Nuclear Pharmacy—Minimum Standards for Operation

PURPOSE: This rule defines minimum standards for the operation of nuclear pharmacies and the preparation, labeling, dispensing, delivering, compounding, and repackaging of radiopharmaceuti cals pursuant to a prescription drug or medication order. This reg ulation is intended to supplement other regulations of the Board of Pharmacy, as well as those of other state and/or federal agencies. (1) Definitions. (A) “Agreement state” (AS) means any state that has entered into an agreement under subsection 274b of the Atomic Energy Act of 1954, as amended, in which the United States Nuclear Regulatory Commission (NRC) has relinquished to such states the majority of its regulatory authority over source material, by-product, and special nuclear material in quantities not sufficient to form a critical mass. (B) “Authorized address or location” means the building or buildings that are identified on the license and where by-prod uct material may be received, prepared, used, or stored as defined by 10 CFR 35.2 or a temporary job site for providing mo bile nuclear medicine services in accordance with 10 CFR 35.80. (C) “Authorized nuclear pharmacist” (ANP) means an autho rized nuclear pharmacist as defined by USP Chapter 825. (D) “Class E: Radiopharmaceutical pharmacy” (also referenced herein as a “nuclear pharmacy”) means the location where radiopharmaceuticals are prepared, compounded, repackaged, dispensed, distributed, or stored. A Class E pharmacy does not include the nuclear medicine facilities of hospitals or clinics where radiopharmaceuticals are compounded, dispensed, or administered to patients under the supervision of a licensed physician, authorized by the NRC/AS regulations. Nothing in this rule shall be construed as requiring a licensed clinical laboratory, which is also licensed by the NRC/AS to handle radioactive materials, to obtain the services of an ANP, or to have a Class E pharmacy permit, unless the laboratory is engaged in the commercial sale or resale of radiopharmaceuticals. (E) “Contingency prescription drug order” means a radio pharmaceutical prescription drug order issued for contingency material for a diagnostic purpose. (F) “Designated person” means a designated person as de fined by USP Chapter 825. (G) “NRC” means the United States Nuclear Regulatory Com mission. (H) “Nuclear pharmacy technician” means a person who has successfully completed a nuclear pharmacy technician train ing program provided by an accredited college program or meets the American Pharmacist’s Association’s (APhA) Guide lines for Nuclear Pharmacy Technician Training Program or an equivalent company sponsored program that meets APhA guidelines for nuclear pharmacy technician training. (I) “Prescription drug order” means an order issued by an authorized prescriber for a specific patient for a diagnostic or therapeutic purpose. (J) “Radiopharmaceutical” means a radiopharmaceutical as defined by USP Chapter 825. (K) “Segregated radiopharmaceutical processing area” (SRPA) means a segregated radiopharmaceutical processing area as defined by USP Chapter 825. (L) “Therapeutic prescription drug order” means a radioactive prescription drug order issued for a specific patient for a therapeutic purpose. (M) “USP Chapter 825” means the United States Pharmacopeia– NF (2023), General Chapter 825 Radiopharmaceuticals — Preparation, Compounding, Dispensing, and Repackaging (Jan. 1, 2024; DOI: https://doi.org/10.31003/USPNF_M11915_05_01), which is incorporated by reference, except as otherwise provided by law or the board’s rules, and available at 12601 Twinbrook Parkway, Rockville, MD 20852 or at www.usp.org. This rule does not incorporate any subsequent amendments or additions to USP Chapter 825. In the event of a conflict between USP Chapter 825 and Missouri law or board rules, Missouri law and board rules shall control. (2) Except as otherwise provided by law or rule, licensees shall comply with all provisions of USP Chapter 825 and the additional requirements of this rule. (A) No person may receive, acquire, possess, prepare, compound, dispense, repackage, store, distribute, dispose of, or manufacture for sale or resale any radiopharmaceutical except in accordance with accepted standards of nuclear pharmacy practice and applicable state/federal law, USP Chapter 825, and the rules/regulations promulgated by the NRC or applicable AS. Only an ANP or nuclear pharmacy technician, or a licensed pharmacist, intern pharmacist, or pharmacy technician in training under the supervision of an ANP may prepare, compound, repackage, or dispense radiopharmaceuticals. (B) 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. (C) Unless otherwise required by federal law, Class E phar macies are exempt from the required pharmacy reporting requirements in 20 CSR 2220-2.425 for dispensing/preparation of radiopharmaceuticals. (D) The use of technologies, techniques, materials, or pro cedures other than those described in USP Chapter 825 and Chapter 