1. (a) Licensing requirements.

   1. (1) It is unlawful for a person to provide radioactive drug services unless such provision is performed by a person licensed to act as an authorized nuclear pharmacist, as defined by the board, or is a person acting under the direct supervision of an authorized nuclear pharmacist acting in accordance with the Act and its rules, and the regulations of the Texas Department of State Health Services, Radiation Control Program. Subsection (a) of this section does not apply to:

      1. (A) a licensed practitioner or his or her designated agent for administration to his or her patient, provided no person may receive, possess, use, transfer, own, acquire, or dispose of radiopharmaceuticals except as authorized in a specific or a general license as provided in accordance with the requirements of the Texas Department of State Health Services, Radiation Control Program, Texas Administrative Code, Title 25, Part 1, Subchapter F, §289.252 relating to Licensing of Radioactive Material, or the Act;
      2. (B) institutions and/or facilities with nuclear medicine services operated by practitioners and who are licensed by the Texas Department of State Health Services, Radiation Control Program, to prescribe, administer, and dispense radioactive materials (drugs and/or devices).
   2. (2) An applicant for a Class B pharmacy shall provide evidence to the board of the possession of a Texas Department of State Health Services radioactive material license or proof of application for a radioactive material license.
   3. (3) A Class B pharmacy shall register with the board on a pharmacy license application provided by the board, following the procedures specified in §291.1 of this title (relating to Pharmacy License Application).
   4. (4) A Class B pharmacy which changes ownership shall notify the board within ten days of the change of ownership and apply for a new and separate license as specified in §291.3 of this title (relating to Required Notifications).
   5. (5) A Class B pharmacy which changes location and/or name shall notify the board within ten days of the change and file for an amended license as specified in §291.3 of this title.
   6. (6) A Class B pharmacy owned by a partnership or corporation which changes managing officers shall notify the board in writing of the names of the new managing officers within ten days of the change, following the procedures in §291.3 of this title.
   7. (7) A Class B pharmacy shall notify the board in writing within ten days of closing, following the procedures in §291.5 of this title (relating to Closing a Pharmacy).
   8. (8) A separate license is required for each principal place of business and only one pharmacy license may be issued to a specific location.
   9. (9) A fee as specified in §291.6 of this title (relating to Pharmacy License Fees) will be charged for the issuance and renewal of a license and the issuance of an amended license.
   10. (10) A Class B pharmacy, licensed under the provisions of the Act, §560.051(a)(2), which also operates another type of pharmacy which would otherwise be required to be licensed under the Act, §560.051(a)(1), concerning community pharmacy (Class A), is not required to secure a license for such other type of pharmacy; provided, however, such licensee is required to comply with the provisions of §291.31 of this title (relating to Definitions); §291.32 of this title (relating to Personnel); §291.33 of this title (relating to Operational Standards); §291.34 of this title (relating to Records); and §291.35 of this title (relating to Official Prescription Requirements), to the extent such rules are applicable to the operation of the pharmacy.
   11. (11) A Class B (nuclear) pharmacy engaged in the compounding of non-sterile non-radioactive preparations shall comply with the provisions of §291.131 of this title (relating to Pharmacies Compounding Non-Sterile Preparations).
   12. (12) A Class B (nuclear) pharmacy engaged in the compounding of sterile non-radioactive preparations shall comply with the provisions of §291.133 of this title (relating to Pharmacies Compounding Sterile Preparations).

2. (b) Risk levels for compounded sterile radiopharmaceuticals. Risk Levels for sterile compounded radiopharmaceuticals shall be as listed below.

   1. (1) Low-risk level compounded sterile radiopharmaceuticals.

      1. (A) Low-risk level compounded sterile radiopharmaceuticals are those compounded under all of the following conditions.

