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■ IN THIS ISSUE

■ C OV ER STORY Official Media Sponsor of the

INTERPHEX Show
FA C IL ITY OF THE YE A R A W A RD - Volume 24, Number 08
PUBLISHER, MIKE KELLY
R EG ION AL EXCEL L E NCE 973-920-7751
michael.kelly@advantagemedia.com

8 Delivering Excellence On the Cover:

EDITOR-IN-CHIEF, MICHAEL AUERBACH
973-920-7055
mike.auerbach@advantagemedia.com
Orchid Chemicals & Pharmaceuticals Limited’s PRODUCTION MANAGER, SUSAN FRANK
Orchid's Auranga-
Aurangabad, India API facility combines 973-920-7158
bad facility susan.frank@advantagemedia.com
state-of–the-art building/technical concepts with manufactures non- ART DIRECTOR, BEVERLY BLAKE
973-920-7116
innovative equipment applications. penicillin - non- beverly.blake@advantagemedia.com
cephalosporin APIs, ADMINISTRATIVE ASSISTANT
penicillin APIs, and ANA DACOSTA
973-920-7126
carbapenem APIs. ana.dacosta@advantagemedia.com
WEB EDITOR, BRENT TOMASINO
973-920-7479
brent.tomasino@advantagemedia.com
AUDIENCE DEVELOPMENT
GAIL KIRBERGER
973-920-7482
gail.kirberger@advantagemedia.com

12 GSK Cuts Development Time

With Jacketed Lab Reactors CORPORATE OFFICE: 100 Enterprise Drive
Mini versions of production equipment provide a Suite 600, Box 912
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CHIEF EXECUTIVE OFFICER, RICH REIFF
18 Compliance Documents: PRESIDENT, GEORGE FOX
CHIEF FINANCIAL OFFICER, TERRY FREEBURG
Solving The Puzzle VICE PRESIDENT, HUMAN RESOURCES,
SUSANNE FOULDS
Pharmaceutical ERP software for stress-free page 12
regulatory compliance. EDITORIAL ADVISORY BOARD
Michael J. Beier,
Senior Vice President of Operations
22 12 Key Steps To Address USP TITAN PHARMACEUTICALS, INC.
Dr. James V. Blackwell, PhD, Consultant
Changes BIOPROCESS TECHNOLOGY CONSULTANTS, INC.
Ronald C. Branning,
Strategies to stay current with the recent changes Vice President Global Quality
GENENTECH INC.
to chapters <61> and <62>. Robert F. Dream, Vice President
page 18 H.D.R. COMPANY LTD.
26 6 Steps To Ensure Content Johanna Carmel Egan,
VGP Project Management
Compliance ELI LILLY
Girish Malhotra, President
Effective strategies for enforcing content compliance EPCOT INTERNATIONAL
Allan F. Pfitzenmaier, President
and reducing costs in regulated environments. page 20 VECTECH PHARMA CONSULTANTS INC.
Susan Polizzotto, Manager,
R&D QA GMP Compliance
■ DE PA RTME N TS US SANOFI PASTEUR
Carlos Villalobos, Sr. Dir. Global Engineering
BRISTOL-MYERS SQUIBB
6 From The Editor
Richard G. Whitfield, Senior Director
PFIZER
16 What’s Hot Patrick Wong, Director of Global Engineering
BRISTOL-MYERS SQUIBB (BMS)
INNOVATIONS
20 Cleaning and Sanitizing
24 Washing Systems
page 24

■4 AUGUST 2009 | PHARMACEUTICAL PROCESSING

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■ FROM THE EDITOR
It's Time...
■ Michael Auerbach, Editor in Chief
Y
You know you have crossed some irreversible line in the parent/
child relationship when your 68 year old mother asks you if you
know anyone who can get her marijuana.
This request didn’t come from some Woodstock-era hippie look-
ing for a trip (no pun intended) down memory lane. No, this came
from my very square mother who was looking desperately for a
remedy for my father’s unrelenting nausea.
Her request came several months ago, during a particularly bad
patch of time during my father’s treatment for pancreatic cancer. The
combination of the cancer and the chemotherapy was causing
After I picked myself and the phone receiv-
er off the floor and steadied my spinning
head I said, no, I’m sorry I don’t know any-
one who sells the stuff…
almost non-stop nausea and none of the prescribed medica-
tions, OTC products or anecdotal remedies was helping. In fact, it was
their very own doctor who suggested they try marijuana. Of course,
he couldn’t get it for them, but if they knew someone…
After, I picked myself and the phone receiver off the floor and
steadied my spinning head I said, no, I’m sorry I don’t know any-
one who sells the stuff.
It wasn’t long afterwards that she told me a friend of a friend
had some and even came over and showed them how to roll a
“joint” and smoke it.
My reason for relating this story to you is that I believe it’s
time for this country to pass a national law legalizing marijuana
for medical use. According to the National Organization for the
Reform of Marijuana laws website (www.norml.org) only 14 states
- Alaska, California, Colorado, Hawaii, Maine, Maryland, Michigan,
Montana, Nevada, New Mexico, Oregon, Rhode Island, Vermont and
Washington have some sort of medical marijuana law on the books,
allowing its use in some shape or form for medicinal purposes.
I think it’s time for this country to stop making the moms, dads
and grandparents of this country into "criminals".
What's your opinion?
Have a comment or question about Pharmaceutical Processing?
My E-mail is: mike.auerbach@advantagemedia.com
■6
■PHARMPRO.COM
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AUGUST 2009 | PHARMACEUTICAL PROCESSING
■PHARMPRO.COM
Tumble Mixer Achieves Real Time IBC
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7■

