Road to USP <800> Compliance

Section 18 Medical Surveillance

Sections 1 through 17 of USP General Chapter <800> Hazardous Drugs—Handling in Healthcare Settings outlines all the mechanical aspects associated with establishing a hazardous drug safety program.[i] Within USP <800>’s sections, sites must review and update standard operation procedures, facilities, equipment, and handling practices to establish a comprehensive program. Section 18 represents one of the most critical and controversial components of a hazardous safety program – medical surveillance of individuals who handle hazardous drugs as part of their job function. Of note, within section 18 of USP <800>, every aspect of establishing an employee medical surveillance program is a recommendation, not a mandate. This recommendation status is in sync with the OSHA Technical Manual, Section VI: Chapter 2. Categorization of Drugs as Hazardous^[ii], and the 2004 NIOSH Alert: Preventing Occupational Exposures to Antineoplastic and Other Hazardous Drugs in Health Care Settings.

The recommendation status versus the mandate may be due to the lack of definitively, conclusive studies demonstrating a direct effect of handling hazardous drugs and the development of health issues. It is important to note, there are numerous case reports and casual epidemiological surveys that surmise workers exposed to HDs have developed acute problems such as skin disorders and hair loss, adverse reproductive effects, and possibly leukemia and other cancers.^,[iii],[iv]A recent epidemiological evaluation of nurses found a statistically significant, nearly two-fold increase in the risk for spontaneous abortion among those exposed to antineoplastic agents for more than one hour per day during the first trimester of pregnancy.^[v]In such, organizations that handle hazardous drugs should consider a comprehensive medical surveillance program for at risk personnel; those workers who handle, prepare, and administer hazardous drugs.

The discussion of establishing any type of employee surveillance program should not be in a vacuum and should include representatives from Human Resources, Employee Health and Risk Management in the discussions surrounding such programs. Since these types of programs are not mandated, there could be legal implications associated with establishing an employee monitoring program. A risk assessment should be prepared and provided to organizational leadership for guidance.

A simple program site should consider, at a minimum, includes baseline hazardous drug handling acknowledgment questionnaire, education of the risks associated with handling hazardous drugs, education of symptomology associated with a hazardous drug exposure, and education on how to report if an exposure is suspected. Education and establishing a baseline understanding of the risks and effects of acute to chronic exposures builds the basis for a collaborative program.

In addition to the noted simple program, USP <800> outlines more facets to consider when developing a comprehensive program in addition to the acknowledgment and education:

Identifying job codes where hazardous drug exposure is a potential
- stratifying risk of exposure: High; Medium; None to Absolutely No Contact
Using an employee health service to administer, monitor and provide protection of personnel confidentiality;
Baseline health status and medical history; including reproductive history, work history with regards to working with hazardous drugs, physical examination, and laboratory testing (which may be standard employee health on-boarding).
- If an employee has a history of working with hazardous drugs sites may want to gather additional work history information, such as:
  - Summary of hazardous drug handled and estimated quantities;
  - Estimated number of doses handled per day/week/month;
  - Estimated number of hours handling hazardous drugs per day;
  - Laboratory studies to include a complete blood count with differential, liver function test (LFTs), and a urine analysis
  - Repeat laboratory work should be considered annually and when an exposure is suspected;
  - Education of findings of laboratory results should be part of the plan and include documentation of results in the medical record and notification of the employee’s primary care provider of the exposure.
- Surveillance should be documented in medical records as outlined in OSHA;
- Concurrently monitoring and trending at risk employees visits to employee health and self-reported sick calls;
- Establishment of a formal plan with employee health to address suspected or actual exposure risks which should include a complete gap-assessment of all 18 sections of USP <800>;
- Development of an exit employment program for at-risk employees leaving their assigned positions and/or job codes to document information on the employee’s medical record to include reproductive and estimated exposure risks.
  - Sites collecting laboratory specimens on hire and/or due to an exposure may elect to conduct laboratory tests on exit to match with pre-employment results.Health care workers are typically exposed to numerous HDs, and no single biological monitor is suitable for all drugs.

For sites with simple to comprehensive medical surveillance programs, a formal response to a suspected or actual exposure should be clearly outlined in a standard operation procedure. Steps should clearly articulate the actions the employer intends to take and the role of the employee. USP <800> provides guidance on pre-establishing the following steps for a formal follow-up program:

If an individual has been deemed exposed to a hazardous drug, an event-specific hazardous drug post-exposure program should include documentation in the employee’s medical record, tracking of symptom episodes, the date of exposure, the drug(s) involved, the route of exposure,
- Documentation of any additional monitoring of illness events
- Documentation of additional education for individuals reporting symptoms of hazardous drug exposure.
A comprehensive gap assessment of current practices surrounding the event should be conducted and included;
- Review of staffing model, hazardous drug trending volumes, product assessment, drug shortages of hazardous drugs, changes to standard operation procedures and education, new training, new devices for compounding or administration, engineering controls, documentation of cleaning program, drug delivery, drug administration, drug disposal, etc.
- Review and document all events surrounding the exposure with attention to the following:
  - Verification and documentation of all equipment in good working order;
  - Verification, acknowledgment and documentation of compliance with established standard operation procedures,
- Documentation of any out of defined specifications or out of Standard Operation Procedure gaps noted and all corrective and preventative actions
Documentation in the employee medical health record
- Ensure confidentiality between employee and employee health
- Education to employee on notification process for changes in health and progression of adverse effects
- A plan to provide appropriate follow-up to include clinical evaluation, medical history, physical examination, laboratory tests
Offer exposed employee alternative or temporary duty assignment
Documentation of survey results from gap assessment and implementation of plans

Health care organizations stating compliance with hazardous drugs handling standards should have a program in place to monitor the safety of personnel. Medical surveillance can help sites validate and demonstrate a trust with employees and a return on investment for holistically implementing USP <800> standards while mitigating occupational exposure to hazardous drugs.

As the official implementation date of December 1, 2019 for proposed USP <800> and subsequent revisions to USP <795> and USP <797> compliance allows time for sites to prepare for overall compounding compliance. The time for review of USP’s newest chapter in combination with keeping up with USP’s website for revisions to USP is now.

Don’t know where to start with a hazardous drug safety program? Visante offers a full line of sterile compounding consulting services, including USP <795>, USP <797>, USP <800>, and USP <825> 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.

References

[i]USP <800> Hazardous Drugs—Handling in Healthcare Settings. First Supplement to USP 39–NF 34 Physical Tests.https://www.usp.org/compounding/general-chapter-hazardous-drugs-handling-healthcare. Accessed April 5, 2019

[ii]Occupational Safety & Health Administration (OSHA). OSHA Technical Manual. Section VI: Chapter 2. Categorization of Drugs as Hazardous. Accessed April 5, 2019. https://www.osha.gov/dts/osta/otm/otm_vi/otm_vi_2.html

[iii]American Society of Health-System Pharmacists (ASHP). ASHP guidelines on handling hazardous drugs. Am J Health-Syst Pharm. 2006;63:1172-1193.

[iv]Connor TH, McDiarmid MA. Preventing occupational exposures to antineoplastic drugs in health care settings. CA Cancer J Clin. 2006 Nov-Dec;56(6):354-365.

[v]Lawson CC, et al. Occupational exposures among nurses and risk of spontaneous abortion. Am J Obstet Gynecol. 2012 Apr;206(4):327.e1-8. 2011.

Road to USP <800> Compliance

Section 17: Documentation and Standard Operating Procedures

Sections 1 through 16 of USP Chapter 800: Hazardous Drugs—Handling in Healthcare Settings provides the ground work for setting up a hazardous drug safety program for healthcare facilities. In section 17, we have to put the plan to paper. When we commit to putting things to writing we commit to the processes. It can easily be assumed from a safety and legal stand point; if it is not documented, it did not happen.

USP General Chapter <800> Hazardous Drugs—Handling in Healthcare Settings has many steps, tasks, checks and processes that require documentation.[i]Documentation of critical steps are in place for patient safety, but also legally for employee safety. It is a requirement that each site that handles and manages hazardous drugs have standard operating procedures (SOPs) in place. The directional philosophies and processes of how a business runs are defined within SOPs. As a point of clarification of terminology: USP relies on terminology commonly used within scientific quality standards as in the case for the term SOPs; which draws from the International Organization of Standards ISO 9000:5000 definition for Quality Management Systems. In ISO, the words “process,” and “procedure,” are technical terms. In brief, a procedure is a “specified way to carry out an activity or a process,” and, a process is a “set of interrelated or interacting activities which transforms inputs into outputs.” Whereas, policies and procedures (PPs) are generically defined: “policies of an organization are the clear, concise statements of the parameters by which an organization conducts its business, (i.e., the rules staff abide by), and procedures “are the instructions or steps that describe how to complete a task or do a job.”[ii] SOPs are often considered interchangeable with PPs, but as we can see they might not be when it comes to scientific standards.

The following outlines steps should sites consider when drafting SOPs for critical standards.

Use a standard and formal template for all SOPs and accompanying forms;
1. Business may have one developed with legal notations
2. For guidance sites can refer to ISO 9000:2005
Create a team of stakeholders to draft and review SOPs
1. For USP <800> and proposed USP <797> it is a required to assign a designee for SOP development
Work out the purpose for the SOP
1. What are you looking to achieve?
2. What is the regulatory and/or standard requirement?
Determine the structural contents and formatting of the SOP.
Prepare and define the scope of the procedure
Use a consistent style with correct notations
1. Use USP language, example ‘hazardous drugs’ versus ‘oncolytics’
Work out all the necessary steps of the process
1. Consider creating a flow diagram
Try to assess any problems in the process
Establish required documentation points and or metrics
Share the SOP with leadership prior to review with personnel
Test the process
Finalize the SOP if validated through steps 10 and 11
Continually optimize the process
1. Review at least every 12 months

To know whether processes are performing well or poorly, sites should develop metrics to judge it against. It is not good enough to assume processes simply work. Sites should understand how it is performing so that it can be monitored and optimized.

