Connecting a World of
Pharmaceutical Knowledge
Carolina-South
Atlantic Chapter
Volume 22 • Number 6
President’s Message
Greetings ISPE CaSA Chapter! As
2015 comes to an end, it’s the perfect
time to reflect on the past years’
accomplishments for our Chapter. Looking
back, we have had many inspiring
moments! Thanks to the hard work and
dedication of our Board of Directors and
Committee members, the CaSA Chapter
hosted two Education events in Atlanta.
Lisa Kerner
Plans are in the works for more events in
Atlanta, and a new reach into the Tampa market. This is a huge
accomplishment for our Chapter and it is exciting to see our
growth throughout the Southeast!!
RTP happenings remain solid! The 2015-16 Annual Planning
Session…a.k.a. “Oktoberfest” had record-breaking attendance
with 150 attendees. Oktoberfest was designed to re-engage
current members and motivate new industry friends to get
involved and join ISPE. The Networking Committee did an
amazing job organizing the event. This is just the beginning of
what’s to come in 2016!
The ISPE Annual Meeting was held November 8-11 in
Philadelphia with over 1800 industry professionals and students
in attendance. The CaSA Chapter was well represented by our
membership, as well as our Student Chapters. Each year, the
Chapter sponsors a group of Student Chapter representatives
to attend the Annual Meeting. This year, we proudly sponsored
12 students from North Carolina State University, North Carolina
Central University, East Carolina University and Campbell
University. These 12 students have been dedicated to serving
their University Chapters. Engaging the future generations of
leaders is a key initiative for CaSA and the value our Chapter
brings to the industry.
Looking ahead to 2016, I am honored to be working with
such a strong Board of Directors and Committees who have
embraced my vision to re-engage our members, recharge our
events and grow the CaSA Chapter by hosting great education
and networking events! Meaningful education events show the
value that ISPE brings to our membership and the Life Sciences
industry. And, we like to have fun too! So, don’t forget about
the networking opportunities the Chapter has to offer!!
Of course, the Chapter’s successes would not be possible
without you! We hope that you will join us at our upcoming
events! Keep an eye on your email for registration and
sponsorship opportunities.
See next page for a list of what’s coming up. See you soon!!
Lisa Kerner
President, ISPE CaSA Chapter
Re-Engage. Recharge. Grow.
CaSA News
Featured Sponsors
December 2015
4242 Switchbox
Position Indicator
• Class 1 Div 2
• Groups C & D
• High visibility
• Mechanical
• Override
• 24 VDC, AS-I,
• DeviceNet
For more details contact:
dcannon@gemu.com
www.gemu.com
3800 Camp Creek Parkway
Building 2600 • Suite 120
Atlanta, Georgia 30331
Tel: 678-553-3400
Fax: 404-344-9350
2
January 28, 2016
RTP Therapeutic Thursday at Blackfinn Ameripub
Morrisville, NC
INSIDE THIS ISSUE
President’s Message.................................................................1
2015-2016 Board of Directors..................................................2
February 27, 2016
Gala at the North Carolina Museum of Art
Raleigh, NC
Education Committee...............................................................3
CaSA Committees.....................................................................3
Networking Committee............................................................4
March 31, 2016
23rd Annual Technology Conference
Raleigh, NC
Welcome New CaSA Members.................................................5
Member Spotlight....................................................................6
Student Affairs..........................................................................7
April 2016
ATL and RTP Education Events
Technology Conference............................................................7
May 16, 2016
22nd Annual Golf Tournament at Prestonwood Country Club
Cary, NC
Board of Directors
Officers
Lisa Kerner, President
Bruce Craven, Vice President
Wendy Haines, Treasurer
Mike Putnam, Secretary
Heather Denny, Past President
Technology Corner....................................................................9
2015 Advertising and Sponsorship Opportunities..................13
Electronic Media.....................................................................14
2015-2016
Directors
Andy Ferrell
Chip Chappell
Wes Robbins
Committee Chairs
Marisol Patino, Student Affairs
Jim Hubbard, Education
Justin Rothwell, IT/Social Media
Eric Mayer, Networking
Terence Morrison, Membership Development
Jamie Sigmon, Young Professionals
Amy Lineberry, Technology Conference
Rich Stanfield, Newsletter
TrackSense Pro Sky Solution
Real Time Data
•
•
•
•
•
Lyophilization
Sterilization
Depyrogenation
Mapping Applications
Interchangeable sensors
For an in-depth demo contact | P. Roy Snipes
Regional Sales manager | rs@ellab.com | 919.414.9812
Carolina-South
Atlantic Chapter
3
Membership Corner
Education Committee
By Jim Hubbard, Education Committee
January 11, 2016 - Education Committee’s “Call for Partners”
(most spots were filled in 72 hours this year)
March 31, 2016 - Education sessions at the 2016 Tech
Conference in Raleigh
April 13, 2016 - Education/Networking event in Atlanta (new
market)
April 14, 2016 - Education/Networking event in Raleigh
June 23, 2016 - Education/Networking event in Tampa, FL
(new market)
CaSA COMMITTEES
How can you participate in growing Education in our
industry?