■ COVER STORY
Delivering Excellence
Innovative equipment applications and a forward-looking design help build an
advanced API facility
■ By Mike Auerbach, Editor-In-Chief
O
rchid Chemicals & Pharmaceuticals Limited’s
desire to build a cost effective, well-integrated,
intermediate and sterile API facility, with state-
of–the-art building/technical concepts and
equipment has resulted in their Aurangabad carbapenem
facility winning the 2009 Facility of the year award for
Regional Excellence.
ABOUT THE COMPANY
Orchid Chemicals & Pharmaceuticals Limited is an inte-
grated pharmaceutical company based in Chennai (Madras),
India. Located approximately 400 kms away from Mumbai;
the Aurangabad facility is intended for the manufacturing of
non-penicillin - non-cephalosporin APIs, penicillin APIs, and
carbapenem APIs.
The carbapenem based product manufacturing sec-
tion of the factory has four (Intermediate/API/Sterile/
Hydrogenation) production blocks supported by a dedicated
solvent recovery plant, water systems, various utilities, an
effluent treatment plant and warehouse. These facilities
were newly constructed in fiscal year 2006-2007 and are
well integrated in terms of layout planning, cGMP building
design, state-of-the art systems, and innovative equipment.
Special emphasis has been given to the design of the pro-
duction facilities so contamination and cross contamination
can be avoided.
■8
■ PHARMPRO.COM
AUTOMATION A KEY FACILITY DRIVER
At Orchid, automation was implemented for various reasons
and was a major part of the facility design. All equipment is au-
tomated by using tools like Distributed Control System (DCS)
or Programmable Logical Controllers (PLCs). DCS or PLCs are
technological tools commonly available in the market but their
application in API manufacturing is unique.
Commenting on the reason why automation was used so
extensively in the plant, Mr. V .S. Padalkar – Vice President
of Projects & Engineering at Orchid said, “(The) primary
aim in designing the facility (with a high level of automa-
tion) was human and product safety, consistency in all oper-
ations, and technological excellence to motivate and attract
talented employees.”
ADVANCED FACILITY DESIGN – AVOIDING
CONTAMINATION
As the Aurangabad location is designed for multiple prod-
ucts, it was a great challenge to incorporate various types
of product manufacturing blocks with a special emphasis on
avoiding cross contamination, environment awareness and
advanced safety features.
The new facility comprises eight distinct blocks:
1.) Intermediate block (Plant-17)
2.) API block (Plant-31)
3.) Hydrogenation block (Plant-41)
AUGUST 2009 | PHARMACEUTICAL PROCESSING
■ PHARMPRO.COM
Left: Partial view of the Auraganbad facility from the main entrance. Above: Corridor around the cleanroom with the
adjacent technical area. Right: The advanced powder handling system featuring split valves.
4.) Sterile block (Plant-32)
5.) Solvent recovery plant including tank farm (Plant-33)
6.) Effluent treatment block (Plant- 46)
7.) Fire hydrant water tank and pumping station (Plant-43)
8.) Infrastructure facilities like utilities, transformer etc.
(Plant- 44)
All facilities have sufficient systems/equipment to pro-
duce four types of Carbapenem products with easy change
over procedures.
Commenting on the facility layout Mr. Padalkar said, “We
are using various types of toxic chemicals in carbapenem
manufacturing. Suitable systems are provided at each stage
for containment of it. The facility layout was planned to take
care of separate service and production areas with all sup-
port systems in a well designed manner.”
MATERIAL AND PERSONNEL FLOW CRUCIAL TO
SUCCESS
In the Aurangabad carbapenem facility sufficient room
and space is provided for all relevant functions. Designated
routes for personnel, material and product flow prevents
product mix up, cross contamination, contamination from
environment, and operator exposure to product. Waste and
unusable residue disposal systems are in place. The utmost
care was taken during facility design to assure the cleanabil-
ity of each area and its attendant systems and equipment.
Indoor storage areas are controlled to maintain required
temperature, humidity, and illumination which protects against
degradation or chemical alteration of raw material and prod-
ucts. Dispensing and sampling areas are provided with a
greater level of protection in respect to manufacturing blocks.
Support functions such as like utilities, in-process quality
control lab, cafeteria, training room, in plant maintenance,
day storages, laundry, wash rooms etc. are provided within
each production block to control personnel movement
within the campus.
PHARMACEUTICAL PROCESSING | AUGUST 2009
■ COVER STORY
As Mr. Padalkar explains, a fa-
cility mock-up study was done to
ensure proper flow of material/
people to prevent contamination
“Yes, it was part of the pre-de-
sign stage and since all relevant technical functions were
involved in the initial phase of the study, further design basis
and actual implementation faced far less challenges. It is fine
example of good team work.”
ADVANCED PROCESSES REQUIRE ADVANCED
PROCESSING EQUIPMENT
In order to manufacture their products with the speed
and efficiency they needed, Orchid relied heavily on the
ingenuity and cooperation of many equipment suppliers.
Some of the innovations implemented at the Aurangabad
facility are highlighted below:
Agitated Nutsche filter and dryer (ANFD) with gas knife:
Traditionally, filter/dryers and pan dryers have suffered
from the inability to recover the product “heel” left after nor-
mal discharge operations which results in less yield, slower
filtration rates, and concerns about batch to batch product
integrity (degradation of left material). To overcome these
problems engineering solutions such as tilting, providing
pushers, fluidizing beds, and additional ports have been de-
signed, but for Orchid's needs the solutions had limitations
for high level cGMP practices in commercial production.
To overcome this problem, Orchid worked with
Rosenmund – Switzerland who supplied an ANFD with a gas
knife system; this innovative technique was first success-
fully implemented and commissioned in India at Orchid.
Self contained powder handling system for sterile products:
Certain processes, such as powder handling operations
like milling, sifting, blending, and dispensing pose potential
for product exposure to environment as well as risk to op-
erator.
9■

■ COVER STORY
Automated cleanroom operation was designed to avoid operator exposure.
Protection of operators, security of the products and
continuous unrestricted flow of the material were the
main criteria to design this system. To fulfill these basic
requirements Orchid decided to work with Novindustra AG-
Switzerland, and they provided a cost effective, compact,
user friendly, state-of-art, self contained powder handling
system. This high tech system has ‘split valves’ with active
and passive valve sections. This system has components
which are easy to dismantle for cleaning, sanitization, ster-
ilization. All system parts are well designed and engineered
to make a maintenance free system.
Solid charging by closed systems:
Orchid's facility features closed solid charging systems for
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all type of reactors and drying equipment. Conventionally
pneumatically operated systems are available but the company
worked with a supplier to develop a PLC operated, fully auto-
matic system which would be user friendly in terms of opera-
tions, maintenance, cleaning, disassembling and assembling.
The advantages of this proprietary system in comparison to
conventional pneumatic conveying systems are: highly com-
pact, efficient, suitability for a range of powdery non-hygro-
scopic/hygroscopic materials, easy to clean, explosion proof,
non destructive, and totally enclosed dust free operation.
This system not only meets the general requirements of
conveying material for different applications but also is ide-
ally suited for charging material to reactors under inert gas
protection. The system has been designed to comply with
cGMP norms.
Nitrogen blanketing system for centrifuges (filtration
equipment):
In centrifuges, various types of product filtrations having
solvents are processed. Solvents and products are subjected
to very high rotating speed during the separation process.
Also due to high speed, bearing housings may develop
sparks. Therefore, to avoid any kind of explosion, it is es-
sential to purge the centrifuge before start up with nitrogen.
Similarly, when the centrifuge is in operation it is recom-
mended to provide continuous nitrogen blanketing.
As per normal practice followed in the industry as well as
previously used by Orchid, nitrogen is used for inertization of
the centrifuge. Earlier nitrogen purging was operator based and
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AUGUST 2009 | PHARMACEUTICAL PROCESSING
■ PHARMPRO.COM
■ COVER STORY

Exterior view of the sterile and API facility.

its vent was open to atmosphere so there was no assurance the inerti- '“Their timeline and safety record were very good, especially con-
zation of the centrifuge was effective and there was a huge consump- sidering the location. This project was well-executed and the first to
tion of nitrogen as well. To eliminate this unsafe procedure, Orchid use certain technologies in India. They brought in a lot of technology
developed an innovative blanketing system with their supplier. in a place where it’s difficult to do so. The challenges and how they
Nitrogen purging and blanketing of the centrifuges consists of a overcame them are appreciated.
series of pressure reducing valves to get to the required pressure They were able to increase their productivity all with local expertise”'
and has back pressure regulated valves at the vent to hold the We have built a facility for the present and future with advanced
specified nitrogen inside the centrifuge basket for inertization pur- technologies with in-house expertise only. This project is a unique
pose. Pressure switches are provided to monitor the nitrogen pres- blueprint in many ways for our kind of industry - a multi-product
sures which are interlinked to the control system. This blanketing flexible facility, with reduced product cost, increased productivity,
system provided following advantages: fully in-house expertise, an excellent safety record, strict compliance
• Ensure proper inert atmosphere in the centrifuge for safety. to cGMP, and superb team efforts with extraordinary leadership."
• Avoid loss of nitrogen thereby reducing nitrogen consumption.
Orchid has realized a 90% reduction in the use of nitrogen; saving a
lot of energy.
• Since the system is closed solvent lost to the atmosphere is BioSafe™ Pass-Throughs
eliminated and pollution significantly reduced.
• Ensures consistent product quality, less human exposure and
operator interference.
When asked about the relationship between the company and its
suppliers, and the requirement for the development of many new,
proprietary processes/equipment, Mr. Padalkar explains, "Orchid
strives to bring excellence in any work we do, whether it is pro-
cesses, hardware, facility, environmental protection, safety, cGMP
and so on.
This is not just to meet any statutory or regulatory requirements
for the time being, but to surpass such requirements and be at the
forefront of technical superiority in our industry.
Some of the concepts, even though they were new to vendors,
were so well co-ordinated with the vendors that the provided state-
• Seamless — Unique design eliminates cracks, corners
of-art solutions benefitted both our company and the vendors. and other contaminant traps!
Most of them were quite receptive of any changes and trying out • Lipless — Easy material transfer with no clearance
obstruction
new ideas for the first time. It was really a great learning and trail-
• Easy to Clean — Ultra-smooth internal surfaces
breaking experience for both sides." • Easy to Sterilize — 304/316 SS; removable doors can
Non-contaminating be autoclaved
polyurethane BioSeal • Double-Wall, Sealed Construction — adds rigidity
SUMMING IT ALL UP with no-lip design
and houses interlock and utilities
Finally, when asked why he thought the Facility of the Year judges
selected his facility for the award, Mr. Padalkar offer this explanation,
To order : 714-578-6000
"We are very proud and overwhelmed by this prestigious recogni- Fax: 714-578-6020
tion. The following comment by the respected judges reflects our
Low-Cost Solutions for High-Tech Industries
uniqueness and special efforts taken in this project to meet timelines
and budget with utmost safety and cGMP at every step of project.