The SOPs can be globalized within a system for consistency, however, some specific SOPs may need to be site specific. Within USP <800> it requires that SOPs are reviewed every 12 months. For some systems, this may be more frequent than defined for your system for standard review frequencies of SOPs. The importance of continually reviewing, modifying and improving the compounding processes should be a directive for compounding programs. Documentation of the review and any revisions must be documented on each SOP. If revisions to the SOPs occur, the changes must be communicated to all persons in job codes where handling hazardous drugs are defined.

Within section 17, USP provides a listing of suggested SOPs for sights to consider (note it mirrors the sections within the chapter). It is important to keep in mind, USP <800> references the supporting chapters and references which should be referenced within SOPs. At a minimum, sites should use the list and title them as USP has to ease inspections and questions that may arise:

Hazard communication program
Occupational safety program
Designation of hazardous drug areas
Receipt
Storage
Compounding
Use and maintenance of proper engineering controls (i.e., C-PEC’s; C-SECs; CSTDs)
Hand hygiene and use of PPE based on activity (e.g., receipt, transport, compounding, administration, spill, and disposal)
Deactivation, decontamination, cleaning and disinfection
Dispensing
Transport
Administrating
Environmental monitoring (e.g., wipe sampling)
Disposal
Spill control
Medical surveillance

Obviously, sites will have differences between specialties, services, equipment, and state-specific regulatory requirements. The minimal SOP list from USP may not meet all needs for hazardous drug handling. Additional SOPs for sights to consider (disclosure not complete):

Crushing, splitting and compounding oral solids
Intrathecal administration of hazardous drugs
Bladder installation of hazardous drugs
Ampule management of hazardous drugs
Compounding topical hazardous drugs
BCG and biological vector cleaning protocol
Immuno-gene therapy compounding
Immuno-gene therapy cleaning protocol
Immuno-gene therapy disposal protocol
IV-Workflow equipment maintenance and calibration
IV-Workflow equipment cleaning
Visual inspection of hazardous drug products for dispensing
Use of Powered Air Purifying Respirator (PAPR)
Personal Protective Equipment integrity inspection
Linen exchange process for patients receiving hazardous drugs
Laboratory handling of body fluid samples of patients receiving hazardous drugs
Phlebotomy procedures for drawing samples of patient receiving hazardous drugs
Recycling assessment of returned compounding hazardous drugs
Vinca alkaloids safety program

Within the documentation section, USP <800> reminds us that individuals “who transport, compound, or administer HDs must document their training according to OSHA standards (see OSHA Standard 1910.120 Hazardous Waste Operations and Emergency Response) and other applicable laws and regulations.” Highlighting the overall importance of documentation and the documentation requirements of outside agencies.

Here is the link to the OSHA HAZWOPER standard FAQ: https://www.osha.gov/html/faq-hazwoper.html

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.

References

[i]USP <800> Hazardous Drugs—Handling in Healthcare Settings. First Supplement to USP 39–NF 34 Physical Tests. www.usp.org/compounding/general-chapter-hazardous-drugs-handling-healthcare. Accessed August 14, 2018.

[ii]http://www.professionalgrowthsystems.com/systems-process-improvement/policy-procedure-definition-development/; Accessed March 14, 2019

Road to USP <800> Compliance

Section 16: Spill Control

Sections 1 through 15 of USP Chapter 800: Hazardous Drugs—Handling in Healthcare Settings provides the blueprint for safely getting a hazardous drug into our facilities and properly cleaning residues left on surfaces. On our road to compliance, Section 16 provides us with a detailed review of managing a spill. A hazardous drug (HD) spill presents one of the highest risks for exposure to the individual handling the medication, other staff in the area, the hospital environment, and patients.

USP General Chapter 800 Hazardous Drugs—Handling in Healthcare Settings highlights the critical nature of proper HD spill management, mentioning variations of the term spill 50 times therein.[1] Spills may occur throughout the HD management process; for example, broken vials may arrive from the distributor, spills can occur throughout the HD preparation and use process, and spills can occur at the time HDs are wasted. Thus, each step of the HD handling process, from entry-to-exit of the hazard, must be defined and evaluated as part of a comprehensive spill management program. Moreover, the spill management program should cover all forms of HDs: liquids (solutions, reconstituted solutions, suspensions, and sprays), solids (powders, pills, and capsules), and gases.

The prevalence of HD spills in health care is likely under-documented, as it is not uncommon for staff to fail to recognize when a spill incident has occurred. For example, a staff member may simply “clean up the mess,” and not recognize the serious nature of HD contamination. A study evaluating nursing practices found that HD spills are a significant problem in oncology, where 9% of 1,954 nurses surveyed experienced a spill within the week prior to the survey.[2] To identify a site’s spill prevalence, pharmacy should review not only pharmacy documentation, but also nursing and environmental services, and how the documented spill rate compares with the use of HD spill kits.

A comprehensive spill program must include spill education, minimization, control, clean-up, and documentation. Robust spill management allows sites to fully assess the risk of environmental contamination, the skills of staff handling HDs, and the organization’s ability to track and trend spill data. Failure to formally clean and remediate spills allows HD residues to persist on surfaces; because residues do not go away on their own, having a formal spill management program in place is vital to the safety of the staff and the environment.

Regulatory Guidelines for HD Spills

Regulatory information guiding the management and control of HD spills center on protecting the individual responsible for addressing the spill. The United States Department of Labor Occupational Safety and Health Administration’s 2016 document, Controlling Occupational Exposure to Hazardous Drugs, provides key information regarding regulatory compliance for HD spills, including definitions and guidelines to protect employees.[3] The Hazard Communication section requires employers to properly alert, educate, mitigate, follow-up, and document a specific program that is in place to protect staff from HDs. As such, sites that handle HDs must “develop, implement, and maintain at the workplace a written hazard communication program for employees handling or otherwise exposed to chemicals, including drugs that represent a health hazard to employees.”⁴The Guidance section on spill control requires sites to maintain Safety Data Sheets (SDSs, formerly Material Safety Data Sheets, or MSDSs) for each drug. The SDSs must include essential safety information, including spill procedures. Interestingly, a review of existing SDSs from manufacturers demonstrates a lack of consistently robust spill procedures; therefore, sites should develop and implement in-house HD spill policies and procedures (P&Ps) for addressing HD spills.[4] Although commercially available spill kits contain valuable supplies and information, most of the information provided therein relates to general spill cleanup.

Much of the OSHA document, as well as the USP <800> recommendations for managing spills, are built on the recommendations laid out in the 2006 American Society of Health-System Pharmacists’ ASHP Guidelines on Handling Hazardous Drugs recommendations.[5] This document provides health care workers with the most current data and processes for addressing HD spills. State boards of pharmacy that wholly adopt USP standards for compounding, including USP <800>, reference the 2006 ASHP document for spill management details. Since USP has historically provided guidance to the practice of pharmacy, USP <800> guidance for nursing handling and drug administration is new, and sites must include best practice guidelines developed by the Oncology Nursing Society (ONS) as an adjuvant to the ASHP, OSHA, and USP <800> documents when educating nursing.

Developing a Spill Management Strategy

It is inevitable that spills will occur, so sites should expect them. Even with the best processes in place to prevent spills, sites will occasionally receive broken drugs vials, and experience medical device failures and unpredictable events outside of normal processes that may contribute to a spill. Therefore, organizations that manage HDs should consider spill management an integral element of the HD handling process. To ensure staff safety, nursing and pharmacy leadership in partnership with institutional administration should make implementing a robust spill management program an organizational priority.

To begin, pharmacy and nursing must work collaboratively to map out the site’s complete HD workflow, from the receiving dock through drug disposal. Each step in the medication-use process presents a potential spill risk. Consider the staff members involved in each step of the process for possible inclusion in the HD spill team. Some facilities may have a hazardous materials quality team in place to address all hazards (not only HDs); if this is the case, be sure to define each team’s responsibilities to minimize duplication of efforts. Individuals that may be involved in the HD spill team include pharmacy, nursing, surgical services, environmental services, risk management, employee health, and safety officers. The team should review the OSHA, ASHP, and ONS spill management guidance; in addition, USP <800> provides critical information regarding utilizing a cleaning process that incorporates deactivation, decontamination, and cleaning. Discuss the actions required to address different spill volumes; spill types, such as liquid versus powder; spills within a primary engineering control versus outside; spills in a public area; spills on absorbable materials such carpet, furniture and wall paper; spill documentation; spill kit contents; and, spill exposure follow-up. Sub-sections of each defined risk point should be delineated to address spill risks, requirements, and special equipment needs (e.g., zip-lock tote bags to transport HDs, and access to spill management materials [spill kits] and respiratory-protectant devices in the receiving areas).

Educating staff is critical to ensuring proper spill management. Staff must have a clear understanding of what constitutes a spill, addressing spills of multiple volumes, emergency contacts that may be required when addressing a spill, spill kit location(s), and required spill documentation. Training for spills must be a formal, required element of employment and should be documented accordingly. Annual re-education must take place to alert staff to any new hazards—e.g., inclusion of a new viral vector-based drug. Any changes to the spill kit contents and any new tools used for spill mitigation must be included in training.

