Missouri Code of State Regulations › Title 20 - DEPARTMENT OF COMMERCE AND INSURANCE › Division 2220 - State Board of Pharmacy › Chapter 2 - General Rules › Section 20 CSR 2220-2.200 - Sterile Compounding

Current through Register Vol. 49, No. 14, July 15, 2024
PURPOSE: This amendment allows pharmacies to accept
				  aseptic technique skill assessment results for compounding staff from another
				  pharmacy during an emergency.
(1) Definitions.
(A) Aseptic processing: The technique
				involving procedures designed to preclude contamination of drugs, packaging,
				equipment, or supplies by microorganisms during processing.
(B) Batch: Compounding of multiple sterile
				preparation units in a single discrete process, by the same individuals,
				carried out during one (1) limited time period.
(C) Beyond-Use date: A date after which a
				compounded preparation should not be used and is determined from the date the
				preparation is compounded. Because compounded preparations are intended for
				administration immediately or following short-term storage, their beyond-use
				dates must be assigned based on criteria different from those applied to
				assigning expiration dates to manufactured drug products.
(D) Biological safety cabinet: Containment
				unit suitable for the preparation of low to moderate risk agents where there is
				a need for protection of the preparation, personnel, and environment, according
				to National Sanitation Foundation (NSF) International standards.
(E) Buffer area: An ISO Class 7 or better
				area where the primary engineering control is physically located that is
				constructed and used in a manner to minimize the introduction, generation, and
				retention of particles inside the room and in which other relevant variables
				(e.g., temperature, humidity, and pressure) are controlled as necessary.
(F) Compounding: For the purposes
				of this regulation, compounding is defined as in
				20 CSR
				2220-2.400(1). Compounded sterile
				medications may include, but are not limited to:
1. Compounded biologics, diagnostics, drugs,
				nutrients, and radiopharmaceuticals that must or are required to be sterile
				when they are administered to patients, including, but not limited to the
				following dosage forms: bronchial and inhaled nasal preparations intended for
				deposition in the lung, baths and soaks for live organs and tissues, epidural
				and intrathecal solutions, bladder/wound solutions, injectables, implantable
				devices and dosage forms, inhalation solutions, intravenous solutions,
				irrigation solutions, ophthalmic preparations, parenteral nutrition solutions,
				and repackaged sterile preparations. Nasal sprays and irrigations intended for
				deposit in the nasal passages may be prepared as nonsterile compounds;
2. An FDA approved manufactured
				sterile product that is either prepared according to the manufacturers'
				approved labeling/recommendations or prepared differently than published in
				such labeling; and
3. Assembling
				point-of-care assembled systems.
(G) Compounding aseptic containment isolator
				(CACI): A restricted access barrier system (RABS) that is designed for
				compounding sterile hazardous drugs and designed to provide worker protection
				from exposure to undesirable levels of airborne drugs throughout the
				compounding and material transfer processes and to provide an aseptic
				environment for Compounded Sterile Preparation (CSPs).
(H) Compounding aseptic isolator (CAI): A
				RABS specifically designed for compounding sterile non-hazardous pharmaceutical
				ingredients or CSPs and designed to maintain an aseptic compounding environment
				within the isolator throughout the compounding and material transfer processes.
(I) Controlled area: For purposes
				of these regulations, a controlled area is a separate room designated for
				preparing sterile preparations or an area designated for preparing sterile
				preparations that is separated from other activities/operations by a line of
				demarcation that clearly separates the area from other operations.
(J) Critical area: Any area in the
				controlled area where preparations or containers are exposed to the
				environment.
(K) Critical site: Any
				surface, pathway, or opening (e.g., vial septa, injection ports, beakers,
				needle hubs) that provides a direct pathway between a compounded sterile
				preparation or other ingredient used to compound a sterile preparation and the
				air, environment or moisture, or that poses a risk of touch
				contamination.
(L) CSP: Compounded
				sterile preparation.
