2. USP 797 Compliance
What is the USP-NF?
The United States Pharmacopeia and The National Formulary
(USP-NF) is a compilation of drug monographs, biologics,
medical devices, dietary supplements, reference tests and
standards, and standards for compounding of sterile and non-
sterile drug preparations.
3. USP 797 Compliance
Utilizing the USP
USP–NF is recognized by law and custom in most countries.
The United States, the federal Food, Drug, and Cosmetic Act
(FDC Act) defines the term “official compendium” as the
official USP, the official NF, or any supplement to them.
The FDA may enforce compliance with official standards in
USP–NF under the adulteration and misbranding provisions of
the FD&C Act.
A State Board of Pharmacy may be charged with enforcement
of this law.
4. USP 797 Compliance
Utilizing the USP
USP <797> HAS SPECIFIC GUIDELINES FOR:
Design of the Facility
Environmental and Engineering Controls
Environmental Testing
Personnel Training and Competency Testing
Standard Operating Procedures and Documentation
Quality Assurance
Patient Monitoring and Adverse Events Reporting
Storage and Dating
5. USP 797 Compliance
<797> Purpose
“THE INTENT OF <797> IS TO PREVENT HARM AND
FATALITY TO PATIENTS THAT COULD RESULT FROM
MICROBIAL CONTAMINATION (NONSTERILITY),
EXCESSIVE BACTERIAL ENDOTOXINS, LARGE CONTENT
ERRORS IN THE STRENGTH OF CORRECT
INGREDIENTS, AND INCORRECT INGREDIENTS IN
COMPOUNDED STERILE PRODUCTS (CSPs).”
The U.S. Pharmacopeial Convention (USP)
www.USP.Org
6. USP 797 Compliance
<797> Purpose
The purpose of USP 797 is to protect the
health of patients by reducing the potential for
microbial contamination caused by an unclean
environment, excessive bacterial endotoxins,
large errors in the strength of ingredients and
the use of incorrect ingredients.
7. USP 797 Compliance
<797> Purpose
The chapter was developed for use in healthcare
institutions, pharmacies, and physician practice
facilities. It also applies to other facilities in which
compounded sterile preparations (CSPs) are
prepared, stored and dispensed, such as pharmacy
intravenous rooms, chemotherapy clinics, hospital
nursing stations and in operating rooms by
anesthesiologists.
8. USP 797 Compliance
<797> Purpose
The U.S. Pharmacopeia (USP) 797 provides the practice
standards to help ensure that compounded sterile
preparations are of high quality, and is for the pre-
administration phase of sterile preparations. It describes the
CSP requirements (guidelines, USP 797 procedures and
compliance) for CSPs and sets the standards that apply to all
settings in which sterile preparations are compounded.
Adherence to 797 will reduce the potential for contamination
caused by unclean environment, pharmacist error, lack of
quality control, incorrect beyond-use dating and other factors
9. USP 797 Compliance
<797> Purpose
The standard applies to anyone who prepares CSPs and all places where
they are prepared. CSPs include drugs, nutrients, biologics, diagnostics
and radiopharmaceuticals.
The guideline requires environmental controls to include a separate area
for compounding that meets a definite level of cleanliness, and monitoring
to guarantee that control is maintained.
For all preparers and places where CSPs are prepared, the Joint
Commission requires a gap analysis and action plan for USP 797
compliance and is enforcing USP Chapter 797 within their standards. The
Joint Commission may impose stricter compliance to 797 than the states’
Board of Pharmacy.
11. USP 797 Compliance
Complying with <797>
Complying with USP 797 requires the design and use of
cleanroom facilities as well as the development of policies
and procedures for cleaning, sterility testing and personnel
and environmental monitoring.
Aseptic manipulations using only sterile ingredients and
components entirely within ISO Class 5 or better conditions
are considered low risk.
12. USP 797 Compliance
<797> Applies to:
The standards in this chapter are intended to apply to all
persons who prepare CSPs and all places where CSPs are
prepared (e.g., hospitals and other healthcare institutions,
patient treatment clinics, pharmacies,
physicians' practice facilities, and other locations and facilities
in which CSPs are prepared, stored, and transported).
Persons who perform sterile compounding include
pharmacists, nurses, pharmacy technicians, and physicians.
13. USP 797 Compliance
Risk Levels
An increase in complexity or duration of the compounding
process increases the risk level.
Compounding, or pooling, multiple doses of sterile products
for administration to multiple patients or single patient on
multiple occasions is considered medium risk.
For example - The transfer of multiple ampules or vials into a single
final sterile container or product. If a sterility test is not performed,
the usable shelf life is 3 days at room temperature, 7 days at
refrigerated temperature, and 45 days frozen at -20°C or colder.
14. USP 797 Compliance
Risk Levels
High-risk conditions include the use of non-sterile ingredients or
components or the exposure of sterile ingredients or components to
conditions less than ISO Class 5.
For example - Measuring and mixing sterile ingredients in non-sterile devices before
terminal sterilization. If a sterility test is not performed on high-risk preparations, the
usable shelf life is 24 hours at controlled room temperature, 3 days at refrigerated
temperature, and 45 days frozen at -20°C or colder.
Complying with USP 797 requires the design and use of cleanroom
facilities as well as the development of policies and procedures for
cleaning, sterility testing and personnel and environmental monitoring.
15. USP 797 Compliance
Daily Compliance
Maintaining the work space
Are things organized and free of “clutter”?
Does everything work?
Is there enough work space?
Are there hand washing supplies?
