Garbing, Hand Hygiene & Aseptic Technique Materials

PRACTICE MAKES PERFECT: A GUIDE TO MASTERING GARBING, HANDWASHING, AND ASEPTIC TECHNIQUE

LIZ FREDRICKSON, PharmD, BCPS

Liz Fredrickson is an Associate Professor of Pharmacy Practice and Pharmaceutical Sciences at the Northeast Ohio Medical University College of Pharmacy. She serves as the Director of Instructional Labs and is the course director for the Basic Pharmaceutics Lab and Parenteral Products and Parenteral Products Lab courses.

Topic Overview

Every part of the sterile compounding process should be driven by one, critical element: patient safety. Key to achieving this is maintaining excellent aseptic technique, which is defined as a series of methods used to ensure compounded sterile preparations (CSPs) are free from microorganisms, pyrogens, and particulate matter. Preparing CSPs involves numerous factors, each of which has the potential to impact the sterility of these products. These include the environment in which the product is compounded, the equipment utilized to compound the product, and the individual who compounds the CSP. Should a CSP become contaminated and then administered to a patient, major harm and possible death could result. Thus, each factor must be optimized to ensure the safety of the final preparation. This course will provide a review of garbing and hand washing procedures and detail proper aseptic manipulations for pharmacists and pharmacy technicians who compound CSPs. United States Pharmacopeia, Chapter <797> guidelines will be referenced.

Accreditation Statement:

RxCe.com LLC is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education.

Universal Activity Number (UAN): The ACPE Universal Activity Number assigned to this activity is 

Pharmacist 0669-0000-22-083-H07-P

Pharmacy Technician 0669-0000-22-084-H07-T

Credits: 1 hour of continuing education credit

Type of Activity: Knowledge

Media: Internet Fee Information: $4.99

Estimated time to complete activity: 1 hour, including Course Test and course evaluation

Release Date: December 17, 2022 Expiration Date: December 17, 2025

Target Audience: This educational activity is for pharmacists.

How to Earn Credit: From December 17, 2022, through December 17, 2025, participants must:

Read the “learning objectives” and “author and planning team disclosures;”

Study the section entitled “educational activity;” and

Complete the Course Test and Evaluation form. The Course Test will be graded automatically. Following successful completion of the Course Test with a score of 70% or higher, a statement of participation will be made available immediately. (No partial credit will be given.)

Learning Objectives: Upon completion of this educational activity, participants should be able to:

Explain proper handwashing procedures

Describe how to don personal protective equipment properly

Describe the use of aseptic technique when compounding sterile preparations

Recall how to evaluate garbing, hand hygiene, and aseptic technique competency

Disclosures

The following individuals were involved in the development of this activity: Liz Fredrickson, PharmD, BCPS, and Susan DePasquale, MSN, PMHNP-BC. There are no financial relationships relevant to this activity to report or disclose by any of the individuals involved in the development of this activity.

ⓒ RxCe.com LLC 2022: All rights reserved. No reproduction of all or part of any content herein is allowed without the prior, written permission of RxCe.com LLC.

Introduction

When compounding non-hazardous, sterile preparations, every part of the compounding process should be driven by one, critical element: patient safety. The key to achieving this is maintaining excellent aseptic technique. Preparing compounded sterile preparations involves numerous factors, each of which has the potential to impact the sterility of these products. Contamination of sterile compounds can lead to serious injury or death of the patient intended to receive the preparation. This course will provide a review of the United States Pharmacopeia, Chapter <797> guidelines, garbing and hand washing procedures, and detail proper aseptic manipulations for pharmacists and pharmacy technicians who compound CSPs.

Overview of Sterile Compounding

Compounding is the practice in which a licensed pharmacist, pharmacy technician under the supervision of a pharmacist, or other licensed healthcare professional, combines, mixes, or alters ingredients of a drug to prepare a medication for a patient.1 When preparing compounded sterile preparations (CSPs), the product can become contaminated. If a contaminated CSP is administered to a patient, serious harm or death may result.1-3 Thus, protocols and guidelines must be followed by the compounder to ensure the CSP is not contaminated and that the final preparation is safe for the intended patient.