71 are prohibited, unless the technology, technique, material, or procedure is validated in accordance with applica ble 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 Chap ter 825 and Chapter 71 requirements. (E) A Class E pharmacy must have on file a copy of the active NRC/AS radioactive materials license for the licensed facility requesting any radiopharmaceutical prior to dispensing to that facility. The radiopharmaceutical may only be delivered to the authorized addresses or locations listed in, or temporary job sites as authorized by, the NRC/AS license. The authorized physician ordering radiopharmaceuticals is hereby recognized as the patient’s authorized designee for delivery purposes. (F) Compounding of sterile radiopharmaceutical preparations involving one (1) or more non-sterile components must comply with USP Chapter 797, Section 10 (Sterilization and Depyrogenation). (G) The immediate use exemptions/modifications in USP Chapter 825, Section 3 (Immediate Use of Sterile Radiopharma ceuticals), Section 4.4. (Hand Hygiene and Garbing for Imme diate Use Preparations), and Section 10.4 (Preparation of Radio labeled Red Blood Cells for Immediate Use) are not adopted or incorporated in this rule. (H) Preparation/compounding of positron emission tomog raphy (PET) drugs that are not manufactured as United States Food and Drug Administration (FDA) approved drug products must comply with USP Chapter 823. (I) Class E pharmacies shall comply with any applicable local, state, and federal requirements regarding its daily operations and the disposal of any biohazardous medical waste. Appropriately labeled and, when required, shielded disposal containers shall be used for radioactive and biohazardous waste from the preparation or the return of radiopharmaceuticals. (J) Any reusable outer shielding container that is returned shall be considered to be contaminated. No pharmacy shall use reusable outer shielding containers for radioactive doses without either an effective process to decontaminate the container of biohazardous and radioactive substances or an effective mechanism to avoid contamination of the container. No pharmacy may reuse an outer shielding container that remains contaminated with blood, radiation, or other biohazardous substances. (K) A Class E pharmacy may accept returns and waste as authorized by NRC/AS regulations. (3) Permits. All Class E pharmacies must hold a Class E radiopharmaceutical permit issued by the board. The appropriate pharmacy permit classification is required for any pharmacy activities that occur at the Class E site other than Class E services. An additional Class D permit is not required to compound non-sterile radiopharmaceuticals. An additional Class H permit is not required to compound sterile radiopharmaceuticals. (A) The pharmacist-in-charge (PIC) of a Class E pharmacy must be an ANP. The permit holder and PIC are responsible for ensuring compliance with state and federal law and USP Chapter 825, including ensuring compliance for activities delegated to a designated person. Identification of a designated person 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. (B) A permit to operate a Class E pharmacy shall only be issued to a person who is, or who employs/contracts with, an ANP. All personnel performing tasks in the preparation, compounding, dispensing, repackaging, or distribution of radiopharmaceuticals and ancillary drugs/materials must be under the direct supervision of an ANP. (C) The permit to operate a Class E pharmacy is effective only if the pharmacy also holds a current NRC and/or AS radioactive materials license. Copies of the most recent regulatory inspection reports must be made available upon request to the board for inspection. (D) Class E pharmacies shall post in a conspicuous area of the pharmacy a copy of its Class E permit and a copy of the most current NRC or applicable AS license. A reference to the specific location of the NRC/AS license within the pharmacy is acceptable. (E) The PIC shall notify the Board of Pharmacy of the outcome of any hearings under state or federal laws or regulations governing radiopharmaceuticals involving or against the pharmacy location licensed by the board. Notification must be made electronically or in writing within thirty (30) calendar days of the date of the outcome. (4) Space, Security, Recordkeeping, and Equipment. Class E pharmacies must establish and follow proper controls to en sure environmental quality and prevent environmental con tamination, including maintaining air quality in all primary engineering controls (PEC) and ISO classified areas. In addition to USP Chapter 825 requirements, microbiological air and sur face monitoring/testing results must be promptly reviewed by AND INSURANCE a designated person. The reviewer’s identity and date of review must be documented in the pharmacy’s records. (A) Class E pharmacies shall have adequate space and equip ment for the scope of services provided consistent with USP Chapter 825 and as required by the NRC/AS license. (B) Certification of PECs/ISO classified areas must be conducted by competent staff/vendors using recognized and appropriate certification and testing equipment. Certification results must be reviewed by a designated person. 