Sterile Compounding

PURPOSE: This rule establishes standards for the handling, labeling, distribution, and dispensing of compounded sterile preparations by licensed pharmacies, pursuant to a physician’s order or prescription. PUBLISHER’S NOTE: The secretary of state has determined that publication of the entire text of the material that is incorporated by reference as a portion of this rule would be unduly cumbersome or expensive. This material as incorporated by reference in this rule shall be maintained by the agency at its headquarters and shall be made available to the public for inspection and copying at no more than the actual cost of reproduction. This note applies only to the reference material. The entire text of the rule is printed here. (1) Except as otherwise provided by law or the board’s rules, the United States Pharmacopeia–NF (2023), General Chapter 797 Pharmaceutical Compounding – Sterile Preparations (www. usp.org), is incorporated by reference (hereafter “USP Chapter 797”) and available at 12601 Twinbrook Parkway, Rockville, MD 20852. This rule does not incorporate any subsequent amendments or additions to USP Chapter 797. In the event of a conflict between USP Chapter 797 and Missouri law or board rules, Missouri law and board rules shall control. Except as otherwise provided by law or rule, licensees shall comply with all provisions of USP Chapter 797 and the additional requirements of this rule. (A) The use of technologies, techniques, materials, or procedures other than those described in USP Chapter 797 are prohibited, unless the technology, technique, material, or procedure is validated in accordance with applicable provisions of USP Chapter 1223 and USP Chapter 1225 and is approved by the board in advance after submission of scientific data evidencing the specific technology, technique, material, or procedure is safe, effective, and meets or exceeds USP Chapter 797 requirements. (B) The permit holder and pharmacist-in-charge (PIC) are responsible for ensuring compliance with state and federal law and USP Chapter 797, including ensuring compliance for activities delegated to a designated person, as defined by Chapter 797. Identification of a designated person as defined by USP Chapter 797 shall not exempt or modify any duty or responsibility of the permit holder or PIC under the board’s rules or state and federal law. (C) For purposes of this rule, compounding shall be defined as provided in USP Chapter 797, provided that compounded sterile preparations (CSPs) also includes— 1. Docking of proprietary bag and vial systems; and 2. Mixing, reconstituting, or preparing an FDA-approved manufactured sterile product in accordance with the manufac turer’s approved labeling recommendations. (D) The pharmacy must have current reference material(s) related to CSPs available, as applicable to the pharmacy’s com pounding activities. (E) Except as otherwise provided herein, sterile compounding must also comply with 20 CSR 2220-2.400. (F) USP Chapter 797, Section 21, and the exemption in USP Chapter 797, Section 1.1.2, governing allergen extracts are not incorporated in this rule and shall not be applicable. (G) USP Chapter 797, Section 1.3, and the exemption in USP Chapter 797, Section 1.3, governing immediate use CSPs is not incorporated in this rule and shall not be applicable. Preparation of a vaccine for immediate administration pursuant to 20 CSR 2220-6.050 is not considered sterile compounding. (H) The board recommends but does not require compliance with USP Chapter 800. In the interim, pharmacies that compound sterile hazardous drugs, as defined by lists maintained by National Institute for Occupational Safety and Health (NIOSH), are required to establish policies and procedures that include all aspects of handling hazardous drugs, including but not limited to personal protective equipment, use and maintenance of appropriate primary engineering controls, transport, storage, labeling, disposal, spill control, compounding procedures, personnel training, and deactivating, decontaminating, cleaning, and disinfecting. (I) Class E radiopharmaceutical pharmacies must comply with USP Chapter 825, 20 CSR 2220-2.500, and all applicable rules of the board for radiopharmaceutical activities. (J) Unless otherwise provided by law or court of competent jurisdiction, the provisions of this rule are only applicable to pharmacy services under the jurisdiction of the board and are not applicable to hospital pharmacy services under the jurisdiction of the Missouri Department of Health and Senior Services pursuant to Chapter 197, RSMo. (2) Personnel