| and other areas that
are in close proximity to the ISO Class 5 environment during the certification
of the primary engineering control.
(vi) Air sampling frequency and process. Air sampling
shall be performed at least every 6 months as a part of the re-certification
of facilities and equipment. A sufficient volume of air shall be sampled
and the manufacturer's guidelines for use of the electronic air sampling
equipment followed. At the end of the designated sampling or exposure
period for air sampling activities, the microbial growth media plates
are recovered and their covers secured and they are inverted and incubated
at a temperature and for a time period conducive to multiplication
of microorganisms. Sampling data shall be collected and reviewed on
a periodic basis as a means of evaluating the overall control of the
compounding environment. If an activity consistently shows elevated
levels of microbial growth, competent microbiology or infection control
personnel shall be consulted. A colony forming unit (cfu) count greater
than 1 cfu per cubic meter of air for ISO Class 5, greater than 10
cfu per cubic meter of air for ISO Class 7, and greater than 100 cfu
per cubic meter of air for ISO Class 8 or worse should prompt a re-evaluation
of the adequacy of personnel work practices, cleaning procedures,
operational procedures, and air filtration efficiency within the aseptic
compounding location. An investigation into the source of the contamination
shall be conducted. The source of the problem shall be eliminated,
the affected area cleaned, and resampling performed. Counts of cfu
are to be used as an approximate measure of the environmental microbial
bioburden. Action levels are determined on the basis of cfu data gathered
at each sampling location and trended over time. Regardless of the
number of cfu identified in the pharmacy, further corrective actions
will be dictated by the identification of microorganisms recovered
by an appropriate credentialed laboratory of any microbial bioburden
captured as a cfu using an impaction air sampler. Highly pathogenic
microorganisms (e.g., gram-negative rods, coagulase positive staphylococcus,
molds and yeasts) can be potentially fatal to patient receiving compounded
sterile preparations and must be immediately remedied, regardless
of colony forming unit count, with the assistance, if needed, of a
competent microbiologist, infection control professional, or industrial
hygienist.
(vii) Compounding accuracy checks. Written procedures
for checking compounding accuracy shall be followed for every compounded
sterile preparation during preparation and immediately prior to release,
including label accuracy and the accuracy of the addition of all drug
products or ingredients used to prepare the finished preparation and
their volumes or quantities. At each step of the compounding process,
the pharmacist shall ensure that components used in compounding are
accurately weighed, measured, or subdivided as appropriate to conform
to the formula being prepared.
(15) Quality control.
(A) Quality control procedures. The pharmacy shall
follow established quality control procedures to monitor the compounding
environment and quality of compounded drug preparations for conformity
with the quality indicators established for the preparation. When
developing these procedures, pharmacy personnel shall consider the
provisions of USP Chapter 71, Sterility Tests, USP Chapter 85, Bacterial
Endotoxins Test, Pharmaceutical Compounding-Non-sterile Preparations,
USP Chapter 795, USP Chapter 797, Pharmaceutical Compounding--Sterile
Preparations, USP Chapter 800, Hazardous Drugs--Handling in Healthcare
Settings, USP Chapter 823, Positron Emission Tomography Drugs for
Compounding, Investigational, and Research Uses, USP Chapter 1160,
Pharmaceutical Calculations in Prescription Compounding, and USP Chapter
1163, Quality Assurance in Pharmaceutical Compounding of the current
USP/NF. Such procedures shall be documented and be available for inspection.
(B) Verification of compounding accuracy and sterility.
(i) The accuracy of identities, concentrations, amounts,
and purities of ingredients in compounded sterile preparations shall
be confirmed by reviewing labels on packages, observing and documenting
correct measurements with approved and correctly standardized devices,
and reviewing information in labeling and certificates of analysis
provided by suppliers.
(ii) If the correct identity, purity, strength, and
sterility of ingredients and components of compounded sterile preparations
cannot be confirmed such ingredients and components shall be discarded
immediately. Any compounded sterile preparation that fails sterility
testing following sterilization by one method (e.g., filtration) is
to be discarded and not subjected to a second method of sterilization.
(iii) If individual ingredients, such as bulk drug
substances, are not labeled with expiration dates, when the drug substances
are stable indefinitely in their commercial packages under labeled
storage conditions, such ingredients may gain or lose moisture during
storage and use and shall require testing to determine the correct
amount to weigh for accurate content of active chemical moieties in
compounded sterile preparations.
(e) Records. Any testing, cleaning, procedures, or
other activities required in this subsection shall be documented and
such documentation shall be maintained by the pharmacy.
(1) Maintenance of records. Every record required under
this section must be:
(A) kept by the pharmacy and be available, for at least
two years for inspecting and copying by the board or its representative
and to other authorized local, state, or federal law enforcement agencies;
and
(B) supplied by the pharmacy within 72 hours, if requested
by an authorized agent of the Texas State Board of Pharmacy. If the
pharmacy maintains the records in an electronic format, the requested
records must be provided in an electronic format. Failure to provide
the records set out in this section, either on site or within 72 hours,
constitutes prima facie evidence of failure to keep and maintain records
in violation of the Act.
(2) Compounding records.
(A) Compounding pursuant to patient specific prescription
drug orders or medication orders. Compounding records for all compounded
preparations shall be maintained by the pharmacy and shall include:
(i) the date and time of preparation;
(ii) a complete formula, including methodology and
necessary equipment which includes the brand name(s) of the raw materials,
or if no brand name, the generic name(s) or official name and name(s)
of the manufacturer(s) or distributor of the raw materials and the
quantities of each; however, if the sterile preparation is compounded
according to the manufacturer's labeling instructions, then documentation
of the formula is not required;
(iii) written or electronic signature or initials of
the pharmacist or pharmacy technician or pharmacy technician trainee
performing the compounding;
(iv) written or electronic signature or initials of
the pharmacist responsible for supervising pharmacy technicians or
pharmacy technician trainees and conducting finals checks of compounded
pharmaceuticals if pharmacy technicians or pharmacy technician trainees
perform the compounding function;
(v) the container used and the number of units of finished
preparation prepared; and
(vi) a reference to the location of the following documentation
which may be maintained with other records, such as quality control
records:
(I) the criteria used to determine the beyond-use date;
and
(II) documentation of performance of quality control
procedures.
(B) Compounding records when batch compounding or compounding
in anticipation of future prescription drug or medication orders.
(i) Master work sheet. A master work sheet shall be
developed and approved by a pharmacist for preparations prepared in
batch. Once approved, a duplicate of the master work sheet shall be
used as the preparation work sheet from which each batch is prepared
and on which all documentation for that batch occurs. The master work
sheet shall contain at a minimum:
(I) the formula;
(II) the components;
(III) the compounding directions;
(IV) a sample label;
(V) evaluation and testing requirements;
(VI) specific equipment used during preparation; and
(VII) storage requirements.
(ii) Preparation work sheet. The preparation work sheet
for each batch of preparations shall document the following:
(I) identity of all solutions and ingredients and their
corresponding amounts, concentrations, or volumes;
(II) lot number for each component;
(III) component manufacturer/distributor or suitable
identifying number;
(IV) container specifications (e.g., syringe, pump
cassette);
(V) unique lot or control number assigned to batch;
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