PHARMACEUTICAL PROCESSING | AUGUST 2009 11 ■

 ■ PHARMPRO.COM
■ SCALE-UP

GlaxoSmithKline Cuts
Drug Development Time by
Using Jacketed Lab Reactors
Mini versions of production equipment provide a wealth of scale-up information

T
he traditional way to develop a process for pro-
ducing a new drug is to do the initial develop-
ment in round-bottomed laboratory flasks and
make the transition to small-scale production-
type reactors when the process is ready for piloting. Many
pharmaceutical companies still do it this way, but more
and more companies are switching from flasks to labora-
tory-scale jacketed reactors that are miniature versions of
production equipment.
The chief advantage to using a jacketed lab reactor is that re-
searchers can obtain information early in the process-develop-
ment stage on how a process will work in actual production, in-
cluding data on the safety of a process, says Roy Flanagan, team
manager of process safety and design with GlaxoSmithKline’s
Chemical Development
Dept. in Research Triangle
Park, NC. This enables a
company to get a drug to
market faster and more
than justifies the cost of the
equipment, he says.
GlaxoSmithKline plc
(GSK), for example, has
invested hundreds of
thousands of dollars on
jacketed lab reactors for
its Worldwide Research &
Development operations,
says Flanagan, but has
likely saved millions of
dollars by getting critical
information early in the
development of a process.
“A blockbuster drug can
generate revenues of $1
billion/yr, or $3 million/
day,” he points out, “so
getting products to the
Above: A scientist drains product from the manual bottom valve of a 2-L jacketed market faster can have a
lab reactor. large positive effect on
Right: A 2-L reactor with associated vapor trap (right) and distillate receiver (the the bottom line.”
glass ball). An insitu IR probe is inserted into the vessel on the left via a glass In contrast, he says, the
adapter (blue cap).

■ 12 AUGUST 2009 | PHARMACEUTICAL PROCESSING

■ PHARMPRO.COM
fact that a process has worked well through scale-up from
small to large flasks is no indication that it will work well in
production. “In the past, when we used flasks, we had some
unpleasant surprises the first time we tested a process in
a pilot reactor, and many times we had to go back and re-
develop a process. We have had far less of these problems
since we adopted the jacketed lab reactors. We typically
identify problems early and solve them before we get to the
pilot stage.”
Another basic advantage of using a jacketed lab reactor
is safety. Flanagan points out that product is removed from
a lab reactor through a valve at the bottom of the vessel,
whereas a flask is usually emptied by picking it up. “It can
be dangerous having people picking up a 22-L flask,” he
says. “Also, if you heat up a flask using a traditional mantle
and the reaction starts to run out of control, there’s no way
to cool it.”
While GSK has used jacketed lab reactors at some sites
for several years, during 2005 and 2006 Flanagan led a
multi-site group to formalize the implementation of the tech-
nology in all of the company’s five major research centers.
GSK continues to improve the use of the technology through
a laboratory reactor “site champions group” that has a rep-
resentative from each of the five centers.
The Research Triangle Park (RTP) operation is one of
two U.S. headquarters sites for GSK, the other being in
Philadelphia, where the company has one of its pilot plants.
RTP has about 7,000 employees, of whom some 3,000 work
in Research and Development. Chemical Development at
PHARMACEUTICAL PROCESSING | AUGUST 2009
■ SCALE-UP
Left: Another view of the 2-L jacketed lab reactor. In the foreground is a programmable direct-
displacement pump for metered, mass dosing.
Above: A 2-L jacketed lab reactor with a dosing bottle on a scale at left.
RTP is a relatively small department, with about 150 em-
ployees, but it has developed processes for some high-pro-
file drugs, such as the AZT AIDS drug, Valtrex for herpes,
Zyban for smoking cessation, and the Avodart prostate
treatment. At any one time the department may be working
on 15–20 projects, says Flanagan.
SCALED-DOWN PILOT PLANTS
Chemical Development has 29 jacketed lab reactors,
all supplied by De Dietrich Process Systems, Inc. (De
Dietrich calls them Miniplant reactors). GSK also uses De
Dietrich pilot-scale reactors in its pilot plant operations
in Philadelphia. Using equipment from the same manu-
facturer at both the development and pilot stages makes
for a smooth transition in the scale-up of a process, says
Flanagan. “Our lab reactors are scaled-down versions of our
pilot plant vessels,” he says, “just as our pilot plants are
scaled-down versions of production equipment.”
The 29 jacketed lab reactors at RTP consist of five 1-L
kits, six 2-L kits, two 6-L kits, six paired 20-L kits (12 ves-
sels), and two paired 50-L kits (four vessels). All of the
smaller kits are made of durable borosilicate glass and
most are elliptical in shape, rather than round-bottomed, so
their mixing characteristics are similar to those of a typical
production-size reactor. A couple of conical-shaped vessels
have also been installed for specialized studies. The 50-L
kits are made of glass-lined steel and Hastelloy, identical to
those found in pilot plants.
The head of each lab reactor has a large central port for
13 ■

