Newsletter for the regulated industries: pharmaceuticals, biotech and medical devices. This month we discuss steam sterilization, generic drugs, Word macros and orbital welding. Publication date: March 2016

1. Welcome to the first edition of
Since you asked...All about
GMPs and Validation. This news-
letter is intended to educate and
inform readers of all experience
levels in the finer details of GMPs
and validation. We’ll also discuss
best practices, lessons learned
and significant historical events
for the industry we all work in.
This month we have focused on
the most fundamental of valida-
tion topics—steam sterilization.
Validation as we know it really
got started in the early 1970’s
with problems in sterilization. In
response, FDA issued strict regu-
lations for terminally sterilized
products. Industry objected and
the regulations were withdrawn;
however, these set the standards
and procedures we follow each
day. We’ll discuss more of this in
the next edition of this newsletter.
With continued success in the
important work we all do,
WELCOME FROM THE EDITOR
THIS MONTH’S FEATURED TOPIC - STEAM
Steam is used throughout the
pharmaceutical and biotech in-
dustries, most commonly for ster-
ilization and SIP. Some interesting
facts about steam and its use:
Autoclave porous goods cycles
commonly use three steam/vacu-
um pulses to remove air trapped
in the load. Each successive vac-
uum level is lower than the first.
The technical reason for this...the
steam“collapses” and creates its
own vacuum in addition to that
created by the autoclave vacuum
pump or eductor.
Steam’s destructive powers come
from its specific enthalpy or in-
ternal energy. Consider saturated
steam and dry air at 121.1°C. At
this temperature, air has only
about 15% of the same energy as
steam. Sterilization occurs when
this energy is transferred to the
load. A temperature differential
must be present, however for this
transfer to occur. Cooler loads and
jackets are responsible for this.
WELD COUPONS
Sanitary piping systems like WFI require a high
quality weld when two piping sections are
joined. Orbital welding is the method used and
when the weld is complete, it is inspected inter-
nally using a borescope. A borescope’s inspec-
tion depth is only 3-6 feet, however.
A closure weld is a system’s last weld—this
weld cannot be inspected. The solution? Weld
coupons. Test welds (coupons) are performed
before and after the closure weld. If the coupons
are acceptable, closure weld quality is assumed.
YIELD CALCULATIONS
GMP regulations require actual yield and %
theoretical yield calculations when a critical
step is complete. Percent of theoretical must
then be evaluated. Why? A yield discrepancy is
the best indicatorbest indicator that something went wrong.
Since you asked...Since you asked...
All about GMPs and ValidatiAll about GMPs and Validationon
Volume 1
Issue 1
March 2016
Mixer/granulator/dryer - solid dose
Steam traps - plant steam system
Since you asked...All about GMPs and Validation is
a publication of William Garvey and Associates.
Copyright © 2016 William Garvey and Associates

2. Prior to 1984, generic drug com-
panies had to conduct clinical
trials to prove equivalence to the
brand name drug. This allowed
the innovator to continue a nearly
seven year monopoly after the
patent expired.
Bolar Pharmaceutical was a small
generic drug company located
in Copiague, New York. In 1982,
Bolar did something very clever...
it obtained five kilograms of
Roche’s Dalmane active ingredi-
ent (flurazepam) one year before
the patent expired. This allowed
Bolar to develop the generic in
advance and immediately start
clinicals when the patent ran out.
Roche sued Bolar in Federal court
for patent infringement. And lost!
However, Roche won on appeal.
Congress was closely following
this case because of its financial
impact on the consumer.
The result...the Drug Price Compe-
tition and Patent Term Restoration
Act (of 1984)...To be continued.
GENERIC DRUGS - ALL BECAUSE OF BOLAR
PROTOCOLS AND WORD MACROS
Protocols are a way of life in
validation and being skilled in
Microsoft Word is essential. Use
Word Macros to simplify protocol
development. A simple macro can
reduce many keystrokes.
Take °C for instance. Inserting this
common combination takes time.
Create a macro to effortlessly
insert °C into your document. The
macro can be reused with each
protocol you create. Here’s how.
Create a new Word Document,
then click ViewMacroRecord
MacroUse Help (?) to experiment
and guide your way. Start simpleStart simple
with μg.with μg. When you’re finished,
click the icon on the Quick Access
Toolbar—μgμg is inserted.
Are you adding Reviewed by/Date
tables to attachments? Macros are
very useful for this. Use Text Wrap-
ping and Positioning to precisely
place your table at the bottom.
William Garvey and Associates
Lexington, MA
williamgarvey@outlook.com
781.698.9215 www.wgarvey.com
The Word user
interface is coded
in Visual Basic. All
Word commands
(such as Copy) are
just Word macros.
William Garvey and Associates provides
validation and Quality-related services to the
regulated industries—pharmaceuticals, biologics
and medical devices.
Our services include protocol development
and execution, GMP and technical training, and
validation project management.
Follow us on Google+, Facebook or LinkedIn,
or on the web at www.wgarvey.com.
THERMOCOUPLES AND HEAT PENETRATION
Earlier we discussed
steam enthalpy and why
steam is a much more
effective sterilant than hot
air. Thermocouples (TC)
cannot distinguish be-
tween steam and hot air
at any temperature. Place
one TC and one biological
indicator (BI) in each of
two identical containers.
Seal one container to pre-
vent steam from entering,
then sterilize both containers at 121.1°C for 15 min-
utes. Both TCs will indicate the same temperaturesame temperature,
but one BI will survive. Which one? The hot air.
Autoclave with TCs
Tablets and capsules