(M) Cytotoxic
				drugs: A pharmaceutical product that has the capability of direct toxic action
				on living tissue that can result in severe leukopenia and thrombocytopenia,
				depression of the immune system, and the alteration of a host's inflammatory
				response system.
(N) Emergency
				dispensing: Is a situation where a Risk Level 3 preparation is necessary for
				immediate administration of the preparation and no alternative product or
				preparation is available and the prescriber is informed that the preparation is
				being dispensed prior to appropriate testing. Documentation of the dispensing
				of the preparation, the prescriber's approval for dispensing prior to the
				receipt of test results and the need for the emergency must appear within the
				prescription record. A separate authorization from the prescriber is required
				for each emergency dispensing.
(O)
				High-Efficiency Particulate Air (HEPA) filter: A filter composed of pleats of
				filter medium separated by rigid sheets of corrugated paper or aluminum foil
				that direct the flow of air forced through the filter in a uniform parallel
				flow. HEPA filters remove ninety-nine point ninety-seven percent (99.97%) of
				all particles three-tenths (0.3) microns or larger. When HEPA filters are used
				as a component of a horizontal- or vertical-laminar-airflow workbench, an
				environment can be created consistent with standards for a ISO Class 5
				environment.
(P) In-use time/date:
				The time/date before which a conventionally manufactured product or a CSP must
				be used after it has been opened or needle-punctured.
(Q) ISO Class 5: An area with less than three
				thousand five hundred twenty (3,520) particles (0.5 ?m and larger in size) per
				cubic meter.
(R) ISO Class 7: An
				area with less than three hundred fifty-two thousand (352,000) particles (0.5
				?m and larger in size) per cubic meter.
(S) Multiple-dose container: A multiple unit
				container for articles or compounded sterile preparations that contains more
				than one (1) dose of medication and usually contains an antimicrobial
				preservative.
(T) Parenteral: A
				sterile preparation of drugs for injection through one (1) or more layers of
				skin.
(U) Point-of-care assembled
				system: A closed system device that creates a physical barrier between
				diluents, fluids, or other drug components and is designed to be activated by
				the end user by allowing the components to mix prior to
				administration.
(V) Primary
				engineering control (PEC): A system that provides an ISO 5 environment for the
				exposure of critical sites when compounding sterile preparations. PECs include,
				but may not be limited to, horizontal/vertical laminar airflow hoods,
				biological safety cabinets, RABS such as compounding aseptic isolators (CAIs),
				or compounding aseptic containment isolators (CACIs).
(W) Process validation or simulation: Microbiological
				simulation of an aseptic process with growth medium processed in a manner
				similar to the processing of the preparation and with the same container or
				closure system.
(X) Quality
				assurance: For purposes of these regulations, quality assurance is the set of
				activities used to ensure that the processes used in the preparation of sterile
				drug preparations lead to preparations that meet predetermined standards of
				quality.
(Y) Quality control: For
				the purposes of these regulations, quality control is the set of testing
				activities used to determine that the ingredients, components, and final
				sterile preparations prepared meet predetermined requirements with respect to
				identity, purity, nonpyrogenicity, and sterility.
(Z) Restricted access barrier system (RABS):
				A primary engineering control that is comprised of a closed system made up of
				four (4) solid walls, an air-handling system, and transfer and interaction
				devices. The walls are constructed so as to provide surfaces that are cleanable
				with coving between wall junctures. The air-handling system provides HEPA
				filtration of inlet air. Transfer of materials is accomplished through air
				locks, glove rings, or ports. Transfers are designed to minimize the entry of
				contamination. Manipulations can take place through either glove ports or half
				suits. Examples of a RABS may include, but is not limited to, a CAI or
				CACI.
(AA) Repackaging: The
				subdivision or transfer of a compounded preparation from one (1) container or
				device to a different container or device.
(BB) Single-dose/single-unit container/vial:
				A container/vial of medication intended for administration that is meant for
				use in a single patient for a single case, procedure, or injection.
(CC) Sterilization: A validated process used
				to render a preparation free of viable organisms.
