Greetings everyone
hi my name is Mike Bellm I'm the
president of Life Scientific company I
founded in 1992 to represent
manufacturers of parenteral production
machinery I wanted to take this
opportunity to thank you all very much
for taking time out to attend this
segment of the Lunch and Learn webinar
series that we're running at least once
a month we plan on providing these
generally on the third Wednesday of the
month at 11:45 occasionally we'll have
other programs that are coming up we
have one scheduled we'll discuss at the
end for next month from our tank
manufacturer so hope you find everything
useful and informative here just to give
you a little heads-up on the navigation
this is a live stream on our YouTube
channel it'll be available for sharing
and future viewing just share the link
you use today and others can review the
content if you find it appropriate for
your associates so you should be seeing
a screen that looks largely like this
what I'm showing here and just typical
with the YouTube feed if you hit this
button you go into full-screen mode but
if you do come across some content that
you want to address later at the end of
the presentation go ahead and hit escape
and then go to the live chat segment and
just enter any questions or comments
that you have that you might want our
presenter to discuss enter that
information here hit the arrow or send
button and will collect those and give
them to Mike, mr. Lawson at the end of his segment and
then you can just hit the fullscreen
again to see the remainder of the
content and again you'll be able to view
the full presentation at the end of the
session and review it and study it and
take it home and do whatever you like
with it so as mentioned before we
specialize in representation of
pharmaceutical production equipment
largely for parenteral applications but
we do a fair amount of crossover into
chemical and beverage industry we're
based in st. Louis with project
engineers that help us cover a good
portion of the Midwest and our product
lines range from aseptic environments
through container integrity testing and
packaging over the years our company has
been involved in over 5,000 equipment
projects throughout the Midwest and
we're happy to provide more detailed
information via our website or if
there's anything specific that you're
looking for please don't hesitate to
give us a call we began representation
of Bonfiglioli
engineering several years ago now they
were founded in 1974 by Giuseppe
Bonfiglioli
and their manufacturing is based in
Ferrara Italy. Bonfiglioli has developed
a broad range of technology for
container integrity testing in the areas
of leak detection visual inspection and
headspace gas analysis to help ensure
the quality and safety of a wide variety
of packaged products our presenter today
is Michael Lawson and since the mid 80s
mike has been involved in technical
automation and control projects first
with fluid power technology and then SMC
corporation
he now or then started with sister
company to Bonfiglioli
ATC which is a custom automation company and
transferred to Bonfiglioli in
2014 as their sales director and now is
the sales director for the parent
company to Bonfiglioli
which is the TASI test annex
inspection group and today mr. Lawson is
going to discuss the importance and
application of head gas for headspace
gas analysis and sterile drug production
and its applications in quality in
quality assurance we hope you find it
informative and with that I'll turn it
over to mr. Mike Lawson Mike thank you
so much appreciate the opportunity and
the kind words we are very grateful as a
group to be partnered with LSI and what
a great company providing an excellent
service a unique company providing
excellent service to the pharmaceutical
industry there are a lot of folks out
there but not a lot of folks in the
industry that are specifically focused
on Pharma so we're very honored to
partner with you guys so as Mike said
today I'm going to speak about a
headspace gas analysis as an effective
tool for quality assurance in lab
equipment but also in in-line equipment
so in the manufacturing process and this
is a great technology it's one of the
newer technologies that it's out in
industry it's been developed in our in
the last 20 years if you will it started
from University and worked its way out
and out into industry so starting off
I'm going to talk just a little bit
about the company to give you a little
background about CAHSEE test and
inspection
tazzie test inspection is a group of
companies that was formed back about
five years ago it came from the tazzie
group of companies which are 12
companies
you know about 250 million and
throughput so quite a large organization
we are the packaging and testing
division for the company so focused on
testing of packaging type products
testing of devices in our in our group
specifically bonfigliano saifa and alps
focused more on the package side of the
business where cts and eight Shriner
focus on the device so really very nice
group and together we're the world
leader in leak test and inspection so
these are our kind of where we are in
the world as Mike mentioned Avanti glio
levying in Ferrara Italy wonderful old
world location with with all of the
things we we love about Italy about one
hour from Venice and about 45 minutes
from Bologna so very very beautiful
location with with wonderful kind people
in our North American headquarters is
located in the Milwaukee area just in a
suburb called Oak Creek outside of
Milwaukee where we have a 38 thousand
square foot facility that houses our
engineering sales support service and
then our manufacturing is done in
Harrison Ohio at our facility there
70,000 square foot facility where we
have full manufacturing capabilities and
then lastly our on the solid dough side
we have a company called sefa in
Northern Ireland that's a part of our
group in Belfast Northern Ireland
another beautiful location there in
Ireland and they make equipment for
inspecting solid dose type
pharmaceutical packages so these are the
companies that make up CAHSEE tests now
concerning technologies we have a
variety of technologies that we utilize
and we have well over 43 years of
experience in the application of these
different technologies some are vacuum
decaying and pressure decay back in
decay being an ASTM consensus standard F
23:38 we've been applying this for
almost our entire existence our 43 years
as a company
pressure decay long-standing test method
that's very well proven lid deflection
that's utilizing an LVDT or Hall effect
sensor to detect the Flex in they and a
