Pearl Protocol

INTRODUCTION/CREDITS

Our professionals began preparing this procedure manual in 2004 to aid pharmacists/hospitals in complying with USP 797. Two components of compliance exist; first, the physical environment, hoods/workbenches that must be present and certified for use. Second, and equally important, the procedures that need to be in place for personnel to follow while compounding. This manual provides a complete, easy-to-follow accounting of those procedures in an easy to use format.

GAP ANALYSIS

References:

1. Savage SW, Gomez TA, Burrell R. The Gap Analysis and Action Plan. Hosp. Pharm. 2005:40:184-188.

A Gap Analysis is easily performed by first downloading the risk assessment tool from USP 797, completing the survey questions to identify where the gaps in service exist for each level of solutions prepared; Low Risk, Medium Risk, and High Risk Levels.

RISK LEVELS

References:

1. United States Pharmacopoeia, Inc. U.S. Pharmacopoeia 27. Chapter (797): Pharmaceutical Compounding - Sterile Preparations. Rockville, MD: United States Pharmacopoeial Convention, 2004; 2-3.

PERSONNEL

Personnel who prepare sterile compounds should be provided with the appropriate training from qualified personnel, audio-video instructional sources, and professional publications in the principles and practices of aseptic techniques before they begin to compound.

1. Personnel must review ASHP Compounding Video and complete the accompanying video workbook, (compounding sterile preparations video training program companion workbook.)
2. Personnel will perform didactic review and pass written test (yearly).
3. Personnel will be evaluated yearly by qualified compounding personnel to assure appropriate technique and compliance with stated policy and procedures (Compounding/Aseptic Technique Audit Tool).
4. Personnel will pass three media fill validation test (initially), before permitted to compound.
5. Personnel will pass a single media fill validation test yearly after the passing of the initial three tests.
6. Personnel will pass three fingertip validation tests. (Initially)
7. Personnel will pass a single fingertip validation test yearly after passing of the initial three tests.

1. For low and medium risk levels. High risk level requires at least a semiannual media-fill evaluation.
2. Recommended Media-kits include: GroMed Personal Aseptic Technique Test, PATT, and PATT2.

PROCESS TESTING: EVALUATION OF GLOVE FINGERTIPS

Initial Validation:

1. The assigned pharmacist or designee will audit the gloved fingertip sampling of all pharmacists and technicians using the EnviroTest or equivalent sampling media.
2. The audit is performed on all new pharmacy employees prior to compounding products for the pharmacy.
3. The audit is repeated if the employee has a positive gloved fingertip test sample.
4. Each pharmacy employee who will be compounding infusion medications will perform 3 successful gloved fingertip sample texts utilizing the EnviroTest media prior to compounding medications.
5. Results will be evaluated by the assigned pharmacist or designee and documented.

Ongoing Validation:

1. Each pharmacy employee who will be compounding will perform 1 gloved fingertip sampling text annually.
2. Results will be evaluated and documented.
3. Failure of the gloved fingertip sampling text is noted and discussed with the employee. The employee will be re-audited within 7 days and will successfully (0 cfu) complete 1 aseptic technique test daily for 3 consecutive days before compounding medications are dispensed.

PROCESS TESTING: EVALUATION OF COMPOUNDING/ASEPTIC TECHNIQUE

The pharmacy provides initial and on-going evaluation of the performance of pharmacists, pharmacy technicians, and students in the aseptic preparation of infusion admixtures.

Initial Validation:

1. The assigned pharmacist or designee will audit the compounding/aseptic technique of all pharmacists and technicians using the Compounding/Aseptic Audit Tool
2. The audit is performed on all new pharmacy employees prior to compounding products for the pharmacy.
3. The audit is repeated if the employee has a positive aseptic technique test.
4. Each pharmacy employee who will be compounding infusion medications will perform 3 successful aseptic technique tests and 3 successful fingertip testing tests prior to compounding medications. Each test will be performed for 3 consecutive days following the instructions provided with the test kits.
5. Results will be evaluated by the assigned pharmacist or designee and documented.

Ongoing Validation:

1. Each pharmacy employee who will be compounding will perform 1 aseptic test annually and one fingertip test
2. Each pharmacy employee who will be compounding will complete the Compounding/Aseptic Audit Tool annually.
3. Results will be evaluated and documented.
4. Failure of either the audit or the aseptic technique test and/or fingertip test is noted and discussed with the employee. The employee will be re-audited within 7 days and will successfully complete 1 aseptic technique test daily for 3 consecutive days before compounding medications are dispensed.

