Mo. Code Regs. tit. 20 § 2220-2.400

Current through Register Vol. 49, No. 21, November 1, 2024.

Section 20 CSR 2220-2.400 - Compounding Standards of Practice

PURPOSE: This amendment updates rule language to reference compounded preparations, defines a commercially available product for purposes of compounding, and clarifies requirements for bulk drug substances for use in compounding human preparations.

(1) Compounding is defined as the preparation, incorporation, mixing and packaging or labeling of a drug or device as the result of a prescriber's prescription or prescription drug order based on the prescriber/patient/pharmacist relationship in the course of professional practice. Compounding may also be defined as the preparation, incorporation, mixing and packaging or labeling of a drug or device, for the purpose of, or as an incident to, research, teaching or chemical analysis and not for sale or dispensing purposes.

(2) Manufacturing is defined as the production, preparation, propagation, conversion, or processing of a drug or device, either directly or indirectly, by extraction from substances of natural origin or independently by means of chemical or biological synthesis, and includes any packaging or repackaging of the substance(s) or labeling or relabeling of its container, and the promotion and marketing of such drugs or devices.

(3) Batch compounded preparation is defined as a preparation compounded in advance of receipt of a prescription or a preparation compounded in a supply that will be used on more than one (1) dispensing to a patient or patients or any preparation compounded in excess of the filling of an individual prescription. A batch is a specific quantity of preparation compounded in a single, discrete process, by the same individuals, carried out during one (1) limited time period.

(4) Beyond-use date: A date after which a compounded preparation should not be used and is determined from the date the preparation is compounded. Because compounded preparations are intended for administration immediately or following short-term storage, their beyond-use dates must be assigned based on criteria different from those applied to assigning expiration dates to manufactured drug products.

(5) Compounding Area and Equipment Requirements.

(A) The area(s) used for compounding preparations shall be maintained in a sanitary condition and shall be free of infestation by insects, rodents, and other vermin. Trash shall be held and disposed of in a timely and sanitary manner.

(B) If drug products with special precautions for contamination, such as penicillin, are involved in a compounding operation, appropriate measures, including either the dedication of equipment for such operations or the meticulous cleaning of contaminated equipment prior to its return to inventory, must be utilized in order to prevent cross-contamination.

(C) Equipment used in compounding preparations shall be of appropriate design, adequate size, and suitably located to facilitate operations for its intended use and for its cleaning and maintenance. Equipment used in compounding preparations shall be of suitable composition so that surfaces that contact ingredients, in-process materials, or compounded preparations shall not be reactive, additive, or absorptive so as to alter the safety, identity, strength, quality, or purity of the compounded preparation beyond that desired.

(6) Proper controls shall be maintained over drug products/in-gredients, containers, and container closures.

(A) Bulk drugs and other materials used in compounding preparations must be stored in adequately labeled containers in a clean, dry area or, if required, under proper refrigeration.

(B) Pharmacists shall only receive, store, or use drug substances for compounding that have been made and/or distributed by Missouri licensed/registered drug distributors. A bulk drug substance for human use that is not the subject of an applicable United States Pharmacopeia or National Formulary monograph or is not a component of a Federal Drug Administration (FDA) approved drug cannot be used in compounding unless it appears on a list promulgated as a regulation pursuant to section 503A(b)(1)(A)(i)(III) of the Federal Food, Drug, and Cosmetic Act, except as otherwise allowed by the FDA.

(C) Pharmacists shall only use nondrug substances for compounding that are free of any contaminants and which maintain full potency.

(D) Drug products/ingredients, containers, and container closures used in compounding of preparations shall be handled and stored in a manner to prevent contamination.

(E) Drug products/ingredient containers and container closures shall not be reactive, additive, or absorptive so as to alter the safety, identity, strength, quality, or purity of the compounded preparation beyond the desired result. Container systems shall provide adequate protection against foreseeable external factors in storage and use that can cause deterioration or contamination of the compounded preparation.

