1. hobbies and interests
2. games
3. chess

www.nercsqa.org
Vol. 18. Issue 3, October 2014
Northern Highlights
The Quarterly Newsletter of the N ew E ngland R egional C hapter of the S ociety of Q uality A ssurance
President’s Message
Yuki is a beautiful white male Siamese mix my husband
and I adopted from the Sterling Animal Shelter about five
years ago. Like most Siamese, Yuki is vocal, inquisitive,
and shows promise as an acrobat (move over Cirque du
Soleil!). Yuki is also a bit self-centered and is appalled
when we remind him that our sole purpose in life is not to
be at his beck and call. He expresses his disbelief and incredulity at our lack of attention in creative (and often
artistic) ways. His favorite way of letting us know his displeasure is by attacking the toilet paper roll in either the
guest bathroom or our bathroom. Although it is messy
and can be difficult to explain to guests why they need to
use “shredded” toilet paper instead of regular toilet paper
when they visit us, I much rather that Yuki vent his frustration on the toilet paper roll than on me! Of course,
over time we have learned to anticipate his moves. I am
very fortunate to have a husband who is as creative as my
cat. Art has successfully foiled (no pun intended) Yuki’s
toilet paper attacks by wrapping the entire roll in aluminum foil (as if explaining the shredded paper was not
enough, now we have to explain the aluminum foil to
guests!).
But enough about cats and toilet paper! Since we are
on the topic of animals though, I would like to remind you
that Natasha Melfi will be speaking on the topic of GLPs &
Animal Welfare at our fall
member meeting on October 16th. I hope to see
many of you there! This
member meeting is a
different format from previous meetings in that dinner will be served and we
are extending the meeting
invitation to significant
others. My husband, Art,
will be attending, so if any
of you would like to hear
more about his creative
ways of dealing with cats,
this is the time!
The recent training on
Regulated
Bioanalysis
which was held at the
Sturbridge Host Hotel and
Conference Center on
September 16th was both
successful and informaArt’s “preventive action”
tive. Agilux Laboratories
was a gold sponsor for the event which allowed NERCSQA
to provide the training at a reduced rate for members.
Pipette Calibration Services also sponsored a table at the
event to advertise their pipette calibration capabilities for
the GLP and GMP industries. Dr. Richard LeLacheur gave
an excellent talk on the “nuts and bolts” of bioanalysis
while Dr. Viswanathan spoke about the “regulated” aspects of bioanalysis. If you were unable to attend this
training, go to page 6 for a summary of the Q & A session.
I would like to thank everyone who helped organize this
event, with special thanks to Aimee Altemus for coordinating with the hotel and speakers, Deb Buxton and Irma
Annecharico for helping at the registration table, and
Chris Wubbolt for moderating the Q & A session and for
donating an overhead projector to NERCSQA!
NERCSQA elections for 2015 are coming up soon! I
would like to thank Paula Picton for volunteering to chair
the Nominating Committee! Go to page 2 or page 3 if you
would like to find out more about the upcoming elections.
Many people contributed to the content of this newsletter, but Lisa Kennedy is by far the one who has spent the
most time on it! I hope you enjoy the articles, cartoons,
and puzzles in this newsletter! Feedback and contributions are always appreciated!
The cute culprit
Jen Bravo, NERCSQA President
Northern Highlights
Vol. 18. Issue 3, October 2014
www.nercsqa.org
About NERCSQA
NERCSQA Officers & Board of Directors
President
Treasurer
Interested in Joining NERCSQA’s Board?
Jen “Boo” Bravo
President@nercsqa.org
Laura “Haunted” Hoffman
Treasurer@nercsqa.org
Vice President
Director of Membership
Aimee “AHHH” Altemus
VP@nercsqa.org
Danielle “Undead” DeOssie
DirectorM@nercsqa.org
Past President
Director of Sponsorship
Chris “B. Witched ” Wubbolt
PastPresident@nercsqa.org
Jessie “Jeepers” Latchaw
DirectorS@nercsqa.org
Secretary
Director of Publications
Deb “Daunting” Buxton
Secretary@nercsqa.org
NERCSQA?