HD Spill Types

Liquids

Staff handling HDs must have an accurate understanding of what volumes look like when they spread out on a surface. For example, a 5 mL, 50 mL, and 500 mL spill look completely different on a flat surface (and are more complicated to quantify on surfaces that are not smooth). Estimating volumes, if the amount spilled is unknown, is key for staff to understand when they are able to safely handle a spill themselves versus when they may require assistance. It is also critical to understand that the viscosity of liquid formulations can affect the ability to properly clean a spill. Some viscous liquid formulations, including paclitaxel, may leave a sticky residue and may require further dilution of the spill with water to adequately absorb and clean.

Solids

Solid spills can present in the form of a bulk powder, powder for reconstitution (sterile and non-sterile), tablets, capsules and nanoparticles. Solid HD spills presents a unique situation, because some powders (e.g., those that are lyophilized) may be electronically charged and therefore may seek contact with an opposing charged surface and are easily blown around by room air and personnel movement. Because HD solids, powders, tablets, open capsules and nanoparticles can potentially generate airborne particles during the cleanup process, steps must be in place to contain the spill. If not contained, the airborne particles may develop into an inhalation hazard.

Specific cleaning processes must be in place that minimize the generation of dust and particles. This can be accomplished by dampening the solid with a water mist (if the material is not water-reactive) or by covering the material with a damp, absorbent pad and using this pad to address the spill. Reactive materials—for example, spontaneously combustible materials -complicate the ability to clean up a solid spill, as they may need to be covered with oil to protect them from air. Check SDSs and manufacturer recommendations for specific requirements; however, use of these products is extremely rare in pharmacy. Recovery of nanoparticle-based drugs presents a challenge of capturing the particles and preventing aerosolization by the use of a highly specialized HEPA-filtered vacuum. As these technologies emerge in drug therapy, a clear understanding for addressing these spills must include the hazardous drug component and the physical characteristics of the nanoparticle.

Gases

Gaseous HD spills may occur if a liquid or solid formulation of a drug has the ability to change physical phases at room temperature. The following HDs are known to be capable of undergoing a physical phase change (including, but not limited to): carmustine, cisplatin, cyclophosphamide, etoposide, 5-fluorouracil, ifosfamide, nitrogen mustard, and thiotepa. It should be noted that not all drugs have been tested for physical phase changes; the drugs listed here are the most studied and best understood.

It cannot be assumed that a new drug or a research drug does not change physical phase. The concept listed within the solid spill control section, covering with a moist, absorbent pad, may minimize vaporization. The fitted NIOSH-recommended N95 or N100 masks are able to address aerosols and particulates, but not vapors; sites should also have available a chemical cartridge respirator or powered air-purifying respirator (PAPR) designated OV/CN/CS for the listed drugs that potentially vaporize at room temperature and powder.

Spill Kits

Preassembling supplies prior to a spill occurring is critical to proper spill preparation. A spill kit comprises a collection of agreed-upon personal protective equipment (PPE), signage, cleaning materials, disposal systems, and documentation required to address a spill. Organizations may develop their own spill kits based on the ASHP recommended supplies or may purchase a commercially available spill kit. Note that commercially available spill kits are available in a variety of forms and contain varied cleaning supplies/tools and sizes of PPE. In most cases, the basic materials are present in these kits; however, there may be useful items missing or new cleaning devices included that require additional training—e.g., absorbent powders, absorbent pillows, spill mitts, detergents, etc.

Sites that purchase commercially available spill kits must train their personnel on how to use the kits correctly. Be sure that Standard Operating Procedures (SOPs) match the kits’ contents. In most instances, commercially available kits include directions for use on the external packaging or on an accompanying insert. Sites should use these instructions to supplement their internal SOP development.

Each kit has limitations for its use; for example, a kit may address a limited volume and/or may contain only certain sizes of PPE. Blindly ordering kits without reviewing the kits’ contents will lead to downstream issues that may result in an unintended occupational exposure.

ASHP summarizes the minimum supplies that should be included in an HD spill kit (see Table 1). Addendums to spill kit contents may include: a simple pictogram illustrating use of the kit, signage to post for notifying individuals of an active spill event (per USP <800>), site-specific cleaning solutions/products, a spill event documentation form, and a list of additional supplies based on spill type (e.g., water for solid/powder spills).

Both facility-developed and commercially available kits should have a clearly visible expiration date. For example, some kits may be in place for many years and may not have PPE suitable for addressing spills such as vinyl gloves or outdated PPE. Many commercially available kits do not include an expiration date. As a default, sites can place a date of five years (this dating is selected from reviewing various PPE items and cleaning solutions and their corresponding expiration dates) from receipt of kits or sooner as a guide. Over time, PPE and cleaning solutions will deteriorate and may be ineffective to protect personnel. Spill kits should be included as part of the monthly inspection for medications and supplies to ensure products are in-date and stored appropriately; expired products should be replaced. The overall goal is to ensure a visible, auditable expiration date appears on every spill kit.

There are a variety of spill kits commercially available. However, there is a lack of standardization of contents. Kits may be designed to address a specific function of a spill scenario, e.g., drug administration, drug compounding, home drug administration. Due to these differences, sites must work with at risk staff to assure kits match the needs of the specific duties defined for spills.

Commercially available spill kit containers can present in the form of a corrugated cardboard box, non-corrugated cardboard box, sealed plastic cover, zip-lock baggy and in waste buckets. If sites choose one kit with a corrugated cardboard box, it should be placed in a zip lock baggie for storage in cleanroom suites and containment-segregated compounding locations to minimize particulate generation from the cardboard and to ease monthly cleaning.

Spill Kit Locations

It is critical that staff knows where spill kits are located and can access them quickly. To this end, spill kits must be readily accessible and their location visually prominent to staff. Evaluating the site-specific flow of HDs into and out of the facility will help identify areas where spill kits should be housed. In most facilities, kits are located within the compounding and drug administration areas. In addition, USP <800> states that a spill kit must be accessible in the pharmacy receiving area. Additional areas for sites to consider for spill kit deployment include the shipping and receiving dock (not just the pharmacy receiving area); HD compounding areas (sterile and non-sterile); surgical core stations; environmental services department; infusion center nursing stations; medication preparation rooms of patient care units where HDs are administered (e.g., oncology, immunology, rheumatology, urology, ophthalmology, neurology, etc.); and the waste storage locations. Considerations for home infusion and remote infusion locations should include forward-deployed HD spill kits with nursing personnel servicing these locations. It is quite common for spill kits to be stowed away in cabinets or desks. When choosing the locations for spill kit placement, keep in mind the requirement that they be visually prominent.

Developing SOPs for Spill Management

Spill management SOPs should include comprehensive information to address any type of spill. As mentioned earlier, OSHA, ONS, and USP refer to the 2006 ASHP guidance regarding the key steps to address HD spills in the pharmacy, nursing units, and within a primary engineering control. Each of the site-specific identified risk locations (e.g., receiving, drug administration, disposal of wastes) should include specific aspects of the processes utilized in those areas and should appear in the governing SOP.

The first step when addressing a spill is to clear all personnel and restrict access from the area directly adjacent to the spill. Spills should not be left unattended; signage should alert others to the event as it is in process. The ASHP-recommended steps, plus any additional steps required for the use of specific PPE or cleaning solutions/equipment, should serve as the basis for SOP development. See ASHP-recommended general spill procedures and ASHP-recommended procedures for spills in a C-PEC below.

Table 1. ASHP-Recommended General Spill Procedures⁶

Assess the size and scope of the spill. Call for trained help, if necessary.
Obtain spill kit and respirator, if needed. Spills that cannot be contained by two spill kits may require outside assistance.
Don PPE, including double gloves and respirator.
Once fully garbed, contain spill using spill kit.
Carefully remove any broken glass fragments and place them in a puncture-resistant container.
Absorb liquids with spill pads or toweling.
Absorb powder with damp disposable pads or soft toweling.
Spill cleanup should proceed progressively from areas of lesser to greater.
Completely remove and place all contaminated material in HD waste disposal.
Rinse the area with water and then clean with detergent, sodium hypochlorite solution, and neutralizer (if the area may be bleached; if not, use detergent and rinse three times).
Rinse the area several times and place all materials used for containment and cleanup in disposal bags. Seal bags and place them in the appropriate final container for disposal as hazardous waste.
Carefully remove all PPE using the inner gloves. Place all disposable PPE into disposal bags. Seal bags and place them into the appropriate final container.
Remove inner gloves, contain in a small, sealable bag, and then place into the appropriate final container for disposal as hazardous waste.
Wash hands thoroughly with soap and water.
Once a spill has been initially cleaned, have the area re-cleaned by housekeeping, janitorial staff, or environmental services, per facility policy.

ASHP-Recommended Procedures for Spills in a C-PEC

Spills occurring in a C-PEC should be cleaned up immediately.
Obtain a spill kit if the volume of the spill exceeds 30 mL or the contents of one drug vial or ampule.
Additional HD gloves should be worn to remove broken glass in a C-PEC. Care should be taken not to damage the fixed-glove assembly in a CACI.
Place glass fragments in the puncture-resistant HD waste container.
Thoroughly clean and decontaminate the C-PEC. Clean and decontaminate the drain spillage trough located in the C-PEC, if so equipped.
If the spill results in liquid being introduced onto the HEPA filter, or if powdered aerosol contaminates the “clean side” of the HEPA filter, use of the C-PEC should be suspended until the equipment has been decontaminated and the HEPA filter replaced.
Contaminated reusable items, for example, glassware and scoops, should be cleaned with mild detergent and water after use. Items contaminated with HDs should be washed twice with detergent by a trained employee wearing PPE as described in the PPE section.