List of Useful Acronyms

CSP: compounded sterile preparation

LAFW: laminar airflow workbench

ISO: International Organization for Standardization

PPE: personal protective equipment

USP: United States Pharmacopeia

The key to achieving this is maintaining excellent aseptic technique, which is defined as a series of methods used to ensure compounded sterile

preparations (CSPs) are free from microorganisms, pyrogens, and particulate matter.2 These include the environment in which the product is compounded, the equipment utilized to compound the product, and the individual who compounds the CSP.3

Lessons Learned: A Brief History of Sterile Compounding

Guidelines pertaining to sterile compounding evolved over time, and many standards developed due to an unfortunate history of errors related to the compounding process. In 1964, the American Society of Health-System Pharmacy (ASHP) published a report known as Mirror to Hospital Pharmacy.4 Within the report, several major deficiencies in the sterile compounding process were brought to light.4 Since that time, many other instances of patient harm have been documented. In 1977, 1.2 drug-related deaths per 1000 patients were uncovered, with many the result of large volume infusions.4 This included five deaths due to contaminated cardioplegia solutions.4 In 1998, 11 children were administered drugs from contaminated syringes in a hospital.4 In 2011, 9 individuals died due to contaminated parenteral nutrition (PN).4 One of the most notorious cases was the result of contaminated preparations made by the New England Compounding Pharmacy, which resulted in more than 750 fungal infections and 100 deaths.5 These events highlight the absolute importance of maintaining sterility in all compounding settings. As noted by Myers in his review, microbial contamination can happen in any practice setting and with any type of CSP.4 Today, compounding personnel have the opportunity to learn from these errors and continuously work to improve the process of sterile compounding and the safety of CSPs for their patients.

Personal Protective Equipment

Personal protective equipment (PPE) is equipment usually used to protect a compounder from injury when working with a hazardous agent. However, when compounding non-hazardous, sterile preparations, PPE takes on another important purpose: PPE protects the CSP from contamination by the compounder.2,3

Compounding facilities should establish proper policies and procedures for the use of PPE. United States Pharmacopeia (USP), Chapter <797> provides guidance as to types of PPE and the order in which it should be donned (i.e., put on).6 The type of PPE required will depend on the type of CSP being compounded, with differences depending on whether hazardous or nonhazardous compounding is occurring.6

Getting Ready

The process of putting on PPE is also known as “garbing.”2 Donning PPE is the first line of defense against microbial contamination of CSPs.6 Humans shed squamous skin cells at an estimated rate of 106 per hour, and most microorganisms found in cleanrooms have been transferred from individuals.6 Any person who enters a compounding area in which a Category 1, 2, or 3 CSP is being made must ensure they are properly garbed per their facility’s standard operating procedure (SOP).6 Compounding personnel need to ready themselves even before donning PPE.7 This includes the removal of certain items and makeup from their person.6 United States Pharmacopeia, Chapter<797> classifies these items as those not easily cleanable or that are unnecessary for compounding. They include the following:6

Personal outer garments, such as bandanas, coats, hats, and jackets

Cosmetics

Hand, wrist, and other exposed jewelry, including piercings that could alter the fit of PPE, such as eye protection

Earbuds and headphones

Electronic devices not necessary for compounding

Makeup must be removed before donning PPE.6 This is key, as wearing makeup increases an individual’s normal rate of skin cell shedding, leading to the creation of dander that could contaminate the compounding area.7 Like makeup, items including nail polish, perfume, body spray, and cologne cannot be worn during sterile compounding and should be removed before donning PPE.7 While they may seem harmless, these products can emit particles with the potential to contaminate the compounding area.7 Hair products also

cannot be used for similar reasons. These include gels, hairsprays, and similar styling products.7 The nails of compounding personnel should be trimmed short and free from dirt or particulate matter.7 Acrylic nails should never be worn while compounding, as they could potentially tear a compounder’s gloves and/or reduce their ability to compound appropriately.6,7 Compounding personnel can wear their eyeglasses during sterile compounding, but these must be wiped.6

The health of compounding personnel should also be considered. Any individual who is ill or has open cuts, sores, rashes, or burns should not compound sterile preparations, even if these areas are covered.6 These conditions can increase the risk of contamination.6 Per USP Chapter <797>, the designated person can permit various accommodations for personnel, granted the quality of the CSP and the environment will not be impacted.6 Any permitted accommodations must be documented by the designated person.6

Types of PPE

In general, all PPE should be lint-free, with low particle emission rates.2,3 This assists in minimizing dust and other particles from contaminating the sterile compounding area.1 Various types of PPE are detailed in Table 1.2,3,7,8

Table 1. Descriptions of PPE

For personnel compounding Category 1 or Category 2 CSPs, the following are minimal garbing requirements per USP <797>:6

Low-lint garment with sleeves that fit snugly around the wrists and an enclosed neck (e.g., gowns)

Low-lint shoe covers

Low-lint cover for head that covers the hair and ears, and if applicable, cover for facial hair

Low-lint face mask

Sterile powder-free gloves

If a facility compounds Category 3 CSPs, personnel must adhere to additional garbing requirements. These are as follows:6

No skin can be exposed in the buffer room (i.e., face and neck must be covered)