(7) Appropriate quality control measures shall be maintained by the pharmacy and its staff over compounding methods.

(A) Such methods shall include the following and shall be followed in the execution of the compounding process. A separate log shall be maintained which includes -

1. Methods for compounding preparations to ensure that finished preparations have the identity, strength, quality, and purity they purport or are represented to possess;

2. Date of compounding;

3. Identity of the compounding pharmacist;

4. A listing of the drug products/ingredients and their amounts by weight or volume;

5. Description of the compounding process and the order of drug product/ingredient addition, if necessary for proper compounding;

6. The identity of the source, lot number, and the be-yond-use date of each drug product/ingredient, as well as an in-house lot number and a beyond-use date for bulk compounded preparations; and

7. An identifying prescription number or a readily retrievable unique identifier for which the compound was dispensed.

(B) Information related to and the methods of compounding shall be available upon request.

(C) Pharmacists may compound preparations in limited quantities prior to receiving a valid prescription based on a history of receiving valid prescriptions that have been generated solely with an established pharmacist/patient/prescriber relationship.

1. Except as otherwise provided by law, compounding preparations in anticipation of receiving prescriptions without an appropriate history of such prescriptions on file or a documented need shall be considered manufacturing instead of compounding of the drug(s) involved. Limited quantities, for purposes of this rule, are further defined as an amount of batched preparation that represents a three- (3-) month supply.

2. Creams, ointments, lotions, liniments, or other compounded preparations intended for external use may be batched in the same manner as provided for in paragraph (7)(C)1. of this rule that represents a one- (1-) year supply.

(D) Any excess compounded preparations shall be stored and accounted for under conditions dictated by its composition and stability characteristics to ensure its strength, quality, and purity. Excess preparations shall be labeled with the name of the drug(s), an in-house lot number, and beyond-use date.

(E) Records as outlined in this rule shall be retained and made readily retrievable for inspection for two (2) years from the date of compounding.

(F) The actual name of each active or therapeutic ingredient contained in a compound shall be listed on the container of any compounded preparation provided to a consumer.

(8) Management of Compounding.

(A) A pharmacist dispensing a compounded preparation is responsible for ensuring the preparation has been prepared, labeled, controlled, stored, dispensed, and distributed properly. The pharmacist is responsible for ensuring that quality is built into the preparation and ensuring -

1. Personnel are capable and qualified to perform their assigned duties;

2. Ingredients used in compounding have their expected identity, quality, and purity. Drug components must meet compendial standards or maintain a certificate of analysis on file when bulk drug substances are involved. Visual inspection of bulk drug substances must be performed;

3. Reasonable assurance that processes are always carried out as intended or specified;

4. Preparation conditions and procedures are adequate for preventing mix-ups or other errors; and

5. All finished preparations, as a condition of release, are individually inspected for evidence of visible particulates or other foreign matter and for container-closure integrity and any other apparent visual defects.

(B) The pharmacy is responsible for developing a drug monitoring system for compounded preparations. The outcome monitoring system shall provide readily retrievable information suitable for the evaluation of the quality of pharmaceutical services including but not limited to reported infection rates, incidence of adverse drug reactions, incidence of recalls, and complaints from prescribers or clients.

(C) A recall must be initiated when a compounded preparation is deemed to be misbranded or adulterated. The pharmacy shall notify the prescriber of the nature of the recall, the problem(s) identified, and any recommended actions to ensure public health and safety.

1. In cases where the compounded preparation has the potential to harm the patient, the same recall notification as provided for in this subsection shall be provided to all patients that have received the recalled compounded preparation(s).

2. Any recall initiated by a pharmacy shall be reported, in writing, to the board within three (3) business days.

(9) The compounding of a preparation that is a copy or essentially a copy of a commercially available product is prohibited except when there is a specific medical need for a particular variation of a commercially available compound for an individual patient as determined by the prescriber, or when a change or modification for a specific patient would produce for that patient a clinically significant difference between the compounded preparation and the comparable commercially available drug product, as determined by the prescribing practitioner. Documentation from the prescriber of the specific medical need or clinically significant difference for a specific patient must be maintained in the pharmacy's records. A prescription that identifies only a patient name and compounded preparation formulation is insufficient documentation for a pharmacy to rely upon to conclude that the prescriber made a determination regarding a specific medical need or clinically significant difference. A different formulation without a documented specific medical need or clinically significant difference is not sufficient.

