NovemberDecember 2012

Letter
P e o p l e S c i e n c e R e g u l a t i o n
Volume XLVIII Issue 10 www.pda.org/pdaletter November/December 2012
QbD Offers Opportunities,

Challenges for Vaccine Makers
22
26 Simplify Quality 32 Make a Lasting 34 Q10 Implementation Key for

Systems, Experts Say Impression During PAI Executive Management
2013 PDA European
Virus & TSE Safety Forum
4-6 June 2013 | Berlin | Germany
Call for Papers and Posters

On behalf of the Program Planning Committee and the Co-Chairs Hannelore Willkommen (RBS Consulting) &
Kurt Brorson (FDA), we would like to invite you to submit a paper or poster abstract for presentation at the 2013
PDA European Virus & TSE Safety Forum to be held in Berlin, Germany on 4-6 June 2013.
Paper abstracts and posters must be non-commercial in nature, describing new developments or work that
significantly contributes to the body of knowledge relating to all aspects of Virus and TSE safety of medicinal
products (biotech products, plasma products, ATMPs, vaccines).
Suggested topics include, but are not limited to:
Emerging Viruses of Concern Virus Clearance by Specific Unit Operations

(PARV 4, HEV, Heartland Virus) (Mechanism of Action, Robustness, Critical Process
Parameters, Virus Carry-Over Studies, Impact of Virus
Virus Safety of Starting and Raw Materials Spike Quality)
(PCV Inactivation & Removal Studies, Reduction by
Chromatography, Traditional Virus Safety Testing and TSE Clearance
its Limitations, Modern Methods for Virus Detection) (Cell-based Assays, Prion Specific Filtration Methods,
Scaled-down Throughput Studies)
Risk Mitigation
(Root Cause Investigations, Preventive Actions) TSE Risk Evaluation
(Case Studies, Infectivity in Cell Substrates)
Case studies are particularly desired. Commercial abstracts for papers or posters will not be considered.
All submitted abstracts will be reviewed by the Program Planning Committee - submitters will be advised in writ-
ing of the status of their abstract after 31 January 2013, or 17 May 2013, respectively.
PDA Europe will provide one complimentary registration per podium presentation. Additional presenters and post-
er presenters are required to register for the conference at the prevailing registration fee. In addition, all presenters
are responsible for their own travel and lodging. If you have any questions please do not hesitate to contact us.
Submissions received must include the following information:
- Title - Phone number

- Presenter - Fax number
- Presenters biography (approx. 100 words) - E-mail address of the presenter
- Additional authors - Key objectives of your topic
- Full mailing address - 2-3 paragraph abstract, summarizing your topic
Please send your abstract and the required information to Ailyn Kandora (PDA Europe) at kandora@pda.org.
Attention Exhibitors
PDA is seeking vendors who provide excellent products or services in support of the conference. Space is limited
and is allocated on a first-come, first-served basis. To reserve your space, please contact Creixell Espilla-Gilart
at espilla@pda.org or via telephone +49 (0) 33056 23 77 14.
Deadlines Abstracts of papers for presentation: 30 November 2012

Poster abstracts: 3 May 2013
CO NFE R E N CE 4- 6 June | E X HIB I T I O N 4- 6 June

The Parenteral Drug Association presents...
2013 PDA Europe

Pharmaceutical
Microbiology
Product Quality Microbiology
Keys for Successful Implementation
A comprehensive program will include presenta-

tions from regulatory, industry and technology
representatives from around the world.
Some of the highlights of the conference include:

Rapid Microbiological Methods including
validation of the methods
Biofilms and water systems
Environmental monitoring
Contamination control
Open panel discussion with regulators
Following the conference training courses

covering Rapid Microbiological Methods,
Biofilm and Contamination Control are offered.
Register by
4 Jan 2013
and SAVE!
26-27 February 2013

Hotel Marriott
Berlin | Germany
CONFERENCE 26-27 Feb | EXHIBITION 26-27 Feb | TRAINING COURSES 28 Sep-1 Mar
https://europe.pda.org/Microbio2013
Volume XLVIII Issue 10
Letter www.pda.org/pdaletter
Cover
22 QbD Offers Opportunities, Challenges for Vaccine Makers
Can both quality improvements and reductions in regulatory burden be realized by vaccine manu-
facturers who use the Quality by Design approach? Three FDA representatives shared their views
on this very topic at PDAs Applying QbD Principles in Vaccine Development workshop in May to
address this question and other questions regarding QbD and its viability to a cohort of manufactur-
ers that has not readily adopted QbD.
Cover Art Illustrated by Katja Yount
Departments
News & Notes Programs & Meetings

7 PDA Europe is Hiring 44 Explore Manufacturing Trends at the 2013 Annual Meeting
7 Have Impact on the PDA Letter 46 Experts Offer Guidance on Delivering Vaccines Worldwide
People TRI Education

8 Volunteer Spotlight: Lara Soltis, Texwipe, an ITW Company 48 2012 Closes With a Successful Year for TRI
8 2011 Honor Awards Recipients: The Service Appreciation Award
10 Faces & Places: 2012 PDA/FDA Regulatory Conference Voices of PDA
16 Tools For Success: 8 Reasons Why Opportunity Never Knocks On 52 Voices of the Board: Anders Vinther
Your Door
54 Editors Message: Another Volume Year in the Books
Science
18 Science Snapshot: New Process Created for Technical Report
Development; Technical Report Watch: PDAs Latest Technical
Report Demystifies Statistical Methods; Journal Preview: Final
Journal of the Year Looks at Quality
Regulation
34 ICH Q10 Implementation Key for Executive Management
38 Timeline of Relevant FDASIA Deadlines
40 Regulatory Snapshot: Interest Group Corner: New Interest
Group Seeks Answers for Outsourced Operations Issues
43 Regulatory Briefs
Contents
Features
26 Simplification Can Improve Quality Systems, Experts Say
Are pharmaceutical quality systems too complex to be effective? According to an industry expert
and a regulator, they are, and an injection of simplicity will help manufacturers improve quality
performance.
32 Make a Lasting Impression During Preapproval Inspection

Everyone knows how important first impressions are. From a first date to a job interview, being
prepared is always critical, and the lack of preparation can have lasting negative effects. This is
especially true for preapproval/prelicensing insepctions. Preparation for this event is key, even for
companies with products already on the market, for the preapproval inspection is the moment to
demonstrate to the regulatory authorities that your firm is able to produce a quality drug product.
PDAs Mission PDAs Vision

To develop scientifically sound, practical To be the foremost global provider of science,
technical information and resources to advance technology, and regulatory information
science and regulation for the pharmaceutical and education for the pharmaceutical and
and biopharmaceutical industry through the biopharmaceutical community
expertise of our global membership
Executive Staff
Richard Johnson Robert Dana David Hall Wanda Neal
President Sr. VP, Regulatory Affairs & TRI VP, Sales VP, Programs & Registration Services
Craig Elliott Adrienne Fierro Rich Levy, PhD Georg Roessling, PhD
CFO VP, Marketing Services Sr. VP, Scientific & Regulatory Affairs Sr. VP, PDA Europe
PDA Board of Directors

Officers
Chair: Anders Vinther, PhD Chair-Elect: Harold Baseman Treasurer: Rebecca Devine, PhD Secretary: Steven Mendivil Imm. Past Chair: Maik Jornitz
Genentech ValSource Regulatory Consultant Amgen Sartorius Stedim Biotech
Directors
Ursula Busse, John Finkbohner, Zena Kaufman, Junko Sasaki, Dainippon Lisa Skeens, PhD Martin VanTrieste,
PhD, Novartis PhD, MedImmune Hospira Sumitomo Pharmaceuticals Hospira Amgen
Jette Christensen, Gabriele Gori, Michael Sadowski, Sue Schniepp, Christopher Smalley, Glenn Wright,
Novo Nordisk Novartis Baxter Healthcare OSO BioPharmaceuticals PhD, Merck Eli Lilly
News & Notes
Coming Soon
New PDA Member Benefit
Soon to be Added
PDA MEMBERS ONLY:
Welcome to Your Technical Report (TR) Portal
In this new portal, PDA members will be able to
view the complete library (or collection) of PDA
Technical Reports (TR).
The Technical Report Portal will be accessible to

current Standard and Government members only
and is for online viewing only. After logging on
with your PDA ID number and password, you will
be able to view the documents but cannot print,
share or copy the documents. As a reminder,
sharing your PDA ID number and password is not
allowable under PDAs membership rules and
may result in loss of privileges.
All print versions of the PDA Technical Reports are available for purchase at the PDA Bookstore.
PDA members are able to download electronic versions of newly released Technical Reports free of charge
within 30 days of publication as a standard member benefit. Make sure PDA has your current email address to
receive notifications when a new Technical Report is available for download.
PDA Technical Reports are highly valued membership benefits. They are global technical documents, prepared
by member-driven Task Forces comprised of content experts, including scientists and engineers working in the
pharmaceutical and biopharmaceutical industry, regulatory authorities and academia.
By the end of the year, PDA Members will be able

to view all of PDAs Technical Reports for free!
www.pda.org/trarchive
6 Letter November/December 2012

News & Notes
PDA Europe is Hiring The Parenteral Drug Association presents...
PDA Europe is looking for a Senior Director to assist SR. VP

Georg Roessling.
2013 PDA Europe
Position Description
The person in this position will be the deputy to the Head of Parenteral Drug
Development
PDA Europe. He/she will be in close exchange with the PDA
membership, the PDA headquarters in the United States, and
the Advisory Boards of PDA to identify the information needs
of members. Activities according to PDAs strategic plan will
include the development and organization of conferences, A good product development ensures less manu-
workshops, seminars and training courses. facturing problems and reliable product quality.
Tasks
The topics at the meeting deal with:
Develop conferences and training courses
- Workshop on VHP decontamination:
Give presentations and present training courses
Budget responsibility
Risks to development and product stability
Personnel responsibility - Process issues
Travel - Phase appropriate validation
Education/Experience - Future of clinical trial manufacturing
Background and degree in natural sciences (Biology, Phar- - Regulatory inspections of
macy, Physics, Chemistry) or related experiences clinical manufacturing sites
Minimum ten years experience in industry: Pharmaceutical
Including
or related industry with proven experiences
a Site Visit at
Excellent knowledge of CMC and pharmaceutical processes Boehringer
General knowledge about pharmaceutical product develop- Ingelheim
ment and manufacturing
Distinguished service and history of contributions to PDA
sponsored activities
Excellent communication skills
Knowledge of the relevant Microsoft tools
Fluent in German and English
Location of office: Glienicke/Berlin,
Germany
Position is open from January 1, 2013
Contact: Roessling@pda.org.
Register by
14 Dec 2012
Have Impact on the PDA Letter and SAVE!
The PDA Letter Editorial Committee 11-13 February

is looking for active PDA members
to provide ideas for and comment on
2013
articles for the PDA Letter. For more Maritim Hotel
information about this two-year vol- Ulm | Germany
unteer commitment, please contact
Rebecca Stauffer at stauffer@pda.org
WORKSHOP | CONFERENCE | E XHIBI T ION
by December 1.
https://europe.pda.org/ParDrug2013
Letter November/December 2012 7
People
Volunteer
Lara Soltis, Texwipe, an ITW Company
Areas of Volunteerism: Chapter President, Chapter Secretary, Chapter President Elect
Your Job Title: Regional Sales Manager
PDA Join Date: 1998
Interesting fact about yourself: I started taking Karate this year and love it!
Why did you join PDA? I joined to keep abreast of hot regulatory topics in the industry (I was a QC Mi-
crobiologist)
Of your PDA volunteer experiences, which have you enjoyed the most? Seeing a meeting come together
with help from only volunteers.
How has volunteering in PDA benefited you professionally? As a vendor now, it shows my customers that I care about what they
care about, too.
Which PDA conference/training course is your favorite? The Microbiology Conference held in the fall. Im still very interested
in Microbiology, I guess you can take the girl out of the micro lab but you cant take the microbiologist out of the girl!
What would you say to somebody considering volunteering with PDA? Go for it! Its professionally and personally gratifying!
You meet so many great individuals for networking, for friends and for professional advancement.
2011 Honor Awards Recipients

The PDA Honor Awards are bestowed on members who provide exceptional leadership and service to the Association, and have
been awarded at the Annual Meeting since 1958. The 2011 award winners were announced at the 2012 Annual Meeting in April,
and they will be highlighted in each PDA Letter until next years event. This month we highlight the Service Appreciation award.
The Service Appreciation Award

The Service Appreciation Award is presented annually for special acts, contributions or services that have contributed to the success and
strength of PDA. The 2011 Service Appreciation Award recipients are:
Patricia Brown, Myron Dittmer, Jens Eilertsen, PhD, Norbert Hentschel,

Agilent Technologies, Inc. MFD & Associates Novo Nordisk A/S Boehringer Ingelheim Pharma
Maik Jornitz, Stefano Macci, PhD Peter Noverini, Amy Scott-Billman, Ano Xidias,
Sartorius Stedim Biotech CTP Tecnologie di Processo SpA BioVigilant Systems, Inc. GlaxoSmithKline PharmOut Pty Ltd

People
STEEL-BRIGHT IS:
Sterile Delivered with lot specific Certificate
of Analysis and Sterility Report
Filtered at 0.2 Microns
Completely traceable and validated for
Gamma irradiated sterility & shelf life
Residue free; does not rainbow Completely tested according to
or accumulate to a heavy build up
current USP compendium
Quadruple-bagged packaged using ABCD Available in 8oz. spray can and 12x12
Clean Room Introduction System (remove
individually packed wipes
one bag per increased grade of clean room
area, reducing contamination)

People
Faces & Places: 2012 PDA/FDA

Joint Regulatory Conference
Welcoming Remarks
Quality Risk Management Implementation
(l-r) Anders Vinther, PhD, Genentech; Richard Johnson, PDA
Plenary Session
(top l-r) Gregg Claycamp, FDA; Rick Friedman, FDA

(bottom l-r) Emma Ramnarine, Genentech; Markus-
Peter Mueller, Swissmedic
(l-r) Steven Mendivil, Amgen; Steven Solomon, FDA; Martin VanTrieste, Amgen
Plenary Session: Changing the Quality Culture

Quality Systems
(l-r) G.K. Raju, PhD, Light Pharma; Anthony Mire-Sluis,

(l-r ) Bob Rhoades, Quintiles Consulting; Ian Thrussell , WHO
Amgen; Greg Guyer, PhD, Merck Sharp & Dohme

People
Regulatory Considerations During Cell Therapy Innovations

Development of Biotechnology Products
(l-r) Jeffrey Baker, FDA; Patrick Swann, FDA (l-r) Shane Killian, Johnson & Johnson; Kimberly Benton, FDA
Regulatory Submission and Meetings
(l-r) Angela Krueger, FDA; Mai Huynh, FDA; Richard Lostritto, FDA; Karen Long, Abbott Molecular; Nisha Jain, FDA
Plenary Session 3: CMO
Manufacturing in the Future
(l-r) Thirunellai Venkateshwaran, Genentech; David Cummings, FDA; Vilayat Sayeed, FDA
(top l-r) Susan Schniepp, OSO BioPharmaceuticals

Manufacturing; EJ Brandreth, PhD, Althea;
(bottom l-r) Christopher Masterson, SCubist
Pharmaceuticals; Allan Coukell, Pew Charitable Trusts/
Pew Health Group

People

Quality Agreements International Compliance Update
(l-r) Paula Katz, FDA; Kenneth Drost, Amgen; Mahesh Ramanadham, FDA (l-r) Carmelo Rosa, FDA; Robert McElwain, FDA
Emerging API Guidance Foundation Session: User Fees
(l-r) Steven Mendivil, Amgen; Betsy Fritschel, Johnson & Johnson;

Patrick Swann, FDA; Timothy Watson, PhD, Pfizer, Inc.
Excipient Best Practices
(top l-r) Catherine Cook, FDA; Carol Rehkopf, FDA

(l-r) Janeen Skutnik-Wilkinson, Pfizer, Inc.; Jeffrey Medwid, PhD, FDA (bottom l-r) Theresa Mullin, FDA; Peter Beckerman, FDA
Foundation Session: Regulatory Process to Approval
(l-r) Laurie Norwood, FDA; Lisa Severy, Baxter Healthcare Company; Nicole Trudel, FDA; David Doleski, FDA;
Valerie Flournoy; FDA, Mike Popek, FDA

People
Drug Safety Investigations
(l-r) Kris Evans, Amgen, Inc.; David Perkins , Abbott Laboratories; Renee Kyro, Abbott Laboratories
Plenary Session 4: Compliance Update
(top l-r) Steven Wolfgang, PhD, FDA; David Cummings, FDA;

(bottom) Lourdes Gonzales, Genentech, Inc.
Combination Products
(l-r) Bob Dana, PDA; Steven Silverman, FDA; Armando Zamora, FDA; Mary Anne
Malarkey, FDA; Martine Hartogensis, FDA; Douglas Stearn, FDA
(l-r) Donna French, PhD, Genentech, Inc.; Patricia Love, FDA
Plenary Session 5: Center Initiatives
(l-r) Steven Lynn, FDA; Rick Friedman, FDA; Amy Giertych, Baxter Healthcare Corporation; Martine
Hartogensis , FDA; Howard Sklamberg, FDA, Christopher Joneckis, FDA

People

ssions
B reakfast Se
Concurrent Process Validation
Life Cycle Management
Implementation
Q8/Q11, Q9, Q10
Brenda Uratani, FDA (l-r) Hal Baseman, ValSource;

Scott Bozzone, PhD, Pfizer, Inc.
USP Drug Shortages
Stephan Roenninger, PhD, F.

