Okla. Admin. Code § 535:15-10-54

Current through Vol. 42, No. 7, December 16, 2024

Section 535:15-10-54 - CSP microbial contamination risk levels

(a)Sterile preparations. Pharmacies and pharmacists dispensing sterile preparations shall comply with all applicable federal, state, and local law and regulation concerning pharmacy. If the PEC (primary engineering control) is a compounding aseptic isolator that does not meet the environmental requirements described in USP or is a laminar air-flow workbench (LAFW) or a biological safety cabinet (BSC) that cannot be located within an ISO Class 7 buffer area, then only low-risk level nonhazardous CSPs pursuant to a physician's order for a specific patient may be prepared, and administration of such CSPs shall commence within 12 hours of preparation or as recommended in the manufacturers' package insert, whichever is less. Low-risk level CSPs with a 12-hour or less BUD shall meet all of the following criteria:

(1) PECs (LAFWs, BSCs, CAIs, CACIs,) shall be certified and maintain ISO Class 5 as described in USP for exposure of critical sites and shall be in a segregated compounding area restricted to sterile compounding activities that minimize the risk of CSP contamination.

(2) The segregated compounding area shall not be in a location that has unsealed windows or doors that connect to the outdoors or high traffic flow, or that is adjacent to construction. Sinks should not be located adjacent to the ISO Class 5 PEC. Sinks should be separated from the immediate area of the ISO Class 5 PEC device.

(3) Personnel shall follow proper procedures for personnel cleansing and garbing prior to compounding and maintain proper competency of aseptic work practices.

(4) Personnel will follow proper procedures in ensure cleaning and disinfection of sterile compounding areas. Additionally, viable and non-viable environmental air sampling must be performed according to facility written procedures.

(b)Risk level. Requirements for compounding of sterile preparations will be based on the distinction of sterile products as either low-risk, medium-risk or high-risk preparations. These risk levels apply to the quality of CSPs immediately after the final aseptic mixing or filling or immediately after the final sterilization, unless precluded by the specific characteristics of the preparation.

(1)Low-Risk Level CSPs. Sterile preparations compounded under all of the following conditions are at a low risk of contamination:

(A) The CSPs are compounded with aseptic manipulations entirely within an ISO Class 5 environment or better air quality using only sterile ingredients, products, components, and devices.

(B) The compounding involves only transfer, measuring, and mixing manipulations using not more than three commercially manufactured packages of sterile products and not more than two entries into any one sterile container or package (e.g., bag, vial) of sterile product or administration container/device to prepare the CSP.

(C) Manipulations are limited to aseptically opening ampuls, penetrating disinfected stoppers on vials with sterile needles and syringes, and transferring sterile liquids in sterile syringes to sterile administration devices and package containers of other sterile products, and containers for storage and dispensing.

(2)Medium-Risk Level CSPs. When CSPs compounded aseptically under low-risk conditions, and one or more of the following conditions exists, such CSPs are at a medium risk of contamination. 132

(A) Multiple individual or small doses of sterile products are combined or pooled to prepare a sterile product that will be administered either to multiple patients or to one patient on multiple occasions.

(B) The compounding process includes complex aseptic manipulations other than the single volume transfer.

(C) The compounding process requires unusually long duration, such as that required to complete the dissolution or homogeneous mixing.

(3)High-risk Level CSPs. CSPs compounded under any of the following conditions are either contaminated or at a high risk to become contaminated.

(A) Non-sterile ingredients are incorporated, or a non-sterile device is employed before terminal sterilization

(B) Any of the following are exposed to air quality worse than ISO Class 5 for more than 1 hour

(i) Sterile contents of commercially manufactured products,

(ii) CSPs that lack effective antimicrobial preservatives, and

(iii) Sterile surfaces of devices and containers for the preparation, transfer, sterilization, and packaging of CSPs.

(C) Compounding personnel are improperly garbed and gloved as outlined by USP.

(D) Sterile water-containing preparations are stored for more than 6 hours before being sterilized.

(E) It is assumed, and not verified by examination of labeling and documentation from suppliers or by direct determination, that the chemical purity and content strength of ingredients meet their original or Compendial specifications in unopened or in opened packages of bulk ingredients.

(c)Immediate use. The immediate use provision is intended only for those situations where there is a need for emergency or immediate patient administration of a CSP. Such situations may include cardiopulmonary resuscitation, emergency room treatment, preparation of diagnostic agents, or critical therapy where the preparation of the CSP under conditions described for Low-Risk Level subjects the patient to additional risk due to delays in therapy. Immediate use CSPs are not intended for storage for anticipated needs or batch compounding. Preparations that are medium-risk level and high-risk level CSPs shall not be prepared as immediate use CSPs. Immediate use CSPs are exempt from the requirements described for Low-Risk Level CSPs only when all of the following criteria are met:

(1) The compounding process involves simple transfer of not more than three commercially manufactured packages of sterile nonhazardous products from the manufacturers' original containers and not more than two entries into any one container or package (e.g., bag, vial) of sterile infusion solution or administration container/device. For example, anti-neoplastics shall not be prepared as immediate use CSPs because they are hazardous drugs.