All low-lint garb must be sterile

Disposable garbing items must not be reused, and laundered garb must not be reused without being laundered and re-sterilized with a validated cycle.6 Experts recommend storing all garb far from sinks and trash cans and in closed bins to prevent contamination.7

Hair Covers and Face Masks

A compounding personnel’s hair is at a particularly high risk of contaminating CSPs. Hair may emit large quantities of particles.2 The use of hair covers is, therefore, vital to preventing contamination from entering the buffer area.2 Ideal hair covers are well-fitted to prevent any hair from being exposed.2 There are different hair covers available, including bouffants and surgical covers.8 Bouffants are useful for hair longer than a few inches; hair shorter than this can be covered with a surgical cap.8 Long hair should be pulled back and not allowed to drape on the compounder’s shoulders.8 Compounding personnel should ensure ear lobes are completely covered, and hair on the neck should be tucked under the cover securely.2 Facial hair should be completely covered by a beard cover.2 If this is not feasible, the facial hair should be neatly trimmed.2,8 Face masks should cover the entire face starting at the bridge of the nose and going below the chin.8 The ear loops can be placed under or over the hair cover.8 The face cover can be squeezed over the bridge of the nose to form the shape of the nose ensuring the face is firmly covered.8

Gowns

Gowns worn during sterile, nonhazardous compounding should have fitted wrist cuffs and fitted collars.8 Such gowns should close in the front and secure with button snaps or secure string ties.8 If non-disposable gowns are utilized, they should be kept in the compounding room but need to be cleaned appropriately per guidelines.6,8

Gloves

In selecting gloves, compounding personnel should choose a size that fits snugly but not too tightly.2,8 Gloves that are too tight may rip, while gloves worn too loosely can prohibit the compounder from completing processes accurately.2 Regular gloves are nonsterile gloves that are not specific to either hand and may be latex or powder-free.8 While these types of gloves can be worn when cleaning, they cannot be worn while compounding CSPs.8 Sterile, powder-free gloves should be used for this purpose. These gloves are packaged specifically to be worn on the left or right hand.8 Gloves for nonhazardous, sterile compounding should be donned as follows:8

Select and retrieve the appropriate glove size.

Open the outer plastic package. Discard.

Lay the inner package on a clean surface. Unfold to expose the sterile gloves.

Place your thumb (with fingernail facing down) of the hand that will not be gloved (for example, the right hand) inside the cuff of the left- hand glove

With your palms facing up, slide the left hand into the glove while using the right thumb to secure and pull the sterile glove onto the left hand

To don the right-hand glove, take the gloved hand and pinch the folded cuff of the right glove, still laying the package on a clean surface

With your right palm facing up, slide the hand into the glove, placing fingers of the left hand underneath the folded cuff, pulling the glove fully on

Place the cuff of the right glove over the cuff of the gown

Place the cuff of the left glove over the left gown cuff

Compounding personnel should routinely inspect gloves for holes, tears, and punctures and replace their gloves immediately if these are evident.6 Gloves should also be tested for compatibility with alcohol disinfection by the manufacturer.6 Gloves also need to be disinfected regularly at times and

intervals throughout the compounding process. The following times are recommended to disinfect gloves:

Immediately after being donned

Prior to and after cleaning the work area

Prior to reentering an ISO Class 5 environment

If gloves are suspected or known to have been contaminated

If gloves are visibly soiled

Periodically during long durations of compounding in the primary engineering control

Donning PPE

When compounding a Category 1 CSP, garb must be donned within the segregated compounding area perimeter.6 Garb should be donned in a classified area before entering the buffer room when Category 2 or Category 3 CSPs will be prepared.6 An alcohol-based hand sanitizer must be used prior to donning garb if hand hygiene is completed outside of a classified area.6 Additionally, skin must not be exposed inside the ISO Class 5 PEC.6

PPE should be donned in a specific order, which has the compounder garb in the order of “dirtiest to cleanest”.2,6,7 Prior to entering the garbing area, personnel should step on a sticky mat, often called a tak-mat.2 This mat assists with removing debris and particles from the bottoms of shoes.2 The order of garbing is important to reduce contamination and must be adhered to. The steps are listed below.