Training for HD Spill Management

OSHA, ONS, and USP <800> clearly articulate the requirement for personnel training. Training should include education on HD risks, the facility’s mitigating processes to minimize risks to employees, proper HD handling, a list of locations where HDs are handled, spill management SOPs, spill kit locations, spill kit content-specific training, proper decontamination/deactivation/cleaning processes, training on respiratory-protective devices, and hazardous spill documentation requirements. Personnel who have been identified as at-risk should be educated on hire and at least annually thereafter. Staff members must acknowledge in writing that they have received education and that they understand the information they have received. In addition, the employer should state in writing that it has provided the required education.

Implementing mock “spill drills” is an effective way to demonstrate facility competency. Drills should have a strategic goal, such as underscoring timeliness in addressing a spill, reinforcing the documentation process, or addressing spills in obscure locations within a facility. An observer and a timer should be present to document the staff’s actions during the drill. Present the drill results to designated quality or safety committees and include results in the site’s employee safety program for accreditation surveying bodies.

Waste Associated with an HD Spill

All supplies used in addressing an HD spill must be considered contaminated and should not be reused. Absorptive materials used to contain the spill are highly hazardous and should be placed in the appropriate waste stream as defined by the site based on state and federal standards; in most cases, this bulk waste should be classified as EPA RCRA hazardous waste. All PPE used for cleaning a spill should be considered contaminated. However, if the PPE components are not grossly contaminated they may be treated as trace hazardous waste and placed in the yellow waste stream. Sites should work with contracted waste haulers to address HD spill waste based on state and federal regulations.

Documenting HD Spills

Most institutions document blood and body fluid spills as part of their employee safety program; documenting HD spills is equally critical. Documentation should include the following important information: the date and time of the spill event; the specific location of the spill; the persons and witnesses involved; the suspected drug(s) spilled; the persons addressing the spill incident; the estimated volume; the expiration date of the spill kit utilized; the spill management steps taken; any issues encountered when cleaning the spill; the disposal stream of spill wastes; the cleaning process; notation of any damaged equipment/furniture/carpet requiring replacement; and the time the spill was resolved. If any personnel were exposed to HDs as a result of the spill, this information should be conveyed to employee health immediately.

Review information from actual spill events and spill drills to identify potential safety gaps and make any necessary revisions to P&Ps. This approach will maximize the protection of staff, the public, and the environment.

Considerations for HD Spill Outliers

Organizations should consider establishing procedures to address spills caused by patients, including education of patients and family members. For example, specific instructions should include notifying staff and not attempting to address the spill themselves.

A 2004 NIOSH alert addresses concerns with peri- and post-therapy contamination of the patient and corresponding linen and body fluids.[6] SOPs should address emesis or spills of a patient’s body fluid during or immediately post-therapy, including use of an HD spill kit or blood and body fluid spill kit, and identify who is responsible for addressing these spills. Sites should also consider SOPs for addressing spills of body fluids in restrooms for patients on or post HD therapies.

Patient mobility is critical to recovery. In some cases, patients are allowed to roam halls and enter highly populated public areas while their therapy is being administered. It has been documented that spills can occur during this process. Adjuvant services and care of a patient on therapy or post-therapy in radiology, physical therapy, laboratory, physician offices, and departments servicing active patients should have a plan in place to address patients entering designated areas with ongoing therapy. If patients are permitted to move about the hospital, they should be informed that if a spill occurs, they are to contact staff immediately and not attempt to clean the spill themselves.

As the official implementation date of December 1, 2019, for proposed USP <800> and subsequent revisions to USP <795> and USP <797> compliance allows time for sites to prepare for overall compounding compliance. The time for review of USP’s newest chapter in combination with keeping up with USP’s website for revisions to USP is now.

References

[1] USP <800> Hazardous Drugs—Handling in Healthcare Settings. First Supplement to USP 39–NF 34 Physical Tests. www.usp.org/compounding/general-chapter-hazardous-drugs-handling-healthcare. Accessed August 14, 2018.

[2] Boiano JM, Steege AL, Sweeney MH. Adherence to safe handling guidelines by health care workers who administer antineoplastic drugs. J Occup Environ Hyg. 2014;11(11):728-740.

[3] United States Department of Labor. Occupational Safety and Health. Controlling Occupational Exposure to Hazardous Drugs. www.osha.gov/SLTC/hazardousdrugs/controlling_occex_hazardousdrugs.html. Accessed August 14, 2018.

[4] Gonzalez R, Massoomi FF. Manufacturers’ recommendations for handling spilled hazardous drugs. Am J Health Syst Pharm. 2010;67(23):1985-1986.

[5] American Society of Health-System Pharmacists. ASHP guidelines on handling hazardous drugs. Am J Health Syst Pharm. 2006;63(12):1172-1191.

[6] National Institute for Occupational Safety and Health. NIOSH Alert: Preventing Occupational Exposure to Antineoplastic and Other Hazardous Drugs in Health Care Settings. www.cdc.gov/niosh/docs/2004-165/.

Table 2. Minimum Supplies for HD Spill Kit Per ASHP

Sufficient supplies to absorb a spill of about 1000 mL^a
Absorbent, plastic-backed sheets or spill pads to cover the spill
Disposable chemotherapy-resistant gowns (with back closure)^b
Chemical-resistant shoe covers
Two pairs of chemotherapy gloves^c
Chemical splash goggles (note: safety glasses are not protective)
Respirator-protective masks and devices^d
Disposable scoop
Plastic disposable brush
Puncture-proof container (if glass fragments are present)
Large, heavy-duty HD waste sealable disposal bag
Hazardous waste label (if bags are unlabeled)

^aASHP defined limitations to volumes, but site can define and educate staff on the limitations of each kit

^bGowns preferably rated to ASTM 739 testing standards for permeability rating

^cGloves rated to ASTM D6978 or newer testing for permeability rating

^dNIOSH respiratory protection includes N-95 or N-100 suitable for aerosols and particulates only and chemical-cartridge respirator or powered air-purifying respirator designated OV/CN/CS required for drugs that potentially vaporize at room temperature and powder

Road to USP <800> Compliance

Section 15: Deactivating, Decontaminating, Cleaning, and Disinfecting

Sections 1 through 14 of USP Chapter 800: Hazardous Drugs—Handling in Healthcare Settingsprovides the blueprint for safely getting a hazardous drug into our facilities and compounding. On our road to compliance, Section 15 provides us with a very comprehensive overview of the concept of ‘cleaning’ and its importance in the process of safely handling hazardous drugs.

IMPORTANT: Isopropyl Alcohol is NOT a cleaning agent.

Sterile compounding requires a robust contamination control program that must consider personnel and material flow; personnel gowning, training and behavior; aseptic manipulation, interventions management, and environmental monitoring. Integrated within this complex system lies cleaning and disinfection. The concept of a formal cleaning program was brought to light with the introduction of USP <797> in 2004. Prior to the introduction of this minimal practice standards document, compounding locations classified cleaning as a non-formal process in the management of medications. Hospital pharmacy departments, due to the nature of state regulations, accreditation interpretations and fear of pilfering, often limit environmental services (EVS) from conducting formal cleaning programs for which they have been trained. This limitation of EVS to pharmacy departments has relegated the cleaning processes to pharmacy staff with varying, inconsistent and inadequate results due to lack of training and validation.

The Food and Drug Administration (FDA) has highlighted the concern over the cleanliness of compounding conditions for medications for patients in their recently revised guidance document ‘Insanitary Conditions at Compounding Facilities Guidance for Industry.’[1] In the introduction the FDA reminds us that, “Under section 501(1)(2)(A) of the Federal Food, Drug, and Cosmetic Act 351(a)(2)(A)), a drug deemed to be adulterated ‘if it has been prepared, packed, or held under insanitary conditions whereby it may have been contaminated with filth, or whereby it may have been rendered injurious to health’.” Although not an enforceable document, it serves as a guidance for the protection of the public. The guidance document clearly states, ‘Drugs (including biological products) prepared, packed, or held under insanitary conditions are deemed to be adulterated, regardless of whether the drugs qualify for exemptions set forth in sections 503A or 503B of the 28 FD&C Act,’which encompasses hospital and alternate care locations. The unfortunate impetus for FDA publishing this guidance is based on ‘insanitary conditions that FDA has observed’on inspections of compounding locations which include hospitals, 503A pharmacies, 503B compounding manufacturers and the pharmaceutical industry. FDA states the scope of the guidance ‘are applicable to both sterile and non-sterile drug production.’

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.”[2],[3],[4] 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 Cleaning C-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.[5] 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.[6]

The goals for the USP <800> cleaning program must be viewed as protective for the patient, protective for all healthcare individuals all the continuum of handling and the environment. For sites to be compliant with USP <800> for cleaning, they must be compliant with the requirements set under USP <795> for non-sterile and USP <797> for sterile pharmaceutical preparations. Establishing a cleaning program for hazardous drugs must have both under-chapters as the base to build from and sites should not establish a program in a vacuum. USP <800> has devoted an entire section to cleaning, highlighting the importance. Section 15 outlines the 4-step process of DEACTIVATING, DECONTAMINATING, CLEANING, AND DISINFECTING noting that not one single method or cleaning process exists as a universal standard for all hazardous drugs. Due to the importance of the 4-step process, USP <800> defines each step and provides the ‘why’ for each step with the goal of removing hazardous drug residue, returning the cleaned location to baseline (no-residue or contamination), not damaging the cleaned, and providing a suitable work environment to protect personnel and patients. Simplistically defining each step will help staff understand the importance of each step:

Deactivation is intended to render any hazardous drug surface contamination inert or inactive. It is important to recognize that in terms of deactivation, there is no one proven method for inactivating all compounds. EPA-registered oxidizing agents represent the most widely used option and should be used when possible (e.g., peroxide formulations, sodium hypochlorite, etc.). However, it is important to recognize that agents are caustic, and products such as sodium hypochlorite will pit or stain stainless steel surfaces if left in contact too long.