Me?
The positions open for 2015 are Vice
President, Treasurer, Director of
Membership, and Director of Publications. Elections begin the week of
Thanksgiving. Contact Paula Picton
or Danielle DeOssie for a Candidate
Biography form. Candidate Biographies are due November 7th.
Lisa “Killer” Kennedy
DirectorP@nercsqa.org
. . . But Seriously, We’re Not Scary CONTACT US!
Inside this issue
NERCSQA
Mission Statement
To serve as a focal point for Quality Assurance
"GXP" professionals in the New England Region
by establishing a forum for education, training,
communication and information exchange
among QA professionals in the environmental,
pharmaceutical and biotechnology fields of
government, private industry, research and
academia.
Letter from
the Editor
Sponsorship
Policy
Page 3
Page 8
QA Q&A
Page 5
Life in QA
Page 11
Crossword
Page 9
True Guidance
Page 10
Upcoming NERCSQA Events
Page 12
Page 2
Northern Highlights
Vol. 18. Issue 3, October 2014
www.nercsqa.org
Letter From the Editor
A message from Lisa Kennedy, NERCSQA Director of Publications
If you’re at all like me then with every accomplishment you make, every obstacle you overcome, somewhere down
the road, waaay back on that journey, you faced a decision: whether to buckle down, put your boot heels down in the
stirrups and get ready to do some work, or to just settle back in the saddle and say “well. . . good enough”. You know,
apply that minimal effort that gets the job done but you might as well just throw your “accomplishment” in a pile somewhere and stamp a big ol’ MEDIOCRE! on it. When it comes to my role as the Director of Publications for NERCSQA, I remember that decision well.
It was February 13th, a day or two before Jen Bravo, my boss and current president of NERCSQA, was to leave for a 10
day vacation in Puerto Rico. That’s 7 business days without the Director of Quality & Regulations at an up-and-coming
bioanalysis CRO—yikes! The audits were scheduled, the documents were filed ahead of time, and my co-worker and I
knew exactly the QA roles we needed to fulfil in Jen’s absence. Needless to say, my next week was packed and there
wasn’t exactly an easy atmosphere in the QA office. It was on this day, well after lunch, that Jen casually (or was it cautiously?) mentioned to me, newly elected Director of Publications at NERCSQA, that I should aim to publish the year’s
first edition of Northern Highlights, the quarterly newsletter, at the end of March, in time for the annual SQA meeting—
double yikes?
And so I was faced with a decision. Do I nod my head vacantly at Jen’s comment and then file that memory deep in my
brain, hide it like a monster under the bed, and continue to procrastinate until mid-March? Or do I spend a few hours a
week on content and formatting to produce something that attempts to be tolerable to read and look at, something I can
be happy to distribute to readers and stand behind as part of an organization? There was a time when the former might
have appealed to me, but I did learn one thing from my master’s thesis: things get done by doing them, and as hard as I
tried, the damn newsletter would not write itself, so I chose the latter.
Three publications of Northern Highlights later I can say with certainty that not only did I make the right decision—I
knew that after the first publication when other NERCSQA members took the time to share their thoughts and comments
with me— but also, as a member of NERCSQA and Northern Highlights reader, you should run for a Board Position. Holding an office will increase the viability of NERSCQA as well as your own career.
Don’t believe me? Every two years the Director of Publications, responsible for creating Northern Highlights,
changes. Check out each Director’s earliest issues compared to those veteran later ones; suffice it to say newsletter quality correlates positively with experience, my own run being no exception! Increasing your skill set and professional network really never hurt anyone, and an organization is nothing without the talents of its members.
Already held an office? Well, since we all work in quality, I guess we can agree that the first time we try something
we do it completely perfectly and there is no room for improvement. Experience never bettered anything and nothing
ever changes in this industry, right?