16. USP 797 Compliance
Daily Compliance
Refrigerators:
Are there opened, undated and non-initialed
Single Dose Vials (SDV) and Multiple Dose Vials
(MDV)?
Is there food or other prohibited items?
Check the Temperature log
17. USP 797 Compliance
Daily Compliance
Check for Waste and Sharp disposal
Check Gauges
Check Temp recording “wheels”
Check Hood certification stickers
Are policies and procedures in place and guidelines
up to date and documented?
18. USP 797 Compliance
Cabinets/Hoods - Working Aseptically
Unidirectional Airflow
First Air Zone
Nothing to be placed between the HEPA filter and the critical
compounding zone
Zone of Confusion
Turbulent area downstream of an obstruction possible source of
cross contamination
The advantages of unidirectional airflow should be exploited when
considering placement of materials within the DCCA.
19. USP 797 Compliance
Cabinets/Hoods - Working Aseptically
Improper hand placement disrupts first air
Good aseptic technique in sterile compounding requires the
understanding and proper use of “First-Air”.
“First-Air” is the air exiting the HEPA filter in a unidirectional airstream
and is virtually free of particulate contaminants.
All critical manipulations must be carried out in the unobstructed
“first air” zone in the direct path of the HEPA filter discharge.
Proper product and process - placement with respect to the supply and
discharge will provide a contamination free compounding area.
20. USP 797 Compliance
Meeting Sterility Requirements
The ante-area or room is where personnel hand hygiene and
garbing procedures, staging, order entry, CSP labeling, and other high
particulate generating activities are preformed.
This room leads into the sterile IV and compounding room. This
transition room needs to be an ISO 8 or better approved room that is
pressurized to move particulate filled air through HEPA filters.
The sterile IV products should be mixed in a positive pressure room
and in a ISO 5 or better approved hood
21. USP 797 Compliance
Meeting Sterility Requirements
CHEMOTHERAPY:
A negative pressure hood that is vented to the outside is
needed that is ISO 5 or better IN a negative pressure room
23. USP 797 Compliance
CSP’s stratification MICROBIAL CONTAMINATAION RISK LEVELS
LOW-RISK LEVEL
Compounded entirely under ISO Class 5 (Class 100) conditions
Compounding involves only transfer, measuring, and mixing manipulations with
closed or sealed packaging systems
Manipulations are limited to aseptically opening ampule, penetrating sterile stoppers
on vials with sterile needles and syringes and transferring sterile liquids in sterile
syringes to sterile administration devices and packages of other sterile products
In the absence of passing a sterility test, periods cannot exceed the following time
periods: Before administration, the CSP’s are properly stored and are exposed for
not more than 48 hours at a controlled room temperature, for not more than 14 days
at a cold temperature, and for 45 days in solid frozen state at – 20 degrees or colder.
24. USP 797 Compliance
CSP’s stratification
MEDIUM-RISK LEVEL
All conditions apply as listed under low-risk level
Compounding involves only transfer, measuring, and mixing manipulations with closed or
sealed packaging systems that are performed promptly and attentively
Manipulations are limited to aseptically opening ampules, penetrating sterile stoppers on vials
with sterile needles and syringes and transferring sterile liquids in sterile syringes to sterile
administration devices and packages of other sterile products
Multiple individual or small doses of sterile products are combined or pooled to prepare a CSP
that will be administered either to multiple patients or to one patient on multiple conditions
Compounding process includes complex aseptic manipulations other than the single-volume
transfer
Compounding process requires unusually long duration
The sterile CSPs do not contain broad-spectrum bacteriostatic agents, and are administered
over several days In the absence of passing a sterility test, periods cannot exceed the
following time periods: Before administration, the CSP’s are properly stored and are exposed
for not more than 30 hours at a controlled room temperature, for not more than 7 days at a
cold temperature, and for 45 days in solid frozen state at – 20 degrees or colder
25. USP 797 Compliance
CSP’s stratification
HIGH-RISK LEVEL
Non-sterile ingredients are incorporated or a non-sterile device is employed before
terminal sterilization
Sterile ingredients, components, devices and mixtures are exposed to air quality inferior
to ISO Class 5 (Class 100)
Non-sterile preparations are exposed for not more than 6 hours before being sterilized
Non-sterile preparations are terminally sterilized but are not tested for bacterial
endotoxins
It is assumed that the chemical purity and content strength of ingredients meet their
original or compendia specifications in unopened or in opened packages of bulk
ingredients
The sterile CSPs do not contain broad-spectrum bacteriostatic agents, and are
administered over several days In the absence of passing a sterility test, periods cannot
exceed the following time periods: Before administration, the CSP’s are properly stored
and are exposed for not more than 24 hours at a controlled room temperature, for not
more than 3 days
26. USP 797 Compliance
Ongoing Compliance
USP <797> requires policies and procedures for all aspects of
sterile compounding from personnel to product that:
Communicates information
Perform audit and peer review activities
Follow Standard Operating procedures
Provide data for benchmarking
Documents regulatory compliance
Provides data valuable in cost evaluations
Applicable in a court of law
27. USP 797 Compliance
Ongoing Compliance
Documents should be kept up-to-date
1. Correct form
2. Correct information on form
3. Form is complete
4. Information is legible and readily accessible
5. Demonstrates conformity: No gap between actual performance
and established policy
28. USP 797 Compliance
Ongoing Compliance
Personnel Training
Facility Staff
1. Daily calibration
2. Proper use of equipment
3. Documentation
Competency Evaluation of Garbing
Competency Evaluation of Cleaning & Disinfecting Procedures
Competency Evaluation of Aseptic Work Practices
Environmental Monitoring