closed package visual inspection we
apply this to mainly to the
pharmaceutical industry that can be
applied to other industries as well and
then force decay for like IV bags and
things of that nature but today we're
going to focus on headspace gas analysis
and so why headspace gas analysis let's
talk just a little bit about that so
taking a look at the offering that we
have within the range we have a full
range of products starting with those
very small lab piece of equipment that
can test maybe four to six parts a
minute it utilizes laser tunable diode
laser technology and this is great for
creating your your methods creating
validating your product package types
and an excellent for that upfront
development work the next type of
machine would be an offline machine that
could run roughly what it says about 50
to 100 parts a minute this is a single
laser head but it's more of an an
automated type piece of equipment but
just low speed production or maybe if
you're going through clinical trials and
you need more throughput than a lab
machine the the last chassis type would
be an inline system so this is a cam
driven system that has been proven for
many years in different types of filling
machines capping machines similar
technology that we utilize for leak
testing utilizing many different
technologies but including headspace gas
analysis so this would be once you go
into full production this would be the
type of machine that you're looking at
we can run up to 600 parts per minute
then in conjunction with that as a high
speed piece of equipment we can combine
multiple technologies so in headspace
gas analysis many people wants to detect
the oxygen content in a headspace so we
we have lasers that are tuned to that
frequency but you can also in
combination
have moisture analysis lasers as well so
lasers that are tuned to sense moisture
and so we can combine those two in the
same machine and have a combination
system as well we can also combine other
technologies such as vacuum or pressure
decay with headspace gas analysis or
visual inspection with headspace gas
analysis essentially we can create a
total package testing solution so it's
one chassis that can detect all the
things that you want to detect on your
package we could even include some type
of other new technologies such as
thermal imaging or x-ray within the same
type of system so and kind of lastly as
far as equipment goes many people as
they have these headspace gas analysis
they want to be able to validate these
systems they need to by requirement at
the FDA and so we make actually the test
samples reference samples if you will so
these are vials that have a specific
concentration of oxygen a certified
amount of oxygen in in the container and
you can use these as reference samples
to validate the the equipment is working
correctly so kind of taking a look at
the technology and giving an overview so
what what is the purpose of headspace
gas analysis and how is it used well
really as the slide states it's it's to
ensure the sterility and the stability
in a finished and filled package so this
is a requirement by the FDA it's a
requirement for good good manufacturing
and so this is what the objective was in
creating these machines to look at the
headspace and ensure that that the
product is stable that it's not going to
oxidize and impact the quality of the
product so how what are the types of
packages that typically are used for
headspace gas analysis technology there
can be glass vials it could be liable
eyes product freeze-dried product oxygen
sensitive liquid products we've even had
applique
for plastic products that have modified
atmosphere a noble gas if you will in
the headspace or vacuum in the headspace
so that's how the technology is applied
so kind of drilling down to the to the
technology itself I mentioned earlier we
we use a tunable diode laser absorption
spectroscopy as the the technique or the
technology that we use for conducting
this test and that is a laser beam
that's passed through the headspace and
it is tuned to the frequency of the gas
you're trying to detect in many cases
that's oxygen so oxygen actually
resonates at 760 nanometers so we apply
a laser beam if there's oxygen present
if the oxygen molecules resonate they
degrade the laser beam and you can get a
reading and that reading is directly
correlated to a percentage of oxygen
within the headspace so we could do the
same thing with moisture simply by
having a laser that is tuned to 1854
nanometers or co2 at 1572 so and the
nice thing about these systems is you
can actually combine you can have one
system that has one laser of each type
or two lasers of each type so each each
laser will roughly provide for a
throughput of about 150 parts per minute
so for instance if you have two oxygen
lasers you can run about 300 parts per
minute so you could essentially run and
detect oxygen and moisture at 300 parts
per minute or for oxygen lasers at 600
parts per minute
so just looking at that the diving a
little deeper into the the laser
spectrum itself our lasers operate
basically in the near infrared spectrum
just slightly in the visible range but
mostly in the invisible range is for
oxygen and for moisture and co2 as well
so that one of the nice things about
this technology is it gives you
information both qualitatively as well
as quantitatively so you can not only
get a yes or no that you're beyond the
threshold of oxygen say you have a five
percent oxygen threshold that if it's
above five percent or two percent oxygen
you want to reject it but it can also
tell you things about your actually as
an end process check to tell you that
okay we're currently at 1% and it's
moving up to 1.5 percent now it's at 2%
so it can tell you that your process is
is starting to to creep a little bit and
that something needs to be corrected so
it's a great qualitative or in process
check if you will for your for your
system and along with that many people
pull a vacuum on the headspace and this
can actually tell because when you pull
a vacuum you're removing the oxygen
molecules from the headspace so if you
it can tell you actually container
closure integrity it can confirm that
because if you have a leak the the
vacuum will leak out up and atmospheric
air will leak in and you can see that
there's a change taking place which
tells you is essentially telling you
that the pressure or the vacuum level
within your headspace has changed you've
had a leak at some point so why should
we monitor with with using hga
technology headspace gas analysis well
again the oxygen sensitive liquid