If you’re interested in running for a NERCSQA Board office please fill out a Candidate Biography, available through
Paula Picton or Danielle DeOssie. The following positions are open this year: Vice President, Treasurer, Director of Membership, and Director of Publications. The polls open the week of Thanksgiving. Please submit Candidate Biographies to
Paula Picton by November 7th; a slightly formal process I’ll admit, but don’t sweat it, clearly no one read mine.
Page 3
Northern Highlights
Vol. 18. Issue 3, October 2014
www.nercsqa.org
Regulated Bioanalysis Training
A NERCSQA Training Event with Dr. CT. Viswanathan and Dr. Richard LeLacheur, Sponsored by Agilux Laboratories
Introduction By Deb Buxton, NERCSQA Secretary
“THERE IS NO SPIRIT OF GLP, JUST THE SPIRIT OF
NON-COMPLIANCE” is an often quoted line once
stated at one of the infamous Crystal City meetings
on bioanalytical method validation by the former Associate Director in the Division of Scientific Investigations at the FDA, Dr. C.T. Viswanathan (now, President, CT Viswanathan & Associates).
We were most fortunate to have Dr. Viswanathan
speak to us at the recent NERCSQA training entitled
Regulated Bioanalysis. The training, which also featured Dr. LeLacheur, the Senior Director of Bioanalytical Operations at Agilux Laboratories, took place
at the Sturbridge Host Hotel and Conference Center
on September 16, 2014.
Dr. Viswanathan was the next speaker and presented the reasons and methods of FDA inspections while weaving in stories of his vast experience
at the FDA. Some of Dr. Viswanathan’s key messages about bioanalysis were to make sure accuracy is supported by data, demonstrate reproducibility, demonstrate stability and meet 21 CFR
320.29.
After the formal presentations, Dr. Viswanathan
and Dr. LeLacheur fielded questions from the training attendees. A brief summary of the question
and answer session is presented on the next few
pages.
Dr. LeLacheur opened the day
with a comprehensive presentation about the nuts and bolts of
bioanalysis, the science of quantifying a target chemical substance in a biological matrix. Details of bioanalysis ranging from
the principles of mass spectrometry and liquid chromatography to what could go wrong
during sample analysis were presented in an informative and entertaining manner. Of particular
interest was the analogy between how Dr. LeLacheur’s family met their new neighbors and
the separation of different mole- Dr. LeLacheur led a room of QA professionals through the details & history of LC/MS-MS in an
effort to teach us the science of bioanalysis, and make us more effective auditors; no easy feat.
cules by chromatography.
Page 4
Northern Highlights
Vol. 18. Issue 3, October 2014
www.nercsqa.org
Dr. Viswanathan and Dr. LeLacheur’s QA Q&A
By Aimee Altemus, NERCSQA VP
Q: Is it required that the study protocol specify that ISR cated that method validation performed in support of
is to be performed?
safety studies (TK) should be conducted according to the
A: Both speakers felt that performance of ISR does not GLPs (i.e. protocol, study director, etc) or mention the
need to be specified in a nonclinical toxicology protocol exceptions to the GLPs. Dr. LeLacheur pointed out that
as long as ISR is specified in the analytical plan and/or is unlike the FDA guidance on method validation, the EMA
performed according to established standard operating guidance states that method validations in support of
nonclinical studies should be performed per GLPs.
procedures.
Q: For nonclinical studies, ISR is typically performed
once per compound/species/matrix. When would it be
required to re-do ISR for a particular method? For example, if a method is partially validated due to minor
method changes or change in analyst, would ISR need to
be repeated? What would trigger re-doing ISR?
A: Dr. LeLacheur indicated that determining whether
something is a minor change or a major change is sometimes a hard distinction; therefore redoing ISR is the most
conservative and safest thing to do from a risk-based perspective. With ISR, you are testing whether the method
is reliable and whether the execution of the method is
reliable. Dr. Viswanathan indicated that redoing ISR is not
necessary for an analyst change or other minor method
changes.
