216 R.I. Code R. 216-RICR-40-15-1.7

Current through December 26, 2024

Section 216-RICR-40-15-1.7 - Compounding of Pharmaceuticals

A. General Requirements: Non-sterile and Sterile Compounding

1. A pharmacist/patient/prescriber relationship shall exist in order for a pharmacist to prepare compounds that are not commercially available, except as applied to Outsourcing Facilities.

2. Pharmacists, interns, or Technician IIs engaged in compounding shall operate in conformity with all applicable State and Federal laws and Regulations regulating the practice of pharmacy.

3. The requirements in § 1.7 of this Part shall not apply to the preparation of medications by licensed healthcare professionals in emergency situations for immediate administration to patients.

4. A practitioner's prescription shall be required for the compounding of all pharmaceuticals except as applied to Outsourcing Facilities.

5. Retail pharmacies shall only prepare compounded preparations in limited quantities (i.e., stock preparation, batch processing) prior to receiving a valid prescription based on a history of receiving valid prescriptions that have been generated solely within an established pharmacist/patient/practitioner relationship, provided that the prescriptions are maintained on file for all such products prepared at the pharmacy.

a. Hospital and institutional pharmacies shall only prepare compounded preparations in limited quantities (i.e., batch compounding) in anticipation of receiving a valid practitioner order/prescription or as part of an established hospital or institutionally approved protocol/procedure. Such anticipated compounding shall be based upon a history of receiving valid practitioner orders/prescriptions/protocol/procedure that have been generated solely within an established pharmacist/patient/practitioner relationship provided that the practitioner order/prescription/protocol/procedure is maintained on file in the pharmacy or in the patient's medical record for all such products prepared at the pharmacy.

6. All compounded products shall be labeled with the following information:

a. Complete list of active ingredients (components) (Abbreviations may be included);

b. The assigned beyond-use date.

7. All compounded products shall be stored under conditions dictated by composition and stability characteristics (e.g., in a clean, dry place, on a shelf, or in the refrigerator) to ensure strength, quality, and purity.

8. Pharmacists shall not offer pharmaceutically prepared compounded preparations to other State-licensed persons or commercial entities for subsequent resale, except as applied to Outsourcing Facilities.

9. Compounding personnel shall be responsible for ensuring that compounded preparations are accurately identified, measured, diluted, and mixed; are correctly packaged, sealed, labeled, stored, dispensed, and distributed. Ingredients shall be of the correct identity, quality, and purity. Appropriate cleanliness shall be maintained. Proper labeling and supplementary instructions for the clinical administration of CSPs shall be provided by a pharmacist. Beyond-use dates shall be determined based upon current USP standards and documented testing or literature and professional judgment.

10. Bulk and active ingredients used in the preparation of compounded sterile products (CSPs), and non-sterile compounded products shall be USP or National Formulary (NF) certified or shall be accompanied by a certificate of analysis for inspection by the Department upon request.

B. General Requirements-All Risk Levels: Sterile Compounding. The pharmacist in-charge shall ensure the following activities are accomplished for all sterile compounding as outlined in current USP standards:

1. All CSPs shall be prepared in a manner that maintains sterility and minimizes the introduction of particulate matter;

a. All CSPs shall be accurately identified, measured, diluted, and mixed; and are correctly purified, sterilized, packaged, sealed, labeled, stored, dispensed, and distributed as appropriate. This requirement includes maintaining appropriate cleanliness and providing labeling and supplementary instructions for the proper clinical administration of CSPs;

b. Through appropriate information sources, specific CSPs maintain their labeled strength according to USP guidelines until their beyond-use dates;

c. A written quality assurance procedure includes the following in process checks that are applied, as is appropriate, to specific CSPs: accuracy and precision of measuring and weighing; the requirement for sterility; methods of sterilization and purification; safe limits and ranges for strength of ingredients; bacterial endotoxins, particulate matter, and pH; labeling and storage requirements;

d. Upon discovery of potential contamination, the pharmacist-in- charge shall immediately notify any patient(s) to whom a potentially contaminated CSP was administered. In an institutional setting, the pharmacist-in-charge shall immediately notify the patient's physician of the potential risk. Positive sterility test results shall prompt a rapid and systematic investigation of aseptic techniques, environmental controls, and other sterility assurance controls to identify sources of contamination and correct problems in the methods or processes.

2. Low Risk CSPs shall have quality assurance practices that shall include, at a minimum: routine disinfections and air quality testing of the direct compounding environment; visual confirmation that personnel are properly garbed; orders reviewed to ensure the correct identity and amount of the ingredients used; and a visual inspection of the CSP to ensure proper labeling, accuracy and the absence of particulate matter and leakage. In addition, personnel shall be required to complete a media-fill, or equivalent test, on an annual basis. In the absence of sterility testing, storage periods (before administration) shall not exceed current USP requirements.