• Attend an event!
• Submit an abstract for the Tech Conference.
• Become an Education partner (there are many benefits for
your company).
• Volunteer as a member of the committee.
• Volunteer as a SME to speak at events.
• Offer suggestions for ideas or improvements.
Please call me to discuss how you can get involved in your
local ISPE-CaSA Chapter.
Jim Hubbard, Education Chair, 240-344-1109
√
2015-2016
Student Affairs
Marisol Patino
Young Professionals
Jamie Sigmon
Networking
Eric Mayer
Technology Conference
Amy Lineberry
IT/Social Media
Justin Rothwell
Education
Jim Hubbard
Membership Development
Terence Morrison
Newsletter
Rich Stanfield
ıķłĿĺķŊĿŅń
ĞŅŃŃĿʼnʼnĿŅńĿńĽ
ĜŋŊŅŃķŊĿŅńĠńĽĿńĻĻňĿńĽ
ĬŋķłĿŊŏīňŅĽňķŃʼn
ĮŅļŊōķňĻĨķńķĽĻŃĻńŊ
ĭĻŃĻĺĿķŊĿŅń
ħķĸŅňķŊŅňŏĤįĞŅŃņłĿķńĹĻ
ĮŋņņłŏĞľķĿńĬŋķłĿŊŏ
ĭĻŃŅŊĻĨŅńĿŊŅňĿńĽ
īňŅĹĻʼnʼnĪņŊĿŃĿŐķŊĿŅń
ōōōʼnĻŇŋĻńĹĻŇĹʼnĹŅŃ)ĿńļŅ"ʼnĻŇŋĻńĹĻŇĹʼnĹŅŃ)
ĢķŊĻōķŏĞĻńŊňĻĝłŌĺĮŋĿŊĻĨŅňňĿʼnŌĿłłĻĩĞ
Leadership. Compliance.
Reliability.
Calibration and maintenance services
from startup to operations to shutdown.
• Process systems • Laboratory systems
• Building utilities • Full asset management
877-724-2257
•
www.pci-llc.com
4
Membership Corner
Networking Committee
By Eric V. Mayer, Networking Committee
Thanks to all the ISPE-CaSA team for supporting Oktoberfest 2016! We had 18 great sponsors to insure the event was
a huge success. Thanks so much CRB, CAI, Watson-Marlow,
PCI, Hipp, STI, EMD, PEG, RGD, Avid, Bray, EHS, IPS, Hydro,
FLW Southeast, Statesville Process, Mettler Toledo, and Steris.
NNE Pharmaplan put on a great Therapeutic Thursday on
19 November at the Carolina Ale House. Save the date of 16
May for the ISPE-CaSA Golf Tournament at Prestonwood
Country Club. Sponsorship opportunities will be published
soon.
See below, upcoming networking events.
√
Boost your knowledge. Expand your network.
Date
Event
Sponsored By
ISPE’s
and Chapters
are your
resource for all things
ISPE—from
28 JanAffiliatesTherapeutic
Thursday
in local
Raleigh
ClarkNexsen
translations of ISPE’s world-renowned Guidance Documents to education on regional
industry
trends.
28 Jan and regulatory
Therapeutic
Thursday in Atlanta
TBD
25 involved
Feb
Therapeutic
Thursday
in or
Raleigh
Commissioning
Get
with
your regional
Affiliate
Chapter to meet industry
leaders inAgents
your area,
contribute your expertise to industry-advancing initiatives at the local level and share
best practices with like-minded professionals.
Connecting a World of
Pharmaceutical Knowledge
Get Involved With Your Affiliate or Chapter Today!
ISPE.org/Affiliates-and-Chapters
www.ISPE.org/Affiliates-and-Chapters
Bring it on.
R
mcdonaldyork.com | 919.832.3770
PHARMACEUTICAL/
BIOTECHNOLOGY PROJECT
SPECIALISTS
■
■
■
■
■
Project Planning/Design
Process & Facility Design
Scheduling/Cost Estimating
Construction Support
On-Site Resources
AARON SINK
919.755.1033
www.hipp-usa.com
Double Bonus
When You Join ISPE
By12.31.15!
(See next page for more details)
5
Membership Corner
$40 DISCOUNT NOW AVAILABLE FOR NEW INDUSTRY MEMBERSHIPS!
By Terence Morrison, P.E., CAP, LEED AP BD+C, ISA 84 SFS, Membership Development Committee
$40 DISCOUNT NOW AVAILABLE FOR NEW INDUSTRY
MEMBERSHIPS! Applications can be made online at
www.ispe.org/join, click on “Join Now” under Industry
Membership, and enter CASA2015 in the promotion code box.
