1. (a) The purpose of this rule is to provide standards in the conduct, practices, and operations of a pharmacy preparing and dispensing products requiring sterility, such as:

   1. (1) Injectables;
   2. (2) Ophthalmics; and
   3. (3) Inhalants.

2. (b)

   1. (1) Compounding a drug product that is commercially available in the marketplace or that is essentially a copy of a commercially available Food and Drug Administration-approved drug product is generally prohibited.

   2. (2) However, in special circumstances a pharmacist may compound an appropriate quantity of a drug that is only slightly different than a Food and Drug Administration-approved drug that is commercially available:

      1. (A) Based on documentation provided by the prescribing physician of a patient-specific medical need (e.g., the physician requests an alternate product due to hypersensitivity to excipients or preservative in the Food and Drug Administration-approved product, or the physician requests an effective alternate dosage form); or
      2. (B) If the drug product is not commercially available.

   3. (3)

      1. (A) The unavailability of such drug product must be documented prior to compounding.
      2. (B) The recommended methodology for documenting unavailability is to print the screen of wholesalers showing back-ordered, discontinued, or out-of-stock items.
      3. (C) This or similar documentation must be available when requested by the Arkansas State Board of Pharmacy.
3. (c) Except for those products where stability prohibits advanced compounding, all products dispensed by the pharmacy shall be in a form ready for administration, except in healthcare facilities where medications may be provided as demanded by policies and procedures.

4. (d) Pharmacies and pharmacists dispensing sterile products shall comply with all applicable federal, state, and local regulations, laws, and rules concerning pharmacy and also these additional rules:

   1. (1)

      1. (A) Guidelines for preparation of sterile products will be based on the distinction of sterile products as either low-risk, medium-risk, or high-risk products.
      2. (B) Sterile products compounded under all of the following conditions are considered low-risk sterile products:
5. (i) The finished products are compounded with aseptic manipulations entirely within a Class 100 environment or better air quality using only sterile:
6. (a) (a) Ingredients;
7. (b) (b) Products;
8. (c) (c) Components; and

9. (d) (d) Devices;

   1. (ii) The compounding involves only transfer, measuring, and mixing manipulations with closed or sealed packaging systems that are performed promptly and attentively;

      1. (iii) Manipulations are limited to:
10. (a) (a) Aseptically opening ampules;

11. (b) (b) Penetrating sterile stoppers on vials with sterile needles and syringes; and

    1. (c) (c) Transferring sterile liquids in sterile syringes to sterile administration devices and packages of other sterile products; and

       1. (iv)
12. (a) (a) For a low-risk preparation, in the absence of passing a sterility test, the storage periods shall not exceed the following time periods.

13. (b) (b) Before administration, the sterile products are exposed for no more than forty-eight (48) hours at controlled room temperature, fourteen (14) days at two degrees to eight degrees Centigrade (2°C – 8°C), and forty-five (45) days in solid frozen state at negative twenty degrees Centigrade (-20°C) or colder, while properly stored.

    1. (C) When sterile products compounded aseptically under low-risk conditions and one (1) or more of the following conditions exists, such products are considered medium-risk sterile products:

       1. (i) Multiple individual or small doses of sterile products are combined or pooled to prepare a sterile product that will be administered either to multiple patients or to one (1) patient on multiple occasions;

          1. (ii) The compounding process includes complex aseptic manipulations other than the single-volume transfer;
          2. (iii) The compounding process requires unusually long duration, such as that required to complete dissolution or homogeneous mixing;
          3. (iv) The sterile products:
14. (a) (a) Do not contain broad-spectrum bacteriostatic substances; and

15. (b) (b) Are administered over several days; and

    1. (v)
16. (a) (a) For a medium-risk preparation, in the absence of passing a sterility test, the storage periods shall not exceed the following time periods.

17. (b) (b) Before administration, the sterile products are exposed for no more than thirty (30) hours at controlled room temperature, seven (7) days at two degrees to eight degrees Centigrade (2°C – 8°C), and forty-five (45) days in solid frozen state at negative twenty degrees Centigrade (-20°C) or colder, while properly stored.