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 preparation/compounding in the affected PEC/ISO classified areas, which may include recertification of the PEC/ ISO classified area. (C) PECs, secondary engineering controls (SECs), and SRPAs must be designed and maintained to minimize microbial contamination and maintain air quality. Cleaning and disin fecting 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 minimized. The pharmacy’s policies and procedures must address select ing, handling, and monitoring of cleaning, disinfecting, and sporicidal agents to prevent/minimize equipment damage and decay, and to ensure environmental quality and preparation integrity. The pharmacy must also have policies/procedures for inspecting the PEC, SEC, SRPA, and equipment and correcting/ repairing any damage, rust, or corrosion. (D) Cleaning and disinfecting of surfaces in the PECs, ISO classified areas, and the SRPA must occur at the minimum frequencies specified in USP Chapter 825, Table 5 (Minimum Frequency for Cleaning and Disinfecting Surfaces in Classified Areas and within the Perimeter of the SRPA) or, if activities are not performed daily, cleaning and disinfecting must be completed before use. The walls, bars, torso shield, and any exposed surface of equipment inside the PEC must be cleaned to the extent possible, in accordance with manufacturer recommendations. All cleaning, disinfecting, and sporicidal agents used in the PEC must be sterile. (E) For non-sterile radiopharmaceutical preparations under USP Chapter 825, Section 10.1 (Preparation Following Manu facturer Instructions), the preparation area must be suitably cleaned and uncluttered to ensure the overall integrity and quality of prepared radiopharmaceutical(s). (F) Class E pharmacies must maintain records of acquisition, inventory, preparing, compounding, repackaging, dispensing, and distribution of all radioactive and non-radioactive drugs/ materials in accordance with State Board of Pharmacy and NRC/AS rules/requirements. In addition to USP Chapter 825 requirements, the following must also be documented/ maintained: 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, if applicable; 6. Ingredient validation records, if applicable (e.g., Certifi cate of Analysis); and 7. Documentation of aseptic competency qualification(s) and required media fills, including the name of the person evaluated, qualification/testing dates and results, media and components used, including manufacturer, expiration date and lot number, monitoring of incubation temperatures, and dates of incubation. For temperature monitoring, a continuous temperature monitoring system may be used if the system maintains ongoing documentation of temperature recordings and alerts a pharmacist when temperatures are outside of the required range and provides the amount of variance. (G) Class E pharmacies must maintain a compounding record that complies with USP Chapter 825, Section 9.2 (Records for Preparation with Minor Deviations/Compounding), for all ra diopharmaceuticals prepared, prepared with minor deviations, dispensed, repackaged, or compounded. A compounding record is not required for FDA-approved radiopharmaceuticals dispensed in an unopened manufacturer container if the Class E pharmacy does not manipulate the radiopharmaceutical in any manner. (H) Unless required by other rule or applicable law, all records, policies/procedures, and reports required by this rule or USP Chapter 825 must be maintained electronically or as a hard copy for two (2) years and must be readily retrievable and made available to the board or its representative upon request. At a minimum, records must be physically or electronically produced immediately or within two (2) hours of a board request. (5) Personnel Training and Competency. Licensees/registrants must comply with all USP Chapter 825 education, training, and qualification requirements. The required aseptic competency qualification program must include all elements required by USP Chapter 825, Section 4.1 (Aseptic Qualifications), and must include cleaning and disinfecting the PEC and, if applicable to the individual’s duties, cleaning and disinfection of SEC and the SRPA. (A) Required aseptic competency qualification results can be transferred between facilities under common ownership or control of the same pharmacy or healthcare facility, provided the competency qualification captured the most difficult and challenging conditions the individual will be performing using similar equipment and was completed within USP Chapter 825’s required time frames. Pharmacies accepting transferred aseptic competency qualification results under this section must maintain current and written policies and procedures governing the transfer of results. Licensees