Transcript Introduction to USP 797

USP Chapter <797>:
Updates for 2008
Eric S. Kastango, MBA, RPh, FASHP
Clinical IQ, LLC
Florham Park, NJ, USA
Disclaimer
“Although I am a member of the USP Sterile
Compounding Committee, I am speaking in my
individual capacity and not as a member of the
Committee or as a USP representative. The
views and opinions presented are entirely my
own. They do not necessarily reflect the views
of USP, nor should they be construed as an
official explanation or interpretation of <797>.”
USP Chapter <797> Timeline
• Posted on USP website on December 3rd
– www.usp.org
• The General Chapter will become official via a
Revised Bulletin with an official date of June 1,
2008
• It is “the” revised chapter based on 3 years of
feedback and comments
• 2005-2010 USP SCC has no plans on revising
the chapter again.
• Any changes will be driven by scientific evidence
and will be taken up by the 2010-2015 USP SCC
Members of the SCC Committee
• Chair - David Newton, Ph.D., R.Ph.
• Vice Chair - Lawrence A. Trissel, R.Ph, FASHP
Members:
Samuel Augustine, Pharm. D.
Kenneth Hughes, R.Ph.
Mary Baker, Pharm.D.
Eric S. Kastango, MBA, R.Ph.
James F. Cooper, Pharm.D.
Keith St. John, M.S.
Donald Filibeck, Pharm.D
Laura Thoma, Pharm. D.
Larry Griffin, R.Ph.
James Wagner
Scientific Liaison:
Claudia C. Okeke, Ph.D., R.Ph.
USP Advisory Groups
•
•
•
•
Infection Control Advisory Committee
Radiopharmaceutical Advisory Committee
Allergen Extract Working Group
Compounding Isolator Industry Round
Table
• Food and Drug Administration
Changes and Clarifications in <797>
•
•
•
•
•
•
•
Introduction (Revised)
Definitions section (new)
Immediate-Use category (new)
Low-Risk Level with 12 hour BUD (new)
Single & multiple-dose containers (new)
Proprietary vial/bag systems (new)
Hazardous drugs (revised)
Changes and Clarifications in <797>
•
•
•
•
•
•
Radiopharmaceuticals (revised)
Allergen Extract CSPs (new)
Cleaning and disinfecting facilities (revised)
Personnel cleansing and garbing (revised)
Environmental controls (revised)
Environmental sampling (revised)
Changes and Clarifications in <797>
• Filter integrity testing for High Risk Level
compounding (new)
• Microbiological BUD (revised)
• “Shall vs. Should” Table (new)
• Clarified language throughout
(We hope!)
Key to Understanding <797>:
Read Chapter <797>!!
Introduction
• Complete revision to be more explicit
• Acknowledges direct contact is the principal
source of contamination in CSPs
• New robust Definitions section for 29 key terms
• Alternative technologies proven equivalent or
superior to conventional work practices are OK
• 797 applies to CSPs given via application,
implantation, inhalation, injection, insertion,
instillation, and irrigation
Responsibilities of
Compounding Personnel in <797>
•
•
•
•
•
14 areas of responsibility are cited
Emphasizes training and education
Emphasizes compounding accuracy
Emphasizes avoiding contamination
Emphasizes patient safety
CSP Risk Categories
•
•
•
•
•
Immediate Use CSPs
Low-Risk Level
Low-Risk Level w/12 hour or less BUD
Medium-Risk Level
High-Risk Level
Immediate-Use Category
• Exempt from all requirements in <797>
• Only simple aseptic measuring and
transfer are needed
• NMT 3 sterile non-hazardous drugs
• No delays/interruptions
• No contact contamination of
ingredients or critical sites
Immediate-Use Category
• Dose must be labeled if not administered
by the preparer
• Administration must begin within 1 hour
after the start of preparation
• Dose must be discarded if administration
has not begun within 1 hour after the start
of preparation
(No storing. No recycling.)
