal response. Some agents require up to 5 minutes of direct contact time to be effective; the agent should be applied in the defined quantity and allowed to remain on the surface for the stated time. Wiping away the agent too soon eliminates the cleaning benefits and may allow microbes to proliferate.
- Disinfection is intended to inhibit or destroy microorganisms and must occur in areas that are required to be sterile. EPA-registered disinfectants and/or sterile 70% IPA are appropriate agents for this step. The use of ultraviolet light as a means for disinfection should only be considered as an adjuvant to physically applying and removing liquid disinfecting solutions. Any biofilm that might remain on surfaces can be removed with the physical wiping motion.
The four USP <800> cleaning steps must be employed in all locations where HDs are handled. For example, non-sterile areas where HDs are handled (eg, receiving containment ventilated enclosures [CVE]) and reusable equipment and devices (eg, counting trays, spatulas, unit dose devices) must be deactivated, decontaminated, and cleaned. As directed by USP <797>, sterile preparation areas also must include the final step of disinfecting. Selected cleaning solutions must not be reactive to surfaces to be cleaned and must not harm equipment or impact the protective nature of devices employed (eg, melting surfaces, pitting stainless steel, melting casings of electrical wires, penetrating gloves, and impacting the HEPA filter seals in primary engineering controls).
Following the cleaning process, examine areas for visible residue, often appearing as hazy/white smears or drops, which may be left behind by some products. Visible residue is unacceptable. It must be understood that dried chemicals no longer possess their desired activity and are considered a contaminant; potential air pockets between the surface and the residue can harbor spores that are easily transferred to the sterile field or products. If left for long periods, dried residue also can cause surface corrosion. Regulatory inspectors often view the presence of residue as an indication of inadequate cleaning. Pharmacists should become familiar with the FDA guidance concerning the presence of residues (available at:
www.fda.gov/ICECI/Inspections/InspectionGuides/ucm074922.htm).7 Either sterile water or 70% sterile IPA are effective at removing residue.
Protecting health care workers, patients, and the environment from HD exposure, as required by USP <800>, is the goal of a robust cleaning program. Achieving compliance with USP <800> requires a comprehensive approach to deactivation, decontamination, cleaning, and disinfection, based on FDA guidance and USP <795> and <797> principles. As the date for USP <800> compliance is less than a year away, organizations should investigate their cleaning practices now to ensure any required adjustments are made forthwith.
Contact us and let our project specialists help you better understand the mandatory cleaning requirements under the new revisions. Call 1.800.418.9289 or email support@asepticenclosures.com