Shoe covers

Hair cover

Face mask

Wash hands

Gown

Gloves

Disinfect gloves with 70% IPA

Removal of PPE

Once the compounder is finished with their work and exits the compounding area, PPE should be removed in the opposite order in which it was donned.2 Garb should also be removed and replaced if it becomes visibly soiled or if its integrity has been compromised.6 The process of removing PPE is referred to as “doffing.”3 Gloves should be removed first, followed by the gown, face mask, hair cover, and, finally, shoe covers. PPE used for sterile, nonhazardous compounding can be placed into a regular waste container for disposal.8 The only component of PPE that may be kept for re-use is a gown, given it is not visibly dirty, and this can only be redonned for the same shift work.6 All other PPE should be disposed of.6 The guidelines state that if compounding Category 1 or Category 2 CSPs, personnel may reuse gowns within the same shift, as long as the gown is maintained in a classified area or inside the perimeter of an SCA. When exiting the compounding area, all other garb must be discarded or laundered before being reused.6 Donning and doffing garb should not occur in the anteroom or the SCA at the same time.6

Hand Washing

Hand washing is a crucial step in maintaining the sterility of CSPs. This step is completed after donning shoes, hair, and face covers but before donning the gown and gloves.8 An institution’s policies and procedures should include how to wash hands properly. By washing hands correctly and consistently, compounding personnel can reduce levels of bacteria that could contaminate CSPs.6 Human hands have anywhere from 102 to 103 CFU/cm3 of normal flora present.2 However, healthcare workers are constantly exposed to other bacteria that can result in healthcare-acquired infections.2,3 Numerous infections, including influenza and infectious diarrhea, can be spread via contaminated hands.2,3 In a 2017 review, 11 studies focused on healthcare workers’ hand carriage of Clostridioides difficile were evaluated.9 After caring for patients with Clostridioides difficile infection, anywhere from 0% to 59% of workers’ hands were contaminated.9 Despite the importance of hand washing, many other studies have found that healthcare professionals do not adequately perform this important step.11

Two important notes can be made regarding hand washing. First, sanitizing hands should never replace the physical process of washing one’s hands.2 This is especially important as the process of physically washing hands is the only way to remove Clostridioides difficile and any general particulate matter that could be on a compounder’s hands.2 Second, washing hands before gloving can reduce the risk of touch contamination.2 The Centers for Disease Control (CDC) and World Health Organization (WHO) have published guidelines for handwashing.11,12 The WHO guidelines are depicted in Figure

1.12 USP Chapter <797> also includes handwashing procedures.6,8,12

Figure 1. World Health Organization Hand Washing Procedure

Hand Washing Equipment

Per USP <797>, no person should enter a compounding area before washing their hands and forearms, and hand washing should occur in the anteroom.2,6 Compounding facilities may use various types of sinks for hand washing. Importantly, a sink should be the only water source used for washing hands.8 Ideally, the sink will be turned on and off using a foot pedal or a motion sensor, so the operator does not have to touch the sink.8 However, the sink may be turned off by wrapping a towel around the handle.2,8 Warm water is recommended for use.8 Hot water has the potential to cause dermatitis.8 If the sink does have a faucet to turn on and off the water, the water should be left running for the duration of the hand-washing process.8 Otherwise, compounding personnel risk re-contaminating their hands each time they turn the water on and off.

An approved, antiseptic hand soap, such as chlorhexidine or triclosan, should be utilized to wash hands.2,8 United States Pharmacopeia guidelines suggest facilities use a closed system of soap (such as a nonrefillable container) near the sink to minimize the risk of contamination.6 Disposable nail cleaners should also be used during the hand washing process.6 Once disposable nail cleaners have been picked up, they should not be placed down until the nails have been thoroughly cleaned.7 If it is dropped or placed down, the nail cleaner should be replaced.8 While using the nail cleaner, water should be run over the cleaner to wash away any visible debris.8 United States Pharmacopeia, Chapter <797> does not recommend the use of an antimicrobial scrub brush, as this may cause skin irritation and/or damage, which can harm compounding personnel and release more bacteria.6 Also, hand dryers must not be used.8

Hand Washing Procedure

A suggested handwashing procedure is detailed in Table 2.8 As hands and fingers come in closest contact with CSPs during the compounding process, it is necessary to keep those areas as clean as possible. With this in mind, personnel can envision a conceptual way to think about hand washing.2

Wash particles away from the cleanest areas (hands and fingertips) to the dirtiest areas (elbow).2 The same technique should be used for drying hands as well. Compounding personnel should not dry forearms and hands in an “up- and-down” motion, as this will bring any potential germs from the elbows up to the hands.2 Additionally, once hands have been thoroughly washed and dried, no objects should be touched before completing the gloving step.2

Table 2. Suggested Hand Washing Procedure8

Timing

The amount of time spent washing hands is as important as using the proper technique. Research has demonstrated washing hands for 15 seconds can reduce bacteria anywhere between 0.6 and 1.1 log10 and if this is increased to 30 seconds, bacteria can be reduced between 1.8 and 2.8 log10.2 It is recommended to wash hands for a minimum of thirty seconds. Hands can and should be washed frequently, including when they become visibly dirty or contaminated.2