products or lyophilized products it's a
requirement
there's GMP standards from Europe that
require this USP 1207
that has been put in place is also
driving a lot of this technology and and
what are some of the impacts if we if
how can this affect the drug if you do
lose heads face so first you could have
degradation of an active drug you could
you can have a device that malfunctions
or a decrease in the shelf life or the
potency of the drug someone's taking the
drug it's a life-saving drug and and the
potency has been compromised so all of
these are reasons why we should be be
checking for checking the headspace so
some of the other methods that in the
past they were quite slow
they they were destructive in nature you
had to pierce the septum of a vial in
order to check the headspace basically
even with vacuum decay you couldn't
detect non-conforming parts and allow
liable ization process if you had a leak
when you freeze-dried the product the
stopper might shrink and a leak would
occur so you lost all of the noble gas
the nitrogen in as the case may be out
of the headspace and then when it heats
back up this stopper seals again so when
you conduct a vacuum decay it appears
that the product is good but in reality
the headspace has already leaked out
during the viable ization process so our
as from the cooling the temperature
change if you will so looking at some of
the strengths of our solution we have as
I mentioned before we have a double path
so we pass the layers are being through
the headspace it hits a mirror and is
received back by a transceiver and we
can detect that's how we conduct our
detection so this gives us a very very
strong signal and that overcomes many
flaws and other people's design so we
don't have to use nitrogen as a blanket
on the outside of our product when
conducting our tests which is a major
cost saver and and just makes the
process much easier and then that's
because our signal strength is so so
wrong also it helps inna gate the
etholon effect which is the refraction
of light as the light goes through the
glass of a vial it is refracted and many
times you it causes the test to become
very slow or you get you can't get a
reading but because of our strong signal
as well as some mechanical handling
solutions that we have were able to
overcome the etholon effect and then
also because of our song strong signal
strength we also don't have to use
reference files as a part of our
manufacturing process where many of the
other folks out there actually have to
have reference files that are
continually maybe three vials throughout
each cycle we don't have to do that so
kind of looking at the heart of our
system this is the the laser itself and
the head is really the heart of all the
systems and this is a laser a laser
generator that can actually generate a
beam through the headspace and then
there's a mirror that can be adjusted
the laser can be adjusted so it can be
conformed to many different sized vials
or different different products so
starting to look at them the simplest of
our systems this is the the new laser
cube system which is a very very small
portable lab unit that we've created you
see the yellow laser in the system
itself you see the vial and this system
will automatically adjust and find the
the best location in the headspace for
the test so you put it in you run it
through its cycle it raises and lowers
the vial until it finds the optimal
location to conduct the test and then
the testing began so very very nice
system we're very excited about the to
be delivering this to the marketplace in
the in the days to come so taking a look
at the some of the inline solutions so
this is shows are very flexible
high-speed inline solution and this
solution can run up to 600 parts per
minute and be it's very flexible that
you can start with one head and run at
150 parts per minute and as your
production grows you can also grow with
the technology by adding the laser heads
to the system up to 600 parts per minute
so in combination with that I mentioned
we also make combination systems and
these combination systems can combine to
different technologies and shows an
example of one this is a vacuum decay
test with the chambers and then moving
over to the right is the video moves
over we have a headspace gas analysis
machine that is provided using the laser
technology to check the headspace so in
essence customers could utilize this for
a very flexible solution if they only
want to use one line that can detect
different types of products maybe they
have a liquid product that doesn't have
a modified atmosphere they'd want to use
vacuum decay for that technology for
that type of vial and then they have a
modified atmosphere maybe I'll I applies
product that they want to run through
down the same packaging line so by
utilizing this combine technology can be
very space-saving and give the customer
tremendous amount of flexibility so this
shows how the four lasers are set up in
the system basically the product comes
down the line it goes through an end
feed star wheel it's then traversed
through the different lasers the test is
accomplished it goes to the outfeed and
bad products are rejected where you see
the red arrow and good products or
reject are passed down the line on to
packaging with the green arrow
oh and this shows the same system but a
combined system and kind of how you have
a tray on tray off type system with the
two turrets the first turret being the
we have the infeed and you feed that to
the leak detection system and then you
have the laser inspection system and
then the the out feed and that just kind
of shows a close-up so taking a look at
some of the regulatory part I mentioned
at the beginning that there's a lot of
regular regulations both in Europe and
in North America that are coming that
are already in place as well as new more
new ones coming down the pipeline and
some of the ones for Europe GNP a 2008
and x1 there's a few regulations that
talked about containers sealed under
vacuum require maintenance so you have
to check the headspace that if there's
vac in you want to make sure that vacuum
is maintained if there's a noble gas in
the headspace you want to make sure that
that's maintained to ensure preserve the
the products Cyrilla t and stability so
and again there's more regulations more
stringent regulations even continue to
come down the pipeline and there's a
harmonization globally of regulations
between asia the UN North America and
and Europe to kind of a consensus to
form a consensus on best practices and
concerning USP 1207 the u.s.