Immediate-Use Category
Intended applications:
• At a patient’s bedside
• In an ambulance, ED or during a “Code”
Unintended applications:
• Routine compounding:
– Operating rooms, recovery areas
– Physician offices
Low-Risk Level CSPs
• Compounded from NMT 3 sterile
commercial containers using commercial
sterile devices
• Maintained in ISO Class 5 environment in
an ISO 7 buffer area at all times
• Only a few basic, closed-system, simple
aseptic transfers and manipulations
Low-Risk Level w/12 hour BUD
• Low-Risk Level remains nearly the same
• New subsection for an ISO 5 device in an
uncontrolled air environment
• Must be in a segregated compounding area not
in a high traffic area-Satellite pharmacy
• All personnel cleansing and garbing,
environmental sampling requirements apply
• No Hazardous Drugs: “THINK CONTAINMENT”
• Administration must begin within 12 hours or as
stated in the package insert, whichever is less
Medium-Risk Level CSPs
• Four or more sterile commercial drug
containers
• Multiple pooled sterile commercial
products for multiple patients or one
patient multiple times
• Complex aseptic manipulations
– TPN, PCA
• Compounding requires long duration
High-Risk Level CSPs
• Prepared from non-sterile ingredients
• Preparation from sterile ingredients but
exposed to less than ISO Class 5
• More than 6 hour delay from compounding to
sterilization
• Purity of components is assumed but not
verified by documentation-C of A
• Sterilization by filtration - the
manufacturer’s recommended integrity
test MUST be performed on the filter
– Bubble-Point
Old Expired BUD Paradigm
• Assume the compounded
preparation was sterile
• Historically based solely on the
drug’s chemical stability
Chapter<797> BUD Paradigm
• Recognizes the possibility that the CSP
was inadvertently contaminated during
compounding process
• For patient safety, BUD based on two
factors:
– Drug’s chemical stability in conjunction with
microbiological limits,
• BUD will always be whichever is shorter
Calculated Microbial Growth
Cundell AM, USP Committee on Analytical Microbiology,
Pharmacopeial Forum 2002; 28 (6) Stimuli to the Revision Process
Time (Hours)
Microbial Count
(CFU per mL)
6
10
9
640
12
41,000
18
1.7 X 107
24
6.9 X 109
<797> Microbiological BUD
• There is an ever-present chance, indeed
likelihood, that some CSPs will be inadvertently
contaminated
• Time and warm temperatures are the enemy,
speeding the potential for growth of dangerous
amounts of microbial contamination
• Guidance for limits is needed to avoid
unacceptable risks of harming patients
Microbiological
Beyond-Use Dating
Risk Category Room Temp
Refrigerator
Freezer
(-10 °C)
Immediate
Use
1 hour
1 hour
N/A
Low
48 hours
14 days
45 days
Low w/
12-hr BUD
12 hours or
less
12 hours or less N/A
Medium
30 hours
9 days
45 days
High
24 hours
3 days
45 days
Single/Multiple Dose Vials
• Definitions of SDV and MDV are in the USP
General Notices and Requirements
• Single dose vials – Opened or punctured in ISO 5
environment may be used for up to 6 hours.
Opened or punctured in worse than ISO 5 must
be used within 1 hour or discarded.
• Single dose ampuls must be discarded after
opening and not stored for any time period
Single/Multiple Dose Vials
• Multiple dose vials – Contain antimicrobial
preservative(s)
• Designed for entry on multiple occasions.
BUD – 28 days after initial entry unless
specified otherwise by the manufacturer.
• BUD of 28 days based on USP <51>
Antimicrobial Preservative Testing
• Expiration date on vial is based on an
unopened, properly stored vial.
Proprietary Bag/Vial Systems
• ADD-Vantage; Add-a-Vial, Minibag Plus,
etc.
• Follow the manufacturer’s instructions for
handling and storing.
• These devices and their instructions have
been approved by the FDA
• BUD ranges from 15 days to 10 weeks
Hazardous Drugs
•
•
•
•
Section extensively revised
NIOSH Guidelines for guidance
BSC or CACI required
Hazardous drug storage and preparation in
separate negative pressure ISO 7 with ISO
7 ante area
Hazardous Drugs
• Personnel protection specified
• Use of closed-system transfer devices must
be within BSC or CACI
• Disposal according to state and federal
regulations
Allergen Extracts
• Intradermal and subcutaneous MDVs and
SDVs (No IV or IT)
• Unpreserved allergen extracts must fully
comply with all aspects of <797>
• Allergen extracts are exempt from
personnel, environment, and storage
requirements only if all of the following
criteria are met:
Allergen Extracts
• Personnel perform hand hygiene with
alcohol-based surgical hand scrub
• Hair and beard covers, gown, face mask,
and sterile gloves are used
• Compounded by simple aseptic transfer
• Must contain an effective amount of
antimicrobial preservative
• For one patient only
Allergen Extracts
• Collaboration with AAOA/JCAAI
• Research and discussions with experts
in the field
• Results of a peer-reviewed research
study of 26,795 injections (>98/patient)
with no infections
• Done in an uncontrolled environment
Cleaning and Disinfecting Facilities
• Based on Infection Control Advisory Committee
recommendations
• Goal: Reduce bioburden in compounding areas
• Use of disinfecting agent such as sterile 70% IPA
• Performed in ISO 5 environment:
1. At the beginning of each work shift
2. At the beginning of each batch
3. At least every 30 minutes
4. When surface contamination is known or
suspected
Cleaning and Disinfecting Facilities
• Cleaning should proceed from buffer area
(cleanroom) to ante area
• Use suitable dedicated mops, etc. and
disinfecting cleaners
• Floors, counters, work surfaces – at least
daily
• Walls, ceilings, shelving – at least monthly
Hand Hygiene
• USP Chapter <797> harmonized with CDC
Guidelines for Hand Hygiene
• Hand washing is defined as the vigorous,
brief (30 seconds) rubbing together of all
surfaces of lathered hands, followed by
rinsing under a stream of water.