Q: Do you need to claim that method validation is done
according to GLP? What does that mean in terms of having a protocol, a study director, including the study on
the master schedule, conducting in phase inspections,
etc.? Is there a compliance statement? What should be
on the compliance statement: what was done according
to GLPs and what was not, do you need to add that the
missing compliance components create no negative impact on data?
A: Although not specifically required by FDA GLP regulations or FDA guidances, Dr. Viswanathan indi-
Q: When preparing standards and QCs, would the scenario below be acceptable? Or would you need to prepare the standards and QCs from separate stock solutions prepared exclusively from independent weighings?
"Stock solutions were prepared in duplicate, were verified
against each other, then mixed together to create a combined stock. The combined stock solution was diluted with
dilution solution to prepare calibration curve working solutions. The same combined stock solution was then diluted with dilution solution to prepare quality control
working solutions.”
A: The agency’s views on this have not been consistent.
During an FDA inspection last year a 483 was issued to a
local company for this exact situation. The investigator
indicated that standards and quality controls (QCs)
should be prepared from independent stock solutions at
least once during validation. The draft FDA guidance on
bioanalytical method validation (released in Sept 2013)
states that at least one demonstration of precision and
accuracy of calibrators and QCs prepared from separate
stock solutions is expected. Dr. Viswanathan feels that a
483 should not be given strictly based on a departure
from a guidance document. Fundamentally everything
comes back to accuracy. Dr. Viswanathan did not think a
483 issued for a situation like this would cause nonapproval of an NDA.
(Continued on next page)
Page 5
Northern Highlights
Vol. 18. Issue 3, October 2014
www.nercsqa.org
Dr. Viswanathan and Dr. LeLacheur’s QA Q&A
(Continued from previous page)
Q: If a bioanalytical laboratory analyzes samples for
both GLP animal studies and human clinical studies,
when inspecting for GLP compliance, would the agency
review anything related to the human studies? Would it
be considered wrong if the laboratory were to list the
human clinical studies on the master schedule?
A: Dr. Viswanathan feels that clinical studies should not
be on a company’s Master Schedule. It was pointed out
that some companies add clinical studies to the master
schedule but will sort out the GLP studies for an FDA investigator.
Q: If a bioanalytical laboratory was doing analysis for
samples for Phase I PK studies (i.e. these would not be
bioequivalence or bioavailability studies) what standards would be used when performing an inspection?
A: Dr. Viswanathan felt that you need to follow guidance
and Part 320.29 from CFRs. You need to have confidence
in the concentration data generated.
Questions for
Viswanathan
Dr.
Q: Now that you are on
the “other side”, working for sponsor companies, has anything surprised you about sponsor-FDA interactions?
A: Dr. Viswanathan
does not consider himself as being on the
“other” side. He is still
focusing on doing the
right thing for the safety of the American people and facilitating drug development. The difference is that his
clients do not have to take his advice, but that from a
business perspective it pays to prevent and protect
against problems. He indicated that if all other things are
equal, the company with the highest compliance level
will win out in the end.
Q: Guidance documents prominently state that guidances represent FDA’s current thinking on a given topic
and that alternative approaches can be used to satisfy
the requirements of the applicable statutes and regulations. Yet, it appears that guidances are treated by FDA
inspectors as binding, regardless of whether scientifically valid alternatives are used. If a company is given a
483, is it counterproductive to challenge the FDA?
A: Dr. Viswanathan stated that guidance documents are
not enforceable in a court of law; however, he does not
advise taking FDA to court for obvious reasons. He indicated that it is not counterproductive to ask diplomatically for more information about an issue. Dr.
LeLacheur suggested approaching FDA by proactively engaging them; using it as an opportunity to
exchange information and
ideas. Ask them to help
you understand the details around the specific
issue.
