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TEXT OF RULE
Section 1. Repeals and recreates ch Phar 15 to read:
COMPOUNDING PHARMACEUTICALS
15.01 Intent. The intent of this chapter is to create a state regulatory standard that aligns with compounding standards found in the United States Pharmaceopeia (USP) general chapters lower than the number 1000.
15.015 Definitions. In this chapter:
(1) “Active pharmaceutical ingredient” or “API” means any substance or mixture of substances intended to be used in the compounding of a drug preparation and that, when used in the compounding of a drug preparation, becomes an active ingredient in the preparation intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment or prevention of disease in humans and animals or affecting the structure and function of the body.
(2) “Added substances” means ingredients that are necessary to compound a drug preparation that are not intended or expected to cause a pharmacologic response if administered alone in the amount or concentration contained in a single dose of the compounded preparation.
(3) “Adverse drug event” means an injury resulting from the use of a drug.
(4) “Beyond use date” or “BUD” means one of the following:
(a) The date after which a non-sterile compounded preparation shall not be used.
(b) The date and time after which a sterile compounded preparation shall not be used.
(5) “Certificate of analysis” means a report from the supplier of a component, container or closure that accompanies the component, container or closure and contains the specifications and results of all analyses and a description.
(6) “Chemical stability” means each active pharmaceutical ingredient retains its chemical integrity and labeled potency, within specified limits.
(7) “Classified area” means a space that maintains an air cleanliness classification based on the International Organization for Standardization (ISO).
(8) “Component” means any active pharmaceutical ingredient, or added substances used in the compounding of a drug preparation.
(9) “Compounding” means the preparation, mixing, assembling, altering, packaging, and labeling of a drug, drug delivery device, or a device in accordance with a prescription, or medication order. Compounding does not include repackaging. Compounding includes any of the following:
(a) Preparation of drug dosage forms for both human and animal patients.
(b) Preparation of drugs or devices in anticipation of prescription drug orders based on routine, regularly observed prescribing patterns.
(c) Reconstitution or manipulation of commercial products that may require the addition of one or more ingredients. Notwithstanding this paragraph, the reconstituting, mixing, or storage and beyond use dating that is performed for non-sterile preparations in accordance with the directions contained in approved labeling provided by the manufacturer is not compounding.
(d) Preparation of drugs or devices for the purposes of, or as an incident to, research, teaching or chemical analysis.
(10) “Container-closure system” means the sum of packaging components that together contain and protect a dosage form, including primary packaging components and secondary packaging components.
(11) “Controlled room temperature” means a temperature maintained thermostatically that encompasses the usual and customary working environment of 68 degrees to 77 degrees Fahrenheit.
(12) “FDA” means the United States food and drug administration.
(13) “Freezer” means a place in which a the temperature is maintained between -13 degrees and 14 degrees Fahrenheit.
(14) “Microbiological stability” means sterility or resistance to microbial growth is retained according to specified requirements and antimicrobial agents that are present retain effectiveness within specified limits.
(15) “NF” means the National Formulary.
(16) “Physical stability” means the original physical properties, including appearance, palatability, uniformity, dissolution, and suspendability, are retained.
(17) “Refrigerator” means a cold place in which the temperature is maintained between 36 degrees and 46 degrees Fahrenheit.
(18) “Stability” means the extent to which a compounded preparation retains, within specified limits and through its beyond use date, the same properties and characteristics that it possessed at the time of compounding.
(19) “Therapeutic stability” means the therapeutic effect remains unchanged.
(20) “Toxicological stability” means no significant increase in toxicity occurs.
(21) “USP” means the United States Pharmacopeia.
SUBCHAPTER I – General
15.10 Facilities. A pharmacist engaged in compounding shall ensure all of the following:
(1) An area designated for compounding.
(2) Orderly placement of compounding equipment, materials, and components in order to minimize the potential for compounding errors.
(3) The compounding area is maintained in a clean and sanitary condition.
(4) The compounding area is easily accessible to all of the following:
(a) Hot and cold running water, exclusive of the bathroom sink.
(b) Soap or detergent.
(c) Single-use towels.
(5) All compounding equipment, materials and components shall be stored off the floor and in a manner to prevent contamination and permit inspection and cleaning of the compounding and storage areas
15.11 Equipment and Drug Preparation Containers.
(1) A pharmacy shall possess equipment and drug preparation containers or packaging appropriate to the type of compounding performed at the pharmacy.
(2) Equipment and drug preparation containers or packaging used in compounding shall be of appropriate design and capacity, and shall be suitably stored in a manner to facilitate use, cleaning, maintenance, and protect it from contamination.
(3) Equipment and drug preparation containers or packaging used in compounding drug products shall be of suitable composition and may not be reactive, additive, adsorptive or absorptive so as to alter the stability of the compounded preparation.
(4) Equipment used in compounding shall be thoroughly cleaned and sanitized after each use, and when necessary, prior to use, according to written policies and procedures, in order to reduce bioburden and reduce the opportunity for cross-contamination.
(5) All equipment utilized in compounding preparations shall be inspected, maintained, calibrated and validated at appropriate intervals, consistent with manufacturer’s recommendations, to ensure the accuracy and reliability of equipment performance. Records shall be kept indicating the equipment was inspected, maintained, calibrated and validated.
15.12 Records of compounding. The managing pharmacist shall ensure written or electronic compounding documentation to systematically trace, evaluate, and replicate the compounding steps throughout the process of a preparation. The compounding documentation shall be maintained for a period of 5 years after the date of the last refill. The compounding documentation shall include all of the following:
(1) Official or assigned name, strength, and dosage form of the preparation.
(2) List of all APIs and added substances and their quantities.
(3) Vendor or manufacturer, lot number and expiration date of each APIs and added substances.
(4) Equipment and supplies needed to prepare the preparation.
(5) Mixing instructions pertinent to the replication of the preparation as compounded.
(6) Compatibility and stability information, including references or laboratory testing.
(7) Container or container-closure system used in dispensing.
(8) Packaging and storage requirements.
(9) Quality control procedures.
(10) Sterilization method when using non-sterile ingredients to make a sterile preparation.
(11) Total quantity compounded.
(12) Name of the person who prepared the preparation.
(13) Name of the person who performed the quality control procedures.
(14) Name of the person who approved the preparation.
(15) Date of preparation.
(16) Assigned control or prescription number.
(17) Assigned BUD.
(18) Copy of the label to dispense final product.
(19) Documentation of any adverse reactions or preparation problems reported by the patient or caregiver.
15.13 Quality control.
(1) One or more pharmacists shall complete a verification of all the following before dispensing:
(a) Written procedures were followed in the compounding process.
(b) Preparation instructions were followed.
(c) Finished preparation appears as expected.
(d) Label includes all required elements.
(e) Quality control procedures were completed.
(f) Compounding records are complete.
(2) A pharmacist shall investigate any discrepancies found during any of verifications and take appropriate corrective action before dispensing.
15.14 Training, Policies and Procedures. (1) Training. All personnel involved in the compounding, evaluation, packaging, and dispensing of compounded preparations shall be properly trained and competency is assessed for the type of compounding conducted. It is the responsibility of the managing pharmacist to ensure personnel training and competency assessments are completed and documented.