or registrants with transferred competency evaluation results must be trained on applicable pharmacy operational procedures as needed to ensure proper compounding and must be skilled and trained to accurately and competently perform the duties assigned. (B) 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 evaluation complies with USP Chapter 825; 2. The pharmacy maintains documentation of the other pharmacy 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 competency qualifications 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 825. (6) Preparation/Compounding. All sterile and non-sterile radiopharmaceuticals must be prepared, compounded, repackaged, and dispensed in accordance with accepted standards of nuclear pharmacy practice and in compliance with applicable state/federal law. Additionally, Class E pharmacies must comply with all applicable rules for compounding sterile and non-sterile non-radioactive preparations, including but not limited to 20 CSR 2220-2.200 (Sterile Compounding) and 20 CSR 2220-2.400 (Compounding Standards of Practice). (A) Appropriate safety and containment techniques must be used in conjunction with the aseptic techniques required for sterile radiopharmaceutical preparations. (B) Materials, equipment, and supplies must be placed in an ISO Class 5 PEC in a manner that minimizes disruption of airflow in the direct preparation area. Furniture, equipment, and other materials in the ISO classified area or SRPA must be low-shedding and easily cleaned/disinfected. (7) Dispensing, Packaging, Labeling. (A) A radiopharmaceutical shall only be dispensed or trans ferred to a practitioner or facility authorized by the NRC or an AS to possess, use, and administer such radiopharmaceutical drug. A radiopharmaceutical shall not be dispensed directly to a patient. A Class E pharmacy may distribute radionuclide elutions to other authorized licensees to meet a radiopharma ceutical drug shortage. (B) Radiopharmaceuticals shall only be dispensed pursuant to a prescription drug order or a contingency prescription drug order from a practitioner or facility authorized by the NRC/AS to possess, use, and administer radiopharmaceuticals or the practitioner’s/facility’s designated agent. Only ANPs may receive verbal therapeutic prescription drug orders or an order for radio-labeled blood components. Except as otherwise provided herein, prescriptions must contain all information required by 20 CSR 2220-2.018 (Prescription Requirements), as applicable. The pharmacy’s prescription record shall also include— 1. The date of dispensing and the calibration time of the radiopharmaceutical; and 2. The patient’s name for therapeutic prescription drug orders and radio-labeled blood components or, if an animal, species and owner’s name. (C) In addition to USP Chapter 825 requirements, the outer shielding container of a radiopharmaceutical to be dispensed must be labeled with— 1. The name and address of the pharmacy; 2. The name and address of the authorized prescriber/ facility where the prescription drug order/contingency prescription drug order is to be administered; 3. The date of dispensing and a prescription or unique identification number; 4. The name of the procedure, if known; 5. If applicable, molybdenum-99 content to United States Pharmacopoeia (USP) limits of <0.15uCi Mo-99 per 1mCi Tc-99m at time of administration or product expiration; and 6. The patient name or, if an animal, the species and owner’s name or the words “Physician’s Use Only,” “Contingency Prescription Drug Order,” “Per Physician’s Order,” or similar wording in the absence of a patient/owner name. If no patient/ owner name is used, the pharmacy must have a policy/ procedure in place for retrieving the name of the patient/owner from the authorized prescriber/facility within three (3) days if requested. The patient/owner name must appear on the label if the prescription is for a therapeutic radiopharmaceutical or radio-labeled blood component. (D) In addition to USP Chapter 825 requirements, the immediate inner container label of a radiopharmaceutical to be dispensed shall be labeled with— 1. The unique, readily retrievable identifier of the radiopharmaceutical; and 2. If known, the patient’s name or, if an animal, the species and owner’s name or the words “Physician’s Use Only,” “Contingency Prescription Drug Order,” “Per Physician’s Order,” or similar wording in the absence of a patient/owner name. (E) Radiopharmaceuticals approved by the United States Food and Drug Administration are not subject to the inner shielding labeling requirements in subsection (D) if the Class E pharmacy does not manipulate the radiopharmaceutical in any manner nor violate the original manufacturer product packaging/labeling. (F) Beyond-use dating (BUD) must comply with USP Chapter 825, Table 7 (Preparation Conditions for Sterile Radiopharma ceuticals). The assigned BUD shall not exceed the sterility-re lated times listed in Table 7, unless a longer time is justified by USP Chapter 71 (Sterility Tests). The use of non-radioactive conventionally manufactured products in preparing, prepar ing with minor deviations, dispensing, or compounding must follow USP Chapter 797 Section 15 (Use of Conventionally Man ufactured Products as Components). (8) Reference Manuals. Each Class E pharmacy shall have a current copy of, or electronic access to— (A) Applicable reference materials commensurate with the scope of services provided; (B) A current print or electronic edition of statutes and rules governing the pharmacy’s practice, including but not limited to Chapters 338 and 195, RSMo, 20 CSR 2220 and, if applicable, 19 CSR 30 governing controlled substances; (C) NRC or AS regulations governing the safe storage, han dling, use, dispensing, transport, and disposal of radioactive material, including but not limited to Title 10 and Title 49 of the United States Code of Federal Regulations; and (D) USP Chapter 825 (Radiopharmaceuticals) and, if ap plicable, USP Chapter 795 (Pharmaceutical Compounding – Non-sterile Preparations), Chapter 797 (Pharmaceutical Com pounding – Sterile Preparations), Chapter 823 (Positron Emis sion Tomography Drugs for Compounding, Investigational, and Research Uses), Chapter 1223 (Validation of Alternative Microbi ological Methods), and Chapter 1225 (Validation of Compendial Procedures). (9) Special Conditions. (A) To comply with NRC exposure guidelines of keeping ra diation exposure as low as reasonably achievable (ALARA), the required pharmacist verification of the preparation shall be deemed satisfied if an ANP has previously verified the correct components and intended radioactivity. Additionally, an ANP must verify the accuracy of the prescription/contingency drug order information used. (B) At its discretion, the board may grant an exemption for a Class E pharmacy from regulation requirements that do not pertain to the practice of a Class E pharmacy for a time period designated by the board, if such exemption is not contrary to any other law and the exemption will provide equal or greater protection of the public safety, health, or welfare. Exemption AND INSURANCE requests must be submitted in writing and identify the specific exemption requested, the grounds for exemption, the requested exemption length, and any proposed procedures or safeguards for protecting the public safety, health, or welfare if the exemption is approved. If deemed appropriate, the board may grant an exemption to all nuclear pharmacies based on one (1) pharmacy’s request. (C) To minimize impact on patient care, Class E pharmacies licensed on the effective date of this rule may also petition the board for a waiver of USP Chapter 825 facility and equipment requirements if immediate compliance with USP Chapter 825 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. (10) Remedial Investigations. A remedial investigation is re quired if any environmental monitoring sample demonstrates a colony forming unit (CFU) count that exceeds USP Chapter 825 recommended action levels for the type of sampling. The remedial investigation must be documented and include resa mpling of all affected areas to ensure a suitable state of micro bial control. The pharmacy must ensure that no misbranded, contaminated, or adulterated compounded sterile radiophar maceutical is administered or dispensed for patient use. (A) If an environmental monitoring sample taken from a PEC exceeds USP Chapter 825 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 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 825 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 825 action levels, the pharmacy must cease compounding in the affected buffer room until resampling shows a suitable state of microbial control has been achieved in the affected 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, disinfecting, and sporicidal agent, or a combination thereof; 2. The beyond-use date assigned to all preparations is not 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 825 action levels, compounding must cease until resampling 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 compounding upon showing 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 and it exceeds USP Chapter 825 action levels. AUTHORITY: sections 338.240, 338.250, 338.280, and 338.350, RSMo 2016, and sections 338.210, 338.220, and 338.330(3), RSMo Supp. 2025.* This rule originally filed as 4 CSR 220-2.500. Original rule filed Sept. 2, 1997, effective April 30, 1998. Moved to 20 CSR 2220-2.500, effective Aug. 28, 2006. Amended: Filed April 23, 2019, effective Nov. 30, 2019. Amended: Filed Dec. 12, 2025, effective July 30, 2026. *Original authority: 338.210, RSMo 1951, amended 2001, 2011, 2020; 338.220, RSMo 1951, amended 1969, 1981, 1989, 1997, 1999, 2001, 2004, 2007, 2009, 2011, 2013, 2014, 2020; 338.240, RSMo 1951, amended 2011; 338.250, RSMo 1951, amended 1990, 1998; 338.280, RSMo 1951, amended 1971, 1981; 338.330, RSMo 1989, amended 1993, 1998, 2011, 2018; and 338.350, RSMo 1989, amended 1993, 1995.