Decontamination focuses on inactivating, neutralizing and physically removing surface contamination by the deactivation agent and hazardous drug residue 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. As a bonus to enhancing the cleaning process, this step should be strongly considered for each drug vial that may come contaminated from the manufacturer. Applying this step to vials can reduce contamination introduced into the sterile compounding engineering controls (hoods). It is important to ensure that the solvent used for wiping vials does not alter the product label.

Cleaning is intended to remove contaminants from surfaces using water, detergents, surfactants, solvents or other chemicals, and the Cleaning section in Chapter <797> is appropriate for both hazardous and nonhazardous drugs. It is very important to make sure that any products used for cleaning do not introduce microbial contamination. Facilities should look to the product material specifications to ensure they are EPA-registered to meet the five “-cidal” criteria: bactericidal, fungicidal, virucidal, tuberculocidal and sporicidal. If an agent states that it “kills spores” or that it kills a specific type of spore, that is not the equivalent of being labeled as a sporicidal agent. If a product that is being used is not clearly labeled as sporicidal, a sporicidal-labeled agent should be added to a scheduled cleaning regimen. Another important note about cleaning agents is the contact time of an agent with a surface to induce the specific -cidal response. Some agents require up to five minutes of direct contact time to be effective, meaning applying the agent in the defined quantity and allowing it to stay on the surface for the noted time. Wiping away the agent(s) too soon removes the benefits of the cleaning agents and may allow microbes to proliferate.

Disinfection is intended to inhibit or destroy any microorganisms and must be done for areas needed to be sterile. EPA-registered disinfectants and/or sterile 70% isopropyl alcohol 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. The biofilm that might be left on surfaces can be removed with the physical wiping motion.

Following the cleaning process, it is important to examine the areas for visible residue that may be left behind by some products, often denoted by hazy/white-ghost smears or drops. Visible residue is unacceptable, and it must be understood that dried chemicals no longer possess their desired activity. Dried residue is considered a contaminant and represents potential air pockets between the surface and the residue that can harbor spores and can easily be transferred to the sterile field or products. In addition, dried residue left on surfaces can lead to corrosion of the surfaces if not removed for long periods. Regulatory inspectors often see residue as an indication of inadequate cleaning and the FDA issued a guidance document on the concern of residues.[7]

As sites define each location where hazardous drugs are handled, they must employ certain steps of the 4-step cleaning program. For example,non-sterile areas where HDs are handled (receiving containment ventilated enclosures (CVE)) and reusable equipment and devices (counting trays; spatulas; unit dose devices) must be deactivated, decontaminated, and cleaned. For sterile preparation areas, as directed by USP <797> must include the final step of disinfecting. It is important that cleaning solutions that are selected are not reactive to surfaces to be cleaned and will not harm equipment or impact the protective nature of devices employed to provide safety (e.g. melting surfaces, pitting stainless steel, melting casing of electrical wires, penetrating gloves, impacting the HEPA filter seals in primary engineering controls).

Clearly written standard operating procedures must be in place and should include the specific name of defined chemicals used for the 4-step cleaning process, any dilutions of solutions, assigned expiration dates to on-site prepared solutions, frequency, and documentation steps.

The process of employing the cleaning methods listed should be classified as a hazardous process, thus, requiring formal education and documentation of training of personnel performing these activities. Sites must clearly define what personal protective equipment must be donned when handling cleaning solutions. Noted cleaning solutions can be caustic to skin and may illicit respiratory reactions. All personal protective equipment (PPE) must be vetted to demonstrate they are resistant to the cleaning solutions use. It should not be assumed that hazardous drug rated PPE is suitable for all cleaning solutions. As a starting point sites should review the literature of their PPE and consider the use of two pairs of hazardous drug gloves rated to ASTM 6978D and impermeable disposable gowns rated to ATM 739. Since the process of cleaning has the potential to splash sites should strongly consider the use of tight-fitting eye protection or face shields. As noted, some solutions may require the addition of respiratory protection beyond a ‘paper-mask’ and sites should consider a fitted N95 mask and to assist solutions with nauseous odors, a carbon based R95 mask.

The World Health Organization (WHO), released a report identifying hospital cleaning solutions as a potential cause of respiratory and reproductive disorders, eye and skin irritation, central nervous system impairment, cancers and other human health effects. Under the U.S. Occupational Safety and Health Administration’s (OSHA) Hazard Communication Standard (HCS) (29 CFR 1910.1200(g)), chemical manufacturers, distributors or importers must provide SDS (formerly known as material safety data sheets or MSDS) to communicate the hazards of hazardous chemical products. The SDS includes the properties of each chemical; the physical, health, and environmental health hazards; protective measures; and safety precautions for handling, storing and transporting the chemical. Sites should share with all staff, especially those with active airway diseases (asthma, COPD), the Safety Data Sheets for cleaning solutions and an employee assessment of risk to exposure must be conducted.

The application of cleaning solutions should be with equipment designed for cleaning cleanrooms and not ‘over-the-counter’ equipment that may react or melt due to repeated exposure. Cleaning equipment should themselves be placed on a routine cleaning schedule and sites should define when equipment must be replaced due to wear/ tear and contamination-risk. Cleaning solutions should be poured onto disposable, low-linting wipes and not ‘sprayed’ due to the aerosolization of the solution(s) and the potential to aerosolized moistened hazardous drug residue. All cleaning materials and PPE must be considered contaminated and disposed according to state and facility policies for hazardous materials.

USP <800> Requires More Frequent Cleaning Than Traditionally Practiced

Twelve published papers have strikingly demonstrated measurable residues of drugs on the outside of vials, accompanying package inserts and outer shipping boxes of vials. USP <800> highlights sites can reduce the amount of contamination by wiping down all vials prior to placing them on any surfaces (preparation tables, staging bins, primary engineering controls). It important that the cleaning solutions used for this process not impact the readability of the label.

In addition to wiping down each hazardous vial, sites must clean their containment primary engineering controls at least daily and the compounding surface of the containment primary engineering controls must be decontaminated between each unique drug to prevent any potential cross contamination of products. This process is clearly supported by the previously mentioned 2018 FDA Guidance Document on Insanitary conditions. As an example, case reports have demonstrated cross contamination of BCG to sterile compounded products subsequently prepared, leading to patient harm and deaths.[8] The deactivation, decontamination, cleaning should immediately take place in the presence of spill, with the addition of disinfecting the surface for compounding surfaces. To minimize the exposure of hazards to maintenance and certifying personnel, surfaces should be cleaned prior any servicing by personnel outside of the department.

Containment primary engineering controls 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, (Figure from Baker). These under-spaces assist with moving air through vents located near to the compounding surface to move contaminates away from the compounding surface. Due to this design, these under-spaces can accumulate hazardous drug residues/spills and other items used during the compounding process (vial caps, syringe packaging, pens, alcohol swabs). USP <800> clearly states that the under spaces must be cleaned (4-step process) on a monthly basis to reduce contamination build-up. It should be noted that access to the under space may be difficult and may require assistance with lifting and holding the upper work surface in place during cleaning. The process of cleaning this surface will disrupt the protect airflow of the containment-primary engineering control and should be classified as a hazardous process requiring additional PPE and specialized training. Sites are encouraged to check with the manufacturer’s maintenance information on the proper process for accessing the under spaces of containment-primary engineering controls.

Commercially Available Cleaning Systems

Currently, the U.S. market has a variety of integrated cleaning systems. These systems have made a point to ease the complicated cleaning process for hazardous drugs. Some systems employ the use of pre-saturated wipes of cleaning solutions used for each step of the cleaning process. It is important to note that some systems may not address each of the 4-steps, thus requiring sites to supplement the step with an additional product. Examples of cleaning systems: Surface Safe®; HDClean®; VIA Wipe 1-2-3®; Peridox RTU®; Pharma-Surface-Guard®.

Some vendors have enhanced their testing to validate that their products can be used for multiple steps of the 4-step cleaning process.

For any product(s) that sites may choose to use, you must get validation from the company that demonstrates the desired result of the product(s). In addition, sites should work with their infection control, employee health. Safety and EVS departments to assist with the selection, training and monitoring the use of products.

Assessing Cleaning Programs

Due to the increased number of hazardous drug wipe sampling test kits, sites can use results as a process to validation cleaning practices and cleaning solutions. There are the traditional wipe analysis kits which quantify defined hazardous drugs and the newly introduced quick test systems that detect the presence of defined residues without quantifying. Proposed USP <800> recommends conducting surface sampling for hazardous drug (HD) residue ‘routinely.’ The chapter recommends an initial wipe analysis to establish a baseline and every 6 months thereafter or as determined by the needs of the site. When a facility begins the process of redesigning and reconfiguring workspaces 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 do 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.[9]

Best practice for a hazardous drug safety program would be to 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.[10]

Becton Dickenson (BD) released in 2018 the HD Check Analyzer as a system to provide results in as little as 10 minutes for the hazardous drug residues.

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 U.S. 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 U.S.

Sites should consider the continuum of the hazardous drug handling process and assign routing sampling intervals for assessing for residue.

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.

