Attaining compliance with United States Pharmacopeia (USP) Chapters is of great concern within the practice of sterile compounding, as the process can be quite daunting and also expensive. This is especially true in small and/or rural facilities.
Sharon Hospital, located in a small, rural community in Connecticut, set out to upgrade the sterile processing area with the goal of attaining full compliance with USP Chapters <797> and <800>. The significant obstacles we encountered during the construction process, while frustrating at the time, led us to gather a wealth of knowledge about what to do—and what not to do—when upgrading the sterile processing suite. We hope by sharing our lessons learned, other facilities can avoid similar problems and gain insight into the necessary steps for making positive choices when planning upgrades or build-outs of sterile processing areas.
The planning phase for constructing the sterile processing suite began in Spring 2015 with the choice of the architect and the contractor; construction commenced in Fall 2015. As part of the process, the contractors walled off an area to allow for the construction and relocated the compounding aseptic isolator (CAI) to a temporary location to support compounded sterile preparation (CSP) production.
During the construction process, the hospital underwent significant changes in leadership; in addition to new management at the facility level, there was also a change in pharmacy management. With new management overseeing a construction process that was already underway, it was important to evaluate the process to understand the intricacies of the steps that had already been taken and to determine the remaining steps needed to ensure the project moved forward in a positive direction. Ultimately, it was necessary to develop a plan of action to ensure the project’s goal of building a USP compliant cleanroom complex.
Having more than one large project occurring at a given time requires a division of focus, and there is a risk that this division can have a deleterious effect on the respective end goals. At the same time Sharon Hospital’s sterile processing suite was being upgraded, the hospital also completed a conversion to a new automated dispensing cabinet vendor. Dividing focus between these two simultaneous projects was not ideal, yet the need to overcome operational deficiencies while pursuing USP compliance motivated us to complete both projects concurrently. This challenging process taught us important lessons that have been useful moving forward.
Before undertaking any upgrade planning, hold meetings to assess the facility’s current state. Consider the responsibilities for each of the individuals involved in the project and define end product that is desired. This is the time to identify any logistical issues that will require attention, such as which staff members will need to be trained in cleaning to maintain the upgraded space, who will be responsible for evaluating the project to ensure regulatory compliance is attained, who will conduct the terminal cleaning before commencing use of the new space, etc. It is strongly recommended that you have copies of USP <797> ready for reading and discussion at this stage, and be prepared to explain the general details of the chapter. Many individuals at our facility, in addition to the contractors chosen for the construction, did not have a full grasp of USP <797>, which contributed to several of the challenges we faced during the renovation.
Of utmost importance is the need to work together as a cohesive team. Decisions should not be made in a silo with pharmacy handling all aspects of the upgrades. The team established at our facility to ensure that the sterile processing suite achieved full compliance was comprised of both hospital management and non-management personnel from across the facility, and included the chief executive officer (CEO), the chief nursing officer (CNO), quality department representatives, nursing directors, the pharmacy director, pharmacy employees, and a variety of nursing staff members. The state of Connecticut also requires that an infection control physician and nursing representative(s) be involved throughout the process.
The team must be familiar with both federal and state requirements. It is important to recognize that states require varying levels of compliance with the USP chapters. To begin, determine if your state requires full compliance with USP Chapter <797> and review whether any of the state requirements are more stringent than those of USP. For example, Connecticut takes a stricter approach with certain aspects of sterile processing, including defined requirements for temperature and humidity control.
Establish whether you are required to receive state-level approval (eg, department of public health, state board of pharmacy, etc) before a remodel can move forward. In some states, approval is required before construction can begin; for others, the designated state agency must be informed prior to commencing construction. Also establish whether your state requires the facility to seek approval to move a primary engineering control (PEC), such as a CAI, laminar air flow workbench (LAFW), biological safety cabinet (BSC), or compounding aseptic containment isolator (CACI) into another area. Determine whether these types of approvals must be in writing. Even if not required, creating a formal paper trail to prevent any second-guessing of decisions after the fact is recommended. The state regulations may require that the paper trail be discussed at various meetings and be included within the meeting minutes at your facility.