Please remember ISPE’s Refer-A-Friend Program! Earn one free
month of membership for every friend you refer. All the details
are available at:
http://www.ispe.org/membership-referral-program
ISPE wants YOU! That’s why we have put together a custom-tailored offer that delivers ISPE’s full benefit package to increase your
knowledge, confidence and skill, together with 2 additional benefits that make joining an incredible value:
Technology Transfer (2nd Edition) –
ISPE Good Practice Guide
This easy-to-read, user-friendly resource will guide you step by
step through each phase of the process from planning and
development to final monitoring and improvement. Charts and
diagrams visually reinforce key points and a series of appendices
provide actual examples of technology transfer deployed in
real-world settings.
pharmaceutical lifecycle, chances are ISPE’s conferences cover
topics that meet your needs. Use this discount certificate and
save big $$$ on 4 of the industry’s most significant events.
If you have any question about ISPE or the CaSA Chapter,
please contact me at membership@ispecasa.org.
$250 Conference Discount Certificate
From aseptic processing technologies, to meeting with
regulators, to a showcase of the latest solutions for the
Welcome New Members
Industry
US$269/£219
New Members who joined October 9, 2015 through December 9, 2015
Kevin David Watkins
Larry Yudell
Leallyn T. Murtagh
Thomas Garrett Meshaw
Beth Smullen
Neil Corman
Jon Grutchfield
Kelly Principi
Maegan Leigh Smith
Miss Jordyn C. Weaver
Arinc Leishear
Dereze Juwan Kinsler
Pusp Bhatt
Ashley I. Bowen
Ciara N. Williams
Deshanae Meaders
Mariah Y. Richards
Shante Lunsford
Tydasia Felton
David Lauer
Kahlil DeRoche
Delineliz Zayas
Flavia Hoffmann
Robin Kumoluyi
Ananda Ghimire
Chiagozie Agbai
Eliran Nunez
Allison Lewis
Brittany L. Carson
Joanna M. Cheek
LaPrince Miller-Smith
Maryah E. Wright
Mia B. Hall
Nada Abuzaid
Nathalie Unico
Rommy Guevara
Mary Beth Pugh
Ken Jones
Dawit Sima
Jessica Faulkner
Kaci Kennedy
Porsha Thompson
Shaunetta Campbell
Ashley Stanley
Erik Kopache
Shahid Ali Nafees
Deanna Dahir
Carl B. Richardson
Chandi Carter
Tammy Strickland
Sam Dilks
Christian Estes
Ricardo Rafael Lopez
Daniel Santarsiero
Courtenay Knox
Frank Holley, Jr., Exe.VP
Kevin Hotter
Emily Pait
Jinxiang Zhou
Grant Dietrich
Jesse Faber
Tobin Weiseman
Tommy Thorn, Jr.
Laurene Fitzgerald
Bryan Raborn
Dionna J. Nobles
Join Now
Casey Holbrook
Greg Ahrens
Heather J. Stefan
Kathleen Naylon
Michael Prazma
Christine Knul
Bindu Battineni
Hershel Meadows
Randy Woodard
Michael Contino
Sarah Gabrielle Dillard
Dr. Sandra M. Davern
Hafsa Khanom
William Earl Boyd
Josh Hutson
Bruce Benson
Ann Doscher
Keith Kulowiec
6
Membership
Corner
7
CaSA Member Spotlight: Mariessa Rose-Lorraine Blunt
Q: What is your full name?
A: Mariessa Rose-Lorraine Blunt
.
Q: Birth Place?
A: Tucson, Arizona.
Q: College?
A: Campbell University, Buies Creek, North Carolina for both B.S.
and M.S. in Pharmaceutical Sciences.
Q: What is your present position? What do you
do at your job?
A: Campbell University, Buies Creek, North Carolina for both B.S.
and M.S. in Pharmaceutical Sciences.
Q: Tell me a little about your personal life.
A: I was born and raised in Southern Arizona and have only been
in North Carolina for almost 3 years. I have a 6 year old Cockapoo
dog named Daisy and 3 Siberian cats named R2D2, Skywalker, and
Jar Jar Binks. I am a frequent concert goer and big Star Wars fan.
Q: What is your present position? What do you
do at your job?
A: I am currently a second-year graduate student in the
Masters of Science in Pharmaceutical Sciences program. My
studies primarily focus on biotechnology/bioprocessing and
pharmacology. I am the current ISPE Campbell University Student
Chapter President.
Q: How long have you been with your
current employer?
A: This is my third year at Campbell University.
Q: Tell me how you ended up where you are
today.
A: I initially wanted to be a mathematician but since moving to
North Carolina I have discovered a passion for the pharmaceutical
industry and the role pharmaceutical scientists play in healthcare. I
would like to pursue a career in upstream process development.
Q: What is your favorite part of your job?
A: My favorite part about being a student is the opportunities I
have had to hold various officer’s positions in the ISPE Campbell
University Student Chapter. I truly enjoy being able to lead our Student Chapter to various community events and raise awareness of
the pharmaceutical sciences.
Q: How long have you been a member of
ISPE/when did you first join ISPE?
A: I joined the ISPE Campbell University Student Chapter in the
beginning of 2014. I have since been the 2014-2015 secretary
and the current President of our Chapter.