Using FDA Guidance Can Enhance Cleaning Validation Check-Points

Sites should use this document as a routine inspection template based on the examples. Selective examples cited for consideration for sites:

“Vermin (e.g., insects, rodents) or other animals (e.g., dogs) in the production area or adjacent areas:” Look at light lens with bugs in areas where drugs are located

– “non-microbial contamination in the production area (e.g., rust, glass shavings, hairs, paint chips).” Look for rust, hair, chipped paint on equipment/walls and exposed drywall

-“Exposing sterile drugs and materials to lower than ISO 5 quality air for any length of time. This would include, … open packages of sterile wipes.” Look at how staff use sterile wipes and where they are located.

– “Producing drugs while construction is underway in an adjacent area without adequate controls to prevent contamination of the production area and product.”

-“Standing water or evidence of water leakage in the production area or adjacent areas” Look for water stained ceiling tiles, dried stains on flooring

-“Handling hazardous, sensitizing, or highly potent drugs (e.g., hormones) with inadequate controls to prevent cross-contamination, including: … inadequate cleaning of rooms, work surfaces, and equipment (e.g., utensils)….” Look at hazardous drug wipe residue test results for positive samples and assess risk of cross-contamination.

-“Using non-sterile disinfecting agents and cleaning pads/wipes in ISO-classified areas” NOTE not required under USP <797>, however, this is a best practice in light of the potential for pathogens to grow in non-sterile solutions (fungal spores, etc.)

– “Lack of, improper, or infrequent use of a sporicidal agent in the facility’s ISO 5 areas and other classified areas.” Look at sporicidal agent in use and ensure labeled as ‘Sporicidal’ and not ‘Kills Spores’ or ‘Kills C. difficile Spores’.

-“Failing to appropriately and regularly clean and disinfect (or sterilize) equipment 306 located in the ISO 5 area.” Look at the process how equipment is cleaned within the PEC (hoods) like IV Workflow hardware; Repeater pumps; collaborative robots

Without conducting a hazardous drug residue wipe analysis, facilities are blindly assuming they their cleaning programs are adequate and 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.

References

[1]United States Department of Health and Human Services; Food and Drug Administration Center for Drug Evaluation and Research ; Office of Compliance; Compounding and Related Documents Revision 1: Insanitary Conditions at Compounding Facilities Guidance for Industry; September 2018 https://www.fda.gov/downloads/Drugs Accessed November 19, 2018.

[2]Proposed revision, USP General Chapter: USP <795> Pharmaceutical Compounding – Non-sterile Preparations. http://www.usp.org/compounding/general-chapter-795 Accessed November 19, 2018.

[3]Proposed revision, USP General Chapter: USP <797> Pharmaceutical Compounding – Sterile Preparations. https://www.usp.org/compounding/general-chapter-797 Accessed November 19, 2018.

[4]Proposed, USP General Chapter: USP <800> Hazardous Drugs—Handling in Healthcare Settings http://www.usp.org/compounding/general-chapter-hazardous-drugs-handling-healthcare Accessed November 19, 2018.

[5]United States Health and Human Services: Centers for Disease Control. Guideline for Disinfection and Sterilization in Healthcare Facilities (2008) https://www.cdc.gov/infectioncontrol/guidelines/disinfection/disinfection-methods/chemical.html Accessed November 19, 2018.

[6]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.

[7]United States Department of Health and Human Services; Food and Drug Administration Center for Drug Evaluation and Research ; Office of Compliance; Compounding and Related Documents. GUIDE TO INSPECTIONS VALIDATION OF CLEANING PROCESSES https://www.fda.gov/ICECI/Inspections/InspectionGuides/ucm074922.htm Accessed November 19, 2018.

[8]Merck BCG Package Insert: https://www.merck.com/product/usa/pi_circulars/t/tice_bcg/ticebcg_pi.pdf Accessed November 19, 2018.

[9]Douglass K, Kastango E. USP <800> Let’s Get Started. Pharmacy Purchasing and Products; December 2017 supplement

[10]Crul M, Simons-Sanders K. Carry-over of antineoplastic drug contamination in Dutch hospital pharmacies. J Oncl Pharm Pract. 2018;24(7):483-489.

Road to USP 800 Compliance

Section 14 Administering

Sections 1 through 13 of USP Chapter 800: Hazardous Drugs—Handling in Healthcare Settingsprovides the blueprint for safely getting a hazardous drug into our facilities and on to our shelves into a compounded product for patient administration. On our road to compliance, Section 14 provides us with a brief guidance on drug administration considerations for hazardous drugs.

This section is a new path for USP, traditionally limited to functions of products and compounding, this is the first time the administration of drug group is addressed by USP. The primary goal of this section is to provide guidance on safe administration guidelines while handling hazardous drugs. The guidance on administration provides a safety adjuvant to Centers for Disease Control (CDC) and Association for Professionals in Infection Control (APIC) intravenous drug administration practice standards.

The administration of hazardous drugs poses many challenges to nursing (drug administration) that the pharmacy (compounding) fully appreciates. Nurses are the extension of the pharmacy to the patient and in such must address many challenges associated with direct care. Unlike pharmacy (compounding) which has negative pressure rooms/negative pressure containment primary engineering controls (PEC) and personnel protective equipment, nursing (administration) must rely primarily on personnel protective equipment and pre-primed IV lines with non-HD solution to protect them and the patients. Due to this discrepancy between engineering controls, compounding and administration; USP <800> clearly states that closed-system transfer devices (CSTDs) should be used for compounding and must be used for drug administration. Using a CSTD in compounding provides nursing with protection by eliminating spiking or priming of IV lines at the bedside. Another technique that can be employed for priming lines with drug naïve fluid is the process of back-priming is the line, however, this must be accomplished using a CSTD.

Another risk point for nursing (administration) is with regards to oral solid dosage forms. Oftentimes, nurses are met with a patient who demonstrates a challenge to administer a drug according to the directions denoted on the eMAR. Nurses apply their vast knowledge to assuring the drug(s) are administered to the patient in a manner that meets the intent of the eMAR and the patient’s conditions (e.g., solid oral medications). If a patient is having trouble swallowing, oral solid forms are often crushed or split to allow for a carrier such as water or apple sauce to ease the swallowing process. There are a variety of pill crushers/pulverizers and splitters on the market. The use of these devices with a hazardous drug presents a unique challenge to minimize the aerosolization of powdered residue during the crushing and splitting processes. Sites should always default to commercially available liquid formulations or powders for reconstitution over crushing/splitting of solid dosage formulations. The Pennsylvania Patient Safety Authority just published in September 2018 a report which clearly demonstrates that inappropriately altering tablets and capsules can result in treatment failure and patient harm; specifically crushing and splitting tablets:http://patientsafety.pa.gov/ADVISORIES/Pages/201809_AlteringDosage.aspx

Released at the 2017 ASHP Midyear Clinical Meeting, Healthcare Logistics offered a nurse-designed closed process for crushing + mixing + aliquoting dosage + with ENFit tip for safe administration; Pictures:

Healthcare Logistics: http://shop.gohcl.com/default.aspx?page=item%20detail&itemcode=19847

The proper personal protective equipment must be donned during the drug administration process. It is important to note the 2016 NIOSH Hazardous Drug List; Table 5 gives a great summary of recommended PPE for various increments of risks associated with product type to product risk category; https://www.cdc.gov/niosh/docs/2016-161/pdfs/2016-161.pdf.

For example, NIOSH recommended PPE for oral products:

Source: https://www.cdc.gov/niosh/docs/2016-161/pdfs/2016-161.pdf

Versus the NIOSH recommended PPE for injectable formulations:

Source: https://www.cdc.gov/niosh/docs/2016-161/pdfs/2016-161.pdf

It is important for sites to critically evaluate their practices surrounding hazardous drugs and work as an interdisciplinary team to define the required PPE for each tasks of handling and for everyone involved with the critical tasks of handling hazardous drugs. Sites must educate individuals that all PPE utilized during the handling of hazardous drugs, hazardous drug waste, and patients who receive hazardous drugs should be considered hazardous. In addition to the PPE, all equipment used for compounding and administering hazardous drugs, such as CSTDs, tubing, syringes, delivery bags, shipping bags, patient administration drapes, chemo-pads, and hazardous spill materials, must be considered as ‘Trace Hazardous Waste’ or if grossly contaminated as designated as ‘Hazardous Waste’ and must be disposed of accordingly.

Drugs can be administered through numerous routes to minimize toxicity and maximize effectiveness of the therapy. A gap often overlooked by facilities is the operating room suites. Pharmacy will often compound the hazardous drug and dispense the product in a package (syringe, IV bag) that does not suite the route of administration. For example, drugs instilled into the eye, bladder or intraperitoneal spaces may require ‘opening’ the package to allow the drug to enter the cavity. This process is high risk and in most cases healthcare providers involved with the administration with these special routes may not don the appropriate PPE for protection. This example highlights the importance of sites examining how each hazardous drug is administered to patients within their facilities. Manufacturers of CSTDs have worked through some of the open routes to provide adjuvant devices and processes to help minimize the risk.

References

[1] USP General Chapter 800 Hazardous Drugs—Handling in Healthcare Settings

http://www.usp.org/compounding/general-chapter-hazardous-drugs-handling-healthcare

[2] Pennsylvania Patient Safety Authority: The Breakup: Errors when Altering Oral Solid Dosage Forms; http://patientsafety.pa.gov/ADVISORIES/Pages/201809_AlteringDosage.aspx

[3] 2016 NIOSH Hazardous Drug list: https://www.cdc.gov/niosh/docs/2016-161/pdfs/2016-161.pdf

Section 13: Compounding

Sections 1 through 12 of USP Chapter 800: Hazardous Drugs—Handling in Healthcare Settings provides the blueprint for safely getting a hazardous drug into our facilities and on to our shelves on our road to compliance. Section 13 provides us with a brief guidance on compounding considerations for hazardous drugs. The primary goal of this section is to provide guidance on compounding expectations for hazardous drugs. Without standards, legacy and or observant opinions on compounding often dominate practices which place patients at risk.

