Current through Register Vol. 49, No. 6, March 15, 2024
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.
*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.