Q: What benefits have you realized from being
a member of ISPE?
A: The most important benefit I have gained from being a
member in ISPE is being able to network with people from all
aspects of the pharmaceutical industry that I normally would not
have been able to interact with. Also, being an active member of
my Student Chapter has helped me build my leadership and
organizational skills.
Q: Why are you still involved with ISPE?
A: ISPE provides multiple opportunities to network and continue
my education on current topics and trends that are happening in
industry. It is also enjoyable to be around like-minded, goal
oriented people.
Q: Any Mentors/Role Models that have helped
to shape your life?
A:I have met many great and kind people while being involved
with ISPE; however, Dr. Daniel Shin, Jamie Sigmon, and Dr. Wendy
Haines have been generous with their time and have given advice
that has been invaluable to me.
Q: If you weren’t involved in pharma/ biotech,
what business do you think you’d be in?
A: I have a strong passion for the arts and helping people, so I
could see myself doing Art Therapy with children.
Q: What is one skill you wish you had that you
don’t?
A: I wish I had better cooking skills.
Q: Any hobbies? What are they?
A: I have many hobbies that all revolve around creating art. I
love getting lost in any sort of art project, whether it is oil
painting, graphite sketching or sculpting.
Q: Do you collect anything?
A: I collect Star Wars memorabilia.
Q: Finish this sentence – “I need more….”
A: I need more laughter in my day. Sometimes, I often get caught
up in the stresses of upcoming exams, planning events, or my
research project. I need to remind myself more frequently to stop
and smile for a moment.
Q: Favorite Food?
A: My favorite food is sushi.
Q: What is something that people would be
surprised to learn about you?
A: Despite being born and raised in Arizona, I have never been
to the Grand Canyon.
Q: Last movie you saw?
A: Jurassic World
Q: For those in the early stage of their careers, what advice would you give them?
A: I would say start networking as soon as possible. Even if you are
unsure of what you would like to do in the industry, get yourself
out there and take every opportunity you can to learn and grow.
√
Student Affairs
7
Membership Corner
By Marisol Patiño, Student Affairs Committee
This month several of our ISPE student members attended
the 2015 Annual Meeting. We had a large group attend with
about 14 students representing 4 university student chapters.
Students were able to get a better understanding of all the
roles within the pharmaceutical industry:
“The annual meeting really broadened my knowledge
about the career paths available after graduation. Our department at school really encourages us to go into manufacturing,
but our students aren’t limited to that. They can just as easily
go into something like consulting or validation or supplying.”
They were inspired by the educational sessions:
“The Office of Manufacturing Quality talk made me more
interested in FDA policies and regulations. This talk revealed a
huge gap in my knowledge, and I got an idea about having an
acronym list for students, readily downloadable during the
talk.”
“Interacting with people at the exhibit was my favorite
activity. Whether it was asking about what they look for in
their new recruits or asking them about their instruments and
understanding the variety of latest technology used in Pharmaceutical sciences.”
They learned how to expand their network:
"I bought a GoPro and took selfies with everyone I saw to
help break the ice. I was open about how it was my first ISPE
Annual meeting and the professionals were so willing to open
up and educate.
“After the conference, I feel more confidence about talking
with industrial professionals and networking.”
Some of the highlights for the students included a bowling
social with other students and young professionals, meeting
the local CaSA chapter executive board, and meeting John
Bournas, CEO of ISPE globally (they got a selfie with him!).
Next, the students will be encouraged to begin working on
posters to enter the poster competition in March at the
ISPE-CaSA Technology Conference. The winners earn an
all-expenses paid trip to the 2016 Annual Meeting in Atlanta
and a chance to compete nationally.
√
Technology Conference 2016 Is Right Around the Corner
By Amy Lineberry, CPIP, Technology Conference Committee
We are happy to announce exhibitor registration opened
on December 8, 2015 for the 23rd Annual ISPE-CaSA Life
Sciences Technology Conference. Be sure to visit
www.ispe-casa.org/2016 to reserve your table or booth
today, as they are sure to sell fast! Be sure to keep an eye on
your email for more announcements about the Technology
Conference. This should be the best conference yet, with
more tables and great education sessions. We are also
working to secure a great Keynote with more information
about new things happening in the CaSA region. Attendee
registration will open in January. We hope to see everyone
on March 31, 2016 at the Raleigh Convention Center.
Exhibitor Registration NOW OPEN!!!
√
9
Technology Corner
The cycle development approach
By Kevin Debbs
Senior Pharmaceutical Specialist – CRB
described in this document is fairly
universal and should not be
dependent on individual isolator
systems. The terminology used may
be slightly different depending on
the technology, but the general
principles, process descriptions, and
process and execution steps can still be
applied across various isolator systems.
PURPOSE
The purpose of this white paper is to provide a High-Level
overview and road map to plan and execute of the following
aspects of H2O2 decontamination cycle development.
• A process overview of the Vapor Hydrogen Peroxide (H2O2)
decontamination cycle.
• The planning and pre-requisite activities that must be completed prior to the execution of the H2O2 decontamination cycle
development.
