Phar 15.20 allows components with an expiration date from the manufacturer or distributor may be used before the expiration date provided the component is stored in its original container and there is minimal exposure of the remaining component each time component is withdrawn from the container. Components without an expiration date assigned by the manufacturer or supplier shall be assigned an expiration date based upon the nature of the component and its degradation mechanism, the container in which it is packaged and the storage conditions.
Phar 15.21 requires the beyond use date not be later than the expiration date on the container of any component. In the absence of stability information the beyond use date if based upon the type of formulations. Assignment of the beyond use date includes an assessment of the need for antimicrobial agents or refrigeration to protect against contamination introduced during or after the compounding.
Subchapter III provisions relate to sterile compounding.
Phar 15.30 contains definitions of words used throughout the subchapter.
Phar 15.31 indicates the requirements necessary for the segregated compounding area and the classified area to ensure there is not contamination. The primary engineering control shall be certified prior to initial use and then every six months in addition to a redesign of facility, or the replacement or relocation of the primary engineering control.
Phar 15.32 indicates the personnel hygiene, garbing and protective gear required to ensure there is not contamination.
Phar 15.33 requires the compounding area to be cleaned and disinfected with designated minimum frequency. The pharmacy shall have written standard operating procedures which are followed by all compounding and environmental services personnel for cleaning and disinfecting the compounding area. Storage sites for the compounding ingredients and supplies shall remain free from dust and debris. Supplies and equipments removed from shipping cartons shall be disinfected. Entry points on bags and vials shall be disinfected before piercing.
Phar 15.34 requires urgent use compounded sterile preparations to be prepared within one hour and administration shall begin within one hour of the completion of the preparation. Aseptic technique shall be followed and procedures to minimize contamination. Unless immediately and completely administered or witnessed by the person who prepared the preparation, the preparation shall have a label listing patient identification information, the names and amounts of all ingredients, the name or initials of the person who did the preparation and the 1 hour beyond use date and time.
Phar 15.35 indicates the sterilization methods for maintaining physical and chemical stability and the packaging integrity of the compounding sterile preparations. The sterilization methods are by filtration, steam heat or dry heat based upon the components utilized in the preparation. Dry heat depyrogenation shall be used to render glassware and other thermostable containers pyrogen free.
Phar 15.36 requires after the completion of compounding, the preparation shall be physical inspected and upon any observed defects be discarded or segregated in a manner which prevents it from being dispensed and pass a sterility test. Any preparation containing a preservative shall also pass an antimicrobial effectiveness testing before being dispensed.
Phar 15.37 indicates the requirements for establishing a beyond use date. Sterility and stability considerations shall be considered when establishing a beyond use date. Administration date and times based upon the requirements listed in the rule can’t be exceeded or extended without verifiable supporting valid scientific sterility and stability information that applies to the specific preparation or compound. If the beyond use date is based upon storage in a freezer, the integrity of the container closure system with the specific preparation in it shall have been demonstrated for 45 days at frozen storage.
Phar 15.38 provides that the managing pharmacist, all pharmacists, technicians, interns and externs involved in compounding sterile preparations shall successfully complete didactic and practical training initially and then annually. All personnel shall be evaluated initially and annually on all of the following: visual observation of hand hygiene and garbing; visual observation of aseptic technique; gloved fingertip and thumb sampling; and media-fill tests. Records of the training and evaluations shall be maintained by the pharmacy for 5 years.
Summary of, and comparison with, existing or proposed federal regulation:
None. There is federal compounding regulation relating to outsourcing facilities.
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.