Hand Sanitizing

To sanitize hands before donning gloves, an alcohol-based hand sanitizer should be applied to the skin following the manufacturer’s instructions as to the amount to use.2 The product should be applied to one hand, and then the hands should be rubbed together.2 Personnel should cover all surfaces of their hands and fingers, rubbing until the hands are dry.2 The hands must be thoroughly dry before donning sterile gloves.2 USP <797> recommends the following hand sanitizing procedure:6

Apply an alcohol-based hand sanitizer to dry skin following the manufacturer’s instructions for the volume of product to use

Apply product to one hand and rub hands together, covering all surfaces of hands and fingers, until hands are dry

Allow hands to dry thoroughly before donning sterile gloves

Aseptic Technique

As mentioned above, aseptic technique is defined as a series of techniques used during the preparation of CSPs to ensure products are free of microorganisms, pyrogens, and particulate matter.2 Such techniques involve the correct manipulation of syringes, vials, and ampules to prevent contamination.2 In discussing aseptic technique, compounding personnel should be familiar with the concept of critical sites. A critical site is defined by USP Chapter <797> as a location that includes any component or fluid pathway surface or opening exposed and at risk of direct contact with air, moisture, or touch contamination.6 As noted by the chapter, maintaining sterility of critical sites is a crucial safeguard for CSPs.6 Compounding personnel must protect critical sites from both physical and airborne contamination.6 Airborne contaminants are more likely to reach a critical site than those on the floor or other surfaces, and large and high-density particles can settle on critical sites, despite being in an ISO 5 environment.6

Materials, including syringes, vials, ampules, and needles, all have critical sites, and these are the parts that have the greatest risk of

contamination during sterile compounding.2 Such contamination can occur via touch contamination, including contact with an unclean object or the compounder.2 Touch contamination is the greatest source of contamination during the sterile compounding process.2 Numerous factors can impact the risk of contamination, including the type of critical site, the material of the critical site, the time of exposure to the contaminant, and the number of manipulations involving the critical site.2,6 The material of the critical site can also play a role, with the closure of a vial able to sustain more microorganisms than the neck of an ampule.6 Table 3 lists the critical sites of compounding supplies.2,3

Table 3. Critical Sites of Compounding Supplies

General processes pertaining to the use of aseptic technique during the sterile compounding process are described in detail below.

Gathering Supplies

Prior to compounding a CSP, all necessary supplies must be gathered and assembled.2 Numerous supplies may be needed during the sterile compounding process, including vials, ampules, needles, syringes, additive bags, and alcohol wipes. These supplies and materials need to be kept sterile. Any supplies needed for a particular preparation should be collected and brought into the LAFW at one time.2 Additionally, supplies and components that are packaged, such as needles, syringes, and small-volume parenterals,

should be unpackaged and wiped down using a disinfectant that will not leave a residue in the anteroom before being passed into the buffer room.6

Disinfecting Critical Sites

Vials, ampules, and additive bags all contain critical sites and thus require disinfection prior to compounding.2 It is useful for compounding personnel to disinfect these sites upon bringing materials into the LAFW, as this permits ample time for the critical site to dry.2,8 To assist the disinfection process, all disinfected surfaces should be allowed to remain wet for at least 10 seconds before access.2

For vials, the critical site is the rubber closure.2 To access the closure, the vial’s protective cap should first be removed. This can then be placed in a trash pile. To disinfect the rubber closure, the compounder should use a new, sterile, lint-free alcohol wipe and wipe the closure three times in the direction of the operator.2 This method of disinfecting will prevent potential particulate matter from being directed toward the HEPA filter.2 Personnel should use a new wipe every time a new vial needs to be disinfected to avoid the transfer of particles from one vial to another.2 The critical site of the ampule is the neck, and this can be disinfected by wrapping an unused, sterile alcohol wipe around the neck and wiping in a twisting motion that ensures the entire area is cleaned.2 The additive port of an additive bag is the port into which compounding personnel injects solution.2 This critical site can be disinfected using a sterile, lint-free alcohol wipe.2 Personnel should wipe the port three times in the direction of the operator.2

Preparing Needles and Syringes

Syringes should be kept free of contamination during sterile compounding, and personnel should take care to only touch the non-critical sites of syringes. Syringes can be accessed by carefully peeling back the packaging.2 When holding the syringe, compounding personnel should always face the tip toward the HEPA filter and make sure the tip never touches the

operator or the LAFW.2 As the syringe is connected to the needle, it should maintain constant contact with first air.