pharmacopoeia this is some of the things
that they have are promoting and
encouraging the industry to put into
practice are to use deterministic test
methods so the old types of test methods
were probabilistic and that included
blue dye bubble testing many different
types of tests like that and there were
as you can see not reproducible very
subjective insensitive so high risk of
error because it was operator dependent
but the new deterministic test methods
like headspace gas analysis are
reproducible sensitive
they're very quantitative and low risk
of error so they're very repeatable
types of test methods this info won't
spend a lot of time on this but this is
showing basically the unreliability of
blue dye testing that even at a 20
micron hole in a vial or a syringe you
have a 17% of the time you miss the leak
so it's that just kind of verifies the
unreliability of blue dye testing in
many many types of packages so I talked
a little bit about the hit iterator and
this is a little bit of how it works
you basically we're creating standards
with this to be utilized for the
validation process of our machine and so
basically you would put a vial into the
into the chamber you would close the
chamber
you put the vial and put the stoppers in
then you would close the chamber turn on
your vacuum out the chamber then you
apply a certified gas concentration into
the chamber and once that goes fully
fills the chamber it also goes into the
vial
then you push the stopper down and you
have that certified gas captured inside
of the vial or the pre filled syringe so
really nice tool makes it very easy to
for us to make standards reference
standards for you for your validation
purposes so kind of just wrapping
everything up you know technology
continues to advance and in the old days
blue dye testing or bubble testing was
acceptable it was the only type of test
that were available but technology is
increasing at really an ever-increasing
speed there's new technology coming out
all the time and this is one of those
technologies that's now available to the
marketplace so even simply taking a
reference sample or taking a testing
only a few of your product that are
going down the line there's no need for
that because the technology has
veins to the point that you can have a
100 percent inspection of every product
coming down the vial and can guarantee
that the headspace is good in that in
that product so this technology is
available for the marketplace and we
have a full line of products to provide
for this monitoring type of system so I
think that's most of the things I wanted
to share today and we'll we'll go this
just kind of shows the full line from
lab up to full-scale and we'll go to the
questions and see if we can answer if
you if anyone has posted any questions
and begin to answer those
okay I don't know I guess see I don't
see any questions Mike thus far so well
I guess he covered it all and if there's
anything additional that comes up or any
future views people that are watching
this later any questions that may be
coming up please don't hesitate to get
ahold of our office or any of the other
locations and Mike thank you so much for
giving us the opportunity to learn more
about the importance of headspace
content verification as mentioned if
there are any future interests one of
the things that Mike had discussed was
the laser cube product and that's gonna
be launched at inter FEX
I'm sorry pack Expo coming up next month
in Vegas so we'll have that there but
more importantly after that show is
conducted the unit's gonna be available
in the life scientific territory for
demonstration so we'd be happy to run it
by your site to be able to look at as
demo for production lines but also it's
very applicable and research and
development product development
laboratories and long-term stability
studies that may be going on and
analytical stability group areas so
don't hesitate to get with us relative
to potential demo on that and our next
Lunch and Learn session is going to be
on September 13 at 11:45 JB Northwest is
gonna facilitate content relative to
heat transfer and also mixing systems so
Kyle Sawyer's a mini decade expert in
the field of both mixing and heat
transfer systems so
stay tuned for more information on that
thank you so much Mike for an excellent
presentation I really enjoyed it and
learned several things myself so thanks
again we appreciate appreciate
everybody's time today and hope you
found the content valuable take care
have a good week