Select architects and contractors wisely; do not choose an architect or contractor based simply on the premise that “We have worked with them in the past.” Pharmacy management must be involved in the selection process. If possible, evaluate other facilities in which the contractor and/or architect has completed a sterile processing suite; investigate whether that facility had issues. For example, did the contractors and/or architects understand the legal ramifications for both the state and federal enforcement of the USP chapters? Were they cognizant of the approvals that were required at both the state and federal levels?
Be cautious about choosing a contractor or architect that has limited or no experience planning/building a sterile compounding suite. Choosing the wrong contractors or architects can cause major consternation, as well as possible cost overruns should there be discrepancies with the regulations or even required rebuilds. This level of oversight also must extend to any subcontractors used by the contractor; all parties must have a clear understanding of the process and the possible legal ramifications. It is prudent to evaluate previous projects the subcontractors completed as well.
Consider hiring a consultant specializing in sterile compounding to assist with the planning as well as the final check of the sterile processing suite. Building or rebuilding a sterile processing area can be a costly proposition, with the investment often ranging from hundreds of thousands to millions of dollars. Given the significance of this investment, working with a consulting specialist to assist with the planning process and the final project evaluation may ultimately save money and help prevent costly rebuilds. As part of the process, the specialist typically completes a gap analysis to identify those areas that need special focus and to note areas that are already compliant. Should regulatory issues develop during the process, the specialist can guide the pharmacy in effectively managing the response and ultimately achieving compliance.
Keep in mind that when using a specialist, the facility should follow their recommendations. If there is a desire to deviate from those recommendations for “less expensive” options, engaging in further discussions with the consultant is highly recommended.
Contingency Planning Options
Unfortunately, during the construction process our CAI became inoperable, which required us to quickly develop a second plan for how sterile products were to be produced while the sterile compounding area was under construction. This underscores the importance of having a detailed contingency plan in place to provide CSPs during a facility renovation or upgrade. There are a variety of approaches available to address CSP contingency production; for example, the facility can establish a temporary segregated compounding area (SCA), rely on 503B or 503A compounders, partner with a local hospital or home infusion center, or utilize a CAI. Each of these choices delivers both plusses and minuses that must be evaluated in detail.
Operate in a Temporary SCA
Specific requirements within the current USP <797> must be followed in order to establish a temporary SCA. As noted in the current chapter, an SCA is3:
A designated space, either a demarcated area or room that is restricted to preparing low-risk level CSPs with 12-hour or less BUD. Such area shall contain a device that provides unidirectional air flow of International Standards Organization (ISO) Class 5 air quality for preparation of CSPs and shall be void of activities and materials that are extraneous to sterile compounding.
The facility must note that products compounded in the SCA have a shortened BUD (ie, 12 hours) and can only be low-risk compounds. According to current USP <797>, requirements that must be followed include3:
- PECs (eg, LAFWs, BSCs, CAIs, and CACIs) shall be certified and maintain ISO Class 5 as described in Facility Design and Environmental Controls (section as noted in USP <797>) for exposure of critical sites and shall be in an SCA restricted to sterile compounding activities that minimize the risk of CSP contamination.
- The SCA shall not be in a location that has unsealed windows or doors that connect to the outdoors or high traffic flow, or that is adjacent to construction sites, warehouses, or food preparation. Note that this list is not intended to be all-inclusive.
- Personnel shall follow the procedures described in Personnel Cleansing and Garbing and Additional Personnel Requirements (sections as noted in USP <797>) prior to compounding. Sinks should not be located adjacent to the ISO Class 5 PEC. Sinks should be separated from the immediate area of the ISO Class 5 PEC device.