The needle can be removed from its packaging by peeling back the protective cover; it should never be pushed through this cover.2 Doing so would allow numerous particles to enter the LAFW.2 Once unpackaged, the needle hub should be faced toward the HEPA filter to allow for maximum airflow.2 Throughout the compounding process, the needle should never be placed on the work surface, as this would lead to contamination.2 Once unpackaged, the needle can be uncapped and attached to the syringe.

Entering and Withdrawing from a Vial

Aseptic technique should continue as the needle is used to access a vial.2 Improper insertion of a needle can lead to coring, which happens when a part of the rubber closure becomes stuck in the needle.2 In many cases, this rubber may end up in the final admixture, putting a patient who receives the product at significant risk of harm. To properly enter the vial, the needle should be faced bevel side up and angled at 45 degrees.2 Once the bevel has entered the vial, the needle can then be positioned upright.2 No matter how well this process is done, all final products should be inspected for potential rubber particles.

The first step of withdrawing a solution from a vial is drawing up an amount of air into the syringe that is equivalent to the volume of solution to be withdrawn.2 This is necessary because vials are closed systems that are at an equal pressure with the outside atmosphere.2 After puncturing the vial, the vial and syringe should be inverted, so the vial is above the syringe to ensure first air reaches all critical sites.2 To do this in an aseptic manner, compounding personnel can use a “see-saw” motion.2 The steps include:2

Place one hand on the bottom of the vial (palm facing the HEPA filter) and hold the vial between the thumb and forefinger.

Hold the barrel of the syringe near the flange with the other hand, palm facing the HEPA filter.

Rotate the vial in a vertical fashion upward.

Milking is a technique that can be used to withdraw syringe contents. It involves pushing and releasing the plunger of the syringe to withdraw contents.2 To milk a syringe, push air from the syringe into the vial until resistance is met.2 The plunger is then released, allowing the solution to fill the syringe.2 The process is repeated until the required amount of solution is in the syringe.2 Compounding personnel should note the entire amount of air in the syringe should never be pushed into the vial at once, as this can lead to spraying or bursting of the vial.2 Additionally, personnel should take care never to block first air towards the syringe and rubber closure of the vial with their fingers.2

Withdrawing from an Ampule

Because ampules are open systems, the method of withdrawing solution is not the same as withdrawing from a vial. Before accessing the contents within an ampule, it is important to make sure the entirety of the solution is in the ampule body, and not the head or the neck.2,9 Breaking the ampule neck involves grasping the neck firmly with one hand while holding the body with the other.2 Personnel should face the ampule toward either side of the workbench to avoid glass breaking toward themselves or the HEPA filter.2 The neck is broken by applying pressure where the thumbs meet.2

To withdraw contents on an ampule, hold the ampule in one hand and the syringe in the other.2 The contents of the ampule will not spill whether it is held upright vertically or horizontally.2 The needle can be placed through the ampule opening, bevel side down.2 The plunger can be pulled to draw contents up.1 Importantly, the needle should not touch the ampule opening.8 A critical difference between withdrawing from an ampule compared to a vial is that an ampule requires the use of a filter needle.2

Injecting into Additive Bag

The additive bag should be placed so the additive port faces the HEPA filter.2 This can be done by laying it sideways on the workstation with the port facing the HEPA filter or hanging it vertically on the pool hook.2 When adding the solution to the bag, the port can be bent up and then entered vertically.2 If the bag is hanging, the port should be facing downward.2

Demonstrating Competency in Garbing and Hand Washing

United States Pharmacopeia, Chapter <797> requires any person involved in compounding sterile preparations to be well-trained in the process of aseptic manipulation.6 This encompasses being skilled, educated, instructed, and trained in how to perform hand cleansing, disinfect compounding surfaces, select and appropriately don garb, and maintain and achieve sterility of CSPs.6 United States Pharmacopeia, Chapter <797> guidelines state that a designated person or persons must oversee the process of training personnel for compound CSPs, including both training and observation.6 Every compounding facility should have a written training program describing the training, the frequency of training, and the process of training evaluation.6

Garbing Competency Evaluation

Before compounding a Category 1, Category 2, or Category 3 CSP, personnel must successfully complete an evaluation of garbing competency at least three separate times. This includes a visual observation and gloved fingertip and thumb sampling of both hands.6 Prior to each evaluation, personnel must fully garb, wash their hands, and don sterile gloves in either a classified area or a segregated compounding area.6 Failure can be determined either through visual observation or gloved fingertip and thumb sampling results that exceed action levels. Personnel who will compound Category 1 and Category 2 CSPs must be assessed initially and then every 6 months minimally thereafter.6 For those compounding Category 3 CSPs, competency testing must occur at least every 3 months.6

All personnel should complete this testing with resulting zero CFU at least three times prior to compounding CSPs for patients.7 Any personnel with CFU counts should be retrained and re-evaluated.

