PURPOSE: This rule defines compounding and establishes guidelines for the compounding of drugs.

1. (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. (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. (3) Batch compounded product is defined as a product compounded in advance of receipt of a prescription or a product compounded in a supply that will be used on more than one
4. (1) dispensing to a patient or patients or any product compounded in excess of the filling of an individual prescription. A batch is a specific quantity of product compounded in a single, discrete process, by the same individuals, carried out during one (1) limited time period.
5. (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.

6. (5) Compounding Area and Equipment Requirements.

   1. (A) The area(s) used for the compounding of drugs 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.
   2. (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 crosscontamination.
   3. (C) Equipment used in the compounding of drug products 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 the compounding of drug products shall be of suitable composition so that surfaces that contact ingredients, in-process materials, 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 that desired.

7. (6) Proper controls shall be maintained over drug products/ingredients, containers, and container closures.

   1. (A) Bulk drugs and other materials used in the compounding of drugs must be stored in adequately labeled containers in a clean, dry area or, if required, under proper refrigeration.
   2. (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.
   3. (C) Pharmacists shall only use nondrug substances for compounding that are free of any contaminants and which maintain full potency.
   4. (D) Drug products/ingredients, containers, and container closures used in the compounding of drugs shall be handled and stored in a manner to prevent contamination.
   5. (E) Drug product/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 drug 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 drug product.

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

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

      1. 1. Methods for the compounding of drug

products to insure that the finished products have the identity, strength, quality, and purity they purport or are represented to possess;

1. 2. Date of compounding;
2. 3. Identity of the compounding pharma-

cist;

1. 4. A listing of the drug products/ingre-

dients and their amounts by weight or volume;

1. 5. Description of the compounding

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

1. 6. The identity of the source, lot num-

ber, and the beyond-use date of each drug product/ingredient, as well as an in-house lot number and a beyond-use date for bulk compounded products; and

1. 7. An identifying prescription number

or a readily retrievable unique identifier for which the compound was dispensed.

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

2. (C) Pharmacists may compound drugs 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. 1. The compounding of drug products 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 product that represents a three- (3-) month supply.

1. 2. Creams, ointments, lotions, liniments,

or other compounded products 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.

1. (D) Any excess compounded products shall be stored and accounted for under conditions dictated by its composition and stability characteristics to insure its strength, quality, and purity. Excess product shall be labeled with the name of the drug(s), an in-house lot number, and beyond-use date.
2. (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.
3. (F) The actual name of each active or therapeutic ingredient contained in a compound shall be listed on the container of any product provided to a consumer.

1. (8) Management of Compounding.

   1. (A) A pharmacist dispensing any compounded drug is responsible for ensuring that the product has been prepared, labeled, controlled, stored, dispensed, and distributed properly. The pharmacist is responsible for ensuring that quality is built into the preparation of products, with key factors including at least the following general principles:

      1. 1. Personnel are capable and qualified to

perform their assigned duties;

1. 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;

1. 3. Reasonable assurance that processes

are always carried out as intended or specified;

1. 4. Preparation conditions and proce-

dures are adequate for preventing mix-ups or other errors; and

1. 5. All finished products, as a condition

of release, must be individually inspected for evidence of visible particulates or other foreign matter and for container-closure integri- 20 CSR 2220-2

ty and any other apparent visual defects.

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

2. (C) A recall must be initiated when a product 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. 1. In cases where the compounded prod-

uct 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 product(s).

1. 2. Any recall initiated by a pharmacy

shall be reported, in writing, to the board within three (3) business days.

1. (9) Compounding of drug products that are commercially available in the marketplace or that are essentially copies of commercially available Federal Drug Administration (FDA) approved drug products is prohibited. There shall be sufficient documentation within the prescription record of the pharmacy of the specific medical need for a particular variation of a commercially available compound.
2. (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 drug product to be sold without a prescription is prohibited.
3. (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 drug product being compounded shall be excluded from direct contact with drug products/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 products being compounded.
4. (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 AND INSURANCE

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.

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

   1. (A) The preparation container is labeled with:

      1. 1. Pharmacy name, address, and tele-

phone number;

1. 2. Date of distribution;
2. 3. Veterinarian’s name;
3. 4. Preparation name, strength, dosage

form, and quantity;

1. 5. Name of each active or therapeutic

ingredient included in the preparation;

1. 6. Preparation lot/batch number;
2. 7. Preparation beyond-use date; and
3. 8. Statement: “Office Stock Compound-

ed Preparation”;

1. (B) The pharmacy maintains a record of the distribution to the veterinarian;
2. (C) The pharmacy can retrieve distribution records by specific veterinarian, if requested;
3. (D) In lieu of paragraph (7)(A)7., the veterinarian’s name may be recorded on the compounding log; and
4. (E) The pharmacy complies with all applicable controlled substance laws and regulations.

1. (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 product.

AUTHORITY: section 338.010, RSMo Supp. 2018, and sections 338.140, 338.240, and 338.280, RSMo 2016.* 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. Emergency amendment filed March 20, 2019, effective March 30, 2019, expired Jan. 8, 2020. Amended: Filed March 20, 2019, effective Sept. 30, 2019. *Original authority: 338.010, RSMo 1939, amended 1951, 1989, 1990, 2007, 2009, 2011, 2014, 2017, 2018; 338.140, RSMo 1939, amended 1981, 1989, 1997, 2011; 338.240, RSMo 1951, amended 2011; and 338.280, RSMo 1951, amended 1971, 1981.