USP <800> is a broad chapter and requires the use of specific USP chapters to articulate and define expectations for compounding. It is clearly noted that entities must refer to and follow USP <795> Pharmaceutical Compounding – Non-sterile Preparations and USP <797> Pharmaceutical Compounding – Sterile Preparations for the required standard operating procedures in addition to the 18 sections outlined within USP <800>. Not listed within USP <800>, the newly proposed chapter USP <825> Radio pharmaceuticals must be considered in its entirety for hazardous drugs when these drugs are in combination with a radio isotope. References to other chapters listed within USP <795>, USP <797>, USP <800> and USP <825> must be reviewed and implemented for full compliance.

Chapters USP <795>, USP <797>, USP <800> andUSP <825> all list specific compounding controls which include primary engineering controls (a.k.a., hoods) and secondary controls (a.k.a., rooms). With hazardous drugs the addition of a “C” to PEC and SEC refers to ‘containment’ (C-PEC; C-SEC). For hazardous drugs, containment is key to mitigating any risk of migration of hazardous drug residues to the environment and to personnel.

Historically sites have prepped the compounding surfaces for hazardous drugs with a ‘Chemo-mat’ or ‘Chemo-pad.’ These devices are often introduced onto the compounding space after cleaning and disinfection and serve to absorb any spills and sprays that may occur during compounding. USP <800> does not require the use of these pads, but the chapter does list them as a should. It is important to note that if these pads are used within the ISO 5 C-PEC they must be sterile. The introduction of non-sterile equipment into the compounding space increases the bio burden risk to the sterile compounding processes. For hazardous drugs, the pads should provide a barrier to the compounding surface of the C-PEC by the use of a plastic material such as polypropylene or polyethylene. It is inappropriate to use barrier pads not designed for compounding, such as “bed-chucks”, which are not sterile, bulky, and, may shed particulate material onto the work surface. Pads must be changed if a spill occurs and should be changed between each patient preps to minimize the risk of possible cross-contamination of products.

For hazardous drugs, the use of disposable equipment should be considered. If sites must use permanent or reusable equipment, it must be dedicated for hazardous drugs and must be appropriately cleaned between patient use or between drugs using the USP <800> 4-step cleaning procedure. Refer to the proposed USP <795> and USP <797> standards for cleaning of equipment. Equipment that often eludes cleaning programs include mortar/pestles, counting trays/spatulas, glass-ware, weighing trays, IVPB hanging hooks within the C-PEC, plug-ports/gas-ports within the C-PEC, IV-workflow equipment within C-PEC, small supply storage bins within the C-PEC, waste bins within the C-PEC, and the under-surface of repeater pumps.

This section of the chapter does mention the use of bulk containers of liquid and active primary ingredients and states they must be handled in a manner to prevent spills. Spills can present themselves in the form of a liquid, solid (powders) or gas (through physical phase changes). Consideration should be given to the processes of manipulation that may generate a spill such as transferring powder for compounding, crushing or splitting tablets, opening capsules, opening an ampule, or using a needle/syringe to compound a sterile product. The use of a C-PEC to manipulate hazardous products must be employed to protect the healthcare worker. If there is a likely-hood spill, the use of Chemo-pad should be highly considered with the noted at-risk manipulations.

As the NEW official implementation date of December 1, 2019 for proposed USP <800> and subsequent revisions to USP <795> and USP <797> compliance allows time for sites to prepare for overall compounding compliance. The time for review of USP’s newest chapter in combination with keeping up with USP’s website for revisions to USP is now.

References

[1] USP General Chapter 800 Hazardous Drugs—Handling in Healthcare Settings

http://www.usp.org/compounding/general-chapter-hazardous-drugs-handling-healthcare accessed 2018 September 15.

Road To USP 800 Compliance

Section 12 Dispensing Final Dosage Forms

Sections 1 through 11 of USP Chapter 800: Hazardous Drugs—Handling in Healthcare Settings provides the blueprint for safely getting a hazardous drug into our facilities and on to shelves on our road to compliance. Section 12 provides us with a brief guidance on handling hazardous drug in their final dosage forms. The primary goal of this section is to provide guidance on clarifying products in their most ready to use form for patient administration. This section is primarily devoted to solid oral dosage formulations.

When hazardous drugs do not require any compounding or ‘manipulation’ of the manufacturers commercial products (intact tablets, capsules) outside of repackaging into unit of use forms, the products may be prepared for dispensing without any further requirements for containment. Package inserts of defined hazardous drugs should be reviewed with focus on the manufacturer handling requirements.

Sites should try to purchase defined hazardous drugs in unit of use packaging from the manufacturer to minimize the need to repackage on-site. The process of counting and repackaging of hazardous drug must be done carefully. For products that are not available from manufacturers in unit of use packaging, sites should examine each bulk product and look for tablets and/or capsules that may have powder residue. This is commonly seen with punch tablets without a protective coating. Noting the bulk packages with particulate-potential should prompt sites to have those products handled and repackaged in a containment primary engineering control or a containment ventilated enclosure with a full or partial enclosure that uses ventilation to capture, contain, and remove airborne particulates using HEPA filtration. Staff should be educated on the products that have the potential to illicit particulates. As sites change manufacturers of on-formulary products and add new drugs to the formulary, products should be examined for particulate-generation potential.

Outlined in both USP <800> and in USP <795>, clean equipment should be dedicated for use with hazardous drugs and should be decontaminated after every use. Decontamination as defined by USP <800> denotes the “Inactivation, neutralization, or removal of hazardous drug contaminants on surfaces, usually by chemical means.” Isopropyl alcohol is commonly used for this step, however, isopropyl alcohol is a disinfectant and is not able to inactivate and neutralize any hazardous drug residues. Sites must use the same products used in the compounding of sterile hazardous drugs when preparing the primary engineering controls, e.g., sodium hypoclorite solution followed by sterile isopropyl alcohol. Equipment dedicated to hazardous drugs may include counting trays, counting spatulas, scales, and manual unit dose equipment.

Solid dosage formulations of antineoplastic agents must not be placed in automated unit dose packaging devices. These devices can inadvertently stress drugs or crush them resulting in the generation of hazardous drug particulate matter leading to a dry hazardous drug spill. This should not be confused with the ability to store these medications in automated dispensing cabinets and drug storage carousels.

References

[1] USP General Chapter 800 Hazardous Drugs—Handling in Healthcare Settings

http://www.usp.org/compounding/general-chapter-hazardous-drugs-handling-healthcare accessed 2018 September 15.

Section 11 Labeling, Packaging, Transport, and Disposal of Hazardous Drugs

As we make our way down the Road to USP 800 Compliance, we’ve seen how Sections 1 through 10 of USP Chapter 800: Hazardous Drugs—Handling in Healthcare Settingsprovide the blueprint for safely getting a hazardous drug into our facilities. Moving forward, Section 11 provides us with guidance on communication of hazardous drugs once we move it from compounding area(s) to patient administration to disposal. The primary goal of this section is to alert all personnel involved within the chain of command of the product(s) to be aware of the hazard and identify prevention of exposure procedures. During training, sites must educate personnel on the preventive measures in place, including: spill response and use of a spill kits, use of sealed impervious plastic delivery bags, use of impact-resistant and/or water-tight containers for delivery, and supplementary warning labeling.

Labeling

The label represents the primary mode of communication of the contents of a compounded product. Labels can communicate patient name; drug(s) and diluents; drug dose(s); administration guidelines; date of preparation, date of expiration; compounding/verifying personnel; and supplementary information (e.g.,protect from light). Ancillary labels can be added to products to further highlight information such as “hazardous drug.” It is important that information on the label be discussed with all parties identified along the chain of custody to ensure a common understanding of terminology. For example, some ancillary labels may state ‘Chemotherapeutic’ or ‘Chemotherapy.’ Depending on who handles the product this may not convey the message such as ‘Hazardous Drug.’ Although not listed within USP <800>, the use of line-labels to assist nursing with tracing lines is an additional safety labeling feature. Sites must confirm that any labels used do not leech or impact the overall integrity of the final product(s).

Packaging

Supportive packaging and containers must be defined to physically maintain the integrity of hazardous drug products during transportation. Considerations must take into account sterility and stability integrity of sterile products and stability of non-sterile products. Overall, protection of personnel who deliver the products must be considered in the event of surface contamination of products, spills, breakage and leaks from damage. The use of bubble wrap, external zip-lock baggies and/or outer containers should be considered to protect the contents. If bubble wrap and zip lock baggies are used, sites should consider these items contaminated, not be reused, and disposed of as trace hazardous waste (unless there is a spill). Outer containers can be cleaned according to the USP <800> 4-step method between deliveries and recycled for use. Standard operating procedures must be written to address the defined transport containers and supporting insulating materials. Personnel must be trained and training verified with regards to the use of transport materials packaging and processes.

Transport

The movement of hazardous drugs must be in a manner to minimize breakage and leaks. For liquid based hazardous drugs, the pneumatic tube system must not be used due to the potential impacting the overall integrity of the product, but more importantly the concern for a spill within the pneumatic tube system. Although, zip lock baggies and gasketed pneumatic tubes can be used, in the event of a spill the exposure potential to the receiving party can be unknowing at the time of receipt. Delivery outer containers with hard sides should be considered beyond zip lock baggies to help maintain the integrity of the product. Outer containers must be labeled in a manner to communicate the internal hazard. As noted, if an outer container is used it can be cleaned between uses using the USP <800> 4-step cleaning process and recycled for use. For sites transporting hazardous drugs off-site (e.g., home infusion, alternative care locations), consultation with the transportation company with supporting documents such as Safety Data Sheets of each product, storage directions, disposal directions and spill management procedures must take place. Sites must refer to state regulations surrounding the transportation of hazardous materials.