Table 4 provides a gloved fingertip and thumb sampling procedure.6 To ensure proper pressure is applied during the gloved finger-tip test, experts recommend holding the plate vertically.7

Table 4. Gloved Fingertip and Thumb Sampling Procedure6

Competency Testing in Aseptic Manipulation

All compounding personnel who prepare Category 1, Category 2, and Category 3 CSPs must complete an evaluation of their competency in aseptic manipulation that includes 1) media-fill testing, 2) gloved fingertip and thumb sampling, and 3) surface sampling of the direct compounding area. Personnel who will compound Category 1 and Category 2 CSPs must be assessed initially

and then every 6 months minimally thereafter.6 For those compounding Category 3 CSPs, competency testing must occur at least every 3 months.6

Media-Fill Challenge Testing

Media-fill testing is used to assess aseptic technique and skills of compounding personnel and involves the use of sterile fluid bacterial culture media-fill verification.6 This testing is designed to mimic the most challenging conditions a compounder could encounter.6 United States Pharmacopeia

<797> suggests the media fill simulation capture any factors with the potential to affect CSP sterility, including the following:6

Factors associated with the length of the process that can pose contamination risk (e.g., operator

fatigue, quality of equipment)

Number of aseptic additions or transfers

Number, type, and complexity of manipulations

Number of personnel in the cleanroom suite

Compounding personnel complete this simulation by replacing components used for CSPs with soybean-casein digest media.6 After testing, these vials are incubated at 20⁰C to 25⁰C for 7 days followed by incubation at 30⁰C to 35⁰C for 7 days.6 The presence of visible turbidity, within the medium, indicates failure.6 Gloved fingertip and thumb sampling are done immediately after the media fill test, with success indicated by ≤3 CFU total from both hands. An action level of 3 CFU is recommended for personnel to be retrained and re-evaluated.

Documentation

Per USP Chapter <797> guidelines, planned testing, monitoring, and documentation are all required to demonstrate adequate personnel practices and procedures.6 Results of personnel evaluations and corrective actions in the event there is a competency failure must be documented.6 This

documentation provides a long-term assessment of personnel competency demonstration.6 The following items must be documented at a minimum:6

Name of individual who was evaluated

Evaluation date and time

Media and components used (including the same of the manufacturer)

Expiration date and lot number

Starting temperature for each interval of incubation

Dates of incubation

Results and identification of the observer and personnel reading and documenting the results

Summary

Every part of the sterile compounding process should be driven by one, critical element: patient safety. The key to achieving this is maintaining excellent aseptic technique, which is a series of methods used to ensure CSPs are free from microorganisms, pyrogens, and particulate matter. Preparing CSPs involves numerous factors, each of which has the potential to impact the sterility of these products. These include the environment in which the product is compounded, the equipment utilized to compound the product, and the individual who compounds the CSP. Should a CSP become contaminated and administered to a patient, major harm and possible death could result. Thus, each factor must be optimized to ensure the safety of the final preparation. All personnel involved in sterile compounding should be well-trained in aseptic technique, including proper garbing, handwashing, and aseptic manipulations.

Course Test

Which of the following is true regarding proper handwashing procedures when preparing to compound sterile preparations?

Sinks with a foot pedal or motion sensor should not be utilized

Personnel should use the hottest water temperature which is tolerable

Disposable nail cleaners should be used during the handwashing process

Hands should be washed in the direction of dirtiest to cleanest

Which of the following steps should occur first during the handwashing process?

Apply soap to hands and work around fingers from tip to palm. Keep fingertips up for the remainder of this procedure.

Wash the palms of the hands by rubbing them together, and then wash the tops of the hands.

Wash the arm up to the elbow. Move down the forearm and repeat this process until the elbow is reached on both arms.

Rinse with palms and fingertips up on both arms. Place one hand under the water and rinse until all soap is away. Move the arm through the water to the elbow. Repeat on the other arm.

How much time should compounding personnel minimally spend washing their hands?

10 seconds

15 seconds

30 seconds

60 seconds

Which of the following does not need to be removed prior to donning PPE?

Jewelry

Makeup

Eyeglasses

Headphones

In which of the following scenarios would it be appropriate for personnel to compound a sterile product?

The individual currently has an upper respiratory infection

The individual has a sunburn, but the designated person determined this will not impact the quality or safety of the compounding process

The individual has an open sore on their hands but will wear gloves

The individual has acrylic nails and refuses to remove them

At which of the following times should compounding personnel disinfect their gloves?

Immediately after being donned.

Prior to and after cleaning the LAFW.

If gloves are suspected or known to have been contaminated

All of the above

Which of the following is considered a critical site of an ampule?