(Continued on next page)
Dr. Viswanathan and Dr. LeLacheur weighed in on attendees’ questions
Page 6
Northern Highlights
www.nercsqa.org
Vol. 18. Issue 3, October 2014
Dr. Viswanathan and Dr. LeLacheur’s QA Q&A
(Continued from previous page)
Q: FDA’s current thinking on method validation has
changed and evolved in the last several years. Sometimes there is a time gap between when the method
validation is performed and when the data is submitted
to the agency for review. The method validation may
have been compliant to FDA requirements at the time
of performance, but may not meet current standards. Is
the agency’s expectation that companies bring the
method up to today’s standards?
samples. Dr. Viswanathan indicated that in terms of the 2
different routes, you need to plan for the IV route. He
said that he does not remember a time at the FDA where
there were administrative actions associated with
whether samples were diluted or not diluted.
A: Dr. Viswanathan felt that in terms of accuracy, methods need to be up to current standards; consider adding
additional tests as an addendum to the submission.
A: Dr. Viswanathan said that this has been a concept for a
long time (risk based approach). He has heard that this
risk based approach will be used for BE studies every 2
years. He cannot point to an example of it occurring however in his experience.
Q: For BE studies where two different routes of administration (e.g. IV & PO) are performed, and concentrations for one of the routes (IV) are expected to be AQL,
is pre-dilution acceptable? Or is it necessary to run all
samples undiluted, then go back and dilute all samples
that were AQL? Does the FDA care which approach is
taken?
A: Dr. LeLacheur indicated that for nonclinical work and
early clinical work samples are diluted based on available
information. This saves time, money and resources.
However, for BE studies it is not advisable to dilute. In a
BE trial, you have to ensure that the assay matches the
Q: Can you explain FDA’s risk based approach to inspections? Is it true that companies with good inspection
history can expect to be inspected by FDA less frequently?
Q: Are 483’s that are given by the field investigators ever
reviewed by headquarters?
A: Dr. Viswanathan thinks that this should be done, but it
is not always consistently done.
Q: What do you think about joint inspections with multiple agencies?
A: Dr. Viswanathan indicated that some inspecting authorities will join another authority on that agency’s investigation, but they do so to observe and do not enforce
their own agency’s regulations.
Event Sponsored by
Agilux
laboratories
www.agiluxlabs.com
Interested in Being a Corporate Sponsor?
Contact Jessie Latchaw at
DirectorS@nercsqa.org
Northern Highlights
Vol. 18. Issue 3, October 2014
www.nercsqa.org
The Northern Highlights Crossword
Summer Issue SOLVED
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Did You Know That There Are SIX DIFFERENT WAYS To
Become A NERCSQA CORPRATE SPONSOR!
Platinum — Enjoy FOUR FULL PAGE Advertisements in Northern Highlights!
Gold — Comes with 4 FREE member meeting registrations & 2 FREE Training events
Silver — Four FREE NERCSQA member meeting registrations
Bronze — Two FREE NERCSQA member meeting registrations
Vendor — Set up a booth at NERCSQA events!