Hoffman-La Roche Ltd
Russell Wesdyk, FDA
(l-r) Richard Friedman, FDA; Anthony DeStefano, PhD, USP; Jon Clark, FDA; V. Srini Srinivasan, USP
Patient ctions
Advoca
cy FDA Inspe
Colleen Hoyt, FDA

gins, FDA;
A; Brooke Hig
Doleski, FD
(l-r) David

People
Passport Raffle
Klaus Madsen of Bavarian Nordic won the

David Lino won an American Express giftcard Amazon Kindle Fire from Commissioning Agents
$100 American
from PDA
e rs , o f S h ire, won a
v
Wendy Se Stelmi
t card from
Express gif
Steven Laurenz of Abbott won an American Express giftcard

from PDA
Kyla Neild, of Bayer Healthc

are LLC, won an
Amazon Kindle from Commis
sioning Agents

People
TOOLS FOR SUCCESS

Brought to you by the PDA Career Center.
Go to www.pda.org/careers for the latest opportunities.
8 Reasons Why Opportunity

Never Knocks On Your Door
By Vickie Milazzo
Y ou feel like you do everything right.

You work long hours. Youre at the
boss beck and call. And yet, everyone
it. If you arent driven by your passion or
continuously working toward important
goals, then of course, youre going to feel
In fact, if youre in the running for a
new job or promotion, it might even
cost you the opportunity. When Im hir-
around you seems to get richer and to stuck in one place. But when you focus ing, I actually weed out candidates who
on your goals, plan your steps forward underprice themselves because I assume
gain more success, while youre stuck in
and have a little more faith in yourself, they wont perform at the level I expect.
the same old cubicle. Heres what needs
you can achieve wicked success. In my eyes and in the eyes of many other
to change in order for you to reach CEOs, job candidates actually lose cred-
wicked success. The first step is to hold up a mirror and
ibility when they underprice themselves.
really examine what youre putting in at
Youre a hard worker. You stay late at the Many people mistakenly think theyre
work.
office and never complain. Youre your doing their employers a favor by not
boss go to person on big projects. Youre Long hours dont always mean youre pushing for more or that theyll be more
always taking on extra responsibility. more productive than everyone else. If appealing if they dont ask for what
And yet, your career trajectory is as flat you are working longer hours and still theyre worth. The bad economy might
as a board. getting nowhere, it is important to ob- be the current excuse, but I believe most
jectively assess the value of your output. underpricing occurs because many em-
Meanwhile, you cant help but notice
the coworkers who put in fewer hours For example, how much time do you ployees and job candidates just arent
than you but whove managed to get spend complaining? Do you have to dis- comfortable asking for what they think
themselves promoted over you. Or that cuss every issue ad infinitum no matter theyre worth.
friend of yours whose long-shot cupcake how small? Are you stealing time from Youre Viewed As A Commodity
bakery idea turned into a huge success. the company to manage your personal life Commodities are easy to obtain
Or the countless wealthy businesspeople and counting it as work? Figure out how and easy to replace. And thats
featured in the business magazines and to become truly productive and to con- certainly not how you want to be per-
blogs you read religiously who seem to tinuously make progress toward project ceived at your jobwhether youre an
have reached even greater success over goals. The success you seek will follow. employee, a leader, or an entrepreneur.
the past few years despite the down If youre still stumped as to why success After all, if the people youre working
economy. Of course, youre tired of has eluded you, read on as I explain a with know that others share your skill
merely scraping out an existence, but few success obstacles and how to get set, they wont have any reason to pay
youve concluded real success is all about around them. you more or give you advanced oppor-
luck, and you just dont have any. tunities. Theyll be in control, not you.
You Underprice Yourself Do everything you can to ensure that
Wrong! If you want to achieve my brand Youd love to ask for more money you arent seen as interchangeable or dis-
of wicked success, its all on you. Luck but frankly, youre afraid to. The pensable.
doesnt have anything to do with it. economy still isnt great so Id better lie low,
Do what you need to do to stand out.
I guarantee that the successful people you you reason. This just seems like com-
Get in the middle of everything and
see every day dont have anything you mon sense. But settling for less than
bring new ideas to the table. Build re-
dont have. There is no single factor that youre worth is a big mistakeeven in
lationships throughout the company. If
prevents success or one that guarantees the wake of the Great Recession.

People
youre able to make yourself invaluable When I walked into my first meeting long term. Breaking these addictions
and leverage the things that make you with a potential client, my legs were lit- opens the door to achievement.
unique, youll also make yourself impos- erally shaking. I forced myself to remem-
You Arent Going After Your Big Goals
sible to replace. And when that happens, ber that this attorney needed specialized
youll be in control of your own price. knowledge that only Ia critical care When is the last time you set a
You Downplay Your Accomplishments nursecould give him. That reminder goal and really went after it? I en-
It can be hard to toot your own didnt banish all of my nervousness, but courage people to identify their Big
horn. But if you dont announce it did enable me to make the points I Thingsthose goals that connect to
your own achievements, you can bet that wanted. And I walked out of that meet- their passionate vision. Then choose
no one else is going to do it for you. With ing with my first client. I learned that one to schedule their day around. For
humility, make sure that youre keeping when you expand what youre willing example, your Big Thing might be
your name, your accomplishments, and to believe about yourself, you can trans-
to get promoted. So today you might
your skill set in front of everyone. form who you are and what your life
agree to take on a high-profile work
If you still have doubts, consider that looks like.
project in order to put you in the run-
announcing your accomplishments vali- You Need A Mentor
ning for that promotion. Set a target
dates the investments others have made There are two ways to develop
date for each of your Big Things. And
in you. the skills, habits, mindsets, etc.
begin working steadily toward achiev-
that youll need to achieve wicked suc-
You Dont Network With Big Players ing each of them. Start strong and
cess. The first is to go it alone and learn
Generally, we tend to gravitate by trial and error in the school of hard youll experience genuine elation from
toward people who are similar to knocks. The second (much smarter) achieving real goals and solving real
us: people who think similarly, who path is to learn from others who have problems.
find similar things fun, and who are in encountered and surmounted problems
similar walks of life. Thats fine when You cant snap your fingers and suddenly
that are similar to your own. That be- become successful. And the successful
it comes to your friendships, but you ing the case, surround yourself with as
need to aim higher when it comes to people you envy werent able to do that
many mentors as possible and practice
networking. More than 60 percent of either. They worked for it. Wicked suc-
the skills they pass on to you.
people find jobs through networking, cess can be yours too if you make the
for example, and you can bet that most Ive been in business for three decades, same big commitments.
of them didnt achieve this goal because and I still learn every day from my stu-
they knew someone at the bottom of the dents, staff, writers, speakers, business About the Author
pecking order. experts, and more. And in the early days Vickie Milazzo, RN, MSN, JD, is the author of
of growing my business, I devoured ev- the New York Times bestseller Wicked Success
No, Im not advocating snobbery. Its
ery book on business strategy I could Is Inside Every Woman (Wiley, 2011, ISBN:
normal to gravitate toward people who
find, even though none were aimed pre- 978-1-1181-0052-3, $21.95, WickedSuccess.
are the same as youbut in business,
cisely at the niche I was creating. Aggres- com). From a shotgun house in New Orleans
one of the main reasons people dont get
sive learning is a competitive advantage to owner of a $16-million business, Milazzo
ahead is that they dont get out of their
in achieving any desired goals. shares the innovative success strategies that
groups. If you impress someone who
is more successful than you are, theyll You Are Too Bogged Down In The earned her a place on the Inc. list of Top 10
have a lot more influence than someone Little Things Entrepreneurs and Inc. Top 5000 Fastest-
whose position is equivalent to yours. In todays world, were constantly Growing Companies in America.
sabotaged by nonproductive energy Vickie is the owner of Vickie Milazzo Institute,
You Doubt Your Abilities
wasters. There are emails to read. Face- an education company she founded in 1982.
Its highly unlikely that youll reach
book statuses to update. Files to be or- Vickie has been featured or profiled in numer-
any goal you set for yourself if you
ganized. And on, and on. These are the ous publications, including the New York
dont believe with your whole heart that
easy, albeit often unproductive, tasks Times, Entrepreneur, Womans Day, Success
achieving it is possible. Among other
that make us feel good. They may not Magazine, Houston Chronicle, Ladies Home
things, you wont be confident enough to
get you any closer to accomplishing your Journal, Texas Bar Journal, Los Angeles Times,
take calculated risks if you dont believe
that the limitations in front of you are greater goals, but at least youve checked Philadelphia Inquirer, and in more than 220
surmountable. Anytime you find your- a couple of things off your to-do list. newspapers. Vickie has appeared on national
self entertaining doubts or trying to limit Unfortunately, this addiction comes at radio and TV, including Fox & Friends and the
what you think is possible, remind your- a high price, because that cheap check- National Public Radio program This I Believe
self of your past successes. Let them infuse mark high is guaranteed to frustrate, and more than 200 national and local radio
you with pride and bolster your resolve. overwhelm, and stress you out in the stations.

Science
New Process Created for Technical Report Development

s na ps ho t
Richard Levy and Jahanvi (Janie) Miller, PDA
Over the years PDAs line of technical reports have gained popularity amongst members. Not only are these reports an important
component in PDAs mission to develop scientifically sound, practical technical information and resources to advance science and
regulation for the pharmaceutical and biopharmaceutical industry through the expertise of our global membership but they also
represent the current best practices through expert authorship groups and a rigorous PDA peer review process.
Globally, PDA technical reports are recognized for applying sound scientific practice and current regulatory policy to daily opera-
tions in the production and quality control of medicines. Additionally, these reports offer an important contribution to the scien-
tific literature and provide an enduring resource for best practices in pharmaceutical and biopharmaceutical technology.
In recognition of the importance of our technical reports, PDA announces changes to enhance the development process. These
changes will hopefully ensure that members will continue to have access to thoroughly-investigated and documented reports serv-
ing as an up-to-date industry resource.
Why a New Process?
PDA recognizes that the time it takes to complete a typical technical report has been very lengthy. The traditional process has made
it difficult for the member volunteers to stay engaged in the document development process. Since technical reports are often
written to fill critical knowledge gaps in the practice of pharmaceutical technology or the interpretation of regulatory guidance, a
second priority of the technical report process is speed to publication.
After listening to member feedback and careful analysis of our areas for improvement, PDA has developed a new technical report
development process that should be more time efficient and easier to understand for members. Our aim is to improve the time-
liness of these documents by adhering to this process. The new technical report process is a series of specific steps with defined
timeframes and identified responsible parties intended to allow clear and coordinated teamwork.
Historically, it has taken more than three years to complete a technical report. A revised process for drafting technical reports has
been developed which aims to reduce the time from inception to publishing to 18 months. This will be accomplished by defining
roles and responsibilities, applying time frames to the steps involved, and providing guidance on best practices for producing qual-
ity technical reports. Figure 1 is an overview of the new process.
Figure 1 Overview of the TR Process Task Force Incubator Period
Task Forces are approved by Advisory Boards to de-
velop deliverables within a scope of their project
proposal. These deliverables must be in align-
ment with PDAs mission and vision and the
threshold criteria listed below. Key to the
proper development of those deliverables
is the opportunity for task force members
to learn to work together and develop a plan
for the most valuable deliverables. This stage of
the process cannot always be expected to occur at a
defined rate for all topics or teamsone size does not
fit all. To allow the team to form into a fully functional
group, and clearly define their goals and deliverables, the new
process provides for a period of time off the clock. In the new pro-
cess, rather than entering the technical report development phase, task forces exist in an incubator phase where task force members
meet to determine their deliverables (which may include surveys, conferences, presentations, articles in the PDA Letter and the PDA
Journal of Pharmaceutical Science and Technology, etc.) prior to starting to develop a technical report (Figure 2).
Task Force Formation: Threshold Criteria
Once it has been determined that a technical report is one of or the only team deliverable, the team must request to move into the Technical
Report Team phase. In the past, most task forces moved directly into the report writing phase without achieving certain milestones which are
Continued on page 20

Science
Technical Report Watch Journal Preview
s na ps ho t
PDAs Latest Technical Report Demystifies Statistical Final Journal of Year Looks at Quality
Methods
The PDA Journal of Pharmaceuitcal Science and Technology
The pharmaceutical industry ends 2012 with two Commentaries on quality and a Case
has seen increasing recogni-
Technical Report No. 59
Utilization of Statistical Methods Study on quality risk management. Editor Govind Rao says
for Production Monitoring
tion in the role of statistical it is time to revisit the idea of open innovation, asking if
methods. As manufacturers there is a middle path between proprietary molecules and
seek to consistently produce sharing resources in manufacturing and processing molecules,
products that conform to particularly biologics.
predetermined quality char- Editorial
acteristics, statistical meth-
Paradigm Change in
ods have historically shown

Manufacturing OperationsSM
Govind Rao, Open Innovation
their value in providing ob- Commentary
2012
Bethesda Towers
4350 East West Highway
Suite 200
Bethesda, MD 20814 USA
jective evidence in meeting H. Gregg Claycamp, et al., The Reliability-Quality Relationship
this goal. Statistics are also
Tel: 1 (301) 656-5900
for Quality Systems and Quality Risk Management

Fax: 1 (301) 986-0296
E-mail: info@pda.org
Web site: www.pda.org
fundamental for the process understanding that is requisite

for process improvement and development. Anders Vinther, Jennifer Magnani, Can Quality Solve the
Equation?
Industry and regulatory bodies like the International Com-
mittee for Harmonization, the International Standards Orga- Case Studies
nization and the European Union have provided guidance on Joseph Chen, et al., A Novel Bacterial Contamination in Cell
the use of statistical methods. Culture ProductionLeptospira licerasiae
To help facilitate this process, PDAs Utilization of Statistical
Methods for Production and Business Processes Task Force Tim Sandle, Application of Quality Risk Management To Set
has produced a technical report that provides guidance in Viable Environmental Monitoring Frequencies in Biotechnology
identifying and using statistical methods. The primary objec- Processing and Support Areas
tive of this task force was to convey the appropriate use of
statistical methods at a level most can understand. Research
The purpose of Technical Report No. 59, Utilization of Statistical Christoph Herwig, et al., Information Processing: Rate-Based
Methods for Production Monitoring is to present relevant and Investigation of Cell Physiological Changes along Design
easy to use Statistical Process Control Space Development
Methods that are applicable to our
industry. Advanced Statistical Meth- Technology/Application
ods such as multivariate models and David Meriage, et al., Routine Screening for the Presence
Design of Experiments are covered. of Adulteration in Raw Materials Using Automated Nuclear
The Technical Report is the latest Magnetic Resonance Spectroscopy
produced as part of PDAs Paradigm Felipe Rebello Loureno, et al., How pH, Temperature, and
Change in Manufacturing Opera- Time of Incubation Affect False-Positive Responses and
To purchase, please visit
tionsSM initiative. Uncertainty of the LAL Gel-Clot Test
store.pda.org
Conference Report
Arifa S. Khan, et al., Conference Report:
PDA/FDA Adventitious Agents and Nov-
el Cell Substrates: Emerging Technolo-
gies and New Challenges
You can view the Journal

at http://journal.pda.org/

Science
New Process Created for Technical Report Development continued from page 18
s na ps ho t
Figure 2 Technical Report Development Process Map

Meets TR Threshold
Incubation Period
Concepts often evolve Task Force Technical Report Team

within interest groups
Develop a plan for TR Commit to 18 month TR
Identify Team Leader production process
Identify core TF
Develop Project Proposal volunteers TF must go through
Identify Optimal Establish TOC/Outlines formal PDA training for
Publication Format TR production
Interested Volunteers Project added to PDA
portfolio
PDA resources allocated
AB Approval Conference Survey 18 Month TR Process