• Execution of the H2O2 decontamination cycle development.
• Performance Qualification (PQ) of the H2O2 decontamination
cycle development.
H2O2 DECONTAMINATION CYCLE PHASES
The typical decontamination cycle consists of four separate and
distinct phases: Pre- Conditioning, Conditioning, Decontamination and Aeration.
1. Pre-Conditioning
a. The initial physical conditions of temperature, humidity and
air velocity inside the isolator are established. Additionally,
the vaporizing plates are heated to a set-point temperature
and the liquid H2O2 is delivered to the vaporizing plates.
Typically the control system of the isolator will determine if a
sufficient amount of liquid H2O2 is available to complete the
decontamination cycle. H2O2 is not injected into the isolator
during this phase. This phase only establishes the proper
2.
3.
4.
a.
condition to successfully and repeatedly execute the H2O2
decontamination.
Conditioning
a. During the conditioning phase, vapor phase hydrogen
peroxide is introduced into the isolator chamber and prepares
the isolator environment for the desired decontamination
effect.
Decontamination
a. Decontamination is the process step where the desired de
contamination effect is achieved.
Aeration
Aeration is the final process step that removes the residual
H2O2 from the Isolator to a specified set point.
Figure 1
1.
2.
3.
4.
Preconditioning
Conditioning
Decontamination
Aeration
10
H2O2 DECONTAMINATION CYCLE DEVELOPMENT
PREREQUISITES
Prior to initiating cycle development, there are items that should
be completed. Each of these items will affect the cycle development for the H2O2 cycle. As testing is completed and compiled,
keep in mind that the end goal is to have an effective and efficient
H2O2 cycle.
1. Execute FAT
a. Factory acceptance testing should be completed prior to
executing H2O2 cycle development. A popular approach
recently is to perform as much of the installation verification
(IV) and functional testing as possible during the Factory
Acceptance Test (FAT) and then leverage all this testing going
forward. This leveraged approach enables testing to begin early
in the Commissioning/ Qualification/ Validation (CQV) process
that can help to save time on the overall project schedule and
save significant money. Testing is only executed once and is
referenced or leveraged in subsequent CQV documentation.
This also provides early confidence the system was fabricated
and assembled in accordance with the design documentation
and functions as intended. Problems that are identified during
the FAT can be fixed in the vendor’s shop prior to shipment.
2. Perform Airflow Pattern Testing
a. Airflow pattern testing to visualize the airflow patterns inside
the isolator should be performed during the FAT and then
repeated after installation once the isolator is installed on
the filler. This testing can be used to select the worst case
positions.
3. Perform High Efficiency Particulate Air (HEPA) Filter
Certification
a. The upstream side of the filters is challenged with an Emory
3004 aerosol and then the filter faces are scanned with
photometers to determine overall leakage.
4. Loop Checks and Calibration of Instruments for Critical Process
Parameters
a. Prior to or during the FAT, instrument loop checks should be
performed for all digital and analog inputs and outputs. This
will provide evidence that the instruments are wired correctly,
the proper signals being exchanged and displayed on the HMI
and the instruments are measuring within the proven
acceptable range.
b. Instruments that measure and monitor critical process
parameters must be calibrated to ensure the instruments are
accurate and precise within proven acceptable ranges, thereby
allowing the H2O2 decontamination process to be properly
characterized and defined.
5. Determine the Isolator Load Pattern
a. Isolator Load Pattern should be defined with the worst
case load of items inside the isolator to challenge the
decontamination cycle. The items loaded into the isolator will
affect the airflow, the decontamination time, and the duration
of aeration.
b. The exact quantity and location of each items needs to be
defined and documented so the load pattern can be
consistently repeated without variation which would then help
to ensure that the decontamination cycle can be successfully
re-qualified without deviations.
6. Perform Manual Cleaning
a. The internal surfaces of the isolator including the inside and
outside of each glove, the filler and the ancillary equipment
should be thoroughly cleaned manually with 70% IPA or an
approved cleaning solution. The H2O2 decontamination
process is a surface decontamination process and will not
penetrate into cracks, crevices and other occluded surfaces if
the isolator is not properly cleaned. Therefore, the H2O2 de
contamination process is only as good as the cleaning process.
b. This initial cleaning could be combined with a bio- burden
reduction study to evaluate the bioburden post cleaning.
7. Qualify the Room Environment
a. The background room environment must be commissioned
and qualified to provide a controlled and stable environment
with respect to differential pressure control, temperature and
humidity, so the isolator and the decontamination cycle can be
qualified.
b. The Environmental Monitoring Performance Qualification
(EMPQ) does not necessarily need to be completed prior to
executing cycle development.
8. Determine the Process Sequencing
a. Cleaning and Cooling
i. The cool zone sterilization of the depyrogenation tunnel
(if applicable), the CIP / SIP of the filling equipment and the
H2O2 decontamination cycle should be sequenced in such a
way to avoid hot surfaces during the decontamination cycle.