    1. (D) Sterile products compounded under any of the following conditions are considered high-risk sterile products:

       1. (i) Nonsterile ingredients are incorporated or a nonsterile device is employed before terminal sterilization;

          1. (ii)
18. (a) (a) Sterile ingredients, components, devices, and mixtures are exposed to air quality inferior to a Class 100 environment.

19. (b) (b) This includes storage in environments inferior to a Class 100 environment of opened or partially used packages of manufactured sterile products that lack antimicrobial preservatives;

    1. (iii) Nonsterile preparations are exposed no more than six (6) hours before being sterilized;

       1. (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; or

          1. (v)
20. (a) (a) For a high-risk preparation, in the absence of passing a sterility test, the storage periods shall not exceed the following time periods.

21. (b) (b) Before administration, the sterile products are exposed for no more than twenty-four (24) hours at controlled room temperature, three (3) days at two degrees to eight degrees Centigrade (2°C – 8°C), and forty-five (45) days in solid frozen state at negative twenty degrees Centigrade (-20°C) or colder, while properly stored;

    1. (2) Pharmacist requirements. Any pharmacist-in-charge who performs or supervises the preparation or sterilization of sterile medications shall:

       1. (A)

          1. (i) Have available written policies and procedures for all steps in the compounding of sterile preparations.
          2. (ii) In addition, said policies and procedures shall address personnel education and training and evaluation, storage and handling, clothing, personal hygiene, hand washing, aseptic technique, quality assurance, expiration dating, and other procedures as needed;

       2. (B)

          1. (i) Certify that all participating pharmacists and pharmacy technicians have completed a board-approved training and testing program in sterile product preparation.
          2. (ii) Documentation of training and testing shall be available for review by February 30, 2002; and
       3. (C) Develop policies and procedures to annually test and review the techniques of participating pharmacists and pharmacy technicians to ensure adherence to aseptic procedures;

    2. (3) Pharmacy technician requirements.

       1. (A) Pharmacy technicians participating in the preparation of sterile products shall have completed a board-approved pharmacist-supervised training and testing program in sterile product preparation as described in 17 CAR § 160-906(b).
       2. (B) Documentation of training and testing shall be available;

    3. (4) Work area and equipment. Any pharmacy dispensing sterile parenteral solutions shall meet or exceed the following requirements:

       1. (A)

          1. (i) A separate controlled limited access area, also called a buffer area or buffer room, for compounding sterile solutions, which shall be of adequate space for compounding, labeling, dispensing, and sterile preparation of the medication.
          2. (ii) This area shall have controlled temperature and humidity.
          3. (iii) Cleanliness of the area is of critical importance.
          4. (iv) Drugs and other materials taken into the limited access area shall be removed from cardboard and other particle-generating materials before being taken into the area;

       2. (B)

          1. (i) The controlled limited access area shall have a certified and inspected Class 100 environment.
          2. (ii) Such an environment exists inside a certified laminar airflow hood (clean room, biological safety cabinet, or other barrier isolator meeting Class 100 requirements) used for the preparation of all sterile products.
          3. (iii) The Class 100 environment device or area is to be inspected and certified yearly.
          4. (iv) Barrier isolator workstations are closed systems and are not as sensitive to their external environment as laminar airflow equipment.
          5. (v) It is recommended to place them in a limited access area with cleaning and sanitizing in the surrounding area on a routine basis;

       3. (C)

          1. (i) Hazardous drugs shall be prepared within a certified Class 11, Type A (exhaust may be discharged to the outdoors) or Class 11, Type B (exhaust may be discharged to the outdoors) laminar flow biological safety cabinet.
          2. (ii) The Class 11, Type B can be obtained with a “bag-in-bag-out” filter to protect the personnel servicing the cabinet and facilitate disposal.
          3. (iii) When preparing cytotoxic agents, gowns and gloves shall be worn.
          4. (iv) All new construction, and those undergoing renovation requiring the moving of existing hoods used in the preparation of cytotoxic drugs, shall exhaust the hood to the outdoors unless the board grants an exception.
          5. (v) The cabinet of choice is a Class 11, Type B.
          6. (vi) For the purpose of this rule, hazardous drugs shall be defined as agents that exhibit characteristics of genotoxicity, carcinogenicity, teratogenicity, or evidence of serious organ or other toxicity at low doses;
       4. (D) The area shall be designed to avoid excessive traffic and airflow disturbances;
       5. (E) The area shall be ventilated in a manner not interfering with laminar flow hood conditions; and
       6. (F) Daily procedures must be established for cleaning the compounding area;