(identify and recruit SMEs) Journal Training
article
critical for efficient development of reports. ure 2) provides a high level template the appropriate Advisory Board and the
In the new process, a task force must meet for technical report development. To PDA Board of Directors. Subsequent to
the following criteria before progressing achieve the goal of a timely publication, resolving any Board issues, the document
into the writing stage: the map establishes an 18-month time- moves on to PDAs Publication depart-
There is a project plan and clear defini- line and highlights major milestones for ment. In addition to copy editing, PDAs
tion of the proposed technical report the technical report team, as well as out- designer transforms the word document
The technical report team reaches crit- lining the progression and assignment of into the publication ready format.
ical mass critical technical report team support- New Tools
ing activities, such as peer and Advisory PDA has implemented some valuable
The technical report team agrees to PDA
Board review. tools to enhance the document accessi-
timeline and completion of training
Volunteer agreement forms have been Scientific/Technical Peer Review bility and collaboration and to stream-
completed and signed The first priority of the technical report line the document review process. There
process is to ensure the focus and qual- are new resources in place, including an
As an example, threshold criteria for a
ity of the end product. PDA technical online PDA Workspace, technical report
task force may include the following:
reports are important and widely used training modules and technical report
10-15 identified volunteers with req-
reference documents for pharmaceuti- handbooks for the Advisory Boards and
uisite qualifications
cal professionals in industry, regulatory the technical report teams.
Committed and accessible leader and
agencies and academia. Collective team Results
backup leader
expertise and a formal peer review by Its too early to see the impact of the
Understanding and commitment to a fellow industry experts ensure technical
plan for completion of a technical renew process as existing teams begin to
report quality. Once a technical report integrate into the new plan, and newly
port working draft in 12 months
team has developed a working draft of formed teams enter the incubation
Commitment to completing process their technical report, selected subject phase. The PDA leadership team (Board
training at kickoff matter experts and PDA Advisory Board of Directors) is in full support of the re-
Agreements among task force mem- members are invited to participate in a engineered process. The Scientific and
bers to technical report volunteer peer review process. Peer review requires Regulatory Affairs staff is dedicated to
confidentiality terms and use of PDA adherence to strict timelines to ensure continually improve on this initiative
publication tools that comments are prepared, reviewed moving forward from the feedback of
Responsible party assigned for each stage and approved in a timely manner to our members and volunteers.
Time frame applied for each stage meet specified deadlines.
We sincerely hope the new development
Defined process milestones Publication process provides timelier access to relevant
The TR Development Process Map Before a technical report is published it information for members of the pharma-
The technical report process map (Fig- must be approved by a majority vote of ceutical manufacturing community.

Science
s na ps ho t
Environmental
Monitoring
Particle Counting Microbial Real-Time Validation and Training and Service and
Sampling Microbial Compliance Education Calibration
Viable and Non-Viable. Together. Validated.
Visit us on the web at www.pmeasuring.com or call 1 (303) 443-7100.

QbD Offers Opportunities,
Challenges for Vaccine Makers
Bob Darius, GlaxoSmithKline
C an both quality improvements and reductions in regulatory burden be realized by vaccine manufacturers who use the Qual-
ity by Design approach? Three FDA representatives shared their views on this very topic at PDAs Applying QbD Principles in
Vaccine Development workshop in May to address this question and other questions regarding QbD and its viability to a cohort of
manufacturers that has not readily adopted QbD.
While the FDA have not seen many QbD submissions with respect to vaccines submissions, the general consensus was that QbD
may provide significant benefits for vaccine manufacturers.
Jay Eltermann, Director of Division of Manufacturing and Product Quality, CBER U.S. FDA, discussed the implications of
QbD with regard to the lyophilisation process. At the beginning of his presentation he admitted, I was a little bit surprised when
I got the invitation [to present at the workshop] since Quality by Design is still somewhat new for our products and our product
processes.
Although no submissions have been made using QbD for lyophilisation, Eltermann described lyo as a good fit for the use of
QbD principles as equipment capabilities must be evaluated (such as shelf temperatures, heat transfer, vial types, and formula-
tions), critical quality aspects and process parameters have to be defined, and risk assessments are used to make decisions. Addition-

ally, lyophilisation is a well-understood or per unit. Also, tests not indicative of can be impacted by factors other than
process that can be reliably reproduced. the long-term success of the cycle was a mechanism of action. Measurement
He provided provided illustrative exam- another common testing failure. of biological activity may not have a
ples of how QbD could be applied. The second issue involved inadequate direct relationship to mechanisms of ac-
I think when we look back at lyophilisa- equipment qualification, such as not tion. Changes in product structure and
tion, he said. It equals one attempt to knowing the equipment (not making development often occur late in devel-
come up with a Quality by Design type sure the IQ and OQ is performed cor- opment with unclear understanding of
of submission. He further explained, rectly, variability in temperature control, significance to safety and efficacy. The
When you go through some of the ex- etc.). interaction of all these factors also makes
amples where there were problems with it difficult to demonstrate a link between
Third, loading may not be well-defined
the submissions, if they had followed process parameters and product perfor-
and a loading pattern not determined/
[a QbD] approachbeing proactive, mance at the time of submission.
documented, which can affect aseptic
being systematicunderstanding the processing. Fourth, inadequate valida- Last, but not least, he added, commu-
process control and having it based on tion of the loading cycle can be an issue. nication between the sponsor and FDA
sound scienceyou would have seen And finally, inadequate scale-up or tech- may be complicated because of the need
that many of the issues that we see dur- nology transfer protocols. to review a large amount of data.
ing review and during inspection really
Eltermann noted that all of these are big Like Eltermann, Drews encouraged early
would go away.
issues that come up during review, and communication between companies and
Lyophilisation fits in well with QbD, he a QbD approach could help mitigate the Agency, including Type C meetings,
said, for the following reasons: 1) It is these. to focus on how to implement QbD
a well understood, reproducible process; concepts before submission of either a
Had they taken a more proactive ap-
2) It uses accurate product testing that biological license application or post-
proach [and] understood the process,
verifies process consistency; 3) It features approval supplement.
he said, many of these issues would not
well-known and understood variables
come up during the review. He encour- Drews offered some insights on risk as-
and controls (temperature, time, pres-
aged attendees to engage in dialogue sessments. He told the audience that
sure, etc.); 4) It involves precise process
with FDA, particularly by conducting from FDAs perspective, risk assessments
monitoring and process equipment con-
Type C meetings. may not always include all possible vari-
trol within narrowly defined limits; and
Recent CBER QbD Experiences Shared ables regarding composition of the start-
5) It uses modeling of scale-up and pro-
ing materials (i.e., intermediates from
cess transfers. At the same time, the Agency is starting
preceding unit operations or raw ma-
Eltermann then discussed several points to see more evidence of QbD applica-
terials). The importance of robust risk
regarding what the design space for tions with biological products. At times,
assessments which have been carefully
QbD of lyophilisation could be. Param- a submission may be ObD-like and
challenged by cross-functional teams
eters to be defined include: yet not identified as QbD. I think were
was stated as being a critical starting
going to have to explore more and have
product loading into freeze dryers and point in QbD.
more dialogue with the industry on how
freezing rate In his experience working the submis-
the QbD approach would take place,
control of primary and secondary dry- Eltermann said. sions, he noted that analytical methods
ing (time, vacuum, shelf heating ramp may not always adequately justify the
rates, product temperatures, homoge- As far as recent submissions of QbD-
based applications, Roman Drews, PhD, proposed design space limits for the
neity of product temperatures) critical process parameters. Other times,
Office of Blood Research and Review,
use of direct or surrogate measure-
CBER, shared recent experiences from
ments for process controls (moisture
actual reviews of QbD submissions for Article at a Glance
readings in condenser or chamber,
biological products. His office has mostly
near infra-red technology, etc.) Examples suggest lyophilisation
seen QbD applications for recombinant
vial types and effects on heat transfer processes would be a good fit for
and plasma-derived products.
lot sizes QbD
Drews provided an overview of some of Regulators urge early communicattion
variability among different lyophilizers the challenges with QbD implementa- with the Agency on procedures for
He also provided an overview of recent tion within the industry. Often the re- implementing QbD
lyophilisation issues noted during the relationship between structural/functional
Risk assessments must be strong
view process. Inadequate product testing properties is not well understood. Prod- enough to withstand regulatory
was one, often resulting from firms not ucts never consist of a single moiety, challenges
conducting adequate sampling per shelf and therefore, clinical safety and efficacy

The inherent practice of continuous improvement ing, however, should not be the driver
for implementing QbD, Krause warned.
could be perceived by some that QbD was not FDAs QbD Expectations
fully effective or accurate Ultimately, FDAs overall expectations

of QbD, as shared by the FDA speak-
additional empirical data were not pro- lisation, etc.), platform products that ers, are improved product and process
vided to confirm the boundaries of the share either important attributes or unit understanding, resulting in improved
design space which were extrapolated operations, and process information that process control and lower costs and
by mathematical modeling. He has also can provide additional data on product losses. Additional expectations of QbD
seen that control strategies for other quality. include: establishing well defined as-
process parameters, such as noncritical pects that are critical to product quality,
Understanding the associations between developing product and process under-
process parameters, relevant to the per- clinical end points and process param-
formance of manufacturing steps were standing prospectively during product
eters are one of the challenges for using and process development phases, iden-
not outlined in the licensed application,
QbD in vaccine products that should tifying variables that could impact prod-
nor were they supported by the process
be explored, he noted. Other challenges uct quality, safety and efficacy, ensuring
validation studies. Finally, justification
include performing carefully managed consistent processes through enhanced
of the scores used to assess risk for the
risk assessments that are balanced and process control and monitoring, and
manufacturing process steps and tested
ask the probing questions. There is also establishing more robust manufactur-
parameters should be documented by
the possibility that risk assessment tools ing processes by applying the knowledge
results of process validation and devel-
may not capture the full range of risks. gained.
opment studies and prior knowledge of
Again, Krause stressed the importance
process and product. The consensus among the speakers was
of well-challenged risk assessments. As-
Philip Krause, MD, Acting Deputy Di- that while QbD can improve the over-
say variability is another key area posing
rector, Office of Vaccine Research and all quality and reliability of products,
challenges to the use of QbD for vaccine
Review, CBER, covered the regulatory real benefits in the reduction in regula-
production.
side of QbD for vaccines, noting like tory requirements remain to be seen. All
Another challenge specific to vaccines agreed that there needs to further discus-
other speakers that ICH (which cov-
involves the design of appropriate qual- sion on the topic between industry and
ers QbD), does not explicitly apply to
vaccines. However, he stated, FDA may ity systems through establishing an ap- regulators.
choose to apply appropriate ICH docu- propriate process control strategy, then
[Editors Note: The upcoming February
ments to vaccine reviews. integrating continuous improvement
issue of the PDA Letter will center on
processes. New manufacturing chal-
Areas of QbD Application for Vaccines QbD and we will publish the results of
lenges occur over time, and additional
He admitted that QbD was originally a survey concerning QbD and vaccine
product knowledge is gained with more
developed with the intent to apply it manufacturing. If youre interested in
production experience. However, the in-
to nonvaccine products. The key ques- submitting an article, please email Re-
herent practice of continuous improve-
tion...is whether there are principles of becca Stauffer at stauffer@pda.org.]
ment could be perceived by some that
QbD that could be applied to vaccines. QbD was not fully effective or accurate. About the Author
Because vaccines are given to healthy Managing these potential perceptions, Bob Darius is Vice Presi-
individuals, the tolerance for safety is- and a careful understanding and main- dent of the Regional Qual-
sues is low and changes in efficacy may tenance of a culture of continuous im- ity Unit for GlaxoSmith-
not be immediately apparent for vac- provement, must be supported by both Kline Vaccines four manu-
cine products, Krause said. Therefore, industry and regulators alike. facturing sites located
risk assessment tools may not capture in Germany and North
Krause said that the positive implications America. Previously, he
the full range of potential risks, and risk of using a QbD approach for vaccines worked in the FDAs Cen-
assessments may be difficult to evaluate include development of and support for ter for Biologics Evaluation and Research for
objectively. If risk assessments cannot for specifications during the review and 15 years. After leaving FDA in 2005, he worked
withstand a challenge by regulators, the approval process. Improvements in pro- at Biologics Consulting Group, then started
validity of the QbD approaches will ob- cess consistency over time would result an independent consulting company, Radius
viously be challenged. in longer term benefits to manufacturers Biotechnology, LLC.
Krause outlined the following examples through reduced rejections and waste. Bob is a Microbiologist by training and at-
where QbD could be applicable to vac- The potential reductions which could tended George Mason and Johns Hopkins
cine products: unit operations (lyophi- be gained on regulatory filings or test- Universities.

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Simplification Can Improve Quality Systems, Experts Say
Rebecca Stauffer, PDA
Are pharmaceutical quality systems too picked it up and dusted it off, he said, way, he said. This is one of the chal-
complex to be effective? According to an referring to the book. The original was lenges that management has to deal
industry expert and a regulator, they are, written in 2003almost ten years ago. with. Ultimately, we ask employees to
and an injection of simplicity will help When I picked it up and started reading sit down and read 80-90 page SOPs and
manufacturers improve quality perfor- it again, probably the most startling fea- then go follow it to the letter. Unsur-
mance. ture is that it really all reads like I wrote prisingly, he noted that when FDA in-
Giving their respective takes on this idea it yesterday. spectors encounter lengthy prose SOPs,
were Rob Rhoades, VP, Quintiles, who He added that this scared him as an these inspectors realize compliance re-
represented industry, and Ian Thrus- awful lot of it deals with kind of all the mains on shaky ground.
sell, Head of Inspections, World Health things that go bump in the nightbe- We really as responsible managers have
Organization, representing regulators, cause, frankly thats a lot of the things to find ways to push simplicity, he im-
both of whom spoke at the Quality that my team gets called in to deal with. plored.
Systems session of the 2012 PDA FDA He went on to mention that around 80-
Decision-making is another area that of-
Joint Regulatory Conference. Despite rep- 90% of his teams work deals with 483
ten falls through.
resenting opposite sides of the industry, warning letters, consent decrees, etc.
both concurred that a quality system can This has really become a truly global is- Trying to get clear decisions articulated
be designed as user-friendly without sac- sue, he said. and carried out and executed is a really
rificing expectations for clear and direct tough thing, he said. You really have to
information. He then went on to note that most have a mechanism for problem-solving.
problems begin gradually and often re- He followed up by noting that having a
Drawing on his experience providing main unnoticed until the problems get
regulatory consulting for pharmaceutical clear decision-making path is important
big enough. due to the dynamic nature of the indus-
and biotechnology companies, Rhoades
discussed managements responsibility We didnt get there in a day, he said. try. Often, issues will occur at one site that
to quality. He began by drawing from Nobody goes to work and says Gee, staff at another site remains unaware of.
Risky Business: Managing the Quality of what non-compliant, non-quality work The single biggest missing skillset in our
Americas Medicines, a book he wrote can I do today?.
industry today is the ability to conduct
many years ago that remains pertinent. Ultimately, this breeds complexity. a proper investigationsolve a problem,
It probably has been awhile since I Weve allowed complexity to get in our get to root cause, and then turn that into
an effective corrective action or preven-
tive action, he said. If you can teach
your folks to do that [root cause analy-
sis], I will be out of a job.
He noted that most firms are not proac-
tive enough to conduct this deep level of
analysis and instead are merely reactive, fo-
cusing on merely completing paperwork.
Rhoades then discussed an epiphany that
occurred on vacation in Ireland when he
visited Newgrange, an ancient, massive
passage tomb built in 3200 B.C. All the
stones used to build this 5,000-year-old
structure were quarried from a site 70
km away by canoe.
Pointing out that it took three to four
generations for the structure to be com-
pleted, he mused that today we have a
It took at least four generations of people to build the ancient Newgrange tomb in Ireland while today it hard time getting people to follow an
can be difficult to get somone to follow an SOP twice in two days. SOP twice two days in a row.