         1. (i) The compounded sterile preparations are compounded with aseptic manipulations entirely within ISO Class 5 or better air quality using only sterile ingredients, products, components, and devices.
         2. (ii) The compounding involves only transfer, measuring, and mixing manipulations with closed or sealed packaging systems that are performed promptly and attentively.
         3. (iii) Manipulations are limited to aseptically opening ampuls, penetrating sterile stoppers on vials with sterile needles and syringes, and transferring sterile liquids in sterile syringes to sterile administration devices and packages of other sterile products.
         4. (iv) For a low-risk preparation, in the absence of passing a sterility test, the storage periods cannot exceed the following periods: before administration, 48 hours at controlled room temperature, for not more than 14 days if stored in cold temperatures, and for 45 days if stored in a frozen state at minus 20 degrees Celsius or colder). For delayed activation device systems, the storage period begins when the device is activated.
      2. (B) Examples of low-risk compounding include radiopharmaceuticals compounded from sterile components in closed sterile containers and with a volume of 100 mL or less for a single-dose injection or not more than 30 mL taken from a multidose container.

   2. (2) Medium-risk level compounded sterile radiopharmaceuticals.

      1. (A) Medium-risk level compounded sterile radiopharmaceuticals are those compounded aseptically under low-risk conditions and one or more of the of the following conditions exists.

         1. (i) Multiple individual or small doses of sterile products are combined or pooled to prepare a compounded sterile radiopharmaceuticals that will be administered either to multiple patients or to one patient on multiple occasions.
         2. (ii) The compounding process includes complex aseptic manipulations other than the single-volume transfer.
         3. (iii) The compounding process requires unusually long duration, such as that required to complete the dissolution or homogenous mixing.
         4. (iv) The sterile compounded radiopharmaceuticals do not contain broad-spectrum bacteriostatic substances, and they are administered over several days.
         5. (v) For a medium-risk preparation, in the absence of passing sterility test, the storage periods cannot exceed the following time periods: before administration, the compounded sterile preparations are properly stored and are exposed for not more than 30 hours at controlled room temperature for not more than 7 days at a cold temperature, and for 45 days in solid frozen state at minus 20 degrees or colder.

      2. (B) Examples of medium-risk compounding include the following.

         1. (i) Compounding of total parenteral nutrition fluids using a manual or automated device during which there are multiple injections, detachments, and attachments of nutrient source products to the device or machine to deliver all nutritional components to a final sterile container.
         2. (ii) Filling of reservoirs of injection and infusion devices with multiple sterile drug products and evacuations of air from those reservoirs before the filled device is dispensed.
         3. (iii) Filling of reservoirs of injection and infusion devices with volumes of sterile drug solutions that will be administered over several days at ambient temperatures between 25 and 40 degrees Celsius (77 and 104 degrees Fahrenheit).
         4. (iv) Transfer of volumes from multiple ampuls or vials into a single, final sterile container or product.

   3. (3) High-risk level compounded sterile radiopharmaceuticals.

      1. (A) High-risk level compounded sterile radiopharmaceuticals are those compounded under any of the following conditions.

         1. (i) Non-sterile ingredients, including manufactured products are incorporated, or a non-sterile device is employed before terminal sterilization.
         2. (ii) Sterile ingredients, components, devices, and mixtures are exposed to air quality inferior to ISO Class 5. This includes storage in environments inferior to ISO Class 5 of opened or partially used packages of manufactured sterile products that lack antimicrobial preservatives.
         3. (iii) Non-sterile preparations are exposed no more than 6 hours before being sterilized.
         4. (iv) It is assumed, and not verified by examination of labeling and documentation from suppliers or by direct determination, that the chemical purity and content strength of ingredients meet their original or compendial specifications in unopened or in opened packages of bulk ingredients.
         5. (v) For a high-risk preparation, in the absence of passing sterility test, the storage periods cannot exceed the following time periods: before administration, the compounded sterile preparations are properly stored and are exposed for not more than 24 hours at controlled room temperature for not more than 3 days at a cold temperature, and for 45 days in solid frozen state at minus 20 degrees or colder.

      2. (B) Examples of high-risk compounding include the following.