• Hand washing suspends microorganisms
and mechanically removes them by rinsing
with water. The fundamental principle of
hand washing is removal, not killing.
• Single most important way to reduce the
risks of transmitting germs.
Hand hygiene1 is paramount to safety, as this agar imprint of an
unwashed hand shows2
1 http://www.cdc.gov/handhygiene/
2 E Larson. Am J Nurs, AJN. July 1989: 935
Personnel Cleansing and Garbing
• Remove outer garments and jewelry (including
piercings above the neck)
• Garb order from dirtiest to cleanest
• Don shoe covers, hair covers, face masks
• Perform hand/arm hygiene
• Don disposable gowns
Personnel Cleansing and Garbing
• Inside the clean area, cleanse hands and arms
with alcohol-based surgical hand scrub with
persistent activity
• After hands and arms are dry, don sterile powderfree gloves compatible with sterile 70% IPA
• Repeatedly apply sterile 70% IPA to contact
areas of gloves whenever nonsterile surfaces are
touched (e.g. vials, counter tops, carts)
Compounding Personnel
• Hair net
• Beard cover and face
mask
• Gown
– Nonsterile
• Gloves
– Sterile
• Shoe covers
Personnel Cleansing and Garbing
• All of the cleansing, garbing and gloving
requirements also apply to compounding in CAIs
and CACIs.
• Exception: If the manufacturer of the CAI or CACI
provides written documentation of statistically
validated testing supporting any garbing
component(s) that are not required.
• Trust but “verify” claims made by vendors to
ensure that all risks are understood
ISO Class 5 Sources, Buffer Areas,
and Ante Areas
Environmental Controls
• Aimed at creating ISO 5, 7, and 8 environments
• ISO 5 – LAFW, BSC, CAI, CACI are “Primary
Engineering Controls”
• Must maintain ISO 5 during dynamic (in use)
working conditions
• Unidirectional airflow required
Environmental Controls
• ISO 7 buffer area and ISO 8 ante area – are
“Secondary engineering controls”
• Must maintain ISO 7 or 8 during dynamic (in use)
working conditions
• Airflow and balance testing required at the
installation site
• Only personnel and materials essential for
compounding and cleaning are permitted
Environmental Controls
• ISO 5 Primary engineering control (LAFW, BSC,
CAI, CACI) to be in an ISO 7 environment
• Exception: CAI if its design provides ISO 5 and
isolation from the room during dynamic operating
conditions as placed and tested at your site
(including transferring materials in and out) using
CETA testing
• Do your “Due Diligence” to verify the accuracy of
any such claim
Missing Research
• Paucity of independent research
evaluations and comparisons of pharmacy
applications of primary and secondary
engineering controls.
• Unlike BSCs, CAIs and CACIs have not be
tested independently
• CETA CAG-003-2006 is an important
document to ensure consistent testing
Environmental Sampling
Environmental Sampling Task
• Dilemma:
– One of the most contentious section of USP Chapter
<797>
– Since 1970’s, the US Centers for Disease Control
(CDC) has not advocated routine viable
environmental monitoring
– The US Food and Drug Administration requires
sterile processing operations to perform daily
monitoring of viable air, surface and personnel glove
fingertip samples
Environmental Sampling
Routine Viable Microbial
Environmental Sampling (ES)
None
US Centers for
Disease Control
Daily
US Food and Drug
Administration
Environmental Sampling
Routine Viable Microbial
Environmental Sampling (ES)
None
USP 797
US Centers for
Disease Control
Daily
US Food and Drug
Administration
Environmental Sampling
• Designed to demonstrate that the primary and
secondary engineering controls, disinfecting
procedures, and work practices result in a
suitable environment for aseptic compounding
• Utilizes several approaches to assess and
evaluate
Environmental Sampling
• Environmental Sampling section has been
separated into a facility-related performance
metric and a personnel –related performance
metric
• Facility-related Environmental Sampling
– Viable air sampling via volumetric method (impaction) to occur at least
every 6 months
• Personnel-related Environmental Sampling
– Personnel fingertip sampling during initial training, with media fills and
as a competency assessment tool
– Surface sampling for viable microorganisms
Environmental Monitoring
• Viable Air Sampling
– Gravimetric vs. Volumetric Sampling
Courtesy of MSI, Inc. Houston, TX
(www.microbiologyspecialists.com)
Other Changes in <797>
• Radiopharmaceuticals quality assurance based
on Advisory Committee recommendations
• Expanded explanatory and descriptive material
in many sections
• Clarified language throughout
Closing Thoughts
• USP Chapter <797> is about more than just
cleanrooms and facilities
– IT IS A QUALITY SYSTEM and PATIENT SAFETY
• Involves
– Leadership (embrace evidence-based science and
best practices) even when its not convenient or
inexpensive
– Properly educated and trained pharmacists and
technicians
– Proper Employee Supervision and Feedback
– Control of Critical Practices & Consistent Work
Practices
– Documentation-NOT A PRACTICE IN FUTILITY
Be mindful of your practices and remember
there is someone who is loved by someone
receiving your CSP