The break point (neck)

The body

The head

The rubber closure

Which of the following is true regarding the use of aseptic technique pertaining to needles?

Needles should be opened by pushing through the packaging

The hub of the needle is considered a critical site and should never be touched

The needle can be set down on the work surface during the compounding process

The needle hub should be faced away from the HEPA filter during compounding

How often should garbing competency evaluations occur for personnel who compound Category 1 CSPs?

Initially and then every 3 months minimally thereafter

Initially and then every 6 months minimally thereafter

Initially and then every 12 months minimally thereafter

Initially and then every 18 months minimally thereafter

What is the action level (cfu total for both hands) for gloved fingertip and thumb sampling following media fill testing?

>0

>1

>2

>3

References

Shehab N, Brown MN, Kallen AJ, Perz JF. U.S. Compounding Pharmacy- Related Outbreaks, 2001-2013: Public Health and Patient Safety Lessons Learned. J Patient Saf. 2018;14(3):164-173. doi:10.1097/PTS.0000000000000188

Ochoa P and Vega J. Concepts in sterile preparations and aseptic technique. Jones and Barnett Learning. 2015.

Malacos K and Propes D. Sterile compounding for pharmacy technicians. McGraw Hill Education. 2015.

Myers CE. History of sterile compounding in U.S. hospitals: learning from the tragic lessons of the past. Am J Health Syst Pharm. 2013;70(16):1414-1427. doi:10.2146/ajhp130112

The United States Attorney’s Office. Former Owner of Defunct New England Compounding Center Resentenced to 14 Years in Prison in Connection with 2012 Fungal Meningitis Outbreak. 2021. https://www.justice.gov/usao-ma/pr/former-owner-defunct-new- england-compounding-center-resentenced-14-years-prison. Accessed October 31, 2022.

General Chapter: USP. Pharmaceutical Compounding-Sterile Preparations <797>. In: USP-NF. Rockville, MD: USP; September 2021.

USP 797 Chapter Release Countdown Tips. Pure Microbiology. https://www.puremicrobiology.com/app/uploads/2022/12/USP-797- Chapter-Release-Countdown-Tips-12.12.22.pdf. Accessed December 18, 2022.

Jordan Z. Aseptic compounding techniques: learning and mastering the ritual. ASHP publications. 2018.

Jullian-Desayes I, Landelle C, Mallaret MR, Brun-Buisson C, Barbut F. Clostridium difficile contamination of health care workers' hands and its potential contribution to the spread of infection: Review of the literature. Am J Infect Control. 2017;45(1):51-58. doi:10.1016/j.ajic.2016.08.017

Clancy C, Delungahawatta T, Dunne CP. Hand-hygiene-related clinical trials reported between 2014 and 2020: a comprehensive systematic review [published correction appears in J Hosp Infect. 2021 Nov;117:194-196]. J Hosp Infect. 2021;111:6-26. doi:10.1016/j.jhin.2021.03.007

Center for Disease Control. Hand hygiene in healthcare settings. https://www.cdc.gov/handhygiene/index.html. Accessed October 31, 2022.

World Health Organization. WHO guidelines on hand hygiene in health care. https://www.who.int/publications/i/item/9789241597906. Accessed October 31, 2022.

DISCLAIMER

The information provided in this course is general in nature, and it is solely designed to provide participants with continuing education credit(s). This course and materials are not meant to substitute for the independent, professional judgment of any participant regarding that participant’s professional practice, including but not limited to patient assessment, diagnosis, treatment, and/or health management. Medical and pharmacy practices, rules, and laws vary from state to state, and this course does not cover the laws of each state; therefore, participants must consult the laws of their state as they relate to their professional practice.

Healthcare professionals, including pharmacists and pharmacy technicians, must consult with their employer, healthcare facility, hospital, or other organization, for guidelines, protocols, and procedures they are to follow. The information provided in this course does not replace those guidelines, protocols, and procedures but is for academic purposes only, and this course’s limited purpose is for the completion of continuing education credits.

Participants are advised and acknowledge that information related to medications, their administration, dosing, contraindications, adverse reactions, interactions, warnings, precautions, or accepted uses are constantly changing, and any person taking this course understands that such person must make an independent review of medication information prior to any patient assessment, diagnosis, treatment and/or health management. Any discussion of off-label use of any medication, device, or procedure is informational only, and such uses are not endorsed hereby.

Nothing contained in this course represents the opinions, views, judgments, or conclusions of RxCe.com LLC. RxCe.com LLC is not liable or responsible to any person for any inaccuracy, error, or omission with respect to this course, or course material.

ⓒ RxCe.com LLC 2022: All rights reserved. No reproduction of all or part of any content herein is allowed without the prior, written permission of RxCe.com LLC.