Education, Training, and Evaluation. Licensees shall comply with all USP Chapter 797 personnel education, training, and evaluation requirements. (A) Individuals who fail an aseptic manipulation competency evaluation or a garbing and hand hygiene competency evaluation must undergo requalification through additional training by competent compounding personnel. The pharmacy must investigate such failure and take appropriate corrective actions prior to the individual resuming compounding. Corrective actions must be documented in the pharmacy’s records. (B) Required competency evaluation results can be trans ferred between facilities under common ownership or control of the same pharmacy or healthcare facility, provided the competency evaluation captured the most difficult and chal lenging conditions the individual will be performing and was completed within USP Chapter 797’s required time frames. Pharmacies accepting transferred competency evaluation re sults under this section must maintain current and written policies and procedures governing the transfer of results. Licensees or registrants with transferred competency evalu ation results must be trained on applicable pharmacy opera tional procedures as needed to ensure proper compounding and must be skilled and trained to accurately and competently perform the duties assigned. (C) If needed to prevent interruptions in patient care during an emergency, a pharmacy may also accept the required competency evaluations from another pharmacy or hospital in lieu of the required initial competency evaluations, provided— 1. A pharmacist verifies the applicable competency evalu ation complies with USP Chapter 797; 2. The pharmacy maintains documentation of the other pharmacy’s or hospital’s completed competency evaluation(s), including the dates and results. Additionally, the receiving pharmacy must maintain a manual or electronic copy of the other pharmacy’s or hospital’s policies and procedures on aseptic manipulation competency evaluations for board licensees or registrants; 3. The board licensee or registrant has received training on applicable pharmacy operational procedures as needed to ensure proper compounding. The licensee or registrant must be skilled and trained to accurately and competently perform the duties; and 4. Individuals may not assist with compounding under the emergency allowance authorized by this subsection for more than forty-five (45) days without the required competency evaluation by the pharmacy that complies with USP Chapter 797. (3) Facilities and Equipment. The pharmacy shall establish and follow proper controls to ensure environmental quality, prevent environmental contamination, and maintain air quality in all International Organization for Standardization (ISO) classified areas, in addition to compliance with USP Chapter 797. (A) To minimize impact on patient care, Class H sterile com pounding pharmacies licensed on the effective date of this rule may petition the board for a waiver of USP Chapter 797 facility and equipment requirements if immediate compliance with USP Chapter 797 requirements cannot be completed despite the permit holder’s due diligence or would result in an undue hardship or adversely impact patient care. Waivers may be effective for a time period designated by the board, provided all Class H sterile compounding pharmacies must comply with USP Chapter 797 facility and equipment requirements within two (2) years of the effective date of this rule. (B) Certification of primary engineering controls (PECs)/ISO classified areas must be conducted by competent staff/vendors in accordance with USP Chapter 797 using recognized and appropriate certification and testing equipment. Certification results must be reviewed by a designated person as defined by USP Chapter 797. The individual’s identity and date of review must be documented in the pharmacy’s records. Deficiencies or failures that may impact preparation sterility or quality must be investigated and corrected prior to further compounding, which may include recertification of the PEC/ISO classified area. (C) PECs, cleanroom suites, and segregated compounding areas (SCA) must be designed and maintained to minimize mi crobial contamination and maintain air quality. Cleaning and disinfecting supplies must be low-lint, including tool handles and holders. Additionally, dust-collecting overhangs, such as utility pipes, and ledges, such as windowsills, must be mini mized. The pharmacy’s policies and procedures must address selecting, handling, and monitoring of cleaning, disinfecting, and sporicidal agents to prevent/minimize