- The specifications in Cleaning and Disinfecting the Sterile Compounding Areas, Personnel Training and Competency Evaluation of Garbing, Aseptic Work Practices and Cleaning/Disinfection Procedures, and Viable and Nonviable Environmental Sampling (ES) Testing (sections as noted in USP <797>) shall be followed as described in the chapter.
The walls and ceilings of the SCA must be cleaned on a schedule. The material/paint on the walls must be cleanable and the cleaning chemicals used should not cause cracking and flecking. Should cracking or flecking occur, this could lead to particles in the air, which can increase the opportunity for bacterial growth. Similarly, the facility sprinkler system should be flush to the ceiling to allow for easier cleaning. Your state may require the SCA to be inspected and approved prior to use. Certainly there are limiting factors to using a temporary SCA; nevertheless, this may be an option to consider if your facility has a designated space available.
It is critical to note that in the coming updates to USP <797>, the ability to utilize temporary SCAs will be affected.4 In fact, these changes may allow for broader use of an SCA. Under the proposed changes to USP <797>, the definitions of low-, medium-, and high-risk will be replaced with the new nomenclature of Category 1 (compounded in an SCA) and Category 2 (compounded in a cleanroom). The change in categories will be accompanied by a change in BUD definitions (eg, CSPs compounded in an SCA will have a BUD of 12 hours or less at room temperature and 24 hours or less in a refrigerator). For CSPs compounded in fully compliant sterile compounding suites, the BUD will also be impacted by the use of sterile versus non-sterile ingredients, products that are terminally sterilized, and/or items that have undergone sterility testing. Once <797> is updated, facilities will likely be able to compound a broader range of products in a temporary SCA versus what is currently allowed (ie, low-risk CSPs only).
Currently, there is only a defined SCA for non-hazardous processing. When USP <800> is officially enforceable, there will be a newly defined SCA for hazardous sterile products as well (ie, containment segregated compounding area [C-SCA]).5 Both the updates to USP <797> and USP <800> will be officially enforceable on December 1, 2019.
Given the current, published, and enforceable USP <797>, if you choose to utilize a temporary SCA, consider how medium- or high-risk sterile products will be produced. For this situation, utilizing the services of a 503B pharmacy may be a sound solution. A benefit to using a 503B pharmacy is that the products they compound do not have to be produced as patient-specific. In addition, most products produced by 503B facilities have extended BUDs (due to the facility following cGMP processes, as well as completion of extended sterility and potency testing). If a 503B pharmacy is not an option, you may consider a 503A pharmacy. Remember that a 503A pharmacy is required to process patient-specific orders only. With proper planning, this may be a viable option.
When considering either a 503B facility or 503A pharmacy, determine how the product will be delivered to the pharmacy. Can the facility ship to the state in which your facility is located? If yes, how will it be shipped? What will the costs be for the other pharmacy to produce and ship the products?
Partner with a Local Hospital or Home Infusion Center
Another option is to consider working with a local hospital or home infusion center to use their sterile compounding facilities. There are many ramifications to such an approach. First, determine if your state permits this possibility. If so, what are the requirements in regard to facility certification, staff training, fingertip sampling, and media fills? Requirements will vary by state; for example, Connecticut requires that a memorandum of understanding (MOU) be in place between the two facilities in order to share space. Finalizing an MOU requires an evaluation of legal ramifications, and each facility’s legal department must review the document. Such a process can be challenging to complete; nonetheless, this option may be feasible for some operations.
Utilize a CAI
A CAI can be utilized for processing orders while the IV suite undergoes renovations. If your facility already has a CAI, using it outside of a buffer area (ISO Class 7) in a worse than ISO Class 8 environment may be possible under the current USP <797>. Full USP <797> BUD may be possible if your certifier documents that the hood is in proper working order, and the following criteria are met and documented by the manufacturer3:
- The isolator shall provide isolation from the room and maintain ISO Class 5 during dynamic operating conditions, including transfer of ingredients, components, and devices into and out of the isolator and during preparation of CSPs.
