This article describes workflow strategies to reduce environmental and personnel exposure to hazardous drugs (HDs) in the compounding pharmacy.
In accordance with USP chapter <800> guidelines, workflow strategies are involved in handling hazardous drugs in the compounding pharmacy, with an aim to minimize environmental and personnel exposure.
In an article titled, "Can A Class I and Class II Biological Safety Cabinet be in the Same Sterile Hazardous Room”(https://learn.nuaire.com) workflow techniques and the possibilities for exposure points during the pre-sterilization process of HDs are discussed.
Similarly, in another article titled “Facility and Engineering Controls Using USP 800 Guidelines” (https://www.pppmag.com), the synergistic association between Good Lab Practices (GLP), mostly focusing on nonsterile rooms, and the containment primary engineering control (C-PEC) were discussed.
The aim of this article is to combine all these compounding workflow and chemical handling strategies into a more sequential model, so that environmental and personnel exposure can be minimized.
While this article mainly focuses on nonsterile hazardous drug handling processes, GLP principles are relevant to both nonsterile and sterile chemical handling. It is also likely that non-sterile compounding rooms will have airborne and surface contamination in the non-sterile compounding rooms, because of the activity and volume of dry powders being managed.
Where Does Contamination Come From?
Over years of visiting numerous pharmacies, we have observed that similar and consistent workflow processes cause chemical exposure in compounding rooms. There are four typical workflow processes that encourage personnel and environmental exposure.
- Technicians violate the C-PEC while actively manipulating and weighing powders to recover more materials and/or interact with formulation records.
- Dry-contaminated gloves, wipers, and weigh boats are discarded in open-face trashcans in the laboratory environment.
- Contaminated capsule plates, glassware, and weighing utensils are removed from the C-PEC and sent across the laboratory to the sink.
- Bulk-chemical containers are not cleaned before placing them back in storage.
However, these four exposure points can be rectified by implementing some basic process enhancements at little additional cost to the pharmacy. Exchanging old habits for a new culture may be the biggest obstacle to date.
The recommendations given below are established chemical handling workflow methodologies that will reduce and even prevent personnel and environmental exposure. The article sequentially walks through the compounding workflow process, and includes Appendix-1 at the end as a support document. What is guaranteed is that if the process is changed, it will change the results for the betterment of the staff and facility of your pharmacy.
The Integral Step 1: Planning and Staging
The first document that a technician reviews to plan the formulation workflow process, is the "Compounding Record". This record outlines the ingredients and chemicals needed to formulate the script, but it’s not always considered the best directional guide to safe handling procedures or reliable process replication.
As part of the Master Formulation Record, comprehensive steps like mixing and quality control information are usually included but what the compounding record lacks, is a more comprehensive list of the required materials such as mixing vessels, proper utensils, additional tools, as well as the number of weigh boats needed.
While this attention to written detail may appear unimportant, the presence of this brief planning document can help encourage safety workflow habits in technicians in an attempt to prevent the exposure points as defined in the earlier section “where does contamination come from?”
More comprehensive safety process documents in the HD compounding rooms are strongly recommended to fulfill the USP 800 language that states, "Each entity must have a designated person who is qualified and trained to be responsible for developing and implementing appropriate procedures."
These "appropriate procedures" cover all phases of the HD handling process, and particularly the active chemical handling phase during compounding. One can easily achieve this objective by introducing new language to the Master Formulation Record and transferring it onto the compounding record by including references to:
- HD Safety Handling Procedures for the chemicals and workflow processes
Example: Chemical bottles should be opened within the primary engineering control.
- Required Personal Protective Equipment (PPE)
Example: During weighing and mixing of <name of chemical>, a half-mask respirator with P100 cartridge filters should be worn.
- All essential materials required to complete the compounded script
Example: This formulary needs: 3-weighing utensils; 2-small weigh boats; 1-large mortar/pestle; 1-large weigh boat, etc.
- Cleaning, decontamination, or deactivation for the HD chemicals
Example: Initial bulk cleaning must be performed with 70/30 Isopropyl Alcohol; final cleaning should be performed with sporicidal disinfectant based on peroxyacetic acid /hydrogen peroxide.
The language defined in the four exposure points listed above sounds more like Standard Operating Procedures (SOP) language which could be true, but it is contended that the compounding records lack the SOP language. While SOPs are written with good intentions, "repetition is the mother of skill," and therefore if there is no consistent reinforcement of the intended purpose, technicians may probably revert to old habits.
Developing new habits for hazardous drug handling aiming to keep employees safer and make environments cleaner is one of the purposes of USP 800. Therefore, a new iteration of comprehensive compounding records that defines the purpose more clearly is recommended.
