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.
(2) Policies and procedures. The pharmacy and managing pharmacist shall establish written policies and procedures governing all of the following:
(a) Personnel qualifications and training, responsibilities, and competencies.
(b) Personal hygiene, garb, garbing, and personal protective gear.
(c) Use and maintenance of compounding facilities and equipment, including applicable certifications.
(d) Environmental monitoring.
(e) Cleaning and disinfection of compounding area.
(f) Component selection.
(g) Sterilization and depyrogenation, if pharmacy does sterilization and depyrogenation.
(h) Documentation requirements.
(i) Establishing BUD.
(j) Reporting of adverse drug events.
(k) A risk management program, including documentation of incidents, adverse drug reactions and product contamination.
(L) A quality assurance program.
(m) Maintaining the integrity of any classified work areas.
(n) Handling small and large spills of antineoplastic agents and other hazardous substances.
(o) Notification to patients or practioners of a preparation which is recalled.
when there is potential for patient harm.
(3) Review of policies and procedures The policy and procedures shall be reviewed at least once every 36 months and shall be updated, on a continuous basis, to reflect current practice. Documentation of the review shall be made available to the board upon request.
15.15 Labeling. The label of a compounded preparation shall include all of the following:
(2) Storage conditions if other than controlled room temperature.
(3) BUD.
(4) Special handling instructions, when applicable.
(5) Indication that the preparation is compounded unless administered by health care personnel.
15.16 Component Selection. (1) Active pharmaceutical ingredients or added substances used in compounding shall be manufactured by an FDA registered facility or accompanied by a certificate of analysis.
(2) APIs and added substances shall meet USP or NF monograph specifications when monographs are available. A pharmacist shall use professional judgement in selection of APIs if USP or NF grade is not available.
(3) All components shall be stored and handled consistent with the manufacturer’s labeling or USP or NF monographs and in a manner that prevents contamination and deterioration.
(4) A pharmacist compounding for human use may not use components that have been withdrawn or removed from the market for safety or efficacy reasons by the FDA. A pharmacist compounding for food producing animal use may not use components prohibited for use in food producing animals.
15.17 Non-patient specific compounding. Compounded preparations dispensed or distributed to a practitioner pursuant to a non-patient specific order to be administered by a practitioner or practitioner’s agent shall meet all of the following:
(1) The order shall include the name and address of the practitioner, drug, strength, quantity and the purpose of the compounded preparation.
(2) The label shall include the practitioner’s name in place of the patient’s name and state “For Practitioner Administration Only – Not for Dispensing or Distribution”. If the sterility or integrity of the compounded preparation is not maintained after the initial opening of the container, the label shall state “Single-Dose Only”.
(3) The pharmacist shall record the name and address of the location the compounded preparation was dispensed or distributed, and the lot number and BUD of all preparations dispensed or distributed to the practitioner.
SUBCHAPTER II – Non-sterile Compounding
15.20 Component Selection. (1) Components with an expiration date from the manufacturer or distributor may be used before the expiration date provided all of the following:
(a) The component is stored in its original container under conditions to avoid decomposition.
(b) There is minimal exposure of the remaining component each time component is withdrawn from the container.
(2) Components without an expiration date assigned by the manufacturer or supplier shall be labeled with the date of receipt and assigned a conservative expiration date, not to exceed three years after receipt, based upon the nature of the component and its degradation mechanism, the container in which it is packaged and the storage conditions.
(3) Components transferred to another container which shall provide integrity that is minimally equivalent to the original container and shall be identified with all of the following:
(a) Component name.
(b) Original supplier.
(c) Lot or control number.
(d) Transfer date.
(e) Expiration date.
15.21 Assigning BUD. (1) The BUD shall not be later than the expiration date on the container of any component.
(2) Only in the absence of stability information that is applicable to a specific drug product and preparation, the maximum BUD for a non-sterile compounded drug preparation that is packaged in a tight, light-resistant container is as follows:
(a) For nonaqueous formulations stored at controlled room temperature, the BUD shall not be later than the time remaining until the earliest expiration date of any active pharmaceutical ingredient or 6 months, whichever is earlier.