- Particle counts sampled approximately 6 to 12 inches upstream of the critical exposure site shall maintain ISO Class 5 levels during compounding operations.
- Not more than 3520 particles (0.5 µm and larger) per m3 shall be counted during material transfer, with the particle counter probe located as near to the transfer door as possible without obstructing the transfer.
Note that the above approach to CAI use is only permissible under the current version of USP <797>. The proposed changes to the chapter, once officially published (and projected to become enforceable on December 1, 2019), will likely require that a CAI be placed within a secondary engineering control (ie, an ISO Class 7 buffer area).4 If not placed in a buffer area, the CAI must be in a designated SCA and follow newly established BUDs.
Of note, maneuvering within CAIs can be awkward for novices as maintaining dexterity inside the CAI sleeves/gauntlets requires some practice (see PHOTO 1). In addition, cleaning a CAI can be more challenging than cleaning an LAFW (see PHOTOS 2 and 3). As such, consider providing extra training time until staff becomes familiar with maneuvering within the CAI.
If your facility does not have a CAI, rental options are available from various manufacturers. For this approach, determine the features that are most important for your operation and establish a budget.
Keep in mind that the CAI, like any PEC, must be certified in order to meet USP <797> compliance. Also, training and competencies will be required for staff if the facility does not already have a CAI. Competencies should encompass how to properly don the gauntlets and how to don sterile gloves on top of the gloves in the hood (ie, double gloving is required in a CAI), proper cleaning of the CAI, proper technique within the CAI, etc. Establish temporary policies and procedures detailing how to clean, properly garb, and compound inside the device. If these are new processes for employees, consider requiring a new gloved-fingertip test. Follow the exact instructions from the manufacturer in regard to the time frames required for a purge cycle within the antechamber as well as the time frame to replace CAI sleeves.
Each facility must be prepared for possible inspections from state, federal, and/or accreditation inspectors. The inspections could be related to your build-out or normal day-to-day functioning in the sterile processing suite. Review the potential penalties for noncompliance, as this can be a strong motivator for completing the project accurately. Determine whether fines can be leveraged against the hospital/pharmacy if there are deviations from compliance. Is the director of pharmacy or pharmacist in charge personally at risk for being fined? The state of Connecticut, for example, can fine the pharmacy/hospital as well as the pharmacist in charge for USP <797> deviations. An open line of communication with the state is exceedingly helpful to prevent negative ramifications, should fallout occur. Due to the complexities of the process, some states have developed a gap analysis to assist facilities in meeting requirements. To help prevent deviations from occurring in day-to-day activities, ensure that processes are consistently documented via cleaning logs, environmental monitoring logs, etc. Designate an employee to be responsible for monitoring these logs on a regular basis. A facility can also consider implementing an electronic program to maintain logs, competencies, and more.
Ascertain your state’s requirements for reporting day-to-day deviations from compliance during the normal upkeep of your sterile processing suite. Some states require that fallouts within a sterile compounding area be communicated directly to the state. For example, the State of Connecticut requires that actionable levels of growth within the sterile processing suite be communicated to the state along with an action plan for addressing the fallout. Determine whether any required communications must be in writing, and if so, is an email sufficient? Any fallouts and response plans should be communicated to the appropriate committees at your facility, and ensure this information is included in meeting minutes. Tracking and trending alert levels of growth in addition to actionable levels of growth will help your facility better understand how issues are developing and how effective the cleaning processes are within the sterile processing suite.
For many facilities, the process to achieve compliance with USP <797> and <800> is daunting from the outset. In our experience, the entire process was challenging. Due to issues related to state regulations and other delays, the total construction time from planning the cleanroom to final approval/full compliance was almost 2.5 years. Nonetheless, all staff members involved in the process had quite a learning experience and are now well versed in compliant practices. Our current focus is on the process of maintaining compliance for both sterile processing suites.