Every year on the winter solstice sun- spective on quality systems and compli- enced by cost-savings. In itself, this is not
light comes through a passage built ance culture, which mirrored Rhoades necessarily a bad thing, Thrussell indicat-
into the tomb for 17 minutes. The rest talk to some extent. He honed in on ed, citing efforts to reduce the prices of
of the time, the passage is in complete what regulators are specifically looking HIV medications in sub-Saharan Africa.
darkness. All of this was accomplished for when they review a companys qual- Cost is very, very important, he said. But
without computers and other modern ity system. when in an organization it becomes every-
technology, stressed Rhoades. Why are quality systems actually nec- thing and particularly when it becomes
The complexity of this design and the essary, Thrussell mused rhetorically. very short term[when] organizations are
fact that it took multiple generations Well, on the one hand quality systems not planning for a sustainable future thats
to put this thing together such that its are good for you, they allow you to make when it starts to be problematic.
perfect in doing what its doing says to whatever you are making, or the process
Referring back to Rhoades point about
me, you know what, we can do this, that you are running, they allow it to be
simplicity, Thrussell cited the example of
Rhoades said. more consistent.
an investigation he was involved in at a
Somehow or another we can carve On the other hand, for the regulators, facility in Pakistan. Here, an excipient was
through all of the things, all of the prob- the reason were there and why we mixed with an active during the formula-
lems that plague us on a day-to-day basis want to see the quality systems you have tion of a product that contained a massive
to get us to a point where we can create our working effectively is because were in- overdose of Pyrimethamine. Patients who
own little Stonehenge, whether its in the terested, first and foremost, in protect- took the drug received a months treat-
drug industry, medical devices, or whoever ing public health. He then highlighted ment four times a day. This caused the
else from biopharma might be represented that, as shown by the history of medici- deaths of over 120 patients.
here today, he said.
It was one of the simplest
Going back to the industry,
he said that managements
Looking at how companies react when GMP mix-upsa mix-up
in a dispensary adding the
role is to make sure compli- things go wrong is a really, really good wrong material. We talk a
ance happens in a consistent lot about quality systems,
manner. Not surprisingly diagnostic tool rather sophisticated sys-
this is a challenge due to the tems, but when things go
disparate nature of large companies with wrong and they still go wrong today, its
nal regulations, responses have been two
disparate groups of people scattered across sometimes the most basic things, he
to three steps behind the latest disaster,
various sites and even in foreign countries said. So one little message away from
from a recall of 59 million metered dose
where language barriers can be an issue. all this is yes, by all means, we need
inhalers in the late 90s that led to the
That really is the embodiment of com- deaths of 17 children to the heparin cri- good quality systems and we need good
pliance, Rhoades said. It is the corner- sis in 2007. investigations, but we also need to keep
stone of the quality system. things simple.
Those just seem to keep coming up like
Lack of consistency often leads to a per- a bad penny, he said. Every five or six In fact, he noted that continuous im-
ceived disconnect between management years it seems to happen again. And one provement has been a hallmark of the
and the rest of the staff. Rhoades noted really has to ask yourself of why the world industry. Yet, at the same time, while
that he often visits facilities where work- isnt learning about that sort of thing. this is a normal human behavior it is of-
ers on the shop floor feel disconnected ten stifled thanks to complexity.
Thrussell pointed out that the major
from management. In many cases, it is recalls and contamination issues in When people dont understand their
not just a perception but a reality. pharma generally come down to some processes, theyre very difficult to im-
It really is our responsibility to lead the underlying cultural issue in the compa- prove, he said. So, really understand-
organization, he said. Leadership, he nies. He told about his involvement in ing processes, how they work and
pointed out, is one of the key founda- a British facility that manufactured flu keeping them as simple as possible, is
tions of a good quality system. vaccines that were later recalled and how absolutely key.
He wrapped up his presentation by that particular facility had a significant He then discussed what regulators are
managements requirements for a good history, some good and some bad. looking for when they visit a facility.
quality system: simple and clear guide- Underlying what went wrong was mat- Ultimately, theyre looking for the com-
lines, paths for direct action and prob- ters of corporate quality culture, he panys degree of compliance.
lem-solving, and, in general, being pre- said. And some of these issues here have Were interested in the things you do
pared for when things go wrong. to do with culture. well, the things that you do right, the
Thrussell then provided a regulators per- Often a corporate culture can be influ- things you excel in, not just the things

you dont do so well in, he emphasized.
The deeper things we are asking our-
selves is can you be trusted, do we trust Plant Isolate
you, when we walk out the door will
those good things that you showed us in ...Delivering Condence
the procedures and so onwill they con- in Quantitative Microbiology
tinue to do that same standard of work?
He then pointed out that an inspec-
tor, like himself, must often differenti- Your Plant Isolates manufactured
ate between what a company considers
a GMP and what the regulatory agen-
into BioBall format!
cy believes is sound GMP, noting that Now available in 2 formats:
WHOs GMP guidelines are often more 9Single Dose 60 cfu
proscriptive than in industry. 9Multi Dose 550 cfu
Along with a good quality system, Thrus-
sell identified leadership as a core area NO upfront costs
than an inspector looks at because with- Certificate of Analysis supplied stating
out that commitment those powers
actual Mean and Standard Deviation
around there trying to erode your controls
will continue at pace. If theres not leader- 12 month shelf life
ship at the top and belief at the bottom
meeting then theres going to be problems Over 10 years experience in Quantitative
sooner or later. In fact, ICH Q10 spe- Microbiological Contol = REAL EXPERIENCE!
cifically mentions senior managements
responsibility to ensuring quality systems.
As with Rhoades presentation, Thrussell
also keyed in on risk analysis, pointing
out that risk is not a new concept; its
mentioned 90 times within 20 different
documents in EU GMP legislation and
guidances. For more information please visit
Whats perhaps new is the lifecycle ap- www.biomerieux-industry.com/bioballpda12
proach, he said. But the concepts are
not new.
As to why inspectors look at a companys
quality management systems, Thrussell
said that its quite simple.
Looking at how companies react when
things go wrong is a really, really good
diagnostic tool.
So, why are companies still having issues
as far as quality since quality systems are 0000-1_PDAMarch2012Advert.indd 1 21/03/2012 2:31:05 PM
standard across the industry? temic monitoring of process performance and product quality using QRM, CAPA
methodologies that result in improvements not just data, change management, and
Well, clearly the management practices
management review of processes, product performance, and quality. In essence, he said
have failed, said Thrussell. Risk man-
agement has failed. Identification has that quality should be the lifeblood of a company, so that even if it is not spoken of
failed. Often these boil down to lapses continuously, it is still present within the companys culture.
in communication or even failures to le- On that last point, he referenced a colleague who told him that the more times
verage existing knowledge bases. people talk about quality and inspection, the more I know its missing. So, if nothing
He then highlighted the features of a else, when facing your inspectors try and use other words and do walk the walk and
good quality system. These include: sys- walk the talk and show that you are doing things.
Do you really need an led to the recall and developed sugges-
tions for preventing the situation from
compliance with SOPs. He told the au-
dience that when he was doing inspec-
80-page SOP? repeating itself. tions, he would often sit next to a man-
Another audience member asked how a ufacturing supervisor who was blatantly
Ultimately, an inspector wants to leave company can balance simplification while ignoring an SOP that he had just read.
a site with the confidence that when expectations for explicit information. Toward the close of the session, Thrus-
something does go wrong, the company sell discussed his involvement in shut-
Well, dont confuse simplicity with not
has procedures in place to deal with the ting down the British facility involved in
having clarity, responded Rhoades. We
situation effectively. have a complex business to run, theres the infamous flu vaccine recall. He talk-
Richard Friedman, Associate Director no question about it. He noted that ed about how for the four years after the
of Risk Science, Intelligence and Priori- overcoming complexity is a significant shut-down, inspections were conducted
tization at CDER, U.S. and moderator challenge for larger companies employ- by both the FDA and the Medicines and
of the session, opened the Q&A portion ing massive amounts of staff and manag- Healthcare Products Regulatory Agency.
with a query of his own for Rhoades and ing multiple facilities across several loca- The company ultimately implemented
Thrussell: How do you know you have tions. The industry cant get away from procedures to prevent a recurrence. This
a good quality system, he asked the two. the need from the need for clear speci- illustrates that even breakdowns in qual-
Thrussell responded that it helps to have fications and processes. Yet, the goal of ity, no matter how disastrous, can pro-
something tangible to measure. You simplicity, Rhoades emphasized, is to vide a learning opportunity for an orga-
can also measure the absence of things, get away from the minutiae that clouds nization. In the end, bad quality has the
he added, although he cautioned that thinking and understanding. potential to give birth to good quality.
the absence of defects could also mean Do you really need an 80-page SOP, he Sometimes, Thrussell said. Good
that they are under-represented and asked. Do you really need 80 pages79 things happen out of bad experiences.
present. He then pointed out that other of which are written by somebody who
About the Experts
industries do proactive surveys as to the is in another department? Do you really
quality of their products yet this is not have clear understanding of how those in- Bob Rhoades is Vice
typical of pharma. He also recommend- tricacies and inter-relationships between President, Quality & Com-
ed following CAPA processes. departments and how they have to work? pliance Consulting, at
Quintiles. Bob has de-
If they have too few deviations they The effectiveness of training was also signed and implemented
dont have a good quality system, he brought up during the Q&A. Rhoades compliance improvement
said he often tells companies, particu- admitted that training is always a tough initiatives for major manu-
larly in India since he is skeptical that nut to crack. Yet it is often a key point facturers in the United
few things could wrong despite the high that his investigations must address, States, Europe, India and China. Bob has
level of activity. such as operator errors due to lack of ad- worked in concert with client counsel on a
equate training. variety of legal cases and was selected to ad-
Either theyre employing super-humans
vise in the contaminated heparin crisis in 2008.
or robots he said. Or there is some un- In terms of effectiveness, he said. There
derreporting. are a myriad of solutions out there in Ian Thrussell is currently one of the UK
terms of the mechanisms to try and test. MHRA GMP Inspectorate Expert Inspectors
Rhoades added that he thinks one mea- and a member of the UKs GMP Inspector-
sure of effectiveness in the industry is Its a sore spot. I think a lot of companies
ates Strategic Group which amongst its roles
how often bad events recur. He noted struggle with the resources that are re-
represents the Agencys GMP interests at
that some companies do after-action quired to really have an effective training
an EU and international level. Ian has a wide
reviews when things do go wrong. Just system at every level.
experience of international guidance develop-
recently, he worked with company that On the point of training, Friedman in- ment and implementation. He is rapporteur for
was forced to recall a significant batch of dicated that a way to evaluate the effec- the current amendments to Chapter 1 and 2 of
medications and analyzed what factors tiveness of training would be to measure the EU Guide.

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Make a Lasting Impression During Preapproval Inspection
Rebecca Stauffer, PDA
Everyone knows how important

first impressions are. From a first
date to a job interview, being pre-
pared is always critical, and the
lack of preparation can have last-
ing negative effects. This is espe-
cially true for preapproval/preli-
censing insepctions. Preparation
for this event is key, even for com-
panies with products already on
the market, for the preapproval in-
spection is the moment to demon-
strate to the regulatory authorities
that your firm is able to produce a
quality drug product.
At the 2012 PDA/FDA Joint Regu-
latory Conference, Lisa Severy, Sr.
Quality Regulatory Compliance
Manager at Baxter Healthcare
Much like a first date, its best to strive for a good first impression in anticipation of an inspection.
Corporation, and Nicole Trudel,
Quality Assurance Specialist at CBER, U.S. FDA addressed During submission, Severy emphasized keeping the reviewer
prelicensing and preapproval, providing both industry and in mind by drafting a clear scope, summarizing the data, and
regulatory perspectives for one of the foundation sessions. ensuring the data is sufficient enough to minimize requests
for additional information. The submission document should
Representing the industry, Severy recommended that manu-
also be kept on hand during the preapproval inspection.
facturers view regulatory authorities as customers in a sense
and to offer adequate preparations prior to inspection, ensur- Severy also recommended conducting mock inspections prior
ing the facility is ready and GMP compliant. Agents will need to inspection and including related documentation. For the in-
to see the facility in operation, observing manufacturing pro- spection preparation plan, all the parties involved should have
cesses along with documentation. Inspectors will also want to clearly defined roles, rooms should be designated for inspec-
see that effective quality systems have been implemented tion and inspection support, systems should be designed to ef-
these inspectors do not want to be handed draft SOPs. Avail- ficiently retrieve and provide accurate information for specific
able information should be accurate. Any requests for infor- requests, subject matter experts should be identified and delin-
eated along with contact information, and participants should
mation and documents should be handled efficiently so that
be trained adequately for the upcoming inspection.
the preapproval inspection concludes on schedule. Ultimately,
inspectors do not want to see any gaps or surprises. At the late stage, just prior to inspection, relevant documents
should be collected and reviewed then staged for inspection.
Planning for a successful preapproval inspection, she indi-
The SOP index should be prepared. Next, rooms should be
cated, is best started simultaneous with the projects kick- equipped in anticipation. Protective garments in appropriate
off. There should also be at least once team member with a sizes should also be available.
background in quality. As far as scheduling, the inspection is
usually planned for two months after the FDA receives the Once the inspection is underway, Severy said that its impor-
submission, generally, two months before due date for the tant to remain calm and focused.
action. During this time, cross-functional teams will provide Process requests as efficiently as possible, ensure scribe notes
frequent monitoring of readiness. The project team must also are well-written, and be responsive to regulators requirements.
be apprised of the latest GMP requirements and expectations Good communication is key, she explained. She referred back
and then use these guidelines in the development of a timeline to her earlier points about having a customer-service mindset
and Master Project Plan to ensure GMP compliance. This when it comes to preapproval inspectors.
document, however, does not replace other documents, such Daily, there needs to also be wrap up meetings between the
as Master Validation Plan. companys inspection team and regulators. At the end of the

day, she recommends conducting a second, internal meeting To ensure readiness for the procedure, make sure all processes
in order to gather information and ensure pending requests are are validated, all conformance lots manufactured, and all pro-
fulfilled. Additionally, this meeting will explore what needs to duction and testing procedures have been approved. Ensure
be prepared for the next day. Information from this meeting that all personnel have been trained adequately and that all
will also be emailed to key participants as well as management. equipment, facility, and supporting systems are qualified.
After the inspectors have finished is the opportunity to ad- Logistically, regulators like to see that travel considerations
dress any issues that arose during the inspection. If a Form have been considered. It also helps if key personnel have been
483 or other observation was issued, this is the time to make identified and a list of dress requirements and restrictions has
an action plan. Assign an owner for each observation. De- been distributed. Additionally, give the regulators forewarn-
fine the schedule for completion/approval per the Agencys ing regarding any immunization requirements necessary to
requirements and the companys specific policies. Review the enter the facility. Make sure there is adequate administrative
response to ensure it is comprehensive, addressing all con- support, including necessary support systems for badging, es-
cerns. And make certain that responses are submitted on time. corts, and in/out processing.
If a 483 has been issued, after sending in a response, use it as As far as documents, ensure that any documents requested in
a learning tool. Evaluate the things that went well and analyze advance are available upon arrival. These requests may include
if anything could have been done better. Implement whatever the following: batch records, lists of SOPs, validations, devia-
improvements are needed to ensure the issue does not recur. tions, change controls, etc., the quality manual, monitoring
Ultimately, the keys to a successful preapproval inspection in- data and copies of the submission.
The subject matter experts should also be made available to
Its also pertinent to provide a daily the inspectors. The SMEs should represent production per-
sonnel, supervisors, and operators responsible for quality as-
agenda during inspection surance, quality control testing, process validation, equipment
qualification, quality systems, and facility systems (water,
HVAC, cleaning, warehousing, etc.). Make sure that any re-
volve many steps on behalf of the manufacturer. Begin prepa- quests for additional documents and information generates a
rations early. Ensure that activities are GMP compliant. Make timely response. Provide access to any relevant databases. And
sure that all team members involved are professional and ensure that a SME accompanies the documents. If the busi-
knowledgeable. Develop a documented plan and adhere to it, ness is conducted in a different language (since the Food and
acting quickly if deviations occur. Keep organized and com- Drug Administration Safety and Innovation Act, or FDASIA,
mitted to the goals of the inspection. Always meet the regula- allows for more frequent inspections of foreign facilities this
tory agencys requirements, and provide effective and efficient is expected to become more common), ensure that translation
communication throughout the inspection. services are available for both documentation and discussion.
Trudel then offered a regulatory perspective regarding preap- Trudel then offered an overview of past inspection issues shes
proval inspection readiness, noting that the Public Health experienced. In the area of biologics, shes seen incomplete
Service Act and Title 21 Code of Federal Regulations among process validation, uncorrected process failures, unresolved
other regulations require Agency inspections. As far as which media fill failures, lack of in-process controls, lack of data
division performs the inspection, it depends upon the nature supporting in-process hold times, lack of quality oversight,
of the inspection. If it involves a biologics license application, incomplete manufacturing and laboratory investigations,
then it will involve regulators with either CBER or CDER.
unqualified critical components or suppliers, issues with sys-
The Office of Regulatory Affairs handles new drug applica-
temic mold, inadequate lab controls, unresolved enforcement
tion, investigational new animal drug and pre-market applica-
actions or deviations, insufficient development of controls, in-
tion inspections.
Continued on page 45
She agreed with Severy on the importance of providing ade-
quate feedback with regulators, both during and following the
inspection, as well as providing a timely response to a Form
483, that allows for feedback. This would occur mid-cycle (in
general, a cycle lasts for 120-300 days).
Its also pertinent to provide a daily agenda during inspection,
she said. Establish start and end times that fall within reason-
able business hours, with the expectation that production pro-
cesses might require an alternate schedule. This agenda should
also list the production schedule, updated daily, and include
a daily closeout as well as lunch and other breaks as needed.