3. Medium Risk CSPs shall have quality assurance practices that include all of the low-risk CSP conditions. Personnel who are authorized to compound medium-risk CSPs shall also perform a more challenging media-fill test that represents medium-risk level compounding on an annual basis. In the absence of sterility testing, storage periods (before administration) shall not exceed current USP requirements.

4. High-Risk CSPs shall have quality assurance practices that include all of the low-risk CSP conditions. Personnel who are authorized to compound high-risk CSPs shall also perform a media-fill test that represents high-risk level compounding on a semi-annual basis. In the absence of sterility testing, storage periods (before administration) shall not exceed current USP requirements.

C. Responsibilities of Compounding Personnel: Sterile Compounding

1. The pharmacist-in-charge shall be responsible for the overall operation of the compounding pharmacy.

a. The compounding pharmacist shall be responsible for assigning the appropriate risk level (low, medium, or high) to each individual product.

2. CSPs shall be prepared in a manner that maintains sterility and minimizes the introduction of particulate matter.

3. Pharmacies that compound CSPs shall implement a formal quality assurance program for monitoring, evaluating, correcting, and improving the activities, systems and processes that support the preparation of CSPs.

4. The pharmacist-in-charge shall ensure the following are achieved:

a. Compounding personnel shall have demonstrated competencies on file at least annually for low and medium-risk level compounding and semi-annually for high-risk level compounding, and shall be adequately educated and trained to perform and document duties in accordance with USP requirements to include, but not be limited to, the following:

(1) Perform antiseptic hand cleansing and disinfection of non-sterile compounding surfaces;

(2) Select and appropriately don protective garments and equipment;

(3) Use laminar flow clean-air hoods, barrier isolators, biological safety cabinets and other contamination control devices;

(4) Identify, weigh, and measure ingredients; and

(5) Manipulate sterile products aseptically.

(6) Personnel who prepare CSPs shall be trained conscientiously and skillfully by expert personnel and through audio-video instructional sources, and professional publications in the theoretical principles and practical skills of aseptic manipulations and in achieving and maintaining ISO Class 5 environmental conditions before they begin to prepare CSPs.

b. Opened or partially used multi-dose packages of ingredients for subsequent use in CSP shall be properly stored in the compounding area. Such packages shall not be used when visual inspection detects unauthorized breaks in the container, closure, and seal; when the contents do not possess the expected appearance, aroma, or texture, when the contents do not pass identification tests specified by the compounding facility; and when either the beyond-use or expiration date has been exceeded. Single use containers of ingredients for subsequent use in CSP shall be discarded within six (6) hours.

c. Measuring, mixing, sterilizing, and purifying devices shall be clean, appropriately accurate, and effective for their intended use.

d. Packaging selected for CSPs shall be appropriate to preserve the sterility and strength until the beyond-use-date.

e. CSP labels shall list the names and amounts or concentrations of all active ingredients. Before being dispensed, and/or administered, the clarity of the solutions shall be visually confirmed, where appropriate. The identity and amounts of ingredients, procedures to prepare and sterilize CSPs, and specific release criteria shall be reviewed to ensure accuracy and completeness.

D. Facility Requirements: Sterile Compounding

1. Pharmacies that engage in the pharmaceutical preparation of CSPs shall have a specifically designed and adequate space for the orderly placement of equipment and the materials used to prepare sterile preparations in accordance with current USP guidelines. This area shall be separate and distinct from other areas within the pharmacy and no other activity other than the preparation of sterile products shall occur in this area.

2. Pharmacies shall employ the use of either laminar airflow workbenches (LAFWs) or a barrier isolator system to prepare CSPs. These devices shall be located within a buffer or clean-room area that maintains at least an ISO Class 7 environment. Pharmacies choosing to utilize a barrier isolator system shall locate these in accordance with current USP requirements.

3. Pharmacies that compound cytotoxic preparations shall do so in accordance with current USP requirements.

4. A supply of bulk drugs and other materials used for the scheduled preparation of sterile CSPs (i.e., needles, syringes, bags, and transfer tubing) may be stored in an anteroom area. A demarcation line or current USP required barrier shall identify the separation of the buffer or clean room area from the anteroom area.

5. Hand sanitizing and gowning activities shall occur in the anteroom area.

E. Environmental Monitoring: Sterile Compounding

1. Certification that each LAFW, barrier isolator, and biological safety cabinet is working properly and meets the air quality requirement of ISO Class 5 shall be conducted every six (6) months and whenever the LAFW, barrier isolator, or biological safety cabinet is relocated. Such certification shall be performed and documented by qualified operator(s) using current state-of-the-art electronic air sampling.