(A) For purposes of this rule, "essentially a copy of commercially available product" is a compounded preparation that has-

1. The same active pharmaceutical ingredient(s) as the commercially available drug product;

2. The same, similar, or an easily substitutable dosage strength; and

3. The same manner of administration as the commercially available drug product.

(B) For purposes of this rule, "easily substitutable" means the same or similar dosage strength can be achieved by administration of fractional or multiple doses of a commercially available drug product.

(C) When compounding an otherwise commercially available product due to a drug shortage, the pharmacy must confirm and document the commercially available product is not available despite due diligence.

(10) Any alteration, change, or modification to the contents of a commercially manufactured over-the-counter product shall require a prescription or prescription drug order from an authorized prescriber. The compounding of any preparation without a prescription or medication order is prohibited.

(11) Any person shown at any time, either by medical examination or pharmacist determination, to have an apparent illness or open lesion(s) that may adversely affect the safety or quality of a compounded preparation shall be excluded from direct contact with compounded preparations/ingredients, drug product containers, container closures, and in-process materials until the condition is corrected or determined by competent medical personnel not to jeopardize the safety or quality of the compounded preparation.

(12) Except as provided by law, pharmacists shall not offer or provide compounded preparations to other pharmacies, practitioners, or entities for subsequent dispensing, distribution, resale, or administration, except in the course of professional practice for a prescriber to administer to an individual patient by a prescription dispensed by the pharmacy. A pharmacist or pharmacy may advertise or otherwise provide information concerning the provision of compounding services; however, no pharmacist or pharmacy shall attempt to solicit business by making specific claims about compounded preparations.

(13) Pharmacies may provide non-patient specific compunded preparations for veterinary use to a Missouri-licensed veterinarian to administer and dispense to the veterinarians's animal patients, provided the following:

(A) The preparation container is labeled with:

1. Pharmacy name, address, and telephone number;

2. Date of distribution;

3. Veterinarian's name;

4. Preparation name, strength, dosage form, and quantity;

5. Name of each active or therapeutic ingrediant included in the preparation;

6. Preparation lot/batch number;

7. Preparation beyond-use date; and

8. Statement: "Office Stock Compounded Preparation";

(B) The pharmacy maintains a record of the distribution to the veterinarian;

(C) The pharmacy can retrieve distribution records by specific veterinarian, if requested;

(D) In lieu of (7)(A)7., the veterinarian's name may be recorded on the compounding log; and

(E) The pharmacy complies with all applicable controlled substance laws and regulations.

(14) In addition to the requirements outlined in this rule, all standards and requirements as outlined in 20 CSR 2220-2.200, Sterile Compounding, must be adhered to whenever compounding involves the need for asceptic procedures or requires the use of or results in an intended sterile pharmaceutical preparation.

20 CSR 2220-2.400

AUTHORITY: sections 338.010, 338.140, 338.240 and 338.280, RSMo 2000.* This rule originally filed as 4 CSR 220-2.400. Original rule filed Aug. 25, 1995, effective April 30, 1996. Amended: Filed Dec. 3, 2002, effective July 30, 2003. Moved to 20 CSR 2220-2.400, effective Aug. 28, 2006.

Amended by Missouri Register August 15, 2019/Volume 44, Number 16, effective 9/30/2019

Amended by Missouri Register August 15, 2023/Volume 48, Number 16, effective 9/30/2023

*Original authority: 338.010, RSMo 1939, amended 1951, 1989, 1990; 338.140, RSMo 1939, amended 1981, 1989, 1997; 338.240, RSMo 1951; and 338.280, RSMo 1951, amended 1971, 1981.