(b) For water-containing oral formulations, the BUD shall not be later than 14 days when stored in a refrigerator.
(c) For water-containing semisolid mucosal liquid, topical or dermal formulations, stored at controlled room temperature, the BUD shall not be later than 30 days.
(3) Assignment of BUD shall include an assessment of the need for antimicrobial agents or storage in a refrigerator to protect against bacteria, yeast, and mold contamination introduced during or after the compounding process.
SUBCHAPTER III – Sterile Compounding
15.30 Definitions. In this subchapter:
(1) “Ante area” means an ISO Class 8 or better area where personnel hand hygiene and garbing procedures, staging of components, order entry, labeling and other high particulate generating activities are performed. The ante-area is the transition area between the unclassified area of the facility and the buffer area.
(2) “Buffer area” means an ISO Class 7 or ISO Class 8 if using an isolator or cleaner area where the primary engineering control that generates and maintains an ISO Class 5 environment is physically located.
(3) “Category 1” means a compounded sterile preparation compounded with a primary engineering control in a segregated compounding area.
(4) “Category 2” means a compounded sterile preparation compounded with a primary engineering control in a classified area.
(5) “Clean” means to physically remove debris, dirt, dust, and other impurities from surfaces or objects using a cleaning agent with a detergent.
(6) “Compounded sterile preparation” means a compounded final preparation intended to be sterile through the BUD.
(7) “Compounded stock solution” means a compounded solution to be used in the preparation of multiple units of a finished compounded sterile preparation.
(8) “Critical site” means a location that includes any component or fluid pathway surfaces or openings that are exposed and at risk of direct contact with air, moisture or touch contamination.
(9) “Disinfect” means the killing of microorganisms when used according to the disinfectant’s label.
(10) “HEPA” means high-efficiency particulate air.
(11) “ISO Class 5” means conditions in which the air particle count is no greater than a total of 3,520 particles of 0.5 micrometers and larger per cubic meter of air that is supplied by HEPA or HEPA-filtered air.
(12) “ISO Class 7” means conditions in which the air particle count is no greater than a total of 352,000 particles of 0.5 micrometers and larger per cubic meter of air that is supplied by HEPA or HEPA-filtered air.
(13) “ISO Class 8” means conditions in which the air particle count is no greater than a total of 3,520,000 particles of 0.5 micrometers and larger per cubic meter of air that is supplied by HEPA or HEPA-filtered air.
(14) “Isolator” means an enclosure that provides HEPA-filtered ISO Class 5 unidirectional air operated at a continuously higher pressure than its surrounding environment and is decontaminated using an automated system. An isolator uses only decontaminated interfaces or rapid transfer ports for materials transfer.
(15) “Primary engineering control” means a device or zone that provides an ISO Class 5 environment for sterile compounding.
(16) “Restricted access barrier system (RABS)” means an enclosure that provides HEPA-filtered ISO Class 5 unidirectional air that allows for the ingress or egress of materials through defined openings that have been designed and validated to preclude the transfer of contamination, and that generally are not to be opened during operations. RABS include compounding aseptic isolators and compounding aseptic containment isolators.
(17) “Sterility assurance level of 10-6” means an equivalent to a probability that one unit in a million is nonsterile.
(18) “Segregated compounding area” means a designated, unclassified space, area, or room that contains a primary engineering control.
(19) “Urgent use compounded sterile preparation” means a preparation needed urgently for a single patient and preparation of the compounded sterile preparation under Category 1 or Category 2 requirements would subject the patient to additional risk due to delays.
15.31 Facility design and environmental controls. (1) General. Facilities shall meet all of the following requirements:
(a) Be physically designed and environmentally controlled to minimize airborne contamination from contacting critical sites.
(b) Be accessible only to designated personnel.
(c) Have a heating, ventilation, and air conditioning system controlling the temperature and humidity.
(2) Segregated compounding area. A segregated compounding area shall meet all of the following requirements:
(a) Be located in an area away from unsealed windows and doors that connect to the outdoors, or significant traffic flow.
(b) Be located in an area which is not adjacent to construction sites, warehouses and food preparation areas.
(c) Have a defined perimeter.
(d) Locate the primary engineering control at least one meter from any sink.