Hot surfaces present a worst case situation to achieve the
desired killing effect and should be avoided during the
decontamination cycle. Optimizing the sequence of operations
can reduce the overall cycle time between lots / batches.
ii. The optimal way to sequence these activities is to initiate a
cool zone sterilization of the dry heat tunnel (if applicable) and
a CIP cycle concurrently. These two activities can also be
sequenced in series (one after the other) if cycle time is not
important.
iii. Once the surfaces inside the isolator that were exposed to
elevated temperature cool to < 40°C, the H2O2 the
decontamination cycle can be initiated.
iv. When the decontamination cycle progresses to the aeration
phase and is approximately < 10ppm, the SIP cycle can be
initiated. Otherwise the SIP can be started once the aeration
phase is complete and the residual H2O2 acceptance criteria
levels have been achieved. Starting the SIP of the filling loop
during aeration is a way to shave some time off of the entire
cycle time if aeration is a long process.
9. Glove Integrity Testing
a. Both physical and visual glove integrity testing should be
performed prior to each H2O2 decontamination cycle. Physical
tests usually involve one of three methods: a flow test, a pres
sure decay test or a trace gas sensing method to detect leaks.
Each physical test method has their advantages and
disadvantages; therefore, each method must be properly
evaluated. Visual inspection should also be paired with physical
testing to check for gross defects. Furthermore, visual
inspection of isolator gloves should be performed during each
isolator intervention.
b. Following the glove integrity testing, glove extenders or
11
glove holders should be used to extend the gloves inside the
isolator to eliminate folds and creases that prevent the gloves
and sleeves from being fully exposed to H2O2. Depending on
the isolator design, it may be necessary to extend the isolator
glove on the outside of the isolator to execute the glove
integrity testing on select gloves. In this situation, a negative
pressure chamber can be used to extend the gloves outside
the isolator.
c. Glove integrity testing and insertion of the glove extenders
or glove holders are typically the last pre- requisite operation
performed in the isolator prior to initiating the H2O2 deconta
mination cycle.
10.Determine the Biological Indicator (BI) vendor and qualify the
lot of BIs.
a. The BI vendor and the individual lots of BIs must be qualified
prior to cycle development to understand the BI performance
with respect to D-value. Too often cycle development is
executed without knowing the D-value of the BI and how it
performs within a specific isolator with a specific process.
b. The BI also needs to be evaluated for identification and
population.
c. The gold standard BI for H2O2 Decontamination Cycle
Development is Geobacillus stearothermophilus with a
population of 1 x 106 spores per carrier on a stainless steel
coupon as represented by ATCC 12980 from Apex Labs.
H2O2 CYCLE DEVELOPMENT EXECUTION
The cycle development of the H2O2 bio-decontamination can be
executed in a progressive manner. BI qualification and Chemical
and temperature mapping must occur prior to developing a worst
case study.
1. BI Qualification
a. D-value: The resistance of a BI against a defined inactivation
method is expressed by decimal reduction per unit of time
(min).
b. The D-value describes the time unit it takes to reduce the
test organism population 90%.
c. Conduct a series of D-values studies to understand the re
sponse of the BI (relative resistance and behavior) and the
killing effect of the corresponding cycle development
parameters that created the conditions in the target isolator
environment by use of a Fractional-Negative method.
d. The D-value studies are executed by exposing pre- deter
mined groups of BIs with multiple BIs per group to H2O2 vapor.
e. At pre-defined intervals, each group of BIs are removed from
the isolator environment and evaluated using a growth
promotion test.
f. The goal of the fractional negative method is to achieve a
total-kill of the test organism via growth tests and then deter
mine the D-value and survival/kill window.
g. The D-values studies are executed in a location inside the
isolator that will provide the best exposure conditions to the
vaporized H2O2. This will generally be a location immediately
below the HEPA filter where the H2O2 vapor is being
generated or being injected. There should also be no airflow
obstructions above or around the BIs used in these studies.
h. The calculation of the D-value mean is the average of three
D-value evaluations plus a 25% safety factor.
i. Use the D-value mean to design the length of the
decontamination portion of the decontamination cycle.
2. Temperature, Humidity and Chemical Indicator (CI) Mapping
a. Thermocouples and / or temperature and humidity sensors
are used to map the temperature and humidity conditions on
various surfaces inside the isolator.
b. High temperature and low humidity would be indicative
of a worst case location for the killing effect of H2O2.
c. These locations should be included and challenged with BIs
as part of the cycle development worst case study.
d. A chemical indicator is used to demonstrate H2O2
distribution within the isolator system.
e. The chemical Indicator challenge can be executed as an in
dependent test or executed in conjunction with temperature
and humidity mapping. If the chemical indicator challenge is
executed independently, the CIs with the worst color change
should be included and challenged with the BIs in those
locations as part of the cycle development worst case study.