(2) Unless required for the preparation, the compounding procedure is a continuous process not to exceed 1 hour.

(3) During preparation, aseptic technique is followed and, if not immediately administered, the finished CSP is under continuous supervision to minimize the potential for contact with non-sterile surfaces, introduction of particulate matter or biological fluids, mix-ups with other CSPs, and direct contact of outside surfaces.

(A) Administration begins not later than 1 hour following the start of the preparation of the CSP.

(B) Unless immediately and completely administered by the person who prepared it or immediate and complete administration is witnessed by the preparer, the CSP shall bear a label listing patient identification information, the names and amounts of all ingredients, the name or initials of the person who prepared the CSP, and the exact 1-hour beyond use date and time.

(C) If administration has not begun within 1 hour following the start of preparing the CSP; the CSP shall be promptly, properly, and safely discarded.

(d) Opened or needle-punctured single dose containers, such as bags, bottles, syringes, and vials of sterile products and CSPs shall be used within 1 hour if opened in worse than ISO Class 5 air quality and any remaining contents must be discarded.

(e) Single-dose vials exposed to ISO Class 5 or cleaner air may be used for multiple needle entries up to 6 hours after initial needle puncture. Opened single-dose ampuls shall not be stored for any time period. Multiple-dose containers (e.g., vials) are formulated for removal of portions on multiple occasions because they usually contain antimicrobial preservatives.

(f) The BUD after initially entering or opening (e.g., needle-punctured) multiple-dose containers is 28 days unless an alternate time period is otherwise specified by the manufacturer. This does not mean the expiration date of the unopened container.

(g)Quality Assurance. Quality assurance practices include, but are not limited to the following:

(1) Routine disinfection and air quality testing of the direct compounding environment to minimize microbial surface contamination and maintain ISO Class 5 air quality.

(2) Visual confirmation that compounding personnel are properly donning and wearing appropriate items and types of protective garments, such as eye protection and face masks.

(3) Review of all orders and packages of ingredients to ensure that the correct identity and amounts of ingredients were compounded.

(4) Visual inspection of CSPs to ensure the absence of particulate matter in solutions, the absence of leakage from vials and bags, and the accuracy and thoroughness of labeling.

(5) All clean rooms must meet NSF/ANSI standard 49. The aseptic processing for sterile preparations shall be in an area separate and distinct from the area used for the compounding of nonsterile drug preparations. A primary engineering control (PEC), (laminar airflow workbench (LAFW), biological safety cabinet (BSC), compounding aseptic isolator (CAI) or compounding aseptic containment isolator (CACI)) will be used to prepare all sterile preparations, except those compounded for Immediate Use.

(A) Semiannual certification of the primary engineering controls.

(B) Semiannual certification of nonviable environmental monitoring of all ISO 5, ISO 7, ISO 8 and segregated compounding areas.

(C) Semiannual certification of viable environmental monitoring of all ISO 5, ISO 7, ISO 8 and segregated compounding areas.

(D) Removable prefilters shall be inspected monthly, cleaned or changed at least quarterly or as directed by a qualified certifier, and the date documented.

(E) HEPA filters shall be repaired or replaced when recommended by a qualified certifier.

(6) Initial and annual competence documentation of personnel, including:

(A) Written test

(B) Hand Hygiene and garbing

(C) Gloved fingertip sampling

(D) Aseptic manipulation

(E) Aseptic media-fill test

(F) Cleaning and disinfecting

(G) Surface sampling

(H) Equipment

(I) Routine visual inspection of all compounded sterile preparations

(J) Provision of guidelines to nursing education for competence documentation for nonpharmacy personnel who mix sterile preparations for immediate use.

(h)Quality control practices will include:

(1) Daily documentation of temperature in areas where sterile products or sterile preparations are stored or compounded

(2) Daily documentation of the accuracy and precision of devices such as automated compounders and repeater pumps.

(3) Daily documentation of humidity in areas where sterile products or sterile preparations are stored or compounded.

(i) The PIC or designee will prepare a periodic report of infection control procedures to track quality control and quality assurance activities, as appropriate.

(j) Records of laminar air flow workbench maintenance and certification and ante-area, clean-room and buffer area certifications shall be kept in the pharmacy. A certification stamp shall be affixed to the hood.

(k)Storage. All pharmacies preparing and dispensing compounded sterile preparations must provide:

(1) Adequate controlled room temperature storage space for all raw materials.