Regulation
ICH Q10 Implementation Key for Executive Management

A PDA/FDA workshop for operations and quality professionals
Jennifer Magnani, Genentech, and Anders Vinther, PhD, PDA, Genentech
In a cosponsored effort, PDA and the low utilization, high scrap and rework, reality, quality is truly owned by all.
U.S. FDA held a workshop focused on and a high Cost of Quality. The starting point for breeding this at-
managements accountability within a Wilkinson repeated the oft-quoted 2003 titude is the organizational structures.
quality system. The workshop consist- Wall Street Journal passage: The Phar- They need to be designed to push ac-
ed of short presentations that provided maceutical Industry has a little secret: countability and responsibility down to
participants with background informa- Even as it invents new drugs its manu- the lowest level within the corporation.
tion and practical knowledge/experience facturing techniques lag far behind those Governance models need to align to the
from both industry leaders and FDA of potato chip and laundry soap mak- organizational structures. Ingraining
representatives. Participants were very ers. Against this background, industry Quality is a concept that Miller and
active in the Q&A panel sessions, ask- and regulatory experts alike were envi- Vinther described as systems plus pro-
ing for clarifications and for additional sioning a desired state of efficient, agile cesses plus capabilities plus mind-set.
detail or examples. and flexible manufacturing that produc- Once ingrained, a quality culture blos-
es high quality drugs without extensive soms, which places the patient as the
In order to encourage the participants to number one consideration when deci-
engage in a dialog and share with each regulatory oversight. It was obvious that
utilizing W. E. Demings Fundamentals sions are made.
other their experiences, challenges and
of Quality would lead the industry to Regulatory Expectations
tangible real-life examples, the work-
shop had four breakout sessions on the this desired state. FDAs Steven Lynn, Director, OMPQ,
CDER and Rick Friedman, Associate
following aspects of the quality system: With ICH Q10 going into effect in 2008
Director, OMPQ, CDER, spoke about
Best examples of a quality system one would expect that industry had ad-
the Agencys expectations for a pharma-
Bad examples of quality systems opted these principles by now. This is not
ceutical quality system in general and for
Metrics for driving the right behaviors necessarily the case, Wilkinson said, be-
executive management in particular.
cause of several factors: 1) The industry
Governance models that support a ro- A quality system doesnt just mean the
has a less than mature understanding of
bust quality system quality management; 2) The connection quality unit, said Lynn. In other words,
Due to the EU releasing the revised Eu- between manufacturing and supply is its the sum of the whole and its made
draLex Volume 4 Chapter 1-Pharmaceu- generally poor; 3) Quality professionals up of all the functions that are involved
tical Quality System and the connection are not always valued or not seen as add- in the manufacturing of the drug-from
with this workshops focus, an overview ing value; 4) The legal requirement for the purchasing agent who orders the
of the changes was also presented. independence of the quality unit drives raw materials to the operations manager
bad behavior; and 5) The quality unit is who sets the production schedule to the
ICH Q10 Introduction
not viewed as a business imperative. Re- quality manager who checks the batch
The workshop started out with a pre-
garding this latter point, Wilkinson said records. Ultimately, quality is owned by
sentation from Neil Wilkinson, Senior
industry needs to begin thinking about all, end-to-end of the supply chain.
Partner, NSF-DBA, who participated in
the ICH Q10 Expert Working Group quality in true financial terms. Lynn specified concrete Agency expecta-
as EFPIAs representative. He provided The Operations, Quality Partnership tions for executive management. They are:
an overview of how and why ICH Q10 A very visible way that management can Assuring a state of control: Vigilant-
was conceived and the factors that con- demonstrate to the organization that ly oversee quality; detect new variables
tributed to the development of it and they have a quality culture is if qual- or events potentially impacting prod-
the related ICH guidances Q8 and Q9. ity and operations groups have a true ucts; create a proactive quality culture;
He pointed to three factors in particu- partnership. Speakers from Genentech and support continual improvement,
lar: 1) Industry and regulators want- shared how this partnership works at the Commitment to quality: Develop high
ing to change the blind compliance worlds largest biopharma company. quality standards, rather than settling
mentality; 2) FDAs cGMPs for the 21st James Miller, Vice President, Biologics on perceived regulators minimum
Century Initiative; and 3) The Pricewa- and Anders Vinther, PhD, Vice Presi- standards; Here, Lynn mentioned
terhouseCoopers (PWC) 2001 Survey dent, Quality Biologics discussed how the PDA Survey on Cost of Quality (to
of Pharmaceutical Manufacturing. The they work together to align their vision, publish soon) which showed a linkage
2001 PWC report stated that the indus- mission and goals for their organiza- between high costs of business when
try had low process capability, leading to tions. To make the partnership work in identifying and solving quality prob-

Regulation
lems after the fact rather than pursu-

ing truly effective preventive mea- The quality of the work you accept becomes
sures, and
your standard
Reinvest in process and quality im-
provements: Here, Lynn said finan-
cial support from top management is The latter ultimately causes quality is- experts.
key, as reinvestment in systems, pro- sues and poses great risk to the company The challenges involved with establish-
cesses and facilities and active reduc- business and the supply of products to ing a proactive, process-oriented cul-
tion of complaints and investigations the patients. ture in a highly regulated environment
is needed.
On several occasions, Lynn cited CDER was discussed by Migliaccio and other
Friedman focused on the current expec- Director Janet Woodcocks commen- speakers throughout the workshop. The
tations for a quality system, including tary in the May-June 2012 PDA Journal key question is: How do firms encour-
sound risk management, maintaining a of Pharmaceutical Science and Technology. age continually improving operations to
state of control, and the importance of One powerful passage he cited was: lessen variability and raise quality when
a quality culture that leads to sustain- regulatory submission procedures glob-
Clearly the responsibility for maintain-
able compliance. He noted that evalua- ally are tedious, costly and inconsistent
ing quality rests squarely with the man-
tion of a firms quality system is central from region to region? All speakers and
ufacturers themselvesthe widespread
to FDAs systems-based inspection pro- audience participants agreed that every-
and successful adoption of six sigma
gram (7356.002). onepatients, regulators, and compa-
and related quality management tech-
Friedman noted opportunities to lower nieswill ultimately benefit from com-
niques in other manufacturing sectors panies focusing on process and product
risks by implementing contemporary would imply that reliable, high-quality
manufacturing systems (like process an- understanding and efficiency. Quality by
manufacturing is also attainable in the Design (QbD) may be one approach to
alytical technologies, automation, rapid pharmaceutical sector. We must ask our-
access barriers and isolators, etc.) to achieving this, but so far, success has been
selves, in an area where the stakes are so very limited in the industry. A big prob-
improve outmoded or even deficient fa- high, why is this not being achieved? lem currently is that the time it takes to
cilities and processes. Industrys general
Operational Excellence/Efficiency implement manufacturing changes may
lack of understanding of the causes and
One of the common themes through- be measured in years rather than months.
effects of ingredient variability is an im-
out the workshop was how important Another theme at the workshop was how
pediment to adequately managing such
it is for drug manufacturers to use Op- well quality systems and continual im-
risks, he said. He also discussed current
erational Excellence (OE) tools and ap- provements using OE tools go together
expectations regarding CAPA, technolo-
proaches to continually improving qual- to improve both the quality of the prod-
gy transfer, change management, process
ity systems and business processes. ucts and reducing variability and waste
control, and management review.
Gerry Migliaccio, Migliaccio Consult- in operations. Migliaccio mentioned
Regarding corporate leadership and
ing (formerly with Pfizer), who was the that many quality improvements were
quality culture, Friedman emphasized
Industry Rapporteur for ICH Q10, said easier to sell (i.e., met with more excite-
the old adage actions speak louder than
the expert working group believed that ment by upper management) when pre-
words. FDA wants to see quality man-
a robust pharmaceutical quality system sented as OE projects rather than quality
agers involved in business decisions that
starts with GMP and overlays the con- improvement plans.
have direct and even indirect impact
cepts of an ISO Management System The importance of OE was also stresssed
on drug quality. Friedman stated, The
and the principles of OE. during Martin VanTriestes (Senior Vice
quality of the work you accept becomes
your standard. What is written in an He relayed lessons learned during Pfizers President, Quality, Amgen) presentation,
SOP or company credo is not meaning- implementation of a Right First Time An Effective Quality Management Sys-
ful to staff if your daily actions are con- strategy that led to a high performing tem Cost of Doing Business or Com-
trary to them. Employees notice when supply network enabled by OE. Objec- petitive Advantage. He opened with
senior managers keep high quality stan- tives of the OE approach were effective- some classic Deming quality quotes, in-
dards and show commitment to reduce ness, efficiency, predictability and con- cluding, A bad system will beat a good
mistakes/deviations or prevent them tinuous improvement, and it included person every time, and Improve quality,
from happening. It is the companys people at all levels in the organization. you automatically improve productivity.
choice of either moving towards a strong Key to the OE programs success was the VanTrieste said that if we moved our
corporate quality culture and manufac- ability to change the companys culture industry from Three Sigma operations
turing consistency or towards unreliable and structurally supporting it with thor- to Six Sigma operations, we would save
systems and manufacturing problems. ough OE training of key subject matter $50 billion annually.

Regulation
Q10 has moved expections beyond Reflects the companys vision and values that FDA has very clear expectations to
GMP to that of continual improvement, Promotes commitment senior management in terms of assuring
risk management, knowledge manage- a state of control, commitment to qual-
Having a strong quality culture can also
ment, lifecycle, and risk/science-based ity and reinvesting in process and quality
help an organization break down the
opportunitiesall elements that make improvements. The quality system expec-
complexity that adds risk to the supply
good business sense. When integrating tations should be an integral part of the
chain and ultimately the products. Jen-
the quality system into the general busi- quality culture of a company throughout
nifer Grealy, Vice President, Manufac-
ness processes, companies will start to the organization and at all levels.
turing and Supplier Quality Assessment,
see the value for the bottom line.
Pfizer, defines a quality culture as, An The workshop also showed that pharma
VanTrieste said that CAPA systems environment in which each and every companies are still developing in this
should help firms identify weaknesses to area and are actively
avoid issues, promote
working to have a tru-
root cause analysis,
and use relevant met- All employees need to understand that ly shared responsibil-
ity of quality between
rics and management all work is a process quality unit and op-
reviews to monitor
performance and erations departments.
drive continuous im- [Editors Message:
provement. person understands and embraces their Anders Vinther offers his personal per-
Quality Culture responsibility for protecting product spective on the workshop in the first
Health authorities are placing more and quality and patient safety. This culture Voices of the Board, on p. 52.]
more emphasis on organizations and should be created and nurtured by lead- About the Authors
each individual department within an ership because it is one of the most fun-
organization to have a healthy quality damental elements that enable an orga- Anders Vinther is re-
culture. But what does that mean? The nization to deliver quality products. sponsible for the techni-
cal operations at all Roche
bottom-line is that it can mean differ- Importance of Training and Genentech Biologics
ent things to different organizations and Jennifer Magnani, Associate Director sites (ten sites in Europe,
individuals. of Quality, Genentech, discussed the US, and Singapore), and
Catalent Pharma Solutions VP of Qual- importance of a quality education for all for products produced at
ity Operations Dr. Swroop Sahotas def- in the organization. Investing in people these sites. Previously, he
inition of a quality system is simple: A throughout the organization can have a led the Global Quality System and Processes
set of interrelated processes that work to- very strong impact on your quality sys- organization. At PDA he is currently a member
gether to assure product safety, strength, tem. Ensuring that quality professionals of the Board of Directors, Chair Elect, and
identify, purity and quality. All employ- are trained well for their job is essential Quality Systems Interest Group Leader. Most
ees need to understand that all work is but looking beyond that standard train- recently he chaired the PDA Strategic Plan.
a process and to maintain compliance ing is what can take an organization to Jennifer Magnanis areas
system ownership is a must. the next level. of responsibility include
Sahota says a companys quality system Training programs on quality should management of global
should not be a stagnate system; rather, target the people that play a role in get- quality portfolios, strategic
it needs to be continuously improved and ting products to patients, not just qual- global quality projects,
kept up-to-date on current regulations. ity professionals. It should also include GMP document gover-
Sahota suggested the use of OE method- nance for all of Roche Phar-
the procurement, operations, regulatory
mas technical operations,
ologies and tools for identification and and IT departments. Additionally, orga-
strategic communication, global quality training
implementation of changes. One should nizations should look at focused training
program and quality council governance. She is
consider the following elements when de- courses to enable learning on topics such
managing the integration of a global Roche Phar-
veloping a quality system: as investigations or regulations. Certifi- maceutical Quality System (PQS) program. At
Simple to understand cation programs in various fields would PDA, she is consulting the Board on the Strategic
Clear roles and responsibilities help facilitate this kind of learning. Plan development and implementation, as well
Establishes accountability In conclusion, the Q10 Workshop showed as organizational governance.

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Regulation
Timeline of Relevant FDASIA Deadlines

The following timeline represents expected milestones the U.S. FDA must meet concerning provisions of the Food and Drug Ad-
ministration Safety and Innovation Act (FDASIA) over the next five years.
12
July 19
FDASIA signed into law
13
Guidance for Industry July 19 FOR CONGRESS
SHORTAGES
Issue a guidance outlining
the circumstances for de-
nying or limiting required
inspections
December 31
Submit to Congress a report on drug shortages and
mitigating actions (report required annually thereafter)
14
January 19
Issue a draft guidance on accelerated approval requirements for
breakthrough therapies (final guidance required in one year)
February 1
Compile and submit inspection reports to Congress (and annually thereafter)
July 19
Drug importers must demonstrate the regulatory status of the
drug, provide proof of facility registration with the FDA, and
meet CGMP requirements, export regulations, etc.
15
July 19
Commercial importers will have to register with the FDA and
provide a unique identifier for associated establishments
17
October 1
Manufacturers can take advantage of the Agencys ability to
consider single enantiomer drugs as new chemical entities

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Regulation
Interest Group Corner

s na ps ho t
New Interest Group Seeks Answers for Outsourced Operations Issues
Like many industries, pharmaceutical firms are outsourcing portions of their operations for greater cost-savings. Unlike other in-
dustries, the use of outsourcing partners can lead to significant regulatory hurdles. In fact, under 21 CFR 200.10(b), the U.S. FDA
states that the Agency regards extramural facilities as an extension of the manufacturers own facility. Foreign regulatory bodies
are also scrutinizing outsourcing relationships within the industry.
On Sept. 11, the Outsourced Operations Interest Group met for the first time at the 2012 PDA FDA Joint Regulatory Conference.
This meeting could not have been timelier; that same week, Chapter 7 of the European Union GMPs was finalized with the title
Outsourced Operations. Headed by co-chairs Karen Ginsbury, President of PCI Pharmaceutical Consulting Israel Ltd., and
Susan Schniepp, Vice President, Quality and Regulatory Affairs for Allergy Laboratories, the group identified many perceived
problems with outsourced manufacturing operations which the interest group intends to address. Two topics that came up repeat-
edly were communication issues and lack of information flow between parties.
The PDA Letter spoke with both Ginsbury and Schniepp about the new interest group and the next steps the group will take in
the coming months to address these issues.
While a supply chain interest group already exists, Ginsbury said that she and Schniepp felt there was a need for both as supply
chain is big and tends to focus on starting materials and the other end (distribution), tampering and counterfeit medicines.
She also noted that Outsourcing is just thati.e. the increased use of CMOs, outsourced toxicology studies, outsourced validation, cali-
bration activities, outsourced computing / ITand the list is growing all the time. There are major issues experienced by both the Contract
Giver (sponsor) and the Contract Acceptor (contractor) and we thought PDA should have a forum to hone in on those topics.
Were very interested in whats facing the contract organization, agreed Schniepp who will be speaking on behalf of contract
manufacturing organizations at the upcoming supply chain conference. As far as supply chain issues that affect and interface with
outsourced ops, she cited instances of companies restricting where contract organizations can procure excipients.
She expects supply chain issues to become a major topic in the area of outsourced manufacturing.
I do think its a topic thats starting to emerge, she said. Because more and more companies are going to start putting in their
quality agreements issues like where you need to get approval from us before you buy from this company or there needs to be an
audit on hand. So I think its going to be a good element to start adding in.
As far as the biggest issues in outsourced operations the group is facing, Ginsbury said that off the top of her head these included
technical agreements and quality contracts that are too long and cumbersome. Companies often mistakenly believe the contract is
a replacement for risk management tools. In addition: engineering batches and validation; an over - emphasis on customer audits
of the service provider yet none of the Contract Givers (quality systems.
Of the latter, she and Schniepp noted at the interest group meeting that contractors are constantly being auditedat the initiation
of the contact, for the annual GMP inspection, required regulatory audits, etc. Their presentation noted that for CMOs, almost
half the year consists of audits!
Schniepp also highlighted the complex nature of outsourced manufacturing. Despite her 33 years of industry experienceinclud-
ing five in contract manufacturingshe noted I thought I knew everything before I went into contract manufacturing but I
found out I knew very little. Its very complicated. I think the entire industry has to wrestle with the fact that big companies arent
going to build big facilities anymore and what theyre going to do is rely on contract organizations to produce the product.
And I think the most active area is certainly anything done aseptically by a contract manufacturer because those facilities are very
hard and costly to maintain. You have to maintain them even when youre not running product, she added.
With regard to the recently enacted Food and Drug Administration Safety and Innovation Act (FDASIA) law, Schniepp said I
think that it [FDASIA] will affect it [contract manufacturing] because it will definitely raise the standard for everybody.
Ginsbury also added that outside of FDAISA there is ever increasing scrutinyrightly soof outsourced operations.
At this time, Ginsbury and Schniepp are preparing the interest group for the upcoming Annual Meeting.
We definitely would like a speaker, preferably from the FDA for the interest group at Annual, Ginsbury said. And we have asked
our participants if any of them would like to address the group. We have asked participants to prioritize issues and will select one
or two for drill down at Annual.
Continued at bottom of page 46