         1. (i) Dissolving non-sterile bulk drug and nutrient powders to make solutions, which will be terminally sterilized.
         2. (ii) Sterile ingredients, components, devices, and mixtures are exposed to air quality inferior to ISO Class 5. This includes storage in environments inferior to ISO Class 5 of opened or partially used packages of manufactured sterile products that lack antimicrobial preservatives.
         3. (iii) Measuring and mixing sterile ingredients in non-sterile devices before sterilization is performed.
         4. (iv) Assuming, without appropriate evidence or direct determination, that packages of bulk ingredients contain at least 95% by weight of their active chemical moiety and have not been contaminated or adulterated between uses.

3. (c) Environment.

   1. (1) Special requirements for the compounding of sterile radiopharmaceuticals. When the pharmacy compounds sterile radiopharmaceuticals, the following is applicable.

      1. (A) Low and Medium Risk Preparations.

         1. (i) The pharmacy shall have a designated controlled area for the compounding of sterile radiopharmaceuticals that is functionally separate from areas for the preparation of non-sterile radiopharmaceuticals and is constructed to minimize the opportunities for particulate and microbial contamination. This controlled area for the preparation of sterile radiopharmaceuticals shall:

            1. (I) have a controlled environment that is aseptic or contains an aseptic environmental control device(s). If the aseptic environmental control device is located within the controlled area, the controlled area must extend a minimum of six feet from the device and clearly marked to identify the separation between the controlled and non-controlled area;
            2. (II) be clean, well lighted, and of sufficient size to support sterile compounding activities;
            3. (III) be used only for the compounding of sterile radiopharmaceuticals;
            4. (IV) be designed to avoid outside traffic and airflow;
            5. (V) be designed such that hand sanitizing and gowning occurs outside the controlled area but accessible without use of the hands of the compounding personnel;
            6. (VI) have non-porous and washable floors or floor covering to enable regular disinfection;
            7. (VII) be ventilated in a manner not interfering with aseptic environmental control conditions;
            8. (VIII) have walls, ceilings, and fixtures, shelving, counters, and cabinets that are smooth, impervious, free from cracks and crevices, and nonshedding (acoustical ceiling tiles that are coated with an acrylic paint are acceptable);
            9. (IX) have drugs and supplies stored on shelving areas above the floor to permit adequate floor cleaning; and
            10. (X) contain only the appropriate compounding supplies and not be used for bulk storage for supplies and materials. Objects that shed particles may not be brought into the controlled area.

         2. (ii) The pharmacy shall prepare sterile radiopharmaceuticals in a primary engineering control device, such as a vertical air flow hood, which is capable of maintaining at least ISO Class 5 conditions during normal activity.

            1. (I) The primary engineering control shall:

               (-a-) be located in the buffer area or room and placed in the buffer area in a manner as to avoid conditions that could adversely affect its operation such as strong air currents from opened doors, personnel traffic, or air streams from the heating, ventilating and air condition system;

               (-b-) be certified by an independent contractor according to the International Organization of Standardization (ISO) Classification of Particulate Matter in Room Air (ISO 14644-1) for operational efficiency at least every six months and when it is relocated, in accordance with the manufacturer's specifications; and

               (-c-) have pre-filters inspected periodically and replaced as needed, in accordance with written policies and procedures and the manufacturer's specification, and the inspection and/or replacement date documented.

            2. (II) The compounding aseptic isolator or compounding aseptic containment isolator must be placed in an ISO Class 8 buffer area unless the isolator meets all of the following conditions.

               (-a-) The isolator must provide isolation from the room and maintain ISO Class 5 during dynamic operating conditions including transferring ingredients, components, and devices into and out of the isolator and during preparation of compounded sterile preparations.

               (-b-) Particle counts sampled approximately 6 to 12 inches upstream of the critical exposure site must maintain ISO Class 5 levels during compounding operations.

               (-c-) The pharmacy shall maintain documentation from the manufacturer that the isolator meets this standard when located in worse than ISO Class 7 environments.