equipment damage and decay and to ensure environmental quality and prepara tion integrity. The pharmacy must also have policies/proce dures for inspecting the PECs, cleanroom suite, SCA, and equip ment and correcting/repairing any damage, rust, or corrosion. (D) For SCAs, the area within one (1) meter of the PEC must be dedicated only for sterile compounding (e.g., not storage, hand hygiene, donning and doffing garb, or other highly particlegenerating activities such as patient care). (4) Garbing and Hand Hygiene. The following requirements apply in addition to USP Chapter 797: (A) For restricted-access barrier systems (RABS) as defined by USP Chapter 797, the RABS and the pharmaceutical isolator sleeves and gloves must be changed per the manufacturer’s recommendations and as defined in the pharmacy’s policies/ procedures; and (B) Disposable gloves must be worn inside the gloves at tached to the RABS sleeves. Sterile gloves must be worn over the gloves attached to the RABS sleeve. (5) Record Keeping. (A) In addition to USP Chapter 797 requirements, the following must be documented/maintained for all sterile compounding: 1. Manufacturer manuals relied on to properly operate equipment; 2. Other facility quality control logs, as appropriate, including all maintenance, cleaning, and calibration records; 3. Sterilization records, if applicable; 4. Quarantine records, if applicable; 5. End-preparation evaluation and testing records; and 6. Ingredient validation records, if applicable (e.g., Certificate of Analysis). (B) All records, policies/procedures and reports required by USP Chapter 797 or this rule must be maintained electronically or as a hard-copy for two (2) years and must be readily retrievable and subject to inspection by the board of pharmacy or its agents. At a minimum, records shall be physically or electronically produced immediately or within two (2) hours of a request from the board. (C) In lieu of a compounding log as required by 20 CSR 22202.400, Class H pharmacies must maintain a compounding record for each preparation that complies with USP Chapter 797. The compounding record must include a prescription number or other readily retrievable unique identifier assigned for which the compound was dispensed. (6) End-Preparation Evaluation. (A) In addition to USP Chapter 797 requirements, the phar macy must have a procedure for a pre-release check of the potency of the active ingredients in a CSP prepared from non-sterile active ingredients. The procedure shall include at least the following verifications by a pharmacist: 1. The lot of the active ingredients used for compounding have the necessary labeling, potency, purity, certificate of anal ysis, and other relevant qualities; 2. All weighings, calculations, volumetric measurements, and additions of ingredients were carried out properly; and 3. The compounding or control records include documen tation that the fill volumes of all units available for release were checked and were correct. (B) A CSP may be released for emergency dispensing pending test results, if approved by the prescriber. A separate autho rization from the prescriber is required for each emergency dispensing. For purposes of this rule, emergency dispensing is defined as a situation where a preparation is necessary for im mediate administration and no alternative product or prepara tion is available. Documentation of the emergency dispensing, the prescriber’s approval, and the need for the emergency must appear within the prescription record. (7) Microbiological Air and Surface Monitoring. The pharmacy shall establish and follow proper controls to ensure environ mental quality, prevent environmental contamination, and maintain air quality in all ISO classified areas. Applicable envi ronmental monitoring of air and surfaces must be conducted as required by USP Chapter 797. In addition to USP Chapter 797 requirements, microbiological air and surface monitoring/ testing results must be promptly reviewed by a designated person as defined by USP Chapter 797. The reviewer’s identity and date of review must be documented in the pharmacy’s records. When conducted, routine surface sampling must be performed under dynamic conditions, but before the area has AND INSURANCE been cleaned and disinfected. (8) Remedial Investigations. A remedial investigation is required if any environmental monitoring sample demonstrates a colony forming unit (CFU) count that exceeds USP Chapter 797 recommended action levels for the type of sampling. The remedial investigation must be documented and include resampling of all affected areas to ensure