(DD) Temperatures:
1. Frozen means temperatures between
				twenty-five degrees below zero and ten degrees below zero Celsius (-25 and
				-10°C) (thirteen degrees below zero and fourteen degrees Fahrenheit (-13
				and 14°F));
2. Refrigerated
				means temperatures between two and eight degrees Celsius (2 and 8°C)
				(thirty-six and forty-six degrees Fahrenheit (36 and 46°F)); and
3. Controlled room temperatures means a
				temperature maintained thermostatically that encompasses the usual and
				customary working environment 20° to 25° Celsius (68 to 78° F).
				Excursions between 15° and 30° Celsius (59 to 86° F) as commonly
				experienced in pharmacies and other facilities shall be deemed
				compliant.
(EE) USP:
The United States Pharmacopeia and the National Formulary
(USP-NF) as adopted and published by the United States Pharmacopeial
				Convention, effective May 2013. Copies of the USP-NF are published by, and
				available from, USP, 12601 Twinbrook Parkway, Rockville, MD 20852-1790 or
				online at
http://www.usp.org/
. The
				USP-NF is incorporated herein by reference. This rule does not include any
				later amendments or additions to the USP-NF.
(FF) Validation: Documented evidence providing a high
				degree of assurance that specific processes will consistently produce a
				preparation meeting predetermined specifications and quality
				attributes.
(GG) Definitions of
				sterile compounded preparations by risk level:
1. Risk Level 1: Applies to compounded
				sterile preparations that exhibit characteristics A., B., or C., stated below.
				All Risk Level 1 preparations shall be prepared with sterile equipment and
				sterile ingredients and solutions in an ISO Class 5 environment. Risk Level 1
				includes the following:
A. Preparations:
(I) Stored at controlled room temperature and
				assigned a beyond-use date of forty-eight (48) hours or less; or
(II) Stored under refrigeration and assigned
				a beyond-use date of seven (7) days or less; or
(III) Stored frozen and assigned a beyond-use
				date of thirty (30) days or less;
B. Unpreserved sterile preparations prepared
				for administration to one (1) patient or batch-prepared preparations containing
				suitable preservatives prepared for administration to more than one (1) patient
				with an assigned beyond-use date that does not exceed the beyond-use date
				allowed under subparagraph (1)(GG)1.A. of this rule;
C. Preparations prepared by closed-system
				aseptic transfer of sterile, nonpyrogenic, finished pharmaceuticals (e.g., from
				vials or ampules) obtained from licensed manufacturers into sterile final
				containers obtained from licensed manufacturers with an assigned beyond-use
				date that does not exceed the beyond-use date allowed under subparagraph
				(1)(GG)1.A. of this rule;
2. Risk Level 2: Sterile preparations exhibit
				characteristic A., B., or C., stated below. All Risk Level 2 preparations shall
				be prepared with sterile equipment and sterile ingredients in an ISO Class 5
				environment and with closed-system transfer methods. Risk Level 2 includes the
				following:
A. Preparations stored under
				refrigeration and assigned a beyond-use date greater than seven (7) days, or
				preparations stored frozen and assigned a beyond-use date greater than thirty
				(30) days, or preparations stored at controlled room temperature and assigned a
				beyond-use date greater than forty-eight (48) hours;
B. Batch-prepared preparations without
				preservatives that are intended for use by more than one (1) patient;
C. Preparations compounded by complex or
				numerous manipulations of sterile ingredients obtained from licensed
				manufacturers in a sterile container or reservoir obtained from a licensed
				manufacturer by using closed-system aseptic transfer (e.g., automated
				compounder);
3. Risk Level
				3: Sterile preparations exhibit either characteristic A. or B.:
A. Preparations compounded from nonsterile
				ingredients or compounded with nonsterile components, containers, or equipment
				before terminal sterilization;
B.
				Preparations prepared by combining multiple ingredients (sterile or nonsterile)
				by using an open-system transfer or open reservoir before terminal
				sterilization.