      2. (B) High-risk Preparations. In addition to the requirements in subparagraph (A)(i)(I) of this paragraph, when high-risk preparations are compounded, the aseptic environment control device(s) shall be located in a controlled area that maintains at least an ISO Class 7 environment.
      3. (C) Automated compounding device(s). If automated compounding device(s) are used, the pharmacy shall have a method to calibrate and verify the accuracy of automated compounding devices used in aseptic processing and document the calibration and verification on a routine basis.

   2. (2) Security requirements.

      1. (A) All areas occupied by a pharmacy shall be capable of being locked by key, combination or other mechanical or electronic means to prohibit unauthorized access, when a pharmacist is not on-site except as provided in subparagraph (B) of this paragraph.
      2. (B) The pharmacy may authorize personnel to gain access to that area of the pharmacy containing dispensed sterile radiopharmaceuticals, in the absence of the pharmacist, for the purpose of retrieving dispensed prescriptions to deliver to patients. If the pharmacy allows such after-hours access, the area containing the dispensed sterile radiopharmaceuticals shall be an enclosed and lockable area separate from the area containing undispensed prescription drugs. A list of the authorized personnel having such access shall be in the pharmacy's policy and procedure manual.
      3. (C) Each pharmacist while on duty shall be responsible for the security of the prescription department, including provisions for effective control against theft or diversion of prescription drugs, and records for such drugs

4. (d) Prescription dispensing and delivery.

   1. (1) Generic Substitution. A pharmacist may substitute on a prescription drug order issued for a brand name product provided the substitution is authorized and performed in compliance with Chapter 309 of this title (relating to Substitution of Drug Products).

   2. (2) Prescription containers (immediate inner containers).

      1. (A) A drug dispensed pursuant to a radioactive prescription drug order shall be dispensed in an appropriate immediate inner container as follows.

         1. (i) If a drug is susceptible to light, the drug shall be dispensed in a light-resistant container.
         2. (ii) If a drug is susceptible to moisture, the drug shall be dispensed in a tight container.
         3. (iii) The container should not interact physically or chemically with the drug product placed in it so as to alter the strength, quality, or purity of the drug beyond the official requirements.
      2. (B) Immediate inner prescription containers or closures shall not be re-used.

   3. (3) Delivery containers (outer containers).

      1. (A) Prescription containers may be placed in suitable containers for delivery which will transport the radiopharmaceutical safely in compliance with all applicable laws and regulations.
      2. (B) Delivery containers may be re-used provided they are maintained in a manner to prevent cross contamination.

   4. (4) Labeling.

      1. (A) The immediate inner container of a radiopharmaceutical shall be labeled with:

         1. (i) standard radiation symbol;
         2. (ii) the words "caution-radioactive material" or "danger, radioactive material";
         3. (iii) the name of the radiopharmaceutical or its abbreviation; and
         4. (iv) the unique identification number of the prescription.

      2. (B) The outer container of a radiopharmaceutical shall be labeled with:

         1. (i) the name, address, and phone number of the pharmacy;
         2. (ii) the date dispensed;
         3. (iii) the directions for use, if applicable;
         4. (iv) the unique identification number of the prescription;
         5. (v) the name of the patient if known, or the statement, "for physician use" if the patient is unknown;
         6. (vi) the standard radiation symbol;
         7. (vii) the words "caution-radioactive material" or "danger, radioactive material";
         8. (viii) the name of the radiopharmaceutical or its abbreviation;
         9. (ix) the amount of radioactive material contained in millicuries (mCi), microcuries (uCi), or bequerels (Bq) and the corresponding time that applies to this activity, if different from the requested calibration date and time;
         10. (x) the initials or identification codes of the person preparing the product and the authorized nuclear pharmacist who checked and released the final product unless recorded in the pharmacy's data processing system. The record of the identity of these individuals shall not be altered in the pharmacy's data processing system.
         11. (xi) if a liquid, the volume in milliliters;
         12. (xii) the requested calibration date and time; and
         13. (xiii) the expiration date and/or time.
      3. (C) The amount of radioactivity shall be determined by radiometric methods for each individual preparation immediately at the time of dispensing and calculations shall be made to determine the amount of activity that will be present at the requested calibration date and time, due to radioactive decay in the intervening period, and this activity and time shall be placed on the label per requirements set out in paragraph (4) of this subsection.