Regulation
s na ps ho t
The Parenteral Drug Association presents...
2012 PDA/EMA
Joint Conference
Compliance: A Prerequisite for Availability
of Medicinal Products
Falsified medicines regulation and its impact to
regulators and industry
Ensure availability and quality of drugs in a
challenging environment
Risk management to control product shortage
due to manufacturing quality problems;
business continuity plans
New trends in manufacturing and controls
Closing plenary: The regulatory and industry
environment 2020
Four Interest Group Meetings:

EU Inspection Trends
Stephan Rnninger, F. Hoffmann-La Roche
EU Regulatory
Barbara Jentges, PhACT
Quality Systems
Lothar Hartmann, Crucell
GMP Links to Pharmacovigilance
John Ayres, Eli Lilly
PDA-PIC/S
Training:
4-7 December 2012

GMP for APIs
(ICH Q7)
Hotel Cascais Miragem

Lisbon (Cascais) | Portugal
CONFERENCE 4-5 DEC | EXHIBITION 4-5 DEC | TWO-DAY TRAINING COURSE 6-7 DEC
https://europe.pda.org/PDAEMA2012
Regulation
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NE WS TH IS ISS
UE FDA Sending More
Dr
FDA warnings going increa
singly global Warning Letters to ug GMP
FDAs drug GMP warnin
g letters to foreign fa-
J S. E
Foreign Sites
cilities have increased OANNE
How to avoid criminal Park Doctrine

steadily over the past . GLOVITCH J
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IER.COM
two years as the agenc DA is showing its enfor
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abroad, while total GMP letters going to facilit number of
liability if your company cuts

warning letters dropp ters issued in the secon ies abroad. Of the
ed slightly from year d part of calendar 18 drug GMP let-
before. Top violations and API manufactu year 2011, 10 went
are inadequate OOS
in- rers. to foreign drug
vestigations followed
corners on quality
by faulty testing of drug These included three
components. Contaminat to China, two to Germ
ion was also a com- to Mexico, one to Polan any, one to India, one
mon issue. ........................ d, and one to Switz to the UK, one
...................................Cover warning letters has erland. Yet the numb
decreased slightly er of drug GMP
from calendar year
Of the 40 drug GMP 2010, from 50 to 40.
Fingerprinting for dollar letters issued in calen
s drug and API manu
facturers (see chart
dar year 2011, 20 or
half went to foreign
How to make sure recalls dont

As biosimilar develo below).
pers fingerprint mole- Thanks to budget
cules with state-of-the increases, FDA has
-art assays in hopes seas to meet the challe increased its inspe
winning reduced clinica of nges of globalizatio ctional presence over-
n, has opened 11 intern
cause shortages of your drug

l trials or more, inno- and has hired intern
vators are updating ational inspectors ational offices
their analytical metho of foreign and dome to staff these offices.
ds, stic inspections for The total number
hoping to alert FDA from 16,236 in fiscal all FDA-regulated
before their competitors year 2009 to 18,109 products increased
products
about any issues the Enforcement as Drug in FY 2010 (FDA Continues
old methods may have GMP Warning Lette Aggressive
missed. As the totali rs Mount The Gold
ty of the evidence
on This translates into Sheet, April 2011).
their molecules increa more inspectors condu
ses exponentially, con- is likely to result cting international
cerns are raised about in inspections, which
the proliferation of more warning letter
non-critical specification s.
s. ..................................10 Number Of Foreign Drug
GMP Warning Letters Increasing
How to win FDA approval for big
Top citations not 60
EU GDP guideline attracts much changed
comments
changes like single-use systems

The European Comm
ission needs to fine The most frequently 50
Warning Letters
tune its good distrib 34 Domestic

ution practices (GDP) cited GMP provi
guideline, the pharm sion
aceutical industry said in warning letters
that 40
in comments on a FDA issued in the past
proposed draft revisio
Key issues include segreg n. six months is deficient 20 Domestic
ating EU and non-
How to protect your supply chain

EU product, transportatio out-of-specification 30
n vs. storage condi- in- 18 Domestic
Number Of Drug GMP
tions, applicability to vestigations, but mov-

investigational produ
and time limits for transp cts ing up a bit in terms
ortation hubs.........16 of 20
from high rollers in procurement

top GMP failings
are 18 Foreign 20 Foreign
inadequate testing
News in Brief of 10 12 Foreign
drug components,
in-
FDA hits heparin supply cluding identity test-
chain; Ranbaxy con-
sents to data integrity ing for contaminants. 0
oversight; Chinas vac-
CY 2009
AND MUCH MORE!

cine compendial crisis; CY 2010
EU seeks comment on Also, data integrity CY 2011
safety measures, API still Years
imports ...........................17 remains an issue.
One Source: The Gold Sheet
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Regulation
Regulatory Briefs
Regulatory briefs are compiled by PDA member volunteers and staff directly from official government/compendial
releases. Links to additional information and documentation are available at www.pda.org/regulatorynews.
North America
U.S. FDA Issues Draft GDUFA Guidance requires information about the type of
The U.S. FDA announced availability business operations, and if necessary, the Key Regulatory Dates
of a draft guidance, titled Initial Com- DUNS number and FEI number. Comments Due
pleteness Assessments for Type II API The information can be submitted elec- Dember 31 U.S. FDA Draft
DMFs Under GDUFA. This guidance tronically through the following tools: Guidance on Initial Completeness
is intended to clarify criteria the Agency eSubmitter, Xforms, internally designed Assessments Under GDUFA Available
will use in the initial completeness as- software that uses SPL technical speci-
sessment required for holders of certain fications, and other commercially avail- ropean Variations Regulation concerning
drug master files that are referenced in able applications.
generic drug applications or in amend- centrally authorized medicines are now in
ments or prior approval supplements
Europe effect, per Commission Regulation (EU)
to these applications, under GDUFA. EMA Begins Infringement Procedure to No 712/2012. Changes effecting autho-
Comment are due by December 31. Investigate Roche Non-Compliance rized medicines include: decision-making
EMA has begun an infringement proce- process changes that allow for changes
U.S. FDA Announces Notification
dure against Roche Registration Ltd to important for public health are mirrored
Requirement for Generic Facilities
investigate allegations the company did in marketing authorizations within two
For fiscal year 2013, the U.S. FDA now
not comply with pharmacovigilance ob- months (other changes can be reflected
requires generic drug facilities, and other
ligations pertaining to 19 medicines. The in regular updates provided within one
sites and organizations identified in ge-
Agency will investigate the allegations year), and inclusion of compliance state-
neric drug submissions, to provide iden- under Regulation (EC) No 658/2007
tification information to the Agency. ments that mention the agreed-upon and
and will report the outcome of the inves- completed pediatric investigation plan
The Agency has published a notice outlining tigation to the European Commission, within the marketing authorization.
the types of facilities required to self-identify. which has the authority to impose fines
These include component manufacturers, or periodic penalty payments if it finds EMA will be providing an updated post-
packaging facilities and testing labs. that Roche has committed infringement authorization procedural advice contain-
against the pharmacovigilance obligations. ing the Variations Regulation changes
The information that should be included
within the next few weeks.
is identified in the GDUFA SPL Indus- Roche and the Commission have been
try Technical Specification Information informed that EMA has started infringe- Since Jan. 1, 2010, Variations Regulation
document, and includes the name and ment proceedings. provides instructions for handling applica-
contact information for both the regis- Amendments Impacting Centrally tions from marketing-authorization hold-
trant owner and the facility if they are Authorized Medicines Now in Effect ers with changes to existing marketing au-
two different entities. The Agency also As of, November 2, amendments to Eu- thorizations.
Voices of the Board continued from page 52
driven activities? A good way of doing this The PDA Cost of Poor Quality survey was have gone on much longer, and we be-
is to speak in a language that works well mentioned as a first step to create a model lieve it is important that we continue
for the audience and the company. Link for explaining the benefits of systemati- these discussions to take up the chal-
the quality messages to safety, efficiency cally assuring consistent quality on a daily lenge Janet Woodcock and FDA have
and money. Speak about financial benefits given the industry to improve compli-
basis in accord with the process validation
and use the term Operational Excellence ance and for us to improve our business.
and ICH Q10 lifecycle concepts.
(or whichever words translate into driving PDA will continue to actively lead and
continual improvement and prevention of Moving Forward facilitate this discussion connecting peo-
issues at your organization). The dialog at the breakout sessions could ple, science and regulation.

P&M
Explore Manufacturing Trends at the 2013 Annual Meeting

2013 Annual PDA Meeting Orlando, Fla. April 15-17 www.pda.org/annual2013
Miguel Montalvo, Expert Validation Consulting, Inc.
As we get closer to the end of 2012, it opportunity in addition to offering net- Track 1: Biological Sciences
is my pleasure to invite you to attend working events, among other benefits. Track 2: Sterile Product Manufac-
our next Annual Meeting. Our theme Learn to Adapt to the Global Regulatory turing
for next year is Modern Sterile Product Environment Track 3: Quality Systems
Manufacturing Exploring Best Practices Learning about best practices and new
and Seeking New Approaches. Within the track format, individual ses-
approaches is not just important from the
sions will address specific topics including:
We are always looking for the best prac- standpoint of desirable outcomes but its
Current Trends in Process Validation
tices in everything that we do within also a necessity in the current competitive
our industry, especially if that practice and globalized environment. For us to Innovative Approaches to Sterile
involves a new or modified approach to remain competitive, we need to become Product Packaging
our current processes. The most effective more efficient and effective; applying best Biosimilars
way of learning about these best practices practices and approaches is definitely one Contemporary Practice in the Manu-
and new approaches is by attending in- path to accomplish that goal. The meet- facture of Sterile Products
dustry-focused meetings where these are
presented and provide opportunities for
expert speakers to address any questions Come network with old friends and meet new ones
or concerns you may have. The PDA
Annual Meeting provides this type of
ing will provide presentations by industry Outsourcing Management

leaders on these methods and the oppor- Advances in Single-use Technology
tunity to share opinions and concerns Applications
about the topics being presented.
Viral Safety Strategies
You will not want to miss this opportu-
As at every Annual Meeting, our inter-
nity to discuss these critical topics to our
est groups will also conduct their inde-
industry and to share your experiences
pendent sessions to discuss the latest ad-
and concerns with top industry personnel
vances and news on each particular area
and scientists in order to shape the future
with participation from industry experts
of our business. In addition, the meet-
in their field.
ing will provide an extremely valuable
networking opportunity for experienced In addition to the formal conference
management personnel as well as novices proceedings we have put together an
to our operations and scientific functions. impressive choice of optional and fun
This is the most important PDA event events beginning with the 7th Annual
throughout the year and we expect a large PDA Golf Tournament and the 7th An-
portion of our globalized membership nual Fun Walk/Run on Sunday, April
to be present. Come network with old 14. Make your conference experience a
friends and meet new ones. well-rounded one by taking part in these
Follow the Topics That Interest You networking activities.
The meeting will be conducted in our tra- We all look forward to seeing you in my
Dont miss out on the fun! A performer from PDAs ditional format with three parallel concur- home town of Orlando, Fla. where ev-
last Annual Meeting in Orlando, FL from 2010. rent sessions as follows: erything is certainly Magical.

Regulation
Make a Lasting Impression During Preapproval Inspection continued from page 33

validated autoclave loads, issues with cleaning validation, and
ignored building alarms. The Parenteral Drug Association presents...
Of the latter, she said, please dont tell the FDA inspectors those
tens of thousands of alarms are nuisance alarms, citing events 2013 PDA Europe
that her teams have encountered.
With regard to in-vitro diagnostic test kits, her teams have
Workshop on
encountered lack of design controls, incomplete equipment
qualifications, lack of in-process controls, undefined manage-
ment responsibilities, missing quality oversight, no control
Single Use
over critical suppliers, little to no training, inadequate docu-
ment control, poor CAPA execution, inadequate bioburden Systems for
Pharmaceutical
monitoring, and insufficient preventive maintenance. Teams
inspecting veterinary medicines facilities have come across
systemic mold, biofilms, inadequate cleaning validation, poor
Applications
equipment maintenance, poor equipment maintenance, co-
eluting impurity peaks (HPLC) in analytical method valida-
tion, reference standards improperly stored/labeled, and not
filing three-day field alerts for OOS.
In the end, both Trudel and Severy concurred on the impor- The workshop addresses the importance of Single
tance of adequate preparation and communication, both prior, Use Systems (SUS) in pharmaceutical development
during, and following preapproval inspection. FDASIA expands and manufacturing.
regulatory requirements for inspections, particularly of foreign
Based on the Technical Report, you will hear about
facilities, so it makes sense for regulators and industry to work to-
gether to make the inspection process smoother for both parties. advantages, disadvantages and how you can make
best use of SUS.
About the Experts
Benefit from case studies, discussions with regula-
Lisa Severy, Senior Quality Regulatory Manager
has worked for Baxter for more than 30 years in tors and industry experts. Get in direct contact with
various roles within the Quality organization, includ- the different suppliers of SUS technology.
ing QC Laboratory, Quality Assurance Management
and Quality/Regulatory Compliance. Since 1994,
Lisa has led inspection preparation and manage- Benefit
ment of the inspection process for several pre- from your
approval inspections, in addition to many routine, early
GMP inspections at two major biological manufacturing sites. Currently, Booking!
she works at Baxters BioScience division headquarters, continuing to
provide global support for inspection preparedness and guidance to the
manufacturing sites regarding quality/regulatory compliance.
Nicole Trudel has eight years of experience at CBERs Division of
Manufacturing and Product Quality in the Office of Compliance and
Biologics Quality. Her experience includes a wide range of CMC and
facility reviews and inspections for biologics license applications and
supplements relative to bacterial and viral vaccines, recombinant
products, in vitro diagnostic test kits, plasma fractionated products,
allergenic extracts, and cord blood. She also has experience in the
review and inspection of BLA and Premarket Applications for IVD test
kits. Nicole also supports internal and external training in her various
areas of technical expertise and has participated in numerous policy
groups addressing CGMP, harmonization and inspection related issues.
She holds a B.S. degree in Mechanical Engineering. 15-16 January
Milano | Italy
15-16 JANUARY | WORKSHOP | E XHIBI T ION
https://europe.pda.org/SingleUse2013
P&M
Experts Offer Guidance on Delivering Vaccines Worldwide