3. Worst Case Biological Indicator (BI) Study
a. The worst case study is accomplished by first selecting
the challenge locations inside the isolator. These challenge
locations should be selected based on the results of the
preceding tests that were executed as well as some geometric
locations.
b. The worst case study is executed with three (3) BIs per
location. The worst case study can easily have between 100 –
150 BI Challenge locations depending on the size and
complexity of the filling and isolator systems. Finally, it is
critical that Engineering and C&Q are aligned with the Quality
group on the identification and selection of the worst case
locations. This agreement should be formalized by having
Quality review and approve the H2O2 Cycle Development
protocol.
c. Locations to be considered / selected and included in the
worst case study:
i. The worst case airflow pattern locations can be locations
where there is not turbulent flow or locations that are under
equipment, devices, instruments, motors, conveyors, under
windows, corners, etc. Direct observation and / or video
analysis of the airflow patterns will allow you to easily visualize
the problem areas that may present challenges to achieve the
desired decontamination effect.
ii. The temperature and humidity mapping locations that
demonstrated elevated temperatures and lower humidity
should be included in the worst case study. These temperature
and humidity locations may present more difficulty in
achieving the desired killing effect.
iii. The chemical indicator mapping locations that had the
worst color change should be included in the worst case study.
iv. Occluded Surfaces are all hard to reach locations where the
airflow of the isolator system may have trouble delivering the
vaporized hydrogen peroxide to achieve the desired killing
effect.
v. Critical Zones are areas within the filling and isolator systems
where there is manipulation of product contact parts including
isolator gloves and sleeves. Additional locations should be
selected to properly challenge the isolator system to
consistently and effectively achieve the desired
decontamination effect.
vi. The E-Beam tunnel (if present) is typically part of the sur
face area that is decontaminated with the isolator system. The
E-Beam should be included in all of the appropriate testing to
12
evaluate the system during H2O2 cycle development.
vii. Entrances and Exits to the isolator system need to be i
ncluded in the worst case location study to properly evaluate
the isolator system. This should include all transfer locations
such as Rapid Transfer Ports (RTPs), transfer isolator locations
and piping connections.
viii. BIs should also be placed on gloves and sleeves. Typically,
BIs are placed in two general positions: The first on the sleeve
in the most challenging position as the gloves are extended
into the isolator and secondly on the fingers of the gloves. To
determine the final sleeve position(s), each glove extender
length needs to be determined, fixed and consistently
replicated for each decontamination cycle.
ix. Consult the quality group to see if there are locations inside
the isolator they want to see challenged as part of the worst
case BI study. This strategy may eliminate second guessing and
questions as the CQV activities proceed and the protocols and
summary reports are approved.
4. Aeration Study
The aeration study is executed by running the final cycle that
was determined through the cycle development studies. This
final cycle is then initiated.
a. When the cycle transitions to the aeration phase, use a
Draeger hand pump and Draeger tubes to evaluate the residual
H2O2 levels at various time points.
b. When two consecutive residual H2O2 readings are in the
same Draeger Tube range, the aeration endpoint is established.
However, the endpoint can only be established if the minimum
required H2O2 level has been achieved in accordance
with the residual ppm level defined in the User Requirements
Specification (URS).
Note: The URS endpoint is either established as an Operator
Exposure Level (OEL) requirement of ≤ 1ppm or a product
specific requirement to prevent oxidation and degradation of
the drug product being filled within the isolator environment.
5. Performance Qualification
The PQ for the H2O2 decontamination cycle shall be per
formed by running three consecutive decontamination cycles
with three BIs per location. The PQ runs will use the
parameters and conditions that were established during the
cycle development work. If the filling system requires CIP and
SIP, these activities should be included in the PQ test plan and
protocols. An alter native approach is to use a reduced
decontamination phase of vthe decontamination cycle to
execute the PQ for a more challenging qualification.
1. The number of BIs locations used in the PQ can be reduced
vs. the total number exposed during the worst case study.
2. The reduced number of BIs can be based off the findings and
results for each of the individual tests during cycle
development.
For example, the number of BIs for the PQ Study can be determined from the worst case locations identified during
Temperature and Humidity Mapping, chemical indicator study
and from the airflow pattern testing. Once this strategy is defined
and the number of BIs is determined, this should be
applied to the periodic requalification procedure.
About the Author
Kevin Debbs, CPIP
Kevin Debbs is a Senior Pharmaceutical Specialist at CRB with over 23 years of aseptic manufacturing experience in the
pharmaceutical and biologics industries. He has designed, constructed and qualified new facilities, equipment systems and
manufacturing processes. He has successfully launched new products and line extensions, while continuously
improving product quality, patient safety and value to the organization. Kevin has also led teams in the design,
construction, commissioning and qualification of manufacturing plants, laborites and support services.
His expertise includes aseptic and sterile manufacturing processes, including isolation technology and lyophilization.
He is skilled at preparing and executing protocols, designing experiments, statistical process control, performing risk
analysis and engineering evaluations to ensure designs and processes meet quality and performance standards.
He has developed User Requirement Specifications (URS), Design Qualifications (DQ), System & Component Impact Assessments,
Validation Plans and IQ/ OQ protocols. In additions, Kevin is able to perform job safety analysis to identify and mitigate operational
hazards to minimize or eliminate costs related to health, safety and ergonomic injuries.