5. (e) Equipment. The following minimum equipment is required in a nuclear pharmacy:

   1. (1) vertical laminar flow hood;
   2. (2) dose calibrator;
   3. (3) a calibrated system or device (i.e., thermometer) to monitor the temperature to ensure that proper storage requirements are met, if sterile preparations are stored in the refrigerator;
   4. (4) if applicable, a Class A prescription balance, or analytical balance and weights. Such balance shall be properly maintained and subject to periodic inspection by the board.
   5. (5) scintillation analyzer;
   6. (6) microscope and hemocytometer;

   7. (7) equipment and utensils necessary for the proper compounding of prescription drug or medication orders. Such equipment and utensils used in the compounding process shall be:

      1. (A) of appropriate design, appropriate capacity, and be operated within designed operational limits;
      2. (B) of suitable composition so that surfaces that contact components, in-process material, or drug products shall not be reactive, additive, or absorptive so as to alter the safety, identity, strength, quality, or purity of the drug product beyond acceptable standards;
      3. (C) cleaned and sanitized immediately prior to each use; and
      4. (D) routinely inspected, calibrated (if necessary), or checked to ensure proper performance;
   8. (8) appropriate disposal containers for used needles, syringes, etc., and if applicable, cytotoxic waste from the preparation of chemotherapeutic agents, and/or biohazardous waste;

   9. (9) all necessary supplies, including:

      1. (A) disposable needles, syringes, and other aseptic mixing;
      2. (B) disinfectant cleaning solutions;
      3. (C) hand washing agents with bactericidal action;
      4. (D) disposable, lint free towels or wipes;
      5. (E) appropriate filters and filtration equipment;
      6. (F) cytotoxic spill kits, if applicable; and
      7. (G) masks, caps, coveralls or gowns with tight cuffs, shoe covers, and gloves, as applicable.
   10. (10) adequate glassware, utensils, gloves, syringe shields and remote handling devices, and adequate equipment for product quality control;
   11. (11) adequate shielding material;
   12. (12) data processing system including a printer or comparable equipment;
   13. (13) radiation dosimeters for visitors and personnel and log entry book;
   14. (14) exhaust/fume hood with monitor, for storage and handling of all volatile radioactive drugs if applicable, to be determined by the Texas Department of State Health Services, Radiation Control Program; and
   15. (15) adequate radiation monitor(s).

6. (f) Library. A nuclear pharmacy shall maintain a reference library which shall include the following in hard copy or electronic format:

   1. (1) current copies of the following:

      1. (A) Texas Pharmacy Act and rules;
      2. (B) Texas Dangerous Drug Act and rules;
      3. (C) Texas Controlled Substances Act and rules; and
      4. (D) Federal Controlled Substances Act and rules (or official publication describing the requirements of the Federal Controlled Substances Act and rules);
   2. (2) a current or updated version of Chapter 797 of the USP/NF concerning Pharmacy Compounding Sterile Preparations and other USP chapters applicable to the practice (e.g., USP Chapter 823 Radiopharmaceuticals for Positron Emission Tomography - Compounding); and
   3. (3) a minimum of one current or updated text dealing with nuclear medicine science.

7. (g) Radiopharmaceuticals and/or radioactive materials.

   1. (1) General requirements.

