Comparison with rules in adjacent states:
Illinois: Illinois requires a specific area for compounding; records to be kept of each compounded prescription and the components; reference books; and a pharmacy operations manual with policies and procedures pertinent to the complexity and size of the compounding operations. The pharmacy may compound drug products to be sued by practitioners in their office for administration to patients. Sterile compounding requires: a designated area of sufficient size to accommodate a laminar airflow hood, barrier isolation chamber and proper storage of drugs and supplies; the laminar airflow hood shall be certified annually; sink with hot and cold water; refrigerator and/or freezer with a thermometer or temperature recording device; current resource materials and texts; patient profile or medication system; specific labeling requirements including beyond use date and time; and compounding records are to be maintained for 5 years.
Iowa: Iowa requires compliance with United States Pharmacopeia, Chapters 795 and 797. In addition, an FDA registered outsourcing facility must be licensed as a pharmacy in Iowa. Michigan: Michigan requires a pharmacy that provides compounding services to be licensed as a pharmacy and authorized to provide compounding services. The pharmacy must be accredited by the Pharmacy Compounding Accreditation Board and be in compliance with United States Pharmacopeia standards. In addition, any outsourcing facility must be licensed as a pharmacy in Michigan.
Minnesota: Minnesota requires pharmacies compounding nonsterile drug preparations to follow United States Pharmacopeia, chapter 795 standards and pharmacies compounding sterile drug preparations to follow United States Pharmacopeia, chapter 797 standards.
Summary of factual data and analytical methodologies:
The Pharmacy Examining Board primarily utilized United States Pharmacopeia chapters 795 and 797 which are the recognized pharmacopeial standards. In addition, the Pharmacy Examining Board reviewed the code of other states which have been revised since the New England Compounding Center meningitis outbreak in 2012.
Analysis and supporting documents used to determine effect on small business or in preparation of economic impact analysis:
The Board does not know how many or which pharmacies are compounding sterile pharmaceuticals and UPS 795 and 797 are the recognized pharmacopeial standards. Therefore the Board was unable to determine whether there will be an effect on small businesses. This rule was posted for 30 days for economic comments and none were received.
Fiscal Estimate and Economic Impact Analysis:
The Fiscal Estimate and Economic Impact Analysis is attached.
Effect on small business:
These proposed rules were submitted to the Small Business Regulatory Review Board. The Small Business Regulatory Review Board determined the rules will not have a significant economic impact on a substantial number of small businesses. The Department’s Regulatory Review Coordinator may be contacted by email at Kirsten.Reader@wisconsin.gov, or by calling (608) 267-2435 Agency contact person:
Sharon Henes, Administrative Rules Coordinator, Department of Safety and Professional Services, Division of Policy Development, 1400 East Washington Avenue, Room 151, P.O. Box 8366, Madison, Wisconsin 53708; telephone 608-261-2377; email at DSPSAdminRules@wisconsin.gov. ---------------------------------------------------------------------------------------------------------------------
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.