PDA/FDA Vaccines Conference Bethesda, Md. Dec. 3-4 www.pda.org/vaccines
While advances in science and technology substrate characterization with Arifa FDA on the Evolution of Regulatory
are leading to the development of a wide Khan, PhD, Supervisory Microbiolo- Framework, and
array of new vaccines and novel manufac- gist, from CBER, U.S. FDA and Lau- Review global regulatory challenges
turing approaches, the vaccine industry rent Mallet, PhD, Head of Analytical with Marion Gruber, PhD, Director,
continues to face technical, logistical and Research and Development, North OVRR, CBER, FDA by understanding
regulatory challenges. This is especially America, of Sanofi Pasteur, Ltd., the regulatory environments around the
true for vaccines needed in developing
Hear Regulatory Perspectives on globe including licensing requirements,
countries and other international markets.
QbD during Vaccine Development immunizations schedules, lot release,
We invite you to come to the PDA/FDA
Vaccines Conference to hear about novel in- from Philip Krause, MD, Deputy and pharmacopeial specifications.
dustry approaches for supplying vaccines Director, Office of Vaccines Research Please join us for these topics and more!
along to domestic and international mar- and Review, CBER, FDA, This is a must-attend event for all involved
kets. Industry and regulatory experts will Participate in a session on hot topics in the manufacturing and testing of vac-
also discuss various approaches to manu- in regulation, featuring presentations cines for preventive and therapeutic pur-
facturing and distribution issues. on Rapid Mycoplasma Detection poses. We encourage pharmaceutical and
This two day event includes many infor- Methods from Vladimir Chizhikov, biopharmaceutical professionals with re-
mation-packed sessions, vital for todays PhD, Chemist, CBER, FDA, and sponsibilities in development, manufactur-
vaccine professional . Here are just some Direct Recall Classification from ing, preclinical, quality assurance, quality
of the sessions that will be of high interest: FDA speakers, control and regulatory affairs to participate.
Learn how to navigate the multiple View a presentation from Michael B. Following the conference, PDAs Train-
regulatory requirements and guidances Havert, PhD, Biologist, Office of Cell, ing and Research Institute will also hold
for adventitious agent testing and cell Tissue and Gene Therapies, CBER, two one-day courses on Dec. 5-6.
Interest Group Corner continued from page 40

We had a number of issues that came tract supply chain from their clinical trials Regulatory Affairs and Quality Advisory Board.
up during our talk and I think they have to the commercialization of the product. Sue Schniepp has over
a number of topics they want to address, About the Experts 24 years of experience in
Schniepp said. It will be exciting to see quality assurance, for both
where we can take this group. There are a Karen Ginsbury is a Lon- the food and pharmaceuti-
don trained pharmacist, cal industries, and is cur-
lot of issues facing us Im really excited
with a masters degree rently Vice President, Qual-
that PDA has decided that its a worth- in microbiology. Expert ity and Regulatory Affairs
while subject to be starting to address. in all aspects of clean- for Allergy Laboratories.
Both she and Ginsbury agree that the rooms and microbiology, She has a degree in microbiology from Northern
interest group is focusing on a growing she has a second area Illinois University and began her career in 1980
area of the industry. of expertise in the GMP as a microbiologist in the food industry where
manufacture of investigational drugs and is she first used the U.S. Pharmacopeia. In 1984,
I do think that contract manufactur- currently co-editing a PDA Technical Report on she transitioned to the pharmaceutical industry
ing is going to continue to grow in the the topic. With over 20 years of experience in as an R&D Microbiologist.
industry, said Schniepp. I think it ser- the industry, Karen has hands-on experience
Sue is an active PDA volunteer, serving on the
vices not only the Big Pharma but theres of quality assurance and setting up GMP com-
PDA Letter Editorial Committee and the Regula-
an emerging pharma where there are just pliant quality systems. She regularly lectures
tory Affairs and Quality Advisory Board. She
virtual companies out there working on around the world on related topics. also serves on the PDA/FDA Joint Regulatory
one molecule. And those companies are Karen is an active PDA volunteer, serving on Conference Program Planning Committee,
going to take advantage of the entire con- the PDA Letter Editiorial Committee and the which she has chaired.

P&M
Modern Sterile Product

Manufacturing
Exploring Best Practices
and Seeking New Approaches
April 15-17, 2013 | The Peabody Orlando | Orlando, Florida
CALL FOR POSTERS

The 2013 PDA Annual Meeting Program Planning Committee encourages you to submit an abstract for a one-day
poster presentation at the 2013 PDA Annual Meeting, which will be held on April 15-17, 2013 in Orlando. Abstracts
must be noncommercial, describe developments, strategies or work and significantly contribute to the body of
knowledge relating to biopharmaceutical manufacturing, process knowledge, quality management and technology.
Abstracts related to sterile or related product manufacture are preferable, but those addressing other technologies
are welcome. All abstracts will be reviewed by the Program Planning Committee for consideration.
Suggested topics include, but are not limited to:
BIOLOGICAL SCIENCES STERILE PRODUCT MANUFACTURING QUALITY SYSTEMS
Microbial Control in the Diagnostics Testing Characterization, Stability
Manufacturing Environment Challenges in Quality for ACIs Room Decontamination and H2O2
Bio-film Challenges in Manufacturing Upstream/Downstream:
Combination Products Expiration of Products, Logistics Chromatography
Container Closure Integrity and Shipping Cold Chain
Green/Sustainable Manufacturing Stem Cells Sterilization
PAT Single-use Technology Bio-burden/Bio-film
Cell Culture Processes Mycoplasma/Virus
Viral Clearance Process Validation
Purification Process Cleaning Methods and Validation
Abstracts must be received by January 14, 2013 for consideration.

You will be advised in writing of the status of your abstract by February 8, 2013. Poster presenters are required to
register as a full conference attendee at the rate of $1795 member/$2044 nonmember. Exhibit only registrants are
eligible to present a poster by registering as a full conference participant. In order to be listed in the final program,
your full conference registration must be received no later than March 1, 2013. After March 1, the prevailing
registration fees and policies apply.
Visit www.pdaannualmeeting.org/2013CFP to submit an abstract.
Please include the following information with each abstract:

Presenters name Presenters phone number Take-home benefits
Presenters professional title 2-3 paragraph abstract, Presentation objectives
Presenters full mailing address summarizing your topic and
Presenters e-mail address the appropriate forum (case
study, discussion, traditional,
panel, etc.)
For more information, please contact Melissa Pazornik, Coordinator, Speaker & Logistics Assistant
via e-mail at Pazornik@pda.org or phone at (301) 656-5900 ext. 221.

TRI
2012 Closes With a Successful Year for TRI

Bob Dana, PDA
Its a beautiful October afternoon in up- portunity to have intensive training on courses at the PDA/FDA Joint Regu-
state New York bright blue skies, warm one topic by staying the week and taking latory Conference, including the new
sun but enough of a chill in the air to both courses. Altogether, Lyophilization courses: Good Distribution Practices
remind me that another year is coming Week proved successful once again with for the Pharmaceutical Supply Chain
to close. Recognizing that, its time for almost 50 registrations. and Application of Phase-Appropriate
me to reflect on 2012 and look back at In Phoenix, Arizona at the 2013 PDA GMP to the Development of Protein
what it meant for PDAs Training and Annual Meeting, faculty member Ed Bulk Drug Substances. Both Appli-
Research Institute (TRI). Trappler was awarded the James P. Agal- cation of a Quality Systems Approach
By any measure, 2012 was a very busy loco Award. This award is presented an- to Pharmaceutical GMPs, taught by
and successful year for TRI. We had nually to the PDA TRI faculty member Miguel Montalvo, and Development
unprecedented attendance at training who exemplifies outstanding perfor- of Qualification and Validation Proto-
courses, led by our flagship Aseptic mance in education. Congratulations, cols - A Risk Management Approach
Processing Training Program. Our in- Ed, and thank you for all you do for with Hal Baseman, were particularly
house training programs continued to TRI and our students. Several of our well-received.
grow, including a multi-session course, Annual Meeting courses exceeded our In October, PDA once again offered
Practical Aspects of Aseptic Process- expectations, including Manual Asep- three conferences, starting with the Bi-
ing, which was delivered to one com- tic Processing, taught by Carol Lampe; ennial Training Conference. This confer-
pany. We also enjoyed very strong atten- Quality Risk Management taught by ence provides a forum for profession-
dance at our lecture course series, hosted Jeff Hartman and Emma Ramnarine; als who develop and present training
in conjunction with PDA conferences. and Process Validation and Verifica- programs for our industry. All three
To better serve our students and mem- tion with faculty members Scott Boz- courses at this conference; Qualifying
bers, we added new staff to our team. zone, and Wendy Lambert providing Your Subject Matter Experts as Trainers
These accomplishments and additions the instruction. This marked the first (Vivian Bringslimark), FDA Inspec-
allowed us to contribute to the successes time Jeff, Emma and Wendy had taught tion Readiness for a Training Systems
PDA enjoyed in 2012. courses for PDA and we are looking Audit (Barbara Van der Schalie) and
forward to their future participation in Learning, Knowledge Management
We got the year started quickly with the
these and other courses. and Impact Moving from Theory to
first week of Session 1 of our Aseptic
Processing Training Program starting This summer, we had the opportunity to Practice (Jim Vesper); met or exceed-
Jan. 9. This was the first of five sessions present courses at PDAs Virus and TSE ed our expectations. It seems clear that
in 2012, all of which sold out. In fact, Safety Conference; both Viral Contami- trainers realize the value of being trained!
every session for the year was sold out by nation and Remediation and Basic We closed out our lecture courses for
Marcha new record. This course jus- Virology drew good enrollments. We 2012 with offerings at the Pre-filled Sy-
tifiably remains incredibly popular and also presented courses at the PDA/FDA ringes and Injection Devices Conference,
provides a unique opportunity for the Conference on Glass Quality and, once the 7th Annual Global Conference on
participants to gain insights and hands- again, Identification and Classification Pharmaceutical Microbiology, the PDA/
on experience with the complexities as- of Nonconformities in Molded and Tu- FDA Supply Chain Conference, and the
sociated with aseptic processing. bular Glass Containers was a sellout. PDA/FDA Vaccines Conference. All in all,
Based on the success of hosting several We closed out our summer on-the- it was a very successful year for our lec-
themed weeks last year at our training road events with three courses at PDAs ture courses with the details being capa-
facility, we continued providing topic- Conference on Sterile Technology in Chi- bly managed by Stephanie Ko.
focused, week-long training opportu- cago. Both our courses on Moist Heat While all this was going on with our
nities this year. In March, we hosted Sterilization and Dry Heat Valida- lecture courses, we were also busy at the
Lyophilization Week with two popular tion exceeded our expectations, and TRI facility in Bethesda with our labora-
courses: Fundamentals of Lyophili- our Parametric Release course also had tory courses. In addition to our flagship
zation taught by Ed Trappler, and over ten students hear instructor Mike Aseptic Processing Training Program,
Validation of Lyophilization taught by Sadowski discuss the critical elements TRI delivered a number of hands-on lab
Karen Bossert and Barbara Berglund. associated with this technology. courses. These courses, combined with
Students could register for one course or In September, we traveled up Interstate a lecture component, provide plenty of
both; many took advantage of the op- 95 to Baltimore where we presented six opportunity for the students to put into

TRI
practice in the lab what they learn in the classroom.

Responding to past student feedback, we presented our An PDA Conference
Introduction to Visual Inspection class twice. The combined
enrollment for the two sessions showed that there is still plen- Recordings
ty of interest in this topic in our industry. If you are involved Interactive Online Learning
in this technology, I urge you to consider enrolling in one of
the two sessions well be offering in 2013. PDAs Conference Recordings allow you to
We offered two new courses on virus-related technologies, and affordably hear from todays top presenters in the
were excited that FDA scientists Kurt Brorson and Scott bio/pharmaceutical industry with no traveling!
Lute served as the teachers. Based on this years experiences, Recordings from PDAs events through
we will roll Preparation of Virus Spikes Used for Viral Clear- September 2012 are now available for purchase.
ance Studies and Virus Filtration into a comprehensive The events include:
three-day course in 2013.
Longtime PDA instructors Maik Jornitz and Wayne Gara- PDA/FDA Joint Regulatory Conference and
fola delivered two courses on filtration technologies during Responsibilities of Executive Management ICHQ10
our 2012 Filtration Week in August. Filters and Filtration Workshop Session Recordings
in the Biopharmaceutical Industry Basics Course provided Recordings from the entire conference and workshop are
students the fundamentals of filtration theory and design, and available for purchase for $340 Member/$380 Nonmember.
Price of recordings includes:
Filters and Filtration in the Biopharmaceutical Industry Ad-
Fourteen (14) recorded sessions from the 2012 PDA/FDA JRC
vanced Course provided plenty of hands-on experiences for and six (6) sessions from the ICHQ10 Workshop
the students as they got experience in what happens when, as Access to 58 downloadable presentation handouts
Jornitz likes to say, We put some sand in the gear box. Almost Unlimited playback of the recordings for 90 days from
30 students participated and benefited from the knowledge of receipt of login information.
these two instructors.
Building on the successes of our Aseptic Processing Training PDA/FDA Glass Quality Conference
Program, as well as the lessons we learned last year from the Recordings from the entire conference are available for
purchase for $255 for members and $295 for nonmembers.
initial offering, we again presented Quality Systems for Asep-
Price of recordings includes:
tic Processing. This course, taught by co-lead instructors Dave
All nine (9) sessions from the 2012 Conference
Matsuhiro and Hal Baseman, as well as other faculty, takes the
Access to 24 downloadable presentation handouts
students a step beyond the concepts presented in the two-week Unlimited access to all session recordings for 60 days from
aseptic training program, and provides students the tools to receipt of login information.
answer the question, What do I do when things go wrong?
This year, a capacity group of 17 students participated. Innovation & Best Practices on Sterile
Also, we offered Validation of Biotechnology-related Clean- Technology Conference
ing Processes along with what I believe will be a really unique Recordings from the entire conference are available for
course titled Risk-based Qualification of Sterile Drug Prod- purchase for $215 Member/$255 Nonmember. Price of
recordings includes:
uct Manufacturing Systems. This course, developed and
presented by Phil DeSantis and Walter Henkels, takes the All eight (8) recorded sessions from the 2012 Conference
Access to 19 downloadable presentation handouts and
students through the design and execution of qualification
the A-VAX Case Study
and validation protocols using the equipment and utilities in Unlimited access to all session recordings for 60 days from
TRIs clean room, providing an invaluable experience for in- receipt of login information.
dividuals involved in these activities in their own daily jobs.
In September, we were really excited to offer hands-on training
to FDA staff when 15 members of CDER exclusively partici- Members Save More: Receive 30% off the member price
pated in Practical Aspects of Aseptic Processing. of a single event recording or session recordings bundle
when you purchase or renew your PDA Membership!
In addition to our entire faculty, Lab Manger James Wamsley
received help and support from laboratory technician Gerard
Cornejo and our newly hired Coordinator of Laboratory Edu- For more information on all PDA
cation Jake Wolpe. Gerard spent just over six months with us conference recordings please visit:
before leaving in mid-October to return to school and Jake,
newly graduated from James Madison University, joined us in
www.pda.org/webseminars
late September. We benefited from the hard work of our

TRI
Parenteral Drug Association

Training and Research Institute (PDA TRI)
Customized Training at Your Facility or Ours
PDA TRI can work with you to bring custom in-house training solutions
and expert instructors right to your doorstep. Get training solutions that
meet your specific needs while saving time and money on travel. If your
offices are not conducive to training, PDA TRI can host your programs in
our facility located in Bethesda, MD. Our state-of-the-art facility includes
an aseptic processing suite with a filling room, component prep lab
and gowning/degowning areas, clean-in-place lab, microbiology lab,
biotechnology lab, classrooms and student break areas.
We can deliver one of our existing training courses to your organization

or we can work with you to develop the custom training you need. Below
find a list of available subject areas covered by TRI training.
Aseptic Quality and Regulatory Affairs

Biotech Specialized
Environmental Monitoring Training
Filtration Validation
Microbiology
We look forward to bringing our expert-led pharmaceutical

and biopharmaceutical training to you.
Contact us to discuss your specific needs:

Robert Dana
Senior Vice President Quality and Regulatory Affairs
and PDA Training and Research Institute
+1 (301) 656-5900 ext. 224
dana@pda.org
For more information please visit www.pda.org/courses