      1. (A) Radiopharmaceuticals may only be dispensed pursuant to a radioactive prescription drug order.
      2. (B) An authorized nuclear pharmacist may distribute radiopharmaceuticals to authorized users for patient use. A nuclear pharmacy may also furnish radiopharmaceuticals for departmental or physicians' use if such authorized users maintain a Texas radioactive materials license, and the radiopharmaceutical is labeled "for physician use," provided such distribution is documented in the control system.
      3. (C) An authorized nuclear pharmacist may transfer to authorized users radioactive materials not intended for drug use in accordance with the requirements of the Texas Department of State Health Services, Radiation Control Program, Texas Administrative Code, Title 25, Part 1, Subchapter F, §289.252 relating to Licensing of Radioactive Material,.
      4. (D) The transportation of radioactive materials from the nuclear pharmacy must be in accordance with current state and federal transportation regulations.

   2. (2) Procurement and storage.

      1. (A) The pharmacist-in-charge shall have the responsibility for the procurement and storage of drugs, but may receive input from other appropriate staff relative to such responsibility.
      2. (B) Prescription drugs and devices shall be stored within the prescription department or a locked storage area.
      3. (C) All drugs shall be stored at the proper temperature, as defined in the USP/NF and §291.15 of this title (relating to Storage of Drugs).

   3. (3) Out-of-date and other unusable drugs or devices.

      1. (A) Any drug or device bearing an expiration date shall not be dispensed beyond the expiration date of the drug or device.
      2. (B) Outdated and other unusable drugs or devices shall be removed from dispensing stock and shall be quarantined together until such drugs or devices are disposed of properly.

8. (h) Loading bulk drugs into automated compounding devices.

   1. (1) Automated compounding device may be loaded with bulk drugs only by an authorized nuclear pharmacist or by supportive personnel under the direction and direct supervision of an authorized pharmacist.
   2. (2) The label of an automated compounding device container shall indicate the brand name and strength of the drug; or if no brand name, then the generic name, strength, and name of the manufacturer or distributor.

   3. (3) Records of loading bulk drugs into an automated compounding device shall be maintained to show:

      1. (A) name of the drug, strength, and dosage form;
      2. (B) manufacturer or distributor;
      3. (C) manufacturer's lot number;
      4. (D) expiration date;
      5. (E) quantity added to the automated compounding device;
      6. (F) date of loading;
      7. (G) name, initials, or electronic signature of the person loading the automated compounding device; and
      8. (H) name, initials, or electronic signature of the responsible authorized nuclear pharmacist.
   4. (4) The automated compounding device shall not be used until an authorized nuclear pharmacist verifies that the system is properly loaded and affixes his or her signature or electronic signature to the record specified in paragraph (3) of this subsection.

9. (i) Sterile radiopharmaceuticals.

   1. (1) Beyond-use date.

      1. (A) The beyond-use date assigned shall be based on:

         1. (i) established manufacturer's guidelines;
         2. (ii) published literature; or
         3. (iii) in-house or contracted stability studies.
      2. (B) The method for establishing beyond-use dates shall be documented.

   2. (2) Radioactive Drug Quality control. There shall be a documented, ongoing quality control program that monitors and evaluates personnel performance, equipment and facilities. Procedures shall be in place to assure that the pharmacy is capable of consistently preparing radiopharmaceuticals which are sterile and stable. Quality control procedures shall include, but are not limited to, the following:

      1. (A) recall procedures;
      2. (B) storage and dating;
      3. (C) documentation of appropriate functioning of refrigerator, freezer, and other equipment;
      4. (D) documentation of aseptic environmental control device(s) certification at least every year and the regular replacement of pre-filters as necessary;
      5. (E) a process to evaluate and confirm the quality of the prepared radiopharmaceutical; and
      6. (F) documentation of facility maintenance such as cleaning and environmental testing.

Source Note:The provisions of this §291.54 adopted to be effective March 19, 1998, 23 TexReg 2815; amended to be effective June 1, 2002, 27 TexReg 1781; amended to be effective June 23, 2003, 28 TexReg 4638; amended to be effective June 6, 2004, 29 TexReg 5362; amended to be effective September 14, 2010, 35 TexReg 8357.