2. The air quality of the buffer or clean room and the anteroom area shall be in conformity with ISO Class 7 and ISO Class 8 requirements, as appropriate. Certification inspections shall be conducted every six (6) months and whenever renovations occur. Such certification shall be performed and documented by a qualified operator(s).

3. The pharmacist-in-charge shall be responsible for reviewing and maintaining the certification records required in §§ 1.7(D)(5) and (E)(1) of this Part for a period of no less than two (2) years.

4. A written plan and schedule for the environmental monitoring procedures for viable micro-organisms shall be established and followed. The plan shall be adequate to evaluate the various controlled air environment areas (LAFW, barrier isolators, biological safety cabinets, buffer or clean room, and anteroom) of the designated sterile compounding area(s). For sterile compounding areas used for low and medium-risk preparations, a minimum monthly evaluation shall be required. For sterile compounding areas used for high-risk preparations, a weekly evaluation shall be required.

5. When above action level results for viable sampling are discovered, the pharmacy shall keep records of viable sampling reports and remediation actions and have such records readily retrievable for Board inspection for a period of two (2) years.

6. The pharmacy shall follow current USP requirements relating to cleaning and disinfecting of all affected sterile compounding environments and shall immediately conduct environmental monitoring testing once cleaning and disinfecting is complete.

7. The pharmacy shall not continue to conduct sterile compounding activities if above action level results are not corrected after complete cleaning and retesting in affected ISO 5 primary engineering controls and ISO 7 or lower classified rooms and shall arrange for practical alternatives to continue safe sterile compounding activities including but not limited to alternate locations for sterile compounding. Sterile compounding shall not continue when repeated above action level results occur in primary engine controls or ISO 7 or lower rooms.

8. The pharmacy shall ensure that patients receiving compounded sterile products shall not be exposed to risks of infection resulting from the commencement of sterile compounding activities in environments with above action level results for fungal or bacterial contamination in the air or on surfaces in ISO 7 or lower certified rooms or primary engineering controls.

F. Variance Procedure

1. Any compounding pharmacy that is temporarily unable to meet the requirements of USP or §§ 1.7(D)(1) through (5) or 1.7(E)(1) through (3) of this Part may apply to the Board for a variance.

2. Variances may be granted at the discretion of the Board upon good cause shown as long as the compounding is performed in an ISO 5 environment. Variances will be granted to the minimum amount necessary. Variances will be granted for a compliance date certain. If the date certain cannot be met, a new request for a variance shall be made to the Board.

1.7.1Equipment: Sterile Compounding

Written procedures outlining required calibration, annual maintenance, monitoring for proper function, and controlled procedures for use shall be established and followed for all equipment, apparatuses, and devices used in the preparation of CSPs. Results from calibration, annual maintenance reports, and routine maintenance shall be kept on file for the lifetime of the equipment.

1.7.2Record Keeping Requirements: Sterile Compounding

A. All records required to be retained under this Part, or copies of such records, shall be readily retrievable for inspection by the Department during the retention period at the establishment where activities described in such records occurred.

B. Records required under this Part may be retained either as the original records or as true copies, such as photocopies, microfilm, microfiche, electronic image or other accurate reproductions of the original records.

1.7.3Radiopharmaceuticals as CSPs

A. Compounding of radiopharmaceuticals for Positron Emission Tomography (PET) shall be performed in accordance with the current applicable USP guidance.

B. For the purposes of § 1.7 of this Part, the following shall be designated low-risk level CSPs:

1. Radiopharmaceutical dosage units with volumes of fifteen (15) mL and less and expiration times of twenty-four (24) hours and shorter, such as those prepared from eluates from technetium-99m/molybdenum 99 generator systems; and

2. Commercially manufactured cyclotron radiopharmaceuticals that contain preservatives and bear expiration times of seventy-two (72) hours or shorter.

C. Radiopharmaceuticals shall be compounded using appropriately shielded vials and syringes in a properly functioning and certified vertical LAFW, Class II Type B2 BSC, or other suitable containment device (e.g., CAI) located in an ISO Class 8 or cleaner air environment to permit compliance with special handling, shielding, and negative air flow requirements.

D. Multiuse radiopharmaceutical vials, compounded with technetium-99m, exposed to ISO Class 5 environment and punctured by needles with no direct contact contamination may only be used up to twenty-four (24) hours post compounding.

E. Notwithstanding § 1.7(D)(1) of this Part, nuclear pharmacies may use an electronic dose calibrator within the LAFW to assay non-sterile oral capsules to measure the quantity of radioactive materials being handled and/or dispensed.

216 R.I. Code R. 216-RICR-40-15-1.7

Amended effective 5/17/2021
Amended effective 12/8/2022