■ SCALE-UP
the agitator motor, which has either a single
or double mechanical seal to ensure that
the vessel contents are not compromised
during operation. Several other ports are
available for other purposes, including: the
addition of reactants and other materials
(two ports), a glass riser for distillation
overhead, a thermowell for temperature
measurements, and other process analytical
technology (PAT) functions, such as turbid-
ity, near-infrared and pH measurements.
“The head has as many available ports as
we can get away with,” says Flanagan.
In the glassware above the reactor is
a manual valve that allows either reflux
or removal of distillate. Each of the small
reactors has a graduated receiver for distil-
late, but each pair of 20-L and 50-L vessels
shares a single condenser and valves which
allow distillate to flow from one vessel to
the other. “This gives us the flexibility to re-
flux or distill from either vessel throughout
the entire process,” says Flanagan. “There is
also a phase separator between them, so we
can perform an azeotropic removal of water
and direct either phase to either vessel.”
Product is removed through a valve at
the bottom of the vessel — a manual valve
on the smaller reactors and a pneumatically
operated valve on the 20- and 50-L units.
The design of the valve practically eliminates
dead space and makes for a free flow of
product through the valve, says Flanagan,
so that essentially all of the product can be
evacuated. In contrast, a round-bottomed
flask is normally picked up to be emptied
and this can be a rather hazardous pro-
cedure for larger vessels, as noted earlier.
Alternatively, product may be vacuumed
from a flask — a problematic operation.
Work on new drugs starts in RTP’s Drug
Discovery Department, where potential drug
candidates are made in quantities of up to
a few grams in standard glassware. Those
that show promise are moved on to Chemical
Development, where processes to make ac-
tive ingredients are initially scaled to produce
quantities of up to 100 grams in 1- or 2-L jack-
eted lab reactors. It is at this scale that most
of the process development is done and basic
problems are solved, says Flanagan.
“In these smaller reactors we devote al-
most 100% of the work to process develop-
ment and very little to making material to
support studies,” he says. “When we scale
■ 14
■ PHARMPRO.COM
up to the 6-L and 20-L reac-
tors we are probably down to
30% development, and when
we get to the 50-L scale 90%
of the work is for produc-
tion of material for testing
and we are just tweaking the
process.”
He explains that prepa-
ration of material at the
smaller scale is mostly for
development studies, includ-
ing toxicity tests, but at the
50-L scale an active ingredi-
ent is made in quantities of
up to 5 kilos and supplied
to RTP’s Pharmaceutical
Development Department,
which determines the best
way to formulate a product
for use by patients (e.g., as a
tablet, capsule, or by inhala-
tion). Some of the product
may also be used in early-
phase clinical trials.
The use of jacketed lab
reactors has also enabled
GSK to develop GMP (Good
Manufacturing Practice)
clean-in-place and clean- Close-up of a 20-L jacketed lab reactor with a glass-
ing verification procedures as a process lined, retreat-curve (similar to production vessels) and
a pneumatically operated bottom valve.
is scaled up. In addition, the company has
performed equipment qualification exer- stration of the process on a small scale.”
cises on all the lab reactors that are used Other cases have involved heterogeneous
for clinical material preparations. reactions that use heavy, solid catalysts such
as zinc-based or base metal catalysts that tend
IDENTIFYING to settle to the bottom of the vessel. These
PROBLEMS EARLY processes “may work beautifully in a round-
Flanagan cites a number of examples bottomed flask” because the stir bar or paddle
where the jacketed lab reactors have re- is in contact with the bottom of the flask and
vealed problems in the early stages of pro- grinds up the metal, says Flanagan. In contrast,
cess development. “There have been cases the agitator in a reactor is not in contact with
where we have identified balling issues in the bottom of the reactor, so the mixing is not
our small reactors that we may not have as efficient. “Now, when we identify that kind
seen in round-bottomed flasks.” The reason, of problem in a lab reactor, we work with our
he says, is that mixing is done in a flask by engineers to ensure that the appropriate geom-
a stir bar or paddle, whose mixing action is etry is selected for the scale-up of the agitator
different from that of an agitator in a reac- or of the reactor,” he says.
tor. In vacuum distillation processes, scaling
“The effect of agitation with a miniature on the reactor wall is a problem that may
agitator is similar to that of a full-scale present itself when a process is upgraded
plant agitator in terms of power per unit from a flask to a pilot plant reactor. As the
and shear effects,” he says. “You can also batch is concentrated, scaling occurs on the
model your process to use real heating and vessel wall above the level of the process
cooling times to get a more realistic demon- liquid. This happens because the heated
AUGUST 2009 | PHARMACEUTICAL PROCESSING
■ PHARMPRO.COM
jacket typically covers the entire vessel
and dries residual material entrained in the
solvent evaporated from the process. The
residue attaches to the wall.
"Scaling usually doesn’t happen this way
in a flask,” says Flanagan, “because the
heating mantle normally covers only the
bottom part of the flask, below the liquid
level. The upper part of the flask stays
relatively cool.” In contrast, he notes that
a lab reactor will reveal a potential scaling
problem because the entire vessel wall is
heated, just like that of a pilot reactor.
Phase separations can also create prob-
lems when a process is stepped up from a
flask to a pilot reactor. Flanagan notes that
the way to check a phase separation in
the laboratory is to dump the contents of
a flask into a separatory funnel, shake the
funnel, and wait for the phases to separate.
However, this procedure gives no indication
of how long the separation may take in a
reactor, or whether agitation may produce
emulsions, which is important information
necessary for scale-up. The best way to ob-
tain this information, he says, is to do the
phase separation in a lab reactor that mim-
ics the pilot and production equipment.
The use of jacketed lab reactors has also
enabled GSK to save considerable time by
cutting back on the use of reaction calo-
PHARMACEUTICAL PROCESSING | AUGUST 2009
rimetry to support intermediate (10–50-L)
scale-up. This is a time-consuming proce-
dure in which a process is run in a reaction
calorimeter — a small, highly automated
jacketed reactor — to obtain detailed infor-
mation on the safety of the process, such as
heat of reaction and gas output.
In the past, when RTP worked with flasks,
each process was tested in a reaction calo-
rimeter prior to scale-up beyond the 6-L
size, says Flanagan. “Today, 90% of the time
we don’t use reaction calorimetry for initial
scale-up. Instead, we use data collected
from jacketed lab reactors.” GSK obtains
heat-output data by monitoring process
temperatures in the lab reactors, each of
which has been characterized to determine
its heat-transfer coefficient. Gas-flow moni-
tors are installed on all the smaller vessels
to measure offgases.
“With reaction calorimetry it usually
takes my group a couple of days to run the
tests and evaluate the data,” he says, “but
with already available data from the lab re-
actors we can do an evaluation in a couple
of hours. We probably do 100 risk assess-
ments per year, so we save about 200 days
a year by not doing reaction calorimetry at
this point in the development cycle.”
For the future, Flanagan feels the reac-
tors will prove valuable in helping GSK meet
■ SLUG
Left: A pair of 50-L, glass-lined steel jacketed lab reac-
tor’s with shared overhead glassware.
Above: A pair of 20-L jacketed lab reactor’s with
shared overhead glassware.
the challenges of the U.S. Food and Drug
Administration’s Quality By Design (QBD) ini-
tiative. One goal of the initiative is to reduce
the regulatory burden on industry (and the
FDA’s work load) by streamlining the agen-
cy’s approval of changes in the manufactur-
ing process for drugs already in production.
As in any other industry, pharmaceutical
companies are periodically motivated to
modify a process to make it more efficient.
However, the time and effort required to
support such changes, and to get FDA ap-
proval, makes it difficult to justify, says
Flanagan. QBD would make it easier by
allowing a drug company to show that its
knowledge of a process is broad enough to
permit modifications safely.
Through the use of the lab reactors, com-
bined with process analytical technology
(PAT), GSK already collects a broad range
of data on its processes, says Flanagan, and
this will be useful for QBD. The data provide
a good understanding of the “design space”
for each process, such as temperature limita-
tions and other parameters, he says, “so we
would have plenty of information to support
a process modification.” ■
15 ■

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■ 16
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The CF-1000 Series gravimetric additive feeder,
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AUGUST 2009 | PHARMACEUTICAL PROCESSING
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Low-Cost Solutions for High-Tech Industries