ADMIXTURE, PREPARATION, PROCEDURE

All parenteral admixtures, including hyper alimentation requiring the Pharmacy's preparation will be performed in the ISO 5 environment of the buffer room employing aseptic technique. The following procedure should be followed in the preparation of any parenteral admixture. If a technician prepares the solution, all of his/her work must be supervised and checked by a pharmacist.

Hand washing Refer to Hand Hygiene in Healthcare setting athttp://www.cdc.gov/handhygiene/.

1. Hands, wrists and arms to elbows will be washed before each work space cleaning, prior to each compounding procedure set-up immediately prior to preparing sterile products, and when returning to the sterile compounding area from performing a separate function.
2. All finger and wrist jewelry is removed before hand washing.
3. Scrub hands, wrists and arms to the elbows with Betadine soap or Hibiclens. Scrub under fingernails and between fingers. Rinse hands clean of soap. Dry hands, wrists and arms with disposable, non-shedding towels or air dryer.

Compounding Attire

1. Don uniform (outlined below) in the stated order.
2. Shoe covers - disposable booties
3. Hair cover - disposable bonnet
4. Face mask - disposable, form-fitting or rigid. Facial make-up should not be worn
5. Gown/Coveralls - lint and particle free, knee length, long sleeve with elastic or fastened wrists, disposable or cleaned by a qualified service for clean room garments. Legs must be covered by pants and socks must be worn with shoes.
6. Aseptically put on sterile gloves immediately prior to sterile compounding.
7. Uniforms should be removed before leaving the anteroom area. Under no circumstances may any garb worn outside of the anteroom be worn in the buffer room.
8. Gowns/Coveralls can be reused, but should be discarded at the end of the shift or day. Hang gowns/coveralls inside out between uses.
9. Hair covers, shoe covers, face masks, and gloves are not to be re-used. Don new ones upon re-entry to the compounding area.
10. Sterile gloves should be changed when torn or after preparing chemotherapy. Sterile gloves should be re-sanitized minimally between patient orders by spraying sterile 70% isopropyl alcohol, antiseptic foam cleaner, or sterile using alcohol wipes. The sanitizing agent is allowed to evaporate before beginning compounding procedures.

Compounding Area Preparation

1. Clean worktable, laminar flow hoods, or biological safety cabinet with appropriate cleanser according to Admixture Workspace Sanitation procedure prior to compounding, between orders, or in the event of a spill.
2. All compounding devices are to be cleaned and calibrated according to Pharmacy procedure prior to compounding each day with sterile 70% alcohol and allowed to air dry.

Compounding Environment Use - Biological Safety Cabinets

1. Biological Safety Cabinets - compounding should be performed in the center of the work surface, away from the air inlet grids should not be blocked by compounding supplies or products.
2. Biological Safety cabinets should never be turned off while compounding sterile products.
3. Materials used in the preparation of sterile products must be arranged on worktable so there is no overcrowding of the compounding area, permitting air to flow around vials to be admixed.

Buffer Room Procedures

1. Access to the Buffer Room is restricted to qualified personnel with specific responsibilities or assigned tasks. Traffic flow will be minimized to assigned/scheduled personnel.
2. No chewing gum, drink or food will be brought into the Buffer Room.
3. Objects that shed particles (boxes, paper towels, pencils, notebooks, reference books etc.) cannot be brought into the Buffer Room. In the case that calculators need to enter the buffer room, they should be decontaminated with sterile 70% alcohol and placed in a plastic bag. The plastic bag is then decontaminated with sterile alcohol prior to use in the buffer room. The plastic bag remains on the calculator as a protectant. Additionally if 'recipes' are needed for compounding they should be laminated so that alcohol decontamination is possible.
4. Supplies required for the scheduled operations of the shift are prepared and brought into the Buffer Room on movable carts (see Anteroom Supply and Material Entry). The supplies are prepared according to decontamination standards of practice. (sterile 70% alcohol)
5. Operational backup supplies, such as mini bags, syringes, large volume bags, may be stored on designated shelving; excessive accumulation of supplies will be avoided.
6. Supply carts used in the Buffer Room may not be rolled past the line of demarcation (in Anteroom) unless they are thoroughly cleaned and sanitized before re-entry into the Buffer Area.
7. All procedures done in the Buffer Area will be performed in a manner to minimize the risk of touch contamination.
8. Buffer Room pass through window is only for the passing of compounded product out to the dispensing pharmacy. At no time will the pass through window be used to provide supplies to the Buffer Room.
9. When the pass through window is used for checking product, once opened on Pharmacy side, product must be removed and decontaminated if re-entry to buffer side is necessary.