a suitable state of microbial control. The pharmacy must ensure that no misbranded, contaminated, or adulterated CSP is administered or dispensed for patient use. (A) If an environmental monitoring sample taken from a PEC exceeds USP Chapter 797 action levels, the pharmacy must cease compounding in the affected PEC until resampling shows a suitable state of microbial control has been achieved in the PEC. However, a pharmacy may continue to compound during the remedial investigation if— 1. The affected PEC is cleaned and disinfected by using an Environmental Protection Agency (EPA) registered sterile cleaning, disinfecting, and sporicidal agent, or a combination thereof, followed by sterile isopropyl alcohol; 2. The beyond-use date assigned to all preparations is no greater than twelve (12) hours; and 3. The affected PEC is resampled under dynamic conditions. If the resampling exceeds USP Chapter 797 action levels, compounding must cease until resampling shows a suitable state of microbial control has been achieved in the PEC, unless otherwise authorized by the board or board’s authorized designee to continue compounding upon showing the facility can be operated in a manner not to endanger the public health or safety. (B) If an environmental monitoring sample taken from a buffer room exceeds USP Chapter 797 action levels, the phar macy must cease compounding in the affected buffer room until resampling shows a suitable state of microbial control has been achieved in the buffer room. However, a pharmacy may continue to compound during the remedial investigation if— 1. The affected buffer room is cleaned and disinfected by using an EPA registered cleaning, disinfection, and sporicidal agents, or a combination thereof; 2. The beyond-use date assigned to all preparations is no greater than twenty-four (24) hours; and 3. The affected buffer room is resampled under dynamic conditions. If two (2) consecutive resamplings exceed USP Chapter 797 action levels, compounding must cease until res ampling shows a suitable state of microbial control has been achieved in the affected room, unless otherwise authorized by the board or board’s authorized designee to continue com pounding upon a showing that the facility can be operated in a manner not to endanger the public health or safety. (C) Pharmacies must notify the board in writing within three (3) business days if a resample is collected as part of a remedial investigation that exceeds USP Chapter 797 action levels. (9) Recalls. A recall must be initiated when a dispensed CSP is deemed to be misbranded, adulterated, or non-sterile or if end-preparation testing results are out of specification. The pharmacy shall notify the prescriber of the nature of the recall, the problem(s) identified, and any recommended actions to ensure public health and safety. In cases where the CSP has the potential to harm the patient, the same notification must be provided to all patients that received the recalled CSP(s). Any recall initiated by a pharmacy shall be reported, in writing, to the board within three (3) business days. The pharmacy shall document their activities related to the recall. AUTHORITY: sections 338.240 and 338.280, RSMo 2016, and sections 338.010 and 338.140, RSMo Supp. 2025.* This rule originally filed as 4 CSR 220-2.200. Original rule filed May 4, 1992, effective Feb. 26, 1993. Amended: Filed Oct. 28, 1994, effective May 28, 1995. Rescinded and readopted: Filed Dec. 3, 2002, effective July 30, 2003. Moved to 20 CSR 2220-2.200, effective Aug. 28, 2006. Amended: Filed Feb. 6, 2008, effective Aug. 30, 2008. Emergency amendment filed July 25, 2016, effective Aug. 4, 2016, expired Feb. 23, 2017. Amended: Filed July 25, 2016, effective Jan. 30, 2017. Emergency amendment filed Aug. 20, 2018, effective Aug. 30, 2018, expired Feb. 28, 2019. Amended: Filed Aug. 20, 2018, effective Feb. 28, 2019. ** Emergency amendment filed April 14, 2021, effective April 28, 2021, expired Feb. 7, 2022. Amended: Filed April 14, 2021, effective Oct. 30, 2021. Emergency amendment filed Feb. 8, 2022, effective Feb. 24, 2022, expired Aug. 22, 2022. Amended: Filed Feb. 8, 2022, effective Aug. 30, 2022. Amended: Filed Dec. 12, 2025, effective July 30, 2026. *Original authority: 338.010, RSMo 1939, amended 1951, 1989, 1990, 2007, 2009, 2011, 2014, 2017, 2018, 2019, 2021, 2023; 338.140, RSMo 1939, amended 1981, 1989, 1997, 2011, 2019; 338.240, RSMo 1951, amended 2011; and 338.280, RSMo 1951, amended 1971, 1981. **Pursuant to Executive Order 21-09, 20 CSR 2220-2.200, subsection (10)(B) was suspended from March 20, 2020 through December 31, 2021.