Contact Kevin at kevin.debbs@crbusa.com or 919-852-5494.
13
Advertising Opportunities in ISPE-CaSA 2016 Electronic Newsletter
The ISPE CaSA Chapter produces six e-newsletters per year. ISPE CaSA sends out the newsletters via email and via Web link to all of our Chapter Members throughout the Southeastern U.S., which reach top-notch
pharmaceutical, biotechnology, and bio-science professionals and managers. These newsletters are also
posted on our Web site so your ad can be accessed by interested visitors to our site.
The cost for a full color business-card-sized ad is $750 per year. There is also the ability of positioning your
ad on the front page of the newsletter for an additional $750 per year for six issues. Space limits the number
of front page to only four, and is offered to the first four paid advertisers on a first-come, first-served basis.
Also, if you would you like to have your targeted customers go directly to your website by simply clicking on
your ad; a hot-link can be added to your submitted ad file for an additional $500.00 for the entire year.
You may choose one of the special offers below:
$1,500 Full-color ad for six issues on the front page of each newsletter ($250/issue)
 $1,500 Full-color double-sized ad for two issues ($250/issue)
 $750 Full-color ad for two issues ($125/issue)
 $200 Full-color ad in 1 newsletter of your choice ($200)
 $500 Add a hot link for directing customers to your website by a simple click ($500)
We hope you will take advantage of these opportunities and advertise in the 2015 ISPE CaSA e-newsletter.
To reserve a placement of your ad for 2015 please contact the ISPE-CaSA Headquarters at 919-573-5442 or
via e-mail at info@ispecasa.org. Deadline for 2016 advertisers to be in the February 2016 issue is
January 22.
You will be notified via e-mail or telephone when your advertisement has been accepted by the ISPE-CASA
Newsletter Committee and asked to submit your advertisement digitally.
Full-color business card-sized ads (3.5” x 2”) may contain your logo or other artwork. Artwork should be sent
directly to newsletter@ispecasa.org.
We ask that your text be no smaller than 12 pt so that the text is easily readable in the electronic format.
PDF, JPEG, or TIF formats, are easiest for us to work with. Space is limited, sign up today!
14
ISPE CaSA Chapter
E-Newsletter Ads
Newsletter Ads Work
for Your Business!
Our Chapter produces six enewsletters per year, and we depend
on the support of our advertisers.
We send out the newsletters via
e-mail and via web link to all of our
Chapter Members throughout the Southeastern U.S.
That means you get targeted access to top-notch
pharma, biotech, and bio-science professionals and
managers. These newsletters are also posted on our
website so your ad can be accessed by interested visitors
to our site.
Best of all, the cost is only $750 for your full color,
business-card-sized ad for six insertions. That’s only $750
for targeted advertising in full color for an entire year!
Ask About
HOT LINKS!!
Would you like to have targeted customers simply click
on your ad and get right to your website?
A hot-link can be added to your ad, connecting readers
directly to your company website for an additional
$500.00 for a whole year.
If you are interested in advertising with the ISPE CaSA
e-newsletter, please contact our Chapter headquarters at:
ISPE-CaSA
1500 Sunday Drive
Suite 102
Raleigh, NC 27607
919-573-5442
info@ispeCaSA.org
You will be notified via e-mail or telephone when your
advertisement has been accepted by the ISPE CaSA
Newsletter Committee and asked to submit your
advertisement digitally.
Full-color business card-sized ads (3.5” x 2”) may
contain your logo or other artwork. Artwork should
be sent directly to info@ispeCaSA.org.
We ask that your text be no smaller than 12 pt so
that the text is easily readable in the electronic format.
PDF, JPEG or TIF formats are easiest for us to work
with. Space is limited, sign up today!
15
ISPE Carolina-South Atlantic
Chapter Newsletter
1500 Sunday Drive, Suite 102, Raleigh, NC 27607
Tel: 1-919/573-5442 • Fax: 1-919/787-4916
rich.stanfield@cagents.com
Would you, or someone you know,
like to publish your technical
content in these pages?
Please submit any and all technical content to
info@ispecasa.org or send directly to our Newsletter
Chair at rich.stanfield@cagents.com.
EDITORIAL POLICY
Articles should be written for technical
professionals in the pharmaceutical, biotechnology,
and medical device industries. The author is
responsible for the accuracy and correctness of all
statements contained in the manuscript (ISPE
Carolina-South Atlantic Chapter assumes no liability.)
Manuscripts should be submitted with a brief, three
to four sentence synopsis of the article, as well as a
brief biographical statement about the author that
includes educational background, title and job
affiliation, job responsibilities and major areas of
accomplishment.
A word to the ISPE CaSA Newsletter advertisers:
Thank you all for your continued support. Without it we
could not have the wonderful support staff to get our ISPE
CaSA Members the news in such a timely and professional
fashion. If you have updates to your advertisements or
find any other error, please contact us so that we can serve
you better.