“Staging” is part of the planning document, where the technician has to think all the way through the formulation workflow process before actually starting, placing this as perhaps the most critical step in reducing environmental and personnel exposure. It is important not to disregard the significance of this front-end mental exercise wherein a technician asks, "What do I need to complete this formulation from start to finish?"
If the staging process is handled properly, most of the issues related to environmental exposure can be resolved because all the required materials have been introduced inside the C-PEC by the technician. This would leave little reason for the technician to violate the containment with contaminated gloves just to retrieve additional materials.
A basic example of staging an encapsulation formulation is given below: (also refer Reference-1)
- Three chemicals
- Three weigh boats
- Three weighing utensils
- Mortar and pestle (or mixing vessel)
- Capsule machine and plate
- Capsule tamper
- Wipers for cleaning
Space inside the C-PEC as well as space inside a compounding room is always a premium. Utensils, weigh boats, and staging chemical bottles undoubtedly takes up space, particularly when a capsule machine and an electronic balance are added.
Therefore, to ensure there is sufficient real estate to stage all the required materials, a four-foot wide C-PEC is strongly recommended as this will provide sufficient space for the technician as well as for the CPEC's airflow to carry out properly.
For many individuals, staging all the necessary chemicals inside the C-PEC is perhaps a new concept, because staging the chemicals directly outside the C-PEC and retrieving as required have been more commonly observed and this is the reason why a wider C-PEC will encourage the technician to adhere to the proper workflow process. Just to reiterate, "staging" ensures that after the technicians commit to the C-PEC, they stay within the C-PEC during the whole course of the formulation procedure.
Reference-1. Proper Staging Inside the C-PEC
Step 2: Documenting Chemicals and Weighing
At this crucial point, it has been fully established that all the required materials are staged within the C-PEC, the technician is attired in appropriate Personal Protective Equipment (PPE) and is ready to commit to the compounding formulation.
However, the workflow process of documenting all steps of the formulation presents possibilities for contamination. This article describes the two most common documentation methods – paper-based and software-based, highlighting some possibilities for contamination and solutions for reducing exposure.
It has always been difficult to interact with the formulation software, because the technician has to actively engage the technology, which sometimes causes contaminated hands to violate containment. The following software processes require technician interaction:
- Making an input on the keyboard
- Clicking the mouse to move to the next step
- Scanning the barcode on a chemical bottle
In this article, each of the active software engagement process is analyzed and solutions are provided. It is important that the infrared (IR) scanner is strategically positioned to shine through the C-PEC sidewall as this will enable the IR beam to read and scan the bar code into the software. Therefore, it is still a valid solution for staging all the chemical bottles within the C-PEC.
Scanning one chemical and then weighing that chemical is the best quality control method for interacting with the formulation software. Different methods of this process have been witnessed where all the chemicals are first scanned into the software and then the chemical bottles are loaded inside the CPEC. While the technicians are commended for attempting to make the workflow procedure containment friendly, it supersedes the quality control method of the software.
The electronic balance is interacting with the formulation software, and as soon as the exact chemical weight is accepted by the formulation software the technician often has to click the mouse to move on to the next step. This can be resolved by placing a wireless mouse within the hood proximal to the right sidewall.
As the majority of people are right-handed, the computer monitor workstation displaying the software should be set up on the right area of the C-PEC to ensure the best ergonomics. Mouse contamination can be prevented by placing sticky cellophane wrap (a dental supply product) on top of the mouse or bagging it in a clear sandwich bag, as shown in ‘Reference-2 picture’. The technician can now easily interact with the wireless mouse within the hood without violating the containment.
Reference-2. Wireless mouse inside the C-PEC with plastic protective cover
However, it is not possible to fit the keyboard inside the C-PEC. Fortunately, there are minimal encounters with the keyboard, but it does takes place; but whenever this challenge is encountered the technicians are advised to spray isopropyl alcohol (IPA) solution on their gloves and thoroughly wipe them to remove the visible powder as much as possible.
When the technician breaches containment, it would be useful to have clear cellophane over the keyboard as an additional safety measure. Several visibly contaminated keyboards have been witnessed during site visits and it was recommended to dispose them because all the keys and crevices cannot be cleaned thoroughly.
In compounding pharmacies, a paper-based documentation method is more commonly used than software. Due to this reason, papers that contribute to contamination should be investigated. It is usual to see reams of papers in nonsterile compounding rooms. Each of those papers is a site for harboring contamination, as paper is a porous, organic material.
Moving forward to USP 800 implementation, the nonsterile HD and sterile HD rooms should be minimalist, meaning some level of digital technology should be implemented instead of generating more paper based records.