Anteroom Supply and Material Entry

1. Supplies required frequently but not for daily operations are decontaminated on the dirty side of the Anteroom and stored on the shelving in the Anteroom/clean side of the line of demarcation.
2. Objects that shed particles cannot be brought into the Anteroom; these include boxes, paper towels notebooks, etc.
3. All unpacked cartooned supplies are decontaminated in the Anteroom by spraying or wiping with alcohol, on the dirty side of the Anteroom, and then are to be placed on a sanitized cart for transfer to the Buffer Room.
4. Ante Room pass through window may be used to supply medications, etc. to be compounded in the buffer room. These supplies will be decontaminated before transfer to the buffer room, with sterile 70% alcohol.

Transfer and withdrawal of liquid contents from a vial

1. Select the appropriate size needle and syringe to be used for compounding and aseptically attach the needle to the syringe. Draw the syringe plunger back to the volume equal to that which you want to withdraw from the vial.
2. Remove protective caps from vials.
3. Spray vial stopper with sterile 70% alcohol and allow to dry. Visually inspect the stopper for lint, fibers or particulate matter which may have remained. Reapply alcohol if necessary.
4. Remove the needle's protective cap.
5. Grasp the body of the vial with one hand and hold it securely on the work surface. With the other hand, hold the syringe barrel and place the needle, beveled side up at a 45 degree angle to the rubber stopper on the vial. Insert the needle through the stopper by applying a small amount of pressure down on the barrel of the syringe resulting in the needle to bow slightly. While applying pressure on the barrel, rotate the syringe up and insert the needle into the vial.
6. After the needle is inserted into the vial, the syringe is held in a vertical position with the needle upward. Care is taken not to block the flow of air between the HEPA filter and the container.
7. Gradually inject the air from the syringe into the vial in small increments. Allow the solution to transfer into the syringe until the pressure is equalized. Repeat until the desired volume has been withdrawn.
8. The syringe is tapped gently to allow air bubbles to float to the surface. Remove air bubbles by slowly pushing the plunger of the syringe forward until solution can be seen at the tip of the needle.
9. The desired volume of solution is to be adjusted before the needle is withdrawn from the vial.
10. Transfer or inject the medication into appropriate container. Make sure that the injection port of the final container has been sanitized by spraying with alcohol before making injections into it.
11. Dispose of used devices properly.
12. A 28-day expiration date must be placed on all opened multiple dose vials along with initials and date of opening.
13. 6-hour expiration date on all single dose vials.

Withdrawal of Solution from Ampules

1. A filter straw or needle is used when withdrawing solutions from ampules to filter out any glass particles falling in the solution when the neck of the ampule snaps.
2. The ampule is held in an upright position while the top of the ampule is tapped to release any solution trapped above the constricted neck. If the ampule contains a dry powder, any powder trapped in this way is tapped downward before dissolving with the appropriate diluent.
3. The neck of the ampule is sprayed with sterile 70% isopropyl alcohol to decrease the chance of contamination.
4. The neck of the ampule is snapped with the thumb and index fingers. Slightly rotate the ampule to a weaker point if the neck resists snapping. An antiseptic swab is wrapped around the neck of the ampule during this procedure to decrease the possibility of finger cuts if the ampule should shatter.
5. Tilt the ampule and submerge the filter needle or straw in the shoulder area of the ampule, being careful to avoid touching the broken edge of the ampule.
6. Holding the base of the ampule with one hand and the syringe with the other, the plunger is pulled back to the desired volume.
7. After the desired volume of solution has been drawn into the syringe, remove needle from glass ampule.
8. The filter needle or straw on the syringe is then removed and a regular needle attached.
9. Inject the contents of the syringe into the appropriate container. Make sure that the injection port of the final container has been sanitized by spraying with sterile alcohol before making injections into it.

Reconstitution and withdrawal of powered or lyophilized drugs in a vial.