TRI
Gerard Cornejo, Laboratory Technician, TRI,

In fact, every session for the year was sold out by PDA
March a new record Cheryl Custard
Phil DeSantis, Principal Consultant, DeSan-
tis Consulting Associates
first summer intern, Kyle Nakashima, ing this request, in addition to all the
Josh Eaton, Sr. Project Manager, Scientific
who spent six weeks working in the labs other activities we had already scheduled
& Regulatory Affairs, PDA
with James and Dave Matsuhiro before for 2012, was a daunting task. Thanks to
returning to school in September. The a lot of hard work and dedication by the Wayne Garafola, Application Specialist,
experience provided Kyle the opportuni- TRI staff, most notably James, as well as Sartorius
ty to learn something about the pharma- TRI instructors Hal Baseman, Cheryl Jeff Hartman, Director, Validation Quality
ceutical industry and also provided PDA Custard, Carol Lampe, Joe Lasich, Jim Assurance, Merck
with some additional lab support for our Lyda and Rainer Newman, we delivered
Walter Henkels, ConcordiaValSource
aseptic processing training. a series of one-week sessions which, by all
reports, were very well received and benefi- Maik Jornitz, Vice Presient, G-Con Manuf
The year just ending marked the begin-
ning of a new strategy for TRIs educa- cial to the company. And this was but one Stephanie Ko, Sr. Manager, Lecture Educa-
tion programs. In 2012, we presented of several in-house programs we delivered tion, TRI, PDA
over 20 courses based on PDA-owned in 2012.
Joe Lasich, Consultant
material. By strengthening the partner- So that about brings down the curtain
ship between TRI and PDAs Scientific Wendy Lambert, Director, Quality and Regu-
on the year. By any measure, it was a
and Regulatory Affairs department, led latory, Abbott Labs
very successful one. None of this could
by Rich Levy, we were able to leverage have been accomplished without the Carol Lampe, Sr. Consultant, J.M. Hansen &
the material owned by PDA and build hard work of a lot of people. I have Associates
it into education courses only available tried to recognize and acknowledge Rich Levy, PhD, Senior Vice President, Sci-
from TRI. The course content was cre- them in this article. However, there is entific and Regulatory Affairs, PDA
ated based on the content of the Tech- another group of people without whom
nical Reports by Rich, his staff and the Scott Lute, Biologist, CDER, FDA
we could not have had the success
teams that developed the Technical Re- we had: and that is our students. There Jim Lyda, Senior Science & Reg. Affairs
ports. TRI staff, working with consul- were almost 1,400 of you this year, Advisor, PDA
tant Bethanne Bond and the faculty, and all I can say is thank you for your Dave Matsuhiro, President, Cleanroom
who was drawn from the teams that support of our educational efforts. We Compliance
developed the Technical Reports, then present our courses to help you and its
developed the actual course materials. Janie Miller, Sr. Project Manager, Scientific
extremely gratifying to see that you ap- and Regulatory Affairs, PDA
This approach resulted in a series of preciate our efforts.
high-quality courses, developed and pre- Miguel Montalvo, President, Expert Valida-
sented by the experts who put the Tech- Id like to close by wishing each of you, tion Consulting Inc.
nical Reports together, and presented in the readers, a safe, happy, healthy and
prosperous 2013. I hope to see many of Kyle Nakashima, Intern, TRI, PDA
a brand-identity format which tied them
all together. We owe a big thank you to you at one of our TRI courses next year. Rainer Newman, Consultant
Rich and his staff: Vince Anicetti, Josh PDAs Whos Who Emma Ramnarine, Sr. Manager, Genentech
Eaton, Jim Lyda and Janie Miller, as
Vince Anicetti, PDA Fellow Mike Sadowski, Director, Sterile Manufac-
well as the instructors and Technical Re-
Hal Baseman, COO, Valsource ture Support, Baxter SA
port task forces in making this strategy
a reality. Barbara Berglund, Manager, QA, Boeh- Ed Trappler, President, Lyophilization Tech-
ringer Ingelheim nology
Our in-house training programs contin-
ued to flourish in 2012, demonstrating Bethanne Bond, Consultant Barbara Van der Schalie, Clinical Training
the value of being able to bring custom- Karen Bossert, PhD, Vice President, Lyophi- Manager, SAIC-Frederick
ized educational content right to the lization Technology Jim Vesper, President, LearningPlus
companies that need the training. Of
Scott Bozzone, PhD, Sr. Manager, Quality Sys- James Wamsley, Senior Manager, Labora-
particular note this year was a request
tems and Technical Services-Validation, Pfizer tory Education, TRI, PDA
to provide multiple sessions of the train-
ing course, Practical Aspects of Aseptic Vivian Bringslimark, President, HPIS Consulting Jake Wolpe, Coordinator, Laboratory Educa-
Processing, to a single company. Fulfill- Kurt Brorson, PhD, Staff Scientist, FDA tion, TRI, PDA

Science
Top Industry Leaders Talk Best Practices for

vo i ce s o f the b o a rd
Pharmaceutical Quality Systems

At the 2012 PDA/FDA workshop, Responsibilities of Executive Management Imple-
menting the Principles of ICH Q10, 150 industry and health authority senior leaders
and experts shared best practices on the pharmaceutical quality system (PQS). Ste-
ven Lynn, Director, U.S. FDA, Rick Friedman, Associate Director, FDA, Jennifer
Magnani, Associate Director of Quality, Genentech and Anders Vinther, PhD, Vice
President Quality Biologics, Genentech, and PDA Chair, co-chaired the event.
At the workshop, four highly engaging break-out sessions covered the topics of what
works and what doesnt in creating a PQS, which metrics are useful and what types
of governance models are effective. An industry and a FDA representative facilitated
each session. The dialog was very rich, with many great ideas and experiences shared.
Proactive Metrics
One of the most insightful conclusions reached during the sessions involved mov-
PDA Chair Anders Vinther, PhD ing away from reactive metrics to proactive metrics. It is important for companies to
engage in dialogue regarding the why behind red (stop, risk) and yellow (caution)
metrics. If the company culture is that of must have greens, the company greatly reduces the dialog that can improve the business
on a continual basis.
The metrics should truly reflect the state of control, provide relevant feedback loops, periodically be reviewed for appropriateness
and suitability and communicated broadly, e.g., on visual performance boards, etc.
The attendees spent some time talking about metrics that show whether or not the company has the right quality culture.
It was also acknowledged that the potential to drive improvements by having a solid cost-ofpoor-quality model in place with a
robust feedback loop was not fully understood by company senior leaders.
Some specific metrics discussed were:
Investigations: time to initiate, lack of recurrence, adherence Process capabilities: variability like CpK and other variability
to closure time, percentage of root cause found metrics
CAPA: lack of recurrence, number of time line extensions, Cost of Quality: leading versus lagging indicators use sim-
adherence to closure time ple models
Product disposition cycle time Organizational health metrics as a measure of quality culture:
Risk management: change in risk profile, effectiveness, num- safety metrics, employee satisfaction and engagement, talent
ber of self-identified risks (speak-up culture), comparative retention, adherence to training plans, number of employee
metrics site-to-site suggestions and how many implemented
Right First Time: avoid linking to performance incentives if Governance: no surprises coming out of audit and inspec-
this drives the wrong behavior tional findings i.e., issues should already have been identi-
fied and included in improvement plans
The common theme for governance and organizational structure was that of integrating the business teams more (quality, opera-
tions, etc), co-locate them and share common goals and objectives. This eliminates silos and improves product quality and compli-
ance when done the right way.
It is also important for the company to dedicate time and resources to process improvements and preventive actions rather than
focusing on the corrective part of the CAPA system only.
Where many companies are still struggling is the transition or migration into a culture of quality owned by all. Attendees discussed
whether the quality organization most often leads investigations into quality issues that originates from manufacturing processes
(and therefore probably should be called manufacturing issues rather than quality issues) or have operation taken more ownership?
Several attendees said the shift needs to be a deliberate change that starts at the top in the organization. The shift in culture should
also be encouraged and stimulated by linking the right quality mindset and actions to the company rewards and recognition system.
Speaking the language
How do you sell the message of quality? Or in other words, how does the rest of the organization better appreciate and support quality
Continued at bottom of page 43

Calling All Active
PDA Members
Vote Now!
Instructions for Voting:
Online Voting Opens September 10th Go to www.pda.org/vote
for the 2013 PDA Board of Directors Election Log into the system using
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PDA members, online voting will open on September 10th for the and last name
2013 PDA Board of Directors Election, we encourage you to take a
Please read the instructions
moment and vote for your candidates of choice. for each question carefully
To vote is easy, just follow the instructions below. You will need Review the choices for
each position then select a
your PDA Member ID and last name to log in.
candidate for that position
All PDA members in good standing as of midnight on When you are done voting,
August 31, 2012 are eligible to vote. Voting for this election review your selection and
then check the participant
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cast after this date and time will not be accepted. SUBMIT button
If you need assistance please contact the PDA Membership You have now completed
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Thank you for being a valued PDA Thank you for your participation
member and voting! in this important election process.

Science
Another Volume Year in the Books

Letter
e di to rs me s sa ge
The PDA Letter is published 10 times per year,

exclusively for PDA members.
Subscriptions are not available.
What a year for the PDA Letter. We started off covering human factors testing in Articles in the PDA Letter may be reproduced with
the January issue and are ending it with articles on Quality by Design and Quality permission
Systems. In between, we published feature articles on job aids, rapid microbial meth- contact the PDA Letter Editor for details. PDA 2012
ods, prescription distribution licenses, biofilms, biosimilars regulations, and more.

PDA Letter Staff
We thank the many authors who graced our pages with their work, and we are ever
Walter Morris
grateful for the hard work of the PDA Letter Editorial Committee for suggesting top- PDA Letter Editor,
ics, authoring articles, reviewing articles and finding authors. It is that time of the Director of Publishing
year to say goodbye to a number of PLEC members who have served their two-year +1 (301) 656-5900, ext. 148
morris@pda.org
terms. Departing at the end of the year are: Sue Schneipp, Sandra Zoghbi-Gay,
Winston Brown, Jose Caraballo, Robert Darius, Martha Folmsbee, Janeen Skut- Rebecca Stauffer
Assistant Editor
nik-Wilkinson and Anastasia Lolas. I thank all of these fellow committee members stauffer@pda.org
for their dedication to PDA and the Letter, in particular. Many of these volunteers Katja Yount
are also involved in other PDA activities, and they all are eligible to serve on PLEC Publication Design Specialist
again in the future. yount@pda.org
We are currently looking for dedicated volunteers to serve a two-year term on PLEC.
If you are interested, please email me or Rebecca Stauffer. Tell us why you want to PDA Letter Editorial Committee
serve on PLEC, and we will get back to you by the end of the year. Vincent Anicetti, Keck Graduate Institute of
Applied Life Sciences and PDA
We are always looking for authors, and our editorial calendar for 2013 has a lot of hot Harold Baseman, ValSource
topics. We are accepting 1500-2000 word articles on drug shortages, process valida- John Paul Bevel, Teva Animal Health
tion, career advancement, sterile processing (any aspect), consent decrees, disposable Winston Brown, Alcon Laboratories
systems, and filtration validation. If you would like to author an article on any of
Jos A. Caraballo, Amgen
these topics, contact me with your proposal. The PLEC reviews proposals for articles
Robert Darius, GlaxoSmithKline
and provides outstanding feedback.
Mitchell Ehrlich, Fresenius Kabi USA
Speaking of change, it was with great sadness that I said goodbye to Emily Hough, Martha Folmsbee, Pall
my assistant in putting together the PDA Letter since 2007. Emily was a great contrib- Karen Ginsbury, PCI Pharmaceutical Consulting
utor to the PDA Letter, authoring and editing many articles and managing the PLEC.
Anastasia Lolas, Visionary Pharma Consulting
She is still at PDA plying her trade for the Marketing Department, so I continue to
Mike Long, ValSource
enjoy seeing her and hearing all about her nephews!
Rainer Newman
Rebecca Stauffer has done a great job since joining the Letter staff in September. Kathleen OSullivan, BD
This issue alone contains a number of articles by Rebecca. She has attended the 2012
Susan Schniepp, OSO BioPharma Manufacturing
PDA/FDA Joint Regulatory Conference and the 7th Annual Pharmaceutical Microbiology
Janeen Skutnik-Wilkinson, Pfizer
Conference, and will be at several more before years end. I look forward to even more
Sarah Thomas, Human Genome Sciences
contribution from Rebecca in 2013.
Sandra Zoghbi-Gay, bioMrieux
Well, as we close out 2012, I cant say how much I look forward to 2013, which will
be my tenth year at the helm of the PDA Letter. It is a pleasure working with the vari-
To Advertise, Contact
ous members and PDA staff who make the Letter possible. Please, never hesitate to
Dave Hall, Vice President, Sales
send us an email if you have problems, see errors, want to contribute, or just want to +1 (301) 656-5900 ext. 160
tell us what you like and dont like about the Letter. hall@pda.org
See you all in 2013!

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Correction: The Honor Awards Recipients listing in the September and October issues PDA Training & Research Institute
should have indicated that they were 2011 award winners recognized at the 2012 PDA 4350 East West Hwy., Suite 150
Annual Meeting. Bethesda, MD 20814 USA
Tel: +1 (301) 656-5900 Fax: +1 (240) 482-1659
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PDA Bookstore
2012 Clearance Sale
The PDA Bookstore 2012 clearance sale is going on now! Save 50% now
through November 30, 2012. Enter Coupon Code 2012clearance during
checkout to activate your savings. Deepest
Discounts
Check out a sample of some publications now on sale below! Ever!
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Proceedings from the PDA Workshop on Mycoplasma more today
Contamination by Plant Peptones
The proceedings contain important presentations which will provide
readers with recent information offered by subject matter experts who
presented at the 2005 PDA Workshop on the contamination of plant
peptones. 2007, 257 pages.
Item No.13007
Member $250.00 $125.00
Non-Member $300.00 $150.00
Government $140.00 $70.00
Biological Indicators for Sterilization Processes

Editors: Margarita Gomez and Jeanne Moldenhauer
This book will be of great interest to laboratory supervisors, regulatory and compliance
personnel, validation specialists and professionals engaged in other aspects of pharmaceutical
and biopharmaceutical manufacturing. 2008, 536 pages.
Item No.17268
Member $280.00 $140.00
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Quality Management in the American Pharmaceutical Industry (print version)

Author: Richard Friedman
Chapter excerpted from the book Pharmaceutical Quality. 2006, Softcover, 40 pages.
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For more information and to see all the items on sale

visit www.pda.org/2012clearance

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Letter

Volume XLVIII Issue 10 www.pda.org/pdaletter November/December 2012

QbD Offers Opportunities,

26 Simplify Quality 32 Make a Lasting 34 Q10 Implementation Key for

Call for Papers and Posters

Emerging Viruses of Concern Virus Clearance by Specific Unit Operations

Submissions received must include the following information:

- Title - Phone number

Deadlines Abstracts of papers for presentation: 30 November 2012

CO NFE R E N CE 4- 6 June | E X HIB I T I O N 4- 6 June

2013 PDA Europe

A comprehensive program will include presenta-

Some of the highlights of the conference include:

Following the conference training courses

26-27 February 2013

Cover Art Illustrated by Katja Yount

News & Notes Programs & Meetings

People TRI Education

32 Make a Lasting Impression During Preapproval Inspection

PDAs Mission PDAs Vision

PDA Board of Directors

The Technical Report Portal will be accessible to

By the end of the year, PDA Members will be able

6 Letter November/December 2012

PDA Europe is Hiring The Parenteral Drug Association presents...

PDA Europe is looking for a Senior Director to assist SR. VP

Have Impact on the PDA Letter and SAVE!

The PDA Letter Editorial Committee 11-13 February

2011 Honor Awards Recipients

The Service Appreciation Award

Patricia Brown, Myron Dittmer, Jens Eilertsen, PhD, Norbert Hentschel,

8 Letter November/December 2012

Letter November/December 2012 9

Faces & Places: 2012 PDA/FDA

Quality Risk Management Implementation

(l-r) Anders Vinther, PhD, Genentech; Richard Johnson, PDA

(top l-r) Gregg Claycamp, FDA; Rick Friedman, FDA

Plenary Session: Changing the Quality Culture

(l-r) G.K. Raju, PhD, Light Pharma; Anthony Mire-Sluis,

10 Letter November/December 2012

Regulatory Considerations During Cell Therapy Innovations

Regulatory Submission and Meetings

Plenary Session 3: CMO

Manufacturing in the Future

(top l-r) Susan Schniepp, OSO BioPharmaceuticals

Letter November/December 2012 11

Faces & Places: 2012 PDA/FDA

Emerging API Guidance Foundation Session: User Fees

(l-r) Steven Mendivil, Amgen; Betsy Fritschel, Johnson & Johnson;

Excipient Best Practices

(top l-r) Catherine Cook, FDA; Carol Rehkopf, FDA

Foundation Session: Regulatory Process to Approval

12 Letter November/December 2012

Drug Safety Investigations

Plenary Session 4: Compliance Update

(top l-r) Steven Wolfgang, PhD, FDA; David Cummings, FDA;

(l-r) Donna French, PhD, Genentech, Inc.; Patricia Love, FDA

Plenary Session 5: Center Initiatives

Letter November/December 2012 13