■ COMPLIANCE
Compliance Documents:
Solving the Puzzle
Pharmaceutical ERP software for stress-free regulatory compliance
■ By Jay Deaking, President, Deacom, Inc.
P
harmaceutical manufacturers operate in one of
the most highly regulated industries – facing
an array of restrictions and requirements from
the FDA, EPA, OSHA, various state and foreign
governments, and their individual customers. Integral to
meeting these groups’ standards are the various compliance
documents they require, such as product labels, Material
Safety Data Sheets (MSDSs), SARA reports, Certificates of
Analysis (COAs), and shipping papers.
For many drug makers, producing these documents in
an accurate and timely manner is a significant challenge,
if not an outright headache, because of the use of multiple
software systems to run their businesses. When using dis-
connected systems, spreadsheets, and/or word processing
programs to manage data, manufacturers can spend hours
or days gathering information, making calculations, and en-
tering the results into word processing documents.
But with today’s technology, this labor-intensive and po-
tentially error-ridden process is unnecessary. As this article
will discuss, pharmaceutical manufacturers using a single,
fully-integrated pharmaceutical ERP software system can
integrate regulatory reporting with all other business pro-
cesses to solve the compliance document puzzle and make
regulatory reporting a stress-free operation.
Well-designed
ERP software
should integrate
all the data of a
pharmaceutical
manufacturer,
including formu-
lation, regula-
tory reporting, REGULATORY
LABORATORY REPORTING
purchasing, pro-
duction, inven-
tory, sales, and
accounting in
one system.
ACCOUNTING STORES/POS
■ 18
■ PHARMPRO.COM
PUZZLE PIECES
The typical process of business growth is how most
pharmaceutical manufacturers end up with the patchwork
of software systems that complicates reporting. A company
may start out managing many processes, such as formula-
tion and quality control (QC), with notebooks and spread-
sheets, and others, such as accounting, with standalone
software systems. At this stage, any data that must be re-
ported to the FDA, EPA, or other organizations can be read-
ily found among the relatively small amount of data.
However, as business volume grows, more formulas are
developed and tested, products are pushed into production,
and new customers begin knocking at the door. At that time,
manufacturers struggle to fit the data puzzle pieces together
to create the reports they need. Perhaps a formula manage-
ment software system, or a system to handle inventory man-
agement was added. Now, with more data being created and
stored in more places, generating the required regulatory
reports can become time consuming and tricky.
Often, companies using multiple, disparate systems ask one
person to handle all reporting. This person, perhaps a techni-
cal or compliance director, keeps track of which forms are due
at what times, to what organizations, and what information
they require. He searches each system for the appropriate
ORDER PURCHASING
ENTRY
PRODUCTION INVENTORY
AUGUST 2009 | PHARMACEUTICAL PROCESSING
■ PHARMPRO.COM
data, makes any calculations, enters the information
into the right form, and prints the documents. He
does this for COAs, product labels, MSDSs, an-
nual SARA reports, and more.
Unfortunately, no matter how diligent
this person is, whenever reporting is not
integrated with business data, the process is
open to inefficiencies and errors. For one, manu-
facturers create a bottleneck by funneling all reporting to
one person. Deadline-sensitive documents may stack up
when, for example, this person goes about researching and
completing Form Rs – the lengthy SARA reports required
for each toxic chemical manufactured, processed, or used
beyond certain EPA thresholds. Time spent waiting for docu-
ments in the queue is time wasted, perhaps time that ship-
ments can’t go out the door, and this unnecessarily adds to
the cost of doing business.
Errors are likely, as well. The director may choose the
wrong form, or simply make data entry errors or accidental
omissions. When mistakes are passed along to custom-
ers, companies may face the costs and customer back-
lash associated with returned shipments – such as extra
freight charges, refunds, and potentially a loss of business.
Mistakes reported to the FDA, EPA, or OSHA could results in
fines and regulatory scrutiny.
Overall, a multiple-system environment can complicate
reporting and put a pharmaceutical manufacturer at a com-
petitive disadvantage.
PUTTING IT ALL TOGETHER
Pharmaceutical manufacturers can create a more efficient
and accurate reporting process by integrating all their busi-
ness processes – formulation, QC/QA, production, inventory
control and lot tracking, sales, purchasing, accounting, and
regulatory reporting – in one software system designed for
the pharmaceutical industry.
When all data is stored in a single, pharmaceutical ERP
system, report generation is no longer like trying to assem-
ble a complex puzzle. Because all the pieces required for
each document – raw material usage and properties, QC test
results, sales order information, formula data, and the like
– are all managed in real time within the ERP system, report
generation can become an automatic process.
In a well-designed system, companies would set up config-
urable document templates for each report they are required
to produce. A configurable form is one a manufacturer can
adapt within the ERP system to fit its business needs, without
needing to alter the software’s programming code. A familiar
program such as Microsoft Word will let users configure the
documents by arranging data fields, logos, and other charac-
ters to create the design, and include the data of their choice.
Once configured, the ERP system can automatically popu-
late these forms with the proper data. Each data field on
a form will map to a particular data point in the database.
Because data from all processes is stored in that single da-
PHARMACEUTICAL PROCESSING | AUGUST 2009
■ COMPLIANCE
tabase, there is no need to link to other programs or search
disconnected or paper-systems for document generation.
When a document is regulated in the system, it’s filled in
with the most up-to-date data automatically.
For example, because the system stores all formulation, pro-
duction history, purchasing, and sales data, it can automatically
calculate the hazardous material amounts required for SARA
reports and show the figures in the appropriate template fields.
LOW-STRESS REPORTING
With document generation integrated within a compre-
hensive pharmaceutical ERP software system, drug makers
avoid the problems associated with using a patchwork of
systems. The puzzle-piece approach to reporting is replaced
by a streamlined and compliant reporting process that can
provide greater productivity and a competitive edge.
Efficiency is one advantage gained by managing regula-
tory reports this way. Rather than having your compliance
director search each system for data to calculate and plug in
to each word processing-based report, the system pulls and
populates the data automatically. This saves countless hours
over the course of a year, allowing companies to direct their
compliance efforts to other processes. In fact, any system
user with the proper security clearances can generate a COA
or other document once the template has been configured.
Errors are reduced with this type of system, as well, be-
cause manual data entry is eliminated. Process controls in
a fully-integrated system can also help manufacturers guard
against errors that, if unnoticed, could end up on a regulatory
document. For example, the QC process in a well-designed
ERP system should allow manufacturers to set pre-defined test
ranges for each product. Then, if a user enters a value that
falls outside that range, the system would provide a screen
prompt highlighting the error. Not only does this guard against
typos that could end up on important documentation, it also
helps you more easily identify products that do, in fact, fall
outside QC ranges and need to be altered or discarded.
CONCLUSION
With all the regulations facing manufacturers in the
competitive pharmaceutical industry, companies shouldn’t
spend hours preparing their compliance documentation.
Utilizing a single, integrated ERP software system designed
for pharmaceutical manufacturing can streamline the regu-
latory reporting process through configurable document
templates for a faster, error-free process. With the regula-
tory compliance document puzzle solved, drug makers can
focus on what really matters – their business.
About the author:
Jay Deakins is the President of Deacom, Inc., the producer of
an integrated accounting and ERP software system for mid-
to-large-sized pharmaceutical and chemical manufacturers
with hard-to-handle requirements. Contact Jay at info@dea-
com.net or visit www.deacom.net.
19 ■
 ■PHARMPRO.COM
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Compatible with gamma, ETO and auto-
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sure washers and steam cleaners. The 100%
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■ 20 AUGUST 2009 | PHARMACEUTICAL PROCESSING