Being prepared for the coming updates to USP <797>, as well as <800>, is highly recommended. If you are currently planning to build/upgrade an existing space, adopt a forward-thinking approach. Do not plan to simply become compliant with the current regulations; rather, consider how you can construct a facility that will hold up to future iterations of the chapters.
Taking this approach, our facility made the decision to install a HEPA-filtered pass-through chamber (see PHOTO 4). While this is not a current USP <797> requirement, and it may not even be a future requirement, we are confident that it adds to the effectiveness of our sterile compounding complex. Investing in future compliance is always a wise strategy.
Jay Gilbreath, PharmD, MPA is a Cardinal Health employee working as the director of pharmacy at Sharon Hospital in Sharon, Connecticut. He received his Doctor of Pharmacy degree from Samford University in Birmingham, Alabama and his Master of Public Administration degree from Troy University in Troy, Alabama. Jay also completed a primary care residency at the Tuscaloosa VA Medical Center in Tuscaloosa, Alabama. His professional interests include policy development, USP compliance, Joint Commission readiness, and patient safety.
- United States Pharmacopeia. FAQs: <797> pharmaceutical compounding—sterile preparations (last updated July 27, 2018). www.usp.org/frequently-asked-questions/pharmaceutical-compounding-sterile-preparations. Accessed October 30, 2018.
- The Joint Commission. Pharmacy rules/regulations by state for compliance with USP 797 medication compounding (2/28/17). www.jointcommission.org/assets/1/6/Feb_2017_State_Compounding_Regulations.pdf. Accessed October 30, 2018.
- United States Pharmacopeia. USP chapter <797> pharmaceutical compounding – sterile preparations. www.usp.org/compounding/general-chapter-797. Accessed October 30, 2018.
- United States Pharmacopeia. <797> Pharmaceutical compounding – sterile preparations, USP 41 page 6554 and PF 41(6) [Nov.-Dec. 2015]. www.usp.org/sites/default/files/usp/document/our-work/compounding/proposed-revisions-gc-797.pdf. Accessed October 30, 2018.
- United States Pharmacopeia. USP chapter <800> hazardous drugs – handling in healthcare settings. www.usp.org/sites/default/files/usp/document/our-work/healthcare-quality-safety/general-chapter-800.pdf. Accessed October 30, 2018.
First published in 2004 and in 2008, USP <797>1 is itself not an official federal law or regulation; nonetheless, various departments of the United States Federal Government established enforceability of the chapter. Soon after USP <797> was published, the Federal Drug Administration (FDA) recognized the chapter as enforceable. In addition, the Centers for Medicare and Medicaid Services (CMS) established that USP <797> compliance is a Pharmaceutical Service Condition of Participation (CoP) for hospitals. Attaining compliance with CMS-required CoPs is extremely important, as noncompliance can significantly affect Medicare and Medicaid funding within the hospital.
Many states have followed the lead of the federal government and have established the legal enforceability of USP <797>. Currently, 32 states and territories specifically require compliance with USP <797>.2 Some states have established even more stringent requirements related to the chapter, including specific ramifications for noncompliance. The other 19 states require varying levels of compliance to USP <797>. In light of the federal government and multiple states enforcing USP <797>, The Joint Commission also evaluates USP <797> compliance and may issue findings against a facility related to the chapter.
Most recently, USP has published USP Chapter <800>. This chapter was developed to evaluate and instruct facilities on how to protect employees in the handling and preparation of hazardous drugs. USP <800> will be enforceable on December 1, 2019. As such, USP <800> will work in tandem with USP <797> to help ensure protection for both patients and employees alike when processing any type of sterile product, whether hazardous or nonhazardous. Due to the future state of enforceability of USP <800>, many hospitals and home infusion pharmacies are currently evaluating how they will achieve compliance.
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