    4. (5) Storage. All pharmacies preparing and dispensing sterile products must provide:

       1. (A) Adequate controlled room temperature storage space for all raw materials;

       2. (B)

          1. (i) Adequate storage space for all equipment.
          2. (ii) All drugs and supplies shall be stocked on shelving above the floor;

       3. (C)

          1. (i) Adequate refrigerator storage space for compounded solutions, with routinely documented temperatures.
          2. (ii) Temperature ranges required are thirty-six degrees to forty-six degrees Fahrenheit (36°F – 46°F) or two to eight degrees Centigrade (2°C – 8°C); and

       4. (D)

          1. (i) Adequate freezer storage space if finished products are to be frozen, e.g., reconstituted antibiotics.
          2. (ii) There shall be a procedure to routinely document temperatures;

    5. (6) Labeling. In addition to regular labeling requirements, the label shall include:

       1. (A) Parenteral products shall have the rate of infusion when applicable;

       2. (B)

          1. (i) Expiration date.
          2. (ii) Policies and procedures shall address label change procedures as required by physician orders;
       3. (C) Storage requirements or special conditions;
       4. (D) Name of ingredients and amounts contained in each dispensing unit; and
       5. (E) All products dispensed to outpatients and removed from the site of preparation for administration different than the site of preparation shall have label information as required by state law;

    6. (7) Shipping.

       1. (A) Policies and procedures shall ensure product stability during delivery.
       2. (B) Pharmacy must ensure ability to deliver products within an appropriate time frame;

    7. (8) Home patient care services. The pharmacist-in-charge of the pharmacy dispensing sterile parenteral solutions shall provide the following or ensure that they are provided prior to providing medications:

       1. (A) The pharmacist must ensure that the patient is properly trained if self-administering;

       2. (B) In situations where a pharmacy or pharmacist employs a nurse to administer medications, the pharmacist-in-charge must:

          1. (i) Employ a registered nurse;
          2. (ii) Ensure that proper records are maintained in compliance with laws, rules, and regulations; and
          3. (iii) Make these records available to inspectors from appropriate agencies;
       3. (C) Twenty-four-hour service shall be ensured by the pharmacy;
       4. (D) Pharmacists shall recommend and monitor clinical laboratory data as requested;
       5. (E) Side effects and potential drug interactions should be documented and reported to the physician; and
       6. (F) Patient histories and therapy plans should be maintained;

    8. (9) Destruction of cytotoxic drugs.

       1. (A) Any pharmacy providing cytotoxic drugs shall establish procedures ensuring the return and proper destruction of any unused radioactive or cytotoxic drugs or other hazardous material (destruction containers for needles).
       2. (B) In every instance, the pharmacist-in-charge shall monitor the delivery, storage, and administration records of medications dispensed from his or her pharmacy; and

    9. (10) When preparing high-risk sterile products, the pharmacist-in-charge is responsible for making sure the above procedures, in addition to the following, shall be met:

       1. (A) Compound all medications in one (1) of the following environments:

          1. (i) A separate controlled limited access area with a positive air flow room inspected and certified as meeting Class 10,000 requirements (Class 10,000 as defined by Federal Standard 209E);
          2. (ii) An enclosed room providing a Class 100 environment for compounding; or
          3. (iii)
22. (a) (a) A barrier isolator that provides a Class 100 environment for compounding.

23. (b) (b) It is recommended that all pharmacies have an anteroom designed to be separate from the buffer room.

    1. (c) (c) The anteroom should be available for the:
    2. (1) (1) Decontamination of supplies and equipment; and

    3. (2) (2) Donning of protective apparel.