1. Remove the vial's protective cap.
2. Sanitize the vial's stopper by spraying with a sterile alcohol solution.
3. Aseptically attach an appropriate size needle to an appropriate size syringe.
4. Withdraw the required volume of diluent from the diluent vial.
5. Slowly inject the appropriate volume of diluent into the vial of powered drug. Allow pressure to equalize by adding diluent in small increments.
6. Remove needle from vial after pressure has equalized, then gently swirl the reconstituted drug vial until the drug is completely dissolved.
7. Observe for particulate matter in the reconstituted drug vial. If any is observed, filter solution through a 5 micron particulate filter.
8. Withdraw the reconstituted solution from the vial.
9. Inject the appropriate amount of drug into the final container. Make sure that the injection port of the final container has been sanitized by spraying with a sterile alcohol solution before making injections into it.

End Product Check

1. The completed intravenous preparations will be checked for particulate matter and signs of incompatibility. If, during the preparation check of an IV admixture, particulate matter (e.g., a'core') is observed in the solution, use of the suggested remedies is recommended.
2. Transfer the admixture to an evacuated or empty container using an in-line filter.
3. Discard the admixture and prepare another if a 'core' is transferred.
4. Withdraw contents of vial using syringe with a filter needle attached, replace the needle, and transfer to another container.

Miscellaneous

1. Disposable, plastic lure-lock syringes are used for admixing. Disposable needles are also used. The plastic sheath is not removed until ready for use.
2. Use moderate speed in admixture preparation to minimize the time factor and risk of bacterial contamination.
3. Work in a consistent fashion from one side of the hood / worktable to the other to avoid confusion as to whether a specific additive was or was not added.
4. Stop work if there is a question of contamination of anything in the hood. Discard the contaminated object and replace material and resume work.
5. I.V. solutions are prepared as close to the time of administration as possible. They are then sealed, labeled, and refrigerated, if necessary, until delivered. The IV mini-bag batch prints a 24 hour supply of an I.V. antibiotic which is prepared and sent to each unit daily and placed in the nursing unit's refrigerator.

CLEAN ROOMS

Admixture Workspace Sanitation:

The pharmacy compounding area will be cleaned on a regular basis due to the critical nature of preparing sterile products. Cleaning will be documented on the Admixture Room Quality Assurance Record.

Cleaning of ALL surfaces and equipment (walls, counters, fixture, worktables, BSC, etc.) will be carried out utilizing approved disinfectant/detergents.

Acceptable disinfectants/detergents:

1. Vesphene IIse or equivalent
2. Germicidal Wipes
3. Hospital cleaner disinfectant with bleach (Dispatch)
4. Cleaning agents will be stored in an area that is separate from medications and compounding supplies.
5. Mops used for cleaning the pharmacy compounding area must have replaceable, synthetic sponge heads with metal or plastic handles. The mop used for cleaning the pharmacy compounding area floor MUST be used for cleaning this area only and at NO time used for cleaning other areas.
6. Worktables/LFH and biologic safety cabinets will be decontaminated and cleaned according to Buffer Room Worktables/LFH and Biological Safety Cabinet policy. Wipe with sterile 70% alcohol daily before use at beginning of each work shift.

The following cleaning scheduled will be followed and documented on the Admixture Room Quality Assurance Record:

Daily:

1. Worktables and Biological Safety Cabinet according to compounding area preparation procedure.
2. Compounding equipment (i.e., automated compounders or compounding pumps).
3. Mop buffer/anteroom floors.
4. Empty waste cans and replace plastic liners with minimal agitation.
5. Clean sinks

Monthly:

1. Inspect and clean interior and exterior of refrigerators.
2. Permanent dedicated equipment such as waste cans.
3. Buffer/anteroom walls and ceilings
4. Anteroom carts and shelving.

1. Compounding areas should be cleaned even when there is no compounding going on.
2. Walls, shelving, counters, carts, etc. should be cleaned before cleaning floors.

ENVIRONMENTAL MONITORING: Surface Sampling

Compounding work surfaces will be tested on a monthly basis using the QI Medical EnviroTest. Other sampling media vendors include: Biotest Diagnostic Corporation, Hardy Diagnostics, and Q.I. Medical Incorporated.

Surface sampling will be performed monthly at the end of the compounding day for each worktable and Biological Safety Cabinet. Sampling will be performed even if no compounding has occurred during the week.

Use the following procedure to collect surface samples:

1. Be sure that the work surfaces are dry from the disinfecting/cleaning solution. (sterile 70% alcohol)
2. Put on a new pair of sterile gloves using proper gloving technique prior to handling the EnviroTest.