(2) Adequate storage space for all equipment. All drugs and supplies shall be stocked on shelving above the floor.

(3) Adequate refrigerator storage space for compounded solutions, with routinely documented temperatures. Temperature ranges required are 36-46° F or 2-8° C.

(4) Adequate freezer storage space if finished products are to be frozen (e.g. reconstituted antibiotics.) There shall be a procedure to routinely document temperatures.

(l)Labeling. In addition to regular labeling requirements, the label shall include:

(1) Sterile compounded preparations shall have the rate of infusion when applicable.

(2) Expiration date (Policies and procedures shall address label change procedures as required by physician orders.)

(3) Storage requirements or special conditions.

(4) Name of ingredients and amounts contained in each dispensing unit.

(5) All products dispensed to outpatients, and removed from the site of preparation for administration different than the site of preparation, shall have label information as required by state law.

(m)Shipping. Sterile preparation shipping:

(1) Policies and procedures shall assure preparation storage requirements during delivery.

(2) Pharmacy must assure ability to deliver preparations within an appropriate time frame.

(n)Home patient care services. The pharmacist in charge of the pharmacy dispensing sterile compounded preparations solutions shall provide the following or assure that they are provided prior to providing medications.

(1) The pharmacist must assure that the patient is properly trained if self-administering.

(2) In situations where a pharmacy or pharmacist employs a nurse to administer medications, the pharmacist in charge must:

(A) Employ a registered nurse.

(B) Assure that proper records are maintained in compliance with laws and regulations.

(C) Make these records available to inspectors from appropriate agencies.

(3) 24-hour service shall be assured by the pharmacy.

(4) Pharmacists shall recommend and monitor clinical laboratory data as requested.

(5) Side effects and potential drug interactions should be documented and reported to the physician.

(6) Patient histories and therapy plans should be maintained.

(o)Pharmacist-in-charge responsibilities for high-risk Level CSP preparations. When preparing high risk sterile Level CSP preparations, the pharmacist in charge is responsible for making sure the above procedures, in addition to the following, shall be met:

(1) Compound all medications in one of the following environments:

(A) A separate controlled limited access area with a positive air flow room inspected and certified as meeting ISO Class 7 requirements.

(B) An enclosed room providing an ISO Class 5 environment for compounding.

(C) A barrier isolator that provides an ISO Class 5 environment for compounding. It is recommended that all pharmacies have an anteroom designed to be separate from the buffer room. The anteroom should be available for the decontamination of supplies and equipment, and donning of protective apparel. A sink should be available in the anteroom area so that personnel can scrub prior to entering the buffer room.

(2) Use total aseptic techniques, including gowning, mask, and hair net.

(3) Provide a system for tracking each compounded product including:

(A) Personnel involved in each stage of compounding;

(B) Raw materials used including quantities, manufacturer, lot number, and expiration date;

(C) Labeling;

(D) Compounding records shall be kept for 5 years.

(4) Establishment of procedures for sterilization of all preparations compounded with any non-sterile ingredients by filtration with 0.22 micron or other means appropriate for the preparation components.

(5) All high-risk Level CSP preparations for administration by injection that are prepared:

(A) in groups of more than twenty-five (25) identical individual single-dose packages (such as ampules, bags, syringes, and/or vials), or;

(B) in multiple dose vials for administration to multiple patients, or;

(C) are exposed longer than twelve (12) hours at a two (2) to eight (8) degrees centigrade and longer than six (6) hours at warmer than eight (8) degrees centigrade before they are sterilized; shall be tested to ensure they are sterile, do not contain excessive bacterial endotoxins, and are of labeled potency before they are dispensed or administered as provided below.

(i) Sterility testing (bacterial and fungal) - The USP Membrane Filtration Method is the method of choice where feasible (e.g. components are compatible with the membrane). The USP Direct Transfer Method is preferred when the membrane filtration is not feasible. An alternative method may be used if verification results demonstrate that the alternative is at least as effective and reliable as the USP Membrane Filtration Method or the USP Direct Transfer Method. The pharmacist in charge shall establish written procedures requiring daily observation of the media and 136 requiring an immediate recall if there is any evidence of microbial growth and said procedures must be available to Board inspectors.

(ii) Bacterial endotoxin (pyrogen) testing - The USP Bacterial Endotoxin Test, or verified equivalent, shall be used to ensure compounded sterile products do not contain excessive endotoxins.

(6) Establishment of procedures for semi-annual testing the techniques of pharmacists using simulated aseptic procedures and documentation thereof.

Okla. Admin. Code § 535:15-10-54

Added at 26 Ok Reg 2276, eff 7-1-09

Amended by Oklahoma Register, Volume 32, Issue 23, August 17, 2015, eff. 8/27/2015.

Amended by Oklahoma Register, Volume 39, Issue 24, September 1, 2022, eff. 9/11/2022