■PHARMPRO.COM
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PHARMACEUTICAL PROCESSING | AUGUST 2009 21 ■


■ TESTING
12 Key Steps to
Address USP Changes
Strategies to stay current with the recent changes to Chapters <61> and <62>
R
ecently, the United States Pharmacopeia (USP)
General Microbiology chapters have harmonized
with corresponding microbiology chapters in the
European and Japanese Pharmacopeias (EP and
JP). The goal of pharmacopeial harmonization is to promote
consistency of microbiology methods used by companies glob-
ally. This harmonization includes revisions to the existing USP
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Organisms. Celsis International plc – a provider of life sci-
ence products and laboratory services to the pharmaceutical,
biopharmaceutical, and consumer products industries – out-
Understand how the new chapters impact the requirements for growth and
recovery of specified microorganisms and specified microorganisms tests.
lines the key steps the pharmaceutical industry should take to
ensure they are ready to address these harmonization changes.
KEY STEPS TO PREPARE FOR
HARMONIZATION CHANGES
Following are the top steps companies in the pharmaceu-
tical industry should take to ensure they are prepared for
changes to the General Microbiology chapters USP <61>:
Microbial Limits Testing and the addition of USP <62>:
Absence of Specified Organisms.
1
Understand that changes to the USP will not affect
alternate microbial test methods, such as Rapid
Methods. Rapid Microbial Methods (RMMs), such as
those provided by Celsis, are accepted microbiology tests
that can be used in lieu of the tests as defined in the USP
Microbiology Chapters. Those who have implemented such
alternate methods are unaffected by the changes to the USP.
2
Understand how the new chapters impact the require-
ments for growth and recovery of specified microorgan-
isms and specified microorganisms tests. In USP <61>
(formerly called the Microbial Limits Test, now renamed the
Microbial Enumeration Test), the most obvious change is the
separation of the Absence of Specified Microorganisms test
into a new chapter, USP <62>. USP <62> is a new chapter that
describes the requirements for growth and recovery of speci-
fied microorganisms such as Salmonella or S. aureus. Note
that all of the specified microorganism tests have undergone
■ 22
■ PHARMPRO.COM
changes. Also, media for enrichment, subculture and selec-
tion have changed for most microorganisms.
3
Find out how the changes apply to inventory that was
validated with current (prior to May 2009) standards.
Based on changes in these harmonized chapters, prod-
ucts may need to be revalidated. Reasons include, but are not
limited to, media requirements, testing conditions and the
amount of sample to be used. For example, if you are using
the USP method and want to continue to use it but the media
has changed, you will need to revalidate using the new media.
Companies should also consider the possibility of a sample
that previously used a specified dilution not being acceptable
at that same dilution with the newly specified media.
4
Know how changes to USP <61> will alter sample
amounts for bulk vs. small batches. Depending on
the test or combination of tests, the required sample
amounts may vary. As per harmonized USP <61> in the sec-
tion covering testing of products, the amount used for the
test should be 10g or 10mL. For fluids or solids in aerosol
form, it is necessary to test 10 containers. For transdermal
patches, 10 patches are to be tested. Additional information
to justify using less product is provided in the harmonized
chapters; examples include small dosage units, small batch
sizes or limited number of articles in a batch.
5
Determine when and how often to test (i.e. at which
stages within the production process – from raw materi-
als to finished goods). Given the number of changes to
USP <61> and the addition of USP <62>, it’s important to plan
ahead not only for the type of analysis to be performed, but for
the time and cost required to do so effectively.
Should the analysis not meet the initial requirements, addi-
tional testing may be necessary which could require extra time.
Be sure to build enough flexibility into your schedule to accom-
modate these scenarios, and consider using rapid microbial
screening methods. Absence of contamination can be deter-
mined in 18-24 hours (vs. an average of five days), significantly
reducing production cycle times.
AUGUST 2009 | PHARMACEUTICAL PROCESSING
■ PHARMPRO.COM
■ TESTING

6
If you outsource to an analytical lab, evaluate how this con-
tract facility is meeting the new requirements of USP <61> and
the addition of USP <62>. Since significant changes are a result
of harmonization with EP methods, contract labs with global custom-
ers typically have already screened products to the new USP and EP
Suitability Test, and they must now specify which microorganisms are
required to be absent. The Suitability Test ensures that any antimicro-
bial activity inherent in the test sample will not adversely affect the
reliability of the test.

chapters, giving them a head start. Many contract testing labs such as
Celsis Analytical Services offer validation services in addition to rou-
tine analysis to ensure that testing is in compliance with the new har-
monized requirements. Make sure that your lab partner stays abreast
of changes in the USP so you can be confident that their services are
performed according to current pharmacopeial requirements.
12
Understand that the specified organisms in USP < 61>
and USP <62> may not be all inclusive. The organ-
isms listed in USP <61> and USP <62> are example
organisms. Each user should also consider testing for organisms
that are specific to their facility or to their products.
FOR MORE INFORMATION

7
If you currently have internal testing methods to screen for con- Download the Celsis White Paper Concerning Changes to USP <61>
tamination and to enumerate specific organisms, consider how and the addition of USP <62> online at
you will need to reconcile your current methods with the USP www.celsis.com/usp.
guidelines. Given the significant changes to USP <61>, if you have your
own methods for testing microbial limits, you need to ensure that they
are fully validated and adhere to updated methods. Remember that the
new USP methods are now more inclusive for more organisms, which
can have an impact on microbiological media used in testing for spe- LESER SAFETY VALVES
cific pathogens, incubation temperatures and duration times.

SINGLE-TRIM DESIGN!
8
Recognize how changes to USP <61> and <62> prohibit retest-
ing and determine how this will impact your operations. Under
the new USP guidelines, retesting of an original sample is not
allowed. However, it is acceptable to perform additional analysis on a
sample that screens positive for contamination using a rapid method.
For this reason, non-destructive rapid testing methods are preferred.

9
Familiarize yourself with the additional organisms that have High Performance,
been specified in the new USP <62>. It’s important to note API Series,
that more organisms have been specified in the new USP Compact Performance,
<62> chapter than in previous USP editions. Organisms such as
Clean Service,
Candida albicans, Clostridia species, and bile-tolerant Gram-negative
Critical Service,
bacteria may be necessary to test for, depending on specific product
formulation and utilization. Modulate Action

10
Recognize how changes to USP <61> and USP <62> alter
incubation times. USP <61> describes microbial enu-
meration tests, which are the plate count procedures for
bacteria, yeast and mould. Although the plate count procedure itself
will not change, the incubation temperatures and times for bacteria
do change slightly. In USP <62>, tests for specified microorganisms are
included. Not only do new modifications change many microbiological
media utilized in testing for specific pathogens, but updates also affect
incubation temperatures and duration.
LESER Safety Valves

11
Understand how updated methodology of the Method for every industrial application
Suitability Test in USP <61> and USP <62> impact the types
of organisms and different growth media that are included.
The-Safety-Valve.com
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to revalidate products to conform to the new USP <61> and <62>

PHARMACEUTICAL PROCESSING | AUGUST 2009 23 ■


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PHARMACEUTICAL PROCESSING | AUGUST 2009 25 ■