Working inside the BSC, remove one (1) EnviroTest paddle from the protective tube. Gently press the surface of the agar paddle against the following areas (at least 6 inches inside the work area) in BSC:

1. right side of hood floor,
2. left side of hood floor,
3. left inside panel,
4. right inside panel.

Laminar flow hoods will follow same procedure as BSC for surface sampling. Worktable sampling will include:

1. right upper side of table,
2. left upper side of table,
3. right lower side of table, and
4. left lower side of table.
5. Press the paddle, using a gentle rocking motion, onto the surface to be tested until contact has been made on the entire surface of the paddle. Note: Do not slide agar across the work surface.
6. Replace the paddle into the protective tube. Place gummed label on the cap of the EnviroTest protective tube.
7. Write the date and initials of the person performing the test, and the area (worktable or BSC) that was sampled on the gummed label with permanent/waterproof marker.
8. Incubate the contact slide at 30 degrees C - 35 degrees C for 48 hours.
9. Evaluate the contact slide for growth after 48 hours. Record results on the Work surface Sampling Log. There should be less than three (3) colony forming units (CFU) present on the EnviroTest paddle.

If three (3) or more CFU's are present:

1. Do not compound in the affected BSC/worktable until it is cleaned and disinfected using the BSC/worktable cleaning procedure, paying particular attention to possible areas of contamination (i.e., corners, cracks, crevices, hard to clean areas).
2. Test the BSC/worktable daily, according to the procedure above, until the EnviroTest yields < 3 CFU's.
3. Incubate and evaluate slides according to above procedure.
4. If CFU's are still 3 or greater after cleaning, have the BSC checked by an independent hood certification company for proper operation of the HEPA filter. Likewise, have the buffer room checked for proper operation of the ceiling filters and LFHs.

ENVIRONMENTAL MONITORING: Air Sampling

Worktables and biological safety cabinet air quality will be tested on a monthly basis using the QI Medical EnviroTest. Air sampling will provide information on the operational effectiveness of the buffer room and biological safety cabinet air filtration system.

1. Air sampling will be performed monthly at the end of the compounding day for each worktable and Biological Safety Cabinet. Sampling will be performed even if no compounding has occurred during the week.

Use the following procedure to collect air samples:

1. Be sure that the work surfaces are dry from the disinfecting/cleaning solution.
2. Put on a new pair of sterile gloves using proper gloving technique prior to handling the EnviroTest.
3. Working on or inside the worktable or BSC, remove two (2) EnviroTest paddles from their protective tubes.
4. Using the EnviroTest paddle's cap as a pedestal, set a paddle down on each side of the hood and worktable, so that the agar surface is pointing up (see instructions that accompany the EnviroTest).
5. Expose the EnviroTest agar paddle to airflow for approximately one hour. If the agar appears excessively dry after one hour, reduce exposure time to 30 minutes.
6. Replace the paddle into the protective tube. Place gummed label on the cap of the EnviroTest protective tube.
7. Write the date and initials of the person performing the test, and the type of hood (worktable or BSC) that was sampled on the gummed label with permanent/waterproof marker.
8. Incubate the paddle at 30 degrees C - 35 degrees C for 48 hours.
9. Evaluate the contact slide for growth after 48 hours. Record results on the Surface and Air Sampling Log. There should be less than three (3) colony forming units (CFU) present on the EnviroTest paddle.

If three (3) or more CFU's are present:

1. Do not compound in the affected BSC/worktable until it is cleaned and disinfected using the BSC/worktable cleaning procedure, paying particular attention to possible areas of contamination (i.e., corners, cracks, crevices, hard to clean areas). Check hood prefilters to see if replacement is needed.
2. Test the BSC/worktable daily, according to the procedure above, until the EnviroTest yields < 3 CFU's.
3. Incubate and evaluate slides according to above procedure.
4. If CFU's are still three (3) or greater after cleaning, have the BSC checked by an independent hood certification company for proper operation of the HEPA filter(s). Likewise, have the buffer room checked for proper operation of the ceiling filters.

QUALITY ASSURANCE PROGRAM

References: Kastango, ES. Blueprint for implementing USP Chapter 797 for compounding sterile preparations, AM J Health - Syst Pharm. 2005; 62, 1283 Documentation to be considered in Quality Assurance Program:

• Admixture Room Quality Assurance Record
• Compounding/Aseptic Technique Audit Tool
• Surface and Air Sampling Log
• Adverse Drug Reaction Reporting