Disposal

The proper disposal of pharmaceutical waste and hazardous drug waste resides under the Environmental Protection Agency’s direction with oversight by local and state agencies. States can enact exemptions and additional requirements for the management of the waste and sites must refer to state specific statutes with regards to the management of waste. Individuals who handle and package hazardous drug waste for removal must be formally trained on occupational exposure risks and minimizing contamination of the environment. Commercial waste haulers who are registered to handle hazardous drug waste may be able to assist sites with appropriate designation of waste streams (i.e., hazardous drug waste (commonly known as ‘yellow’ waste) versus EPA RCRA Hazardous Waste (sometimes denoted as ‘black’ waste). As noted, waste management for these products is regulated by local, state and federal statutes.

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.

References

[1] USP General Chapter 800 Hazardous Drugs—Handling in Healthcare Settings

http://www.usp.org/compounding/general-chapter-hazardous-drugs-handling-healthcare accessed 2018 August 13.

On the Road to Compliance, Sections 1 through 9 of USP Chapter 800: Hazardous Drugs—Handling in Healthcare Settings are the blueprint and engineering structures with checks and balances for quality control. They also provide direct protective measures on and an introduction to the rights of the employees. At this stage, a site is ready to test the waters for their safety program. Section 10 addresses the receiving of hazardous drugs which is the first entry point of hazardous drugs into a facility. The receiving of products process is not often a focus for a hazardous drug safety program. Receiving occurs at multiple times in multiple points of the facility, from the actual receipt at the dock from wholesalers or direct order shippments, to receipt at a point of storage for holding for additional activities.

It is important to point out that USP 800 starts out once the physical product enters the system; highlighting the fact that all activities prior to the product arriving are not addressed. Wholesalers and shipping companies do not follow USP and are held to department of transportation and shipping standards which address hazardous materials and are not specific to drugs. The designation of a drug as a hazardous material was first defined within the Resource Conservation and Recovery Act of 1976 and is based on the potential for these chemicals to cause harm to the environment. The list is outdated and does not reflect the specific current hazards. In 1990, the American Society of Health-System Pharmacists (ASHP) published their Technical Advisory Bulletin on the safe handling of hazardous drugs and gave us our first criteria to consider for defining drugs as a hazard outside of the patient. With the adoption of USP 800 deferring to NIOSH’s hazardous drug list, based on the foundation of ASHP’s TAB definitions, this concept of a ‘hazardous drug’ is new and it will take industries outside of immediate patient care to catch on to the concept. Although USP 800 calls out ‘suppliers’ to provide hazardous drugs in segregated, impervious containers; wholesalers have yet to adopt the NIOSH list for defining hazardous drugs. Thus, labeling of totes and boxes of contents as hazards is disappointingly sproradic and cannot be relied upon.

Due to the unknown handling and management of these drugs prior to entry into facilities, it must always be assumed that the products are contaminated, totes and boxes that carry the drugs are contaminated, and the potential for broken vials exist.[2] USP calls out this entry process as a critical touch point and sites must formally address this step(s) for the safety of employees. USP clearly outlines the steps to receive, inspect, handle, address breakage and spills for this process. Ideally, totes and boxes should be opened in a containment ventilated equipment residing in a space that is neutral to negative pressure to adjacent spaces.

USP clearly states that once received on site, drugs are to be delivered to the designated storage area for unpacking. Sites should define the required personal protective equipment for the process of unpacking and must at a minimum include the use of ASTM D6978 rated gloves for this process. Additional equipment may be considered such as an N-95 respirator mask and or a protective gown.

In the event of a tote/box related spill or if a vial inadvertently falls in the area of receiving, unpacking and storage, sites must have readily available a spill kit. Sites should educate all individuals in the receiving to storage processes of the formal management of spills and orientation to spill kit location(s) and their use.

Any damaged shipping containers or their contents with liquid or solid formulations of hazardous drugs must be considered a hazardous drug spill. The use of full PPE must be implemented when dealing with hazardous drug spills. It is important to note that a spill of this type is one of the most concerning since it is the most concentrated formulation of the drug(s) and gross exposure to standard PPE may exceed their potential to protect personnel depending on the drug and the quantity of the spill.

USP covers the proposed safety processes for handling damaged or suspected damaged shipping containers of hazardous drugs. If a container appears to be damaged, USP recommends notifying the supplier, not opening the container and sealing it to minimize any dispersment of materials. The damaged container should be labeled as ‘hazardous’ and should be quarantined in a room/area with neutral to negative pressure awaiting instructions for either returning the product or disposing of the product as hazardous waste onsite.

If a noticably damaged package must be opened, due to a mixture of medications within the shipping container or the spill requires a more intense intervention, staff must first use a hazardous drug kit and don PPE contents to then move the shipping container into a containment-primary engineering control unit designated for receiving or for non-sterile compounding to minimize employee and environmental exposure. The shipping container should be placed on a ‘chemopad’ and not directly on the worksurface to minimize contamination spread. The damaged container should be opened cautiously within a C-PEC and the undamaged products removed. The undamaged products must be wiped with the defined 4-step cleaning process to remove as much of the residue or suspected residue from the drug containers. As a best practice, these products that are to be retained should be placed in a zip lock baggie while stored until their use and the zip lock baggie not opened until the product is within defined primary engineering control. The damaged product and corresponding shipping container should be sealed in a manner to return to the shipper and to quarantine until such time is defined. If the shipper does not want the damaged product returned, the site must follow its defined standard operating procedures the handling of hazardous materials.

Final steps, the C-PEC used for addressing the damaged shipping container must be immediately cleaned using the site’s defined 4-step process of deactivation, decontamination, cleaning and disinfection. Disposal of all disposable materials and PPE used to address the damaged products must be considered to be ‘grossly’ contaminated and disposed of accordingly based on the institutations disposal guidelines. Sites must follow established SOPs for spill management and report it to the appropriate individual, department or agency for formal documentation.

As a thought for consideration, once the damaged shipping container is identified sites should trace the shipping container all the way to the point of entry into the facility. Each area(s) where the shipping container was held should be properly cleaned according the the proposed USP 800 4-step process. In addition, a formal notification to the shipping company as to the spill of a hazardous material should be done and documented. It is important to note that shipping companies, wholesalers and the pharmaceutical industry are not held to USP 800 and may not have a formal program in place to appropriately manage a damaged shipping container.

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.

References

[1] USP General Chapter 800 Hazardous Drugs—Handling in Healthcare Settings

http://www.usp.org/compounding/general-chapter-hazardous-drugs-handling-healthcare Accessed June 2, 2018

[2] Redic KA, Fang K, Christen C, Chaffee BW. Surface contamination of hazardous drug pharmacy storage bins and pharmacy distributor shipping containers. JOPP 2017.

Section 9 Personal Training

Sections 1 through 8 of United States Pharmacopeia (USP) Chapter 800: Hazardous Drugs—Handling in Healthcare Settings are the blueprint and engineering structures with checks and balances for quality control. They also provide direct protective measures on and an introduction to the rights of the employees on our road to USP< 800> compliance. Section 9 seamlessly falls from employer labor requirements into the required training elements specifically for handling hazardous substances (drugs) at facilities.

It cannot be emphasized enough that sites must have a good training program in place to protect employees working with hazards. As discussed in Section 8, USP highlights the OSHA requirement that personnel who may be exposed to hazardous chemicals (drugs) when working must be provided information and training before the initial assignment to work with a hazardous chemical (drugs). In addition, this must be modified whenever the hazard changes, such as the addition of a newly defined hazardous drug.

Within Section 9, specific tasks are listed for minimal competencies:

Overview of the entity’s list of hazardous drug list(s) and their risks
Review of the entity’s standard operating procedures related to handling of HDs
Proper use of personnel protective equipment
Proper use of equipment and devices (rooms, hoods, CSTDs, pumps, etc.)
Response to known or suspected hazardous drug exposure
Spill management
Disposal of hazardous drugs and trace-contaminated materials

Visante has extracted best practices for training for sites to consider as additions to the required training competencies:

Vial handling for hazardous drugs: each defined job code
Site specific specialized preparation for unique routes of administration: bladder instillation; intraocular; intrathecal; intraperitoneal; intraventional radiology; surgical, etc.
Delivery competency
Drug and supply quarantine release
Linen handling for patients receiving hazardous drugs
Operative use of hazardous drugs
Environmental monitoring program
Certification validation

In addition to what is listed in USP <800> for sterile products additionally the following must be minimally trained for an understanding of sterile compounding principles:

Hand hygiene
Garbing
Aseptic technique
- Media fill test
- Glove tip test
Cleaning and disinfection

In addition to what is listed in USP <797> and USP <800> incorporation of new USP <795> for non-sterile hazardous drugs:

Cleaning of equipment between uses
Cleaning of compounding area
Component selection, handling, and transport
Performing calculations
Measuring and mixing
Use of equipment
Documentation of the compounding process (e.g., Master Formulation)
Records and Compounding Records

It is in the best interest of sites to get a signed agreement on hire and on an annual basis confirming education and acknowledgment of the defined competencies.

References

[1] USP General Chapter 800 Hazardous Drugs—Handling in Healthcare Settings

http://www.usp.org/usp-nf/notices/general-chapter-hazardous-drugs-handling-healthcare-settings. Accessed May 10, 2017