■ COMPLIANCE
Content Compliance Within
The Life Sciences Industry
Effective strategies for enforcing content compliance and reducing costs
in regulated environments
■ By Stephen Bergson, Executive Vice-President Commercial Operations, Virtify, Inc.
W
ith global health and regulatory authorities
continuing to push for tighter regulations
surrounding disclosure, transparency and
e-standards, pharmaceutical and other life
sciences companies are increasingly challenged by frag-
mented, quasi electronic, paper-based processes and often
out-of-date technology systems. Many organizations simply
lack the process and technology to effectively operate and
comply in a rapidly changing regulatory environment. The
impact is significant, often translating into costly product
delays, regulatory fines and lost business opportunities.
Life sciences companies must re-evaluate their existing
processes and systems and consider new ways to encourage
collaboration, streamline workflow, and keep costs in check to
improve content compliance. Although there are content man-
agement “like” systems, most are “document-centric” and lack
the underlying standards-based business intelligence required
by life sciences companies. In this article, I recommend strate-
gies and best practices to help life sciences companies manage
and automate these processes to streamline content compli-
ance and reduce development costs while bringing higher qual-
ity products to market faster and more efficiently.
THE COST OF CONTENT COMPLIANCE
The cost of bringing new drugs to market today ranges
from $800 million to $1.2 billion and research firm IDC esti-
mates that roughly 26% of that cost goes toward the content
requirements associated with regulatory compliance.
As the industry and regulators work together to improve
the new drug submission and approval process, there are
a number of different global standards and regulatory man-
dates such as Clinical Trial Disclosure, Electronic Common
Technical Document (eCTD) and Structured Product Labeling
(SPL), which life sciences companies must comply with
throughout the product lifecycle. The impact of non-compli-
ance to these standards is significant and includes costly
product delays, regulatory fines, and lost market opportuni-
ties. A current example of regulatory fines is occurring in the
State of Maine, where there is a $10,000 fine per day for non-
compliance with clinical trial posting rules. Other state, na-
tional and international regulatory bodies are enacting their
own mandates and oversight activities as well.
■ 26
■ PHARMPRO.COM
To satisfy these existing and upcoming compliance man-
dates, avoid costly delays in approval and/or penalties and
the potential negative impacts to their brand image, life sci-
ences companies must take stock of their existing business
processes pertaining to content management and reuse.
These new processes should be enabled through the usage
of state-of-the-art system solutions and technologies provid-
ing an integrated, collaborative solution across the product
life cycle – from discovery through commercialization.
Best practices and information technology can play a huge
role here. The right technologies can promote compliance and
operational efficiency by automating the transactional tasks
within quality compliance, regulatory affairs and clinical sup-
port operations. By automating and streamlining the complex
content exchange and submissions requirements throughout the
product lifecycle, companies can enforce regulatory compliance
and automate the many tasks required for clinical trial disclo-
sure, e-submissions, global labeling, and other standards.
SIX STEPS TO ENSURE CONTENT COMPLIANCE
WITHIN THE LIFE SCIENCES INDUSTRY
1. Automate process and workflow. If your current
processes are manual or “document centric,” you are vul-
nerable to errors and discrepancies. You may also lack the
ability to easily track history and gain visibility into whether
or not a submission is compliant. A two-phase process can
help you achieve an automated workflow:
Phase 1. Look for an easy-to-use content management en-
vironment that has regulatory guidelines built in. It should
include an XML-based technology backbone to comply with
the new technology mandates for communicating with the
regulators during submissions, labeling, disclosure activities
and other forms of interactions. Make sure that the content
compliance system is designed to manage the entire lifecycle
of the regulated content – from internal authoring, review, ap-
proval and external communication, to compare, reconcile and
maintain regulatory documents going forward. It should also
be configurable to automatically track milestones and notify
stakeholders and content contributors when a form has moved
(e.g. parent/child relationship tracking) to the next stage in the
workflow and/or requires an action from them.
Phase 2. During this phase, the content compliance system
AUGUST 2009 | PHARMACEUTICAL PROCESSING
■ PHARMPRO.COM
is integrated with your existing information systems automat-
ing workflow, minimizing data duplication and entry during the
present day highly automated regulatory submissions process.
2. Optimize submissions through collaborative
content authoring and review. Traditionally, regulated
submission procedures have not been conducive to multiple
authors and reviewers. In most cases, a significant amount of
effort and time is ineffectively spent throughout the process as
contributors wait to be emailed their section to add content or
review. Then, once that process is completed, the content and
feedback needs to be compiled, verified and published which
leads to significant resource efforts and time delays.
Ideally, your content system features collaborative author-
ing with role-based access control. This enables authorized
authors and reviewers to work on a document simultane-
ously, greatly reducing cycle time. Reviewers can simultane-
ously add comments for authors allowing all to view their
respective comments by tracking their text edits to show
their suggested changes – hence streamlining the overall
process. The technology should automatically facilitate ver-
sion control, tracking all changes, so there’s no risk of over-
writing another’s work accidentally. In addition, the system
should be based in the XML technology while retaining ev-
ery detail of revision history in the event of a future change
or audit.
PHARMACEUTICAL PROCESSING | AUGUST 2009
■ COMPLIANCE
3. Reuse and repurpose content to satisfy global
requirements. With the advent of common/similar global
regulatory requirements, content management solutions
should be viewed in the context of compliance within both
the U.S. and international regulatory guidelines. To accom-
plish this goal, the content management solution requires a
level of integrated and configuration capabilities to enable
the compliance objective to be met for the client. Submitting
information for the same product in multiple countries
should not require you to reinvent the wheel each time to
ensure compliance with varied submission standards and re-
quirements. Look for a solution that is “standards-ready” and
pre-configured to comply with different global standards and
regulatory mandates such as Clinical Trial Disclosure, eCTD,
SPL/PLR, and other electronic submissions standards so that
your users can focus on content, and not compliance.
4. Enable easy adaptation to evolving standards. As
regulations continually evolve, in such areas as electronic
submissions, disclosure standards, labeling the regulatory
communication process and submissions requirements are
likely to change too. Look for a solution that incorporates
FDA and other global requirements and is designed to
absorb and validate changes as quickly as possible. The
technology should allow you to rapidly add new form fields
or modify existing ones. In addition, look for a solution that
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■ COMPLIANCE

meets 21 CFR Part 11 requirements and provides validation with a
built-in audit trail, security and authentication.
5. Evaluate both Software-as-a-Service and perpetual li-
censing. Look for solutions with flexible delivery options, and
choose the option that best fits your needs: 1) A perpetual software
license allows for the outright purchase, installation and in-house op-
eration of the software with an annual maintenance fee for upgrades
and support; 2) A Software-as-a-Service (SaaS) model allows the pro-
vider to license the application to the customer for use as a service
or “on demand” for a monthly fee, eliminating the often large, upfront
costs associated with software purchase and implementation.
6. Focus on ease-of-use. Your content compliance solution must ap-
peal to the people that need to use it – business users, managers, regu-
latory professionals, clinical staff, etc. As such, your solution should be
able to work within your existing organizational framework and include
Made in the U.S.A since 1969
the ability to extend and adapt over time. It should also leverage a famil-
iar intuitive interface that doesn’t require a change in behavior on the
part of your users. Many Web 2.0 applications provide familiar, desktop
conventions and “Microsoft Office®-like” authoring environments.
SUMMARY
Faced with the daunting challenge of upgrading quasi electronic,
fragmented, often paper-based-processes make timely postings, fil-
ings and ongoing regulatory communications nearly impossible. Life
science companies must look to improved business processes and
technologies to comply with the changing regulatory environment.
The steps recommended above are very practical and achievable
strategies to ensure compliance and manage costs in this environ-
ment. Each of these strategies can be used individually or in conjunc-
tion with others to take greater control of the regulated content life-
cycle. The benefits are multi-dimensional. Streamlining the lifecycle
content management process reduces the risk of delays and poten-
tials for fines, while continuously increasing your overall compliance
and regulatory communications throughout the world. ■

See Website About the author:

For Details.
Stephen Bergson is the executive vice president of commercial
operations for Virtify, Inc. (http://www.virtify.com), a provider of
Enterprise Content Compliance software solutions for life sciences
companies. He can be reached at sbergson@virtify.com.

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125 James Way, Southampton PA. 18966 USA
*See Website For Details. Offer valid for new equipment purchases only.
To order : 714-578-6000
Fax: 714-578-6020

www.etcSterilization.com Low-Cost Solutions for High-Tech Industries

■ 28 AUGUST 2009 | PHARMACEUTICAL PROCESSING

 S P ESCPE
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PPrroodduucctt SShhoowwccaas see

Twist & Dry™ Spray Dry The Digital Met30+ Universal Petro-Canada’s PURETOL
Nozzle Pharmaceutical Metal White Mineral Oil
BETE has expanded the range Detector Produced from
of the Twist & Dry™ series The Met30+ Universal one of the purest
with the new TD-K. A new Pharmaceutical metal base oils in the
high-pressure backup ring on detector remains stable world, PURETOL
the TD body raises capacity to the worst imaginable meets the highest
from 3,500 psi to 10,000 psi for external interference standards of
operating conditions up to 450° like shocks and purity and quality.
F. The modified design provides vibration, while at the • PURETOL USP
greater yield capacity and same time delivering and PURETOL NF
safe, leak-proof operation at unrivalled sensitivity to grades meet FDA
10,000 psi.BETE developed this metal contamination – 21 CFR 172.878
addition to the TD series in response to dryer operators even in the presence of and 21 CFR
who wanted to increase yield by operating at higher extremely high product 178.3620(a) regulations for direct food contact
pressures. The new high-pressure TD nozzle provides signal. It is able to • PURETOL white mineral oils are Kosher, Pareve and
customers the opportunity to increase productivity while detect metal particles as small as 0.25 mm ferrous, Halal certified
maintaining the convenient locking mechanism and 0.3 mm non ferrous, and 0.4 mm stainless steel. Petro-Canada is the world’s largest producer of
superior performance of our TD Twist & Dry™ nozzles. Lock Inspection Systems pharmaceutical grade white oil.
BETE Fog Nozzle, Inc. www.lockinspection.com; 800-227-5539 Petro-Canada
www.bete.com; 413-772-6729 lubricants.petro-canada.ca; 866-335-3369