In Kind — Become an “in kind” sponsor by volunteering meeting space or resources for NERCSQA
~Click Here to see the MANY other perks that Sponsorship offers~
Page 8
Northern Highlights
Vol. 18. Issue 3, October 2014
www.nercsqa.org
The Northern Highlights Crossword
FDA
ACROSS
DOWN
1. A phrase that indicates a unit does not meet a given requirement or specification
2. The state that meets prescribed specifications, contract
terms, regulations or standards
4. The arithmetic average of all measurements in a data set
3. The comparison of a measurement or system of unverified
accuracy to one of known accuracy to detect any variation
from the required performance specification
6. A brainstorming tool designed to represent a meaningful
relationship between an effect and its causes
5. An identified reason for the presence of a defect or problem
7. A set of Requirements governing the quality procedures of
medical device manufacturers
7. The comparison of a current condition to the desired state
9. The measure of dispersion in a data set
8. A specific statement of a desired short-term achievement or
goal
10. A set of requirements that control the procedures and operations of toxicology laboratories
11. A graphical representation of the steps in a process
14. An equation that indicates the magnitude of an experimental effect above the effect of experimental error due to chance
fluctuations
Page 9
12. The act of confirming a product, method or service meets
the requirements for which it was intended
13. A defined quantity of product accumulated under conditions considered uniform for sampling purposes
Northern Highlights
Vol. 18. Issue 3, October 2014
www.nercsqa.org
True Guidance
A summary of the September 16th Training Event
Things really didn't start out all that well
Aimee didn't like the training venue's smell
Then one of the speakers got locked in Jen’s car
They went to dinner but were shown to the bar
The training started just a little too early
It was barely past 8, and QA can get surly
So some ate snacks and took a free water bottle
While others drove in late, gunning full open throttle
Still things turned around when C.T. and Rich,
Our scientist friend from GLP’s BA niche,
Wove an intricate story of science and data
Quality increases business, falsification non grata
Good science makes drugs that benefit all
Don’t ignore results; compounds big ‘n small
But you also should make your validations robust
So industry and inspectors will finally trust
That no one wants their NDA to fail
Or get warning letters, nasty things in the mail
So let’s give up a hand to our trainers, our speakers,
To our members, attendees, and knowledge seekers
For coming together to learn from each other,
But it does beg the question, “So when’s there another?”
...Soon! Hope to see you all at the next NERCSQA training event!
Page 10
Northern Highlights
Vol. 18. Issue 3, October 2014
www.nercsqa.org
Life . . . in QA
“Awdut”
Auditors see it all
Accept the mistakes that we make
Can you please QC this?
“Be a yardstick of quality. Some people are not used to
working in an environment where excellence is expected.”
-Steve Jobs
Interesting FDA Links of the Month
Transparency to Regulated Industry– Listening Sessions 1-3
Recalls and Safety Alerts 2004-2014
FDA Newsfeed and Podcasts
Page 11
Northern Highlights
Vol. 18. Issue 3, October 2014
www.nercsqa.org
Upcoming NERCSQA Events
Date
Time
October 16th
Member Meeting #3
5:308:00
November
Member Meeting #4
5:308:00
Topic/Location
Speakers
Animal Welfare & GLPs
Natasha Melfi,
Waxy O’Connor’s Irish Pub,
Lexington, MA
Training Specialist Quality & Record
Management (Boehringer Ingelheim)
“Negotiating the Challenges of
being a QA Consultant”
Papa Razzi, Framingham, MA
NERCSQA QA Consultants/
Round Table Discussion
Click the latest Member Meeting to Register, the Topic for the Event’s Flyer, and the Location for Directions
*ATTENTION*
~Significant other are Welcomed at the Next Member Meeting~
But more importantly, there’s a cash bar!
10 Things You Won’t Hear at a NERCSQA Member Meeting
1. There was NO traffic in Cambridge this morning
2. They never have enough food at these member meetings
3. The last FDA inspection we had was a BLAST!
4. Man, that Aimee Altemus is a slacker
5. But management can’t downsize Quality!
6. That Mass Spec vendor has very reasonable prices
7. Oh no, our scientists never do that
8. Is Crystal City next to the Emerald City in Oz?
9. Sorry, that’s not a part of NERCSQA that Jen Bravo is involved with
10. Wow, that’s exactly how I interpreted the regulations!
Page 12
Northern Highlights
Vol. 18. Issue 3, October 2014
www.nercsqa.org
~A D V E R T I S E M E N T ~
Quality Assurance, Compliance & Computer
Validation Consulting Services
Calling all volunteers, we’re bringing back the
NERCSQA Member Profile!
I’ll try
it!
The goal of the Member Profile is to allow the NERCSQA community
to get to learn a little something extra about some of its members.
The layout is a mix of professional and personal questions, and Lisa
will probably throw something wacky in there.
Contact Danielle DeOssie,
DirectorM@nercsqa.org
Page 13
Me too!