       1. (d) (d) A sink should be available in the anteroom area so that personnel can scrub prior to entering the buffer room;

       2. (B)

          1. (i) Use total aseptic techniques, including gowning, mask, and hair net.
          2. (ii) Scrubs may be worn, instead of gowning, if not worn or covered outside of the controlled limited access area;

       3. (C) Provide a system for tracking each compounded product including:

          1. (i) Personnel involved in each stage of compounding;
          2. (ii) Raw materials used, including:
24. (a) (a) Quantities;

25. (b) (b) Manufacturer;

    1. (c) (c) Lot number; and

       1. (d) (d) Expiration date;

          1. (iii) Labeling; and
          2. (iv) Compounding records shall be kept for two (2) years;
       2. (D) Establishment of procedures for sterilization of all products prepared with any nonsterile ingredients by filtration with twenty-two hundredths (0.22) micron or other means appropriate for the product components;

       3. (E)

          1. (i) All high-risk-level compounded sterile products for administration by injection into the vascular and central nervous systems that are prepared in groups of more than twenty-five (25) identical individual single-dose packages, such as ampules, bags, syringes, and vials, in multiple-dose vials for administration to multiple patients, or are exposed longer than twelve (12) hours at two degrees to eight degrees Centigrade (2°C – 8°C) and longer than six (6) hours at warmer than eight degrees Centigrade (8°C) before they are sterilized shall be tested to ensure they are sterile, do not contain excessive bacterial endotoxins, and are of labeled potency before they are dispensed or administered as provided below.
          2. (ii) Sterility testing — Bacterial and fungal.
26. (a) (a) The United States Pharmacopeia (USP) Membrane Filtration method is the method of choice where feasible, e.g., components are compatible with the membrane.

27. (b) (b) The USP Direct Transfer method is preferred when the Membrane Filtration method is not feasible.

    1. (c) (c) An alternative method may be used if verification results demonstrate that the alternative is at least as effective and reliable as the:
    2. (1) (1) USP Membrane Filtration method; or

    3. (2) (2) USP Direct Transfer method.

       1. (d) (d) The pharmacist-in-charge shall establish written procedures requiring daily observation of the media and requiring an immediate recall if there is any evidence of microbial growth, and said procedures must be available to board inspectors.

          1. (iii) Bacterial Endotoxin (Pyrogen) testing. The USP Bacterial Endotoxin Test or verified equivalent shall be used to ensure compounded sterile products do not contain excessive endotoxins.
          2. (iv) Potency testing.
28. (a) (a) The potency of all compounded products meeting the criteria described in 17 CAR § 160-2201(d)(10)(E) above must be tested to verify the potency stated on the label.

29. (b) (b) Products for which there is no known or commercially available potency test standard require board approval prior to compounding.

    1. (v)
30. (a) (a) The USP Membrane Filtration method and the USP Direct Transfer method are the Membrane Filtration and Direct Transfer methods described in Chapter 71, United States Pharmacopeia (USP), 2001 Edition.

31. (b) (b) The USP Bacterial Endotoxin Test is the bacterial filtration test described in Chapter 85, USP, 2001 Edition.

    1. (c) (c) Should there be any amendment or change in any of the above methods or test by USP subsequent to the effective date of this paragraph, said change or amendment to USP shall be effective under this rule after the expiration of thirty (30) days from the effective date of said change or amendment, unless within said time period the Executive Director of the Arkansas State Board of Pharmacy objects to said change or amendment.

       1. (d)
    2. (1) (d)(1) In that case, the executive director shall publish the reasons for objection and afford all interested parties an opportunity to present commentary.

    3. (2) (2) Said notice and commentary shall be pursuant to Arkansas Code § 25-15-204, as amended, and the resulting decision by the board shall be reflected by an amendment to this rule;

       1. (F) Establishment of procedures for yearly testing the techniques of pharmacists using simulated aseptic procedures and documentation thereof; and
       2. (G) Any construction requirements as required by this rule, i.e., separate controlled limited access area and certification of Class 10,000, must be complied with by January 2004.

Codification Notes: This section as promulgated prior to codification into the Code of Arkansas Rules provided as follows: “Adopted: 6/85 (Amended 8/2001, 2/2003 & emergency 6/2003, 10/26/2003, and 5/10/2022)."