High Purity Stainless Natoli Continues To Deliver SmartHood™ Ductless

Steel Process Systems and Fette Die Segments Fume Hood
Components For over two years Terra Universal’s
CSI offers state of the now, Natoli has been SmartHood™ features
art custom fabrication in partnership with onboard filtration that
for high purity stainless Fette to manufacture removes organic fumes
steel process systems die table segments. and submicron particles to
and components. Natoli serves as allow safe indoor exhaust
Specific examples the only company release. Its rear baffle
include skid systems, officially authorized system, removable for easy
utility stations and from Fette to cleaning, optimizes non-
flow transfer panels manufacture die turbulent airflow into bonded activated charcoal filters
for the biotechnology table segments. Natoli produces standard die for chemical vapor removal and/or HEPA particle filters.
and pharmaceutical segments and carbide segments that support A Smart Controller monitors operating conditions and
industries. Process skids can include tanks, heat special shape tablets. Natoli’s advanced system issues alarms to indicate carbon filter breakthrough,
exchangers, valves, pumps, wiring and piping. We of micro-precision engineering, delivers superior excessive HEPA backpressure, or a drop in air speed
adhere to ASME BPE standards for design, materials, die segments that are delivered with a quick turn past the operator. Options include GFI outlets and
construction, inspections, and testing. around time at competitive prices. probes to monitor RH, pH or temperature.
CSI Natoli Engineering Company, Inc. Terra Universal, Inc.
www.csidesigns.com; 800-654-5635 www.natoli.com; 636-926-8900 www.terrauniversal.com; 714-526-0100

Advanced Scientifics Sales
Support Expansion
Here at Advanced
Scientifics, as our customer
list grows so too does our
Sales and Marketing staff.
The company has acquired
two new hires, Rob Noss
as a Southeast Sales and
Heather Weaver as a Marketing Representative. Rob
comes to Advanced Scientifics from Glaxo Smith
Kline where he worked as a Pharmaceutical Sales
Representative for two years. Rob graduated from
York College of Pennsylvania with a Bachelor’s of
Science in Marketing. Heather is a recent graduate
of Pennsylvania State University where she received
a Bachelor’s of Arts degree in Advertising/Public
Relations from the College of Communications.
Advanced Scientifics, Inc.
www.advancedscientifics.com; 717-692-2104
Humidity and Temperature Sony’s XCI 100 Series - It’s a
Transmitter Whole New Kind of Smart
The ROTRONIC HygroFlex
5 is the newest product
from ROTRONIC using the
groundbreaking HygroClip2
with AirChip 3000
technology. The HygroFlex
5-series is ideal for all
applications where exact
measurement of humidity
and temperature is of decisive importance for In the world of smart cameras, Sony’s 100 series
the pharmaceutical industry. The HygroFlex 5 is genius for label and packaging inspection, and
innovations include: accuracy of ±0.8% RH and bar code reading. With its 1 GHz VIA Pentium-class
±0.1°C; Auto-diagnostics and automatic correction; processor, Sony smart cameras are open to a
relative humidity, temperature, dew point; variety of software packages, including Cognex®
interchangeable probes for easy maintenance; wide VisionPro™ software.
choice of probes for every application. Sony Electronics, Inc.
Rotronic Instrument Corporation www.sony.com/smart; 201-930-7000.
www.rotronic-usa.com; 631-427-3898
 ■PHARMPRO.COM

■ MARKETPLACE

Clean Air Solutions, Inc.

Ph 208-634-4219 • Fax 208-634-5569
Cleanroom Fogger
• Consistant & Repeatable Fog Output
• Visualize/Video Cleanroom Airflow Patterns
• Trace Migration Paths

www.cleanroomfogger.com

Microorganism Custom Processing Services

• Dry Powders from 0.5 to 40 microns
S u r f a c e De c o n ta m i n a t i o n • Jet & Mechanical Milling
Decanting Centrifuges Super Centrifuges Sanitization & Disinfection of • Inert & Low Temperature Milling
HVAC & Dust Collector Systems, cGMP • High Purity & Contamination Free
Inverting Filter Centrifuges
Clean Rooms, Building Structure, • ISO 9001:2000 Registered
• cGMP FDA Inspected
856-467-3399 Ceiling/Floor Plenums & High Surfaces. • Established 1946
www.heinkelusa.com InnerSite, Inc., provides contracting for
The Jet Pulverizer Co., Inc.
BioProcessing & Pharmaceutical Mfg. 1255 N. Church St.,
Contact Mark Mateson - innersite@msn.com Moorestown, NJ 08057
Ph. (856) 235-5554
800-230-0010 Fx. (856) 778-7712
For information ® www.tollprocessing.com
or to
reserve space contact A world leader in vacuum pump technology
MIKE KELLY Lower operating costs with Busch COBRA vacuum pumps!
E-mail:
Houston, Texas
michael.kelly@ Virginia Beach, Virginia
757-463-7800 281-214-8400

advantagemedia.com S. Plainfield, New Jersey

908-561-3233
Los Angeles, California
562-926-8422
Chicago, IIlinois Bayamon, Puerto Rico
787-798-5045
Phone: 630-971-9739 630-545-1310

1-800-USA-PUMP
Fax: 630-309-2499 www.buschusa.com

The Advertisers Index is provided as a reader service. Although every attempt has been made to make
■ ADVERTISERS INDEX this index as complete as possible, the accuracy of all listings cannot be guaranteed.

Advanced Scientifics . . . . . . . . . . . . . . . . . . . .2 Petro-Canada Lubricants . . . . . . . . . . . . . . . . . 21

Deacom Inc. . . . . . . . . . . . . . . . . . . . . . . . 25 Reed Exhibition Companies . . . . . . . . . . . . . . . 10

Environmental Tectonics Corporation . . . . . . . . . . . . . . .28 Scarab Genomics . . . . . . . . . . . . . . . . . . . . . 31

IMA North America Inc . . . . . . . . . . . . . . . . . . .7 Terra Universal . . . . . . . . . . . . . . . . . 11,17,27,28

ITT Engineered Valves . . . . . . . . . . . . . . . . . . .3 Veltek Associates Inc . . . . . . . . . . . . . . . . . . . .5

Leser LLC . . . . . . . . . . . . . . . . . . . . . . . . . 23 Walker Barrier Systems . . . . . . . . . . . . . . . . . 17

Natoli Engineering . . . . . . . . . . . . . . . . . . . . 32 Western States Machine Co . . . . . . . . . . . . . . . 27

■ 30 AUGUST 2009 | PHARMACEUTICAL PROCESSING

Fette Die Segments
Manufactured by Natoli
…the only licensed manufacturer.

Natoli is proud
to be the only licensed
manufacturer of Fette die table
segments. Natoli’s advanced system of
micro-precision engineering, manufactures
Fette die segments of exceptional quality that
are delivered quickly, worldwide at competitive prices. Natoli
manufactures standard round, special shape, multi-tip and carbide lined die segments.