Manual documentation of chemical information (e.g. NDC, expiration date, lot number, etc.) on the compounding record before staging all the chemical bottles within the C-PEC is a safer practice.
Therefore, the Appendix-1 process map can be edited by introducing an extra step before "1.a" or "1.b" to state "Document NDC, lot #, and expiration dates for all chemicals on formulation record."
Thereafter, all process map boxes will display fresh sequential letters. If the electronic balance is used for safe documentation of chemical weights, it is advisable to attach a printer but this should be placed outside the C-PEC.
Through the formulary process, the ticker-tape of the printer will document all the weights and eliminate the need for technicians to interact with the ticker-tape paper until the formulation is completed. The Pharmacist-In-Charge can also interact with the ticker-tape from a safe distance.
Handling Chemicals during Compounding
Bulk chemical containers should be opened only inside the C-PEC. While this may appear to a logical rule, there have been situations where technicians open a container directly from the storage shelf. Perhaps, this is done to check whether or not an adequate amount of chemical is available to complete the current formulation, but it does occur.
So, it is worthwhile to reinforce the point of opening chemicals only inside the C-PEC verbally during training and in written form on SOPs. One rule of thumb with regards to handling chemicals is, unless an adequate risk assessment has clearly documented that the chemical in question is safe to open outside of the C-PEC and does not need PPE, it is always better to assume that the chemical carries an exposure risk and needs containment.
Even inside a low-flow C-PEC, powder micronizes continuously. Each chemical is weighed separately in boats, or another vessel, before being poured into the mixing vessel; therefore, the discarded weigh boats must remain inside the C-PEC.
All processes like mixing, trituration, manipulation, and encapsulation of dry powders should be carried out inside the C-PEC. Chemicals can be safely removed from the CPEC only when they are in final dosage form like capsules, or in wet solution such as a cream base.
The discarded gloves, wipers, and weigh boats can also be removed from the hood, provided they are in a sealed bag. Waste removal and cleaning of the C-PEC will be discussed in a forthcoming article, but the important point here is dry materials should never be pulled out from the front face opening of the C-PEC.
There’s Always Obstacles
When technicians have to remove their hands from inside the hood to retrieve extra items, this means they have to breach containment. Therefore, they should seek help from another technician who is not actively engaged in the chemical handling process and retrieve the item for them.
Gloves (and possibly sleeve protectors) should be temporarily donned by the additional technician, who can then place the item just within the face opening of the CPEC. The main technician who is actively involved in compounding should never reach out and retrieve the item from the hands of the other technician.
In case technicians are not available to assist, two options remain. The first and most effective option is to fully doff outer gloves and sleeve protectors while inside the C-PEC and retrieve the required items, and then don a fresh set of gloves and sleeve protectors and re-enter the C-PEC. The second but least proficient option is to spray IPA on the sleeves and gloves, thoroughly wipe them clean, and then retrieve the necessary item after removing the gloves.
In the compounding room, a correctly labeled spray bottle of 70/30 IPA should be placed inside each C-PEC. This IPA spray bottle should permanently remain inside the C-PEC. It is not necessary to take out the IPA bottle from the hood.
During the arduous path of HD handling and compounding, there are many possibilities for personnel and environmental exposure. In this article, only “qualitative” examples of exposure during the active chemical handling phase were discussed.
However, the industry lacks a more "quantitative" validation via surface sampling, limiting the possibility to establish a legitimate case for contamination acceptance. The aim of this article was to distinguish common areas where there is a possibility of chemical exposure and provide simple, economical workflow solutions that will have a real impact on the cleanliness of the compounding room.
Safe chemical handling procedures mean safer workplaces, which, in turn, can yield better quality products for patients. Therefore, the synergistic association between quality and safety for overall USP compliance should be well understood.
Appendix-1. Basic Process Map for Nonsterile Compounding Workflow
About the Author
Bryan Prince, MBA is the owner and lead consultant at Lab·Red Pharmacy Consultants. His early career in containment technology allowed him access to pharmaceutical labs around the U.S. where he gleaned extensive knowledge of chemical handling technique and safety strategies.
In 2012 he started visiting compounding pharmacies to observe workflow habits and share his knowledge, which led to writing articles for the International Journal of Pharmaceutical Compounding (IJPC). Bryan has been invited to speak at conferences on “Quality, Safety, and Workflow in the Compounding Pharmacy” for the American College of Apothecaries and PCCA.
Most recently he has spoken on "Facility and Engineering Controls Using USP 800 Guidelines" for the ACA and IACP. He is also a contributor to the ACHC’s USP 800 education conferences and webinars.
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