10. Commercial Readiness, with Vince Narbut

How prepared is your facility? Being prepared is crucial and in this episode Vince Narbut takes you through commercial readiness.

Episode Transcript

James C. Taylor (00:02):
So the question for today is, are you ready?
We're going to talk about commercialreadiness with Vince Narbut, and
we're going to do it right now.
This is Insight at Biologics.

(00:24):
Hi, Vince.
I appreciate you comingby and doing this with us.
So first, tell everybody a littlebit about you and your background.

Vince Narbut (00:30):
Well I'm a consultant with Biologics Consulting and have been
with the company now for, for 12 years.
Prior to that I was in thebiopharmaceutical industry working
for a company called Biogen, b othin the Boston area and in Research
Triangle Park, North Carolina.
My expertise is primarily in allareas of, of operations process

(00:54):
development, clinical and commercialmanufacturing validation, quality
assurance computer systems, quality.
A s an overview, I would saythat's, that, that covers it.

James C. Taylor (01:05):
Okay.
All right.
So we're talking aboutcommercial readiness today.
So let's get right down to the nub of it.
What is commercial readinessand is commercial readiness only
related to regulatory compliance?

Vince Narbut (01:20):
Okay.
Well, in the context of our discussiontoday, James commercial readiness
is intended to mean a state of fullpreparedness for a pre-approval inspection
and for reliable, consistent, continuous,ongoing commercial manufacturing of

(01:40):
drug, substance and drug products.

James C. Taylor (01:43):
All right, so now what areas are important
for commercial readiness?

Vince Narbut (01:48):
Okay.
Well, the, the way I like to thinkabout these areas of highest
importance is pretty much based onthe, the six main quality systems.
We have facility materials,production, laboratory controls
the overall quality managementsystem, and the labeling system.
And these are the six areas that, thattypically FDA dives into when they

(02:13):
come in and, and inspect facilities.
What as it relatesto facility preparedness.

James C. Taylor (02:21):
Mm-hmm.

Vince Narbut (02:22):
This involves sort of all aspects around building
and, and production area accesscontrols utility areas, the utilities
used in the manufacturing, a ll theclean rooms and facilities used for
manufacturing, the equipment usedin manufacturing and testing, the

(02:45):
maintenance program that is in place tosupport all the equipment in utilities
calibration program, the validationprogram, and then all the computerized
systems that are used to support themanufacturing, testing and, and quality
assurance of, of all the products.
On the material side of things we haveraw materials, starting materials, the

(03:11):
purchasing procedures that are in placeat the company, the receiving procedures,
the sampling procedures, testingprocedures the way the materials are
released by quality assurance, the storageand traceability of all the raw materials
in the facility, the, the warehousingof those materials, and also the

(03:32):
warehousing of the products that are made.
On the production side, wehave the flows of the process
through the manufacturing areas.
We have the gowning and, andcontrols used for personnel that
are performing The manufacturing.
We have the, the cleaningof the facilities.
We have all the documentation that'sused to document the manufacturing.

(03:54):
And we have all the personnelrequirements training and,
and qualifications, et cetera.
On the laboratory control side ofthings, we have the actual laboratories
themselves and their readiness, the,the testing instruments, the, the
analysts that work in the laboratoriesand their qualifications and training.

(04:16):
All the reagents used for testingthe reference standards used.
The data integrity program to ensureall the data coming out of the
laboratory can be relied upon and isrobust and, and and well protected.
And then we have all the test methodsthat are used to test the, the, the
products and the materials and thevalidation of all of those test methods.

(04:42):
On the quality management systemside of things we have all the
procedures and activities aroundthe Deviation Kappa and investigation
areas performed within the company.
We have the change control program.
We have the audit program,supplier quality program training.

(05:07):
Program and tracking systems.
We have the documentation program andhow documents are, are, are archived
and, and maintained over the long run.
And then we have themanagement review program.
And then finally on the, on the labelingside of things, we have the, the various
labeling procedures, the controls forlabels, and traceability for all labels.

(05:29):
So that kind of gives you a snapshotof, of the main areas of importance
for, for commercial readiness.

James C. Taylor (05:36):
Okay?
And that is quite a bit.
So when should you start preparingand how much time does it take to
be ready and tell what kind ofresources do you need to be ready?

Vince Narbut (05:50):
Okay.
Well in my experience, the earlieryou start, the better because
it does require quite a bit ofpreparation, especially if, if you
have not been down this road before.
Many times the companies that we dealwith at Biologics Consulting have not
manufactured commercial products before.
This is kind of theirfirst First try at it.

(06:12):
So you certainly want to makesure that you're prepared.
And I, I would generally advisestarting preparation six to 12 months
in advance, probably closer to 12months for, for companies that have
very limited to no experience.
And this actually takes quite a bitof time commitment on the part of
personnel within the organization.

(06:35):
In general, I would say all staff thatare involved in GMP operations will at
least require some level of trainingon how to deal with inspectors.

James C. Taylor (06:47):
Mm-hmm.

Vince Narbut (06:47):
That would be in the facility that they may encounter
in their, in, in their work duringthe inspection how to respond
to questions side of things.
The management supervisory personnelwill, will will need to be involved
in the assessments of their areasto determine where there may be
some areas of improvement needed andthen on an ongoing basis until all,

(07:11):
all improvements have been made.
They'll, they'll need to be involvedin those improvements and, and involved
in the, in the project managementassociated with making sure that all
comes together in a, in an organized andtimely manner to be ready for, for the
inspection when that, when that occurs.

James C. Taylor (07:30):
All right now, What are the key steps to commercial readiness?

Vince Narbut (07:39):
Okay, well, as I alluded to just pre a little bit previously

James C. Taylor (07:45):
mm-hmm.

Vince Narbut (07:45):
Each functional area, I was going to need to do an assessment of their
of all their areas of responsibility.
So what I mean there is, is forinstance, We're talking about the
facilities and maintenance organization,they would need to assess all
their procedures and practicesand determine what is the state

(08:08):
of readiness, if you will, or, ormaturity of the various programs
within their areas of responsibility.
So that would include you know,are all the procedures in place?
Is the, is the facility that that we workout of does it present itself well?
Are all the, the items organized?

(08:31):
Are, are the appropriateprocedures in place?
Are all the appropriatedocumentation systems in place?
Are we up to date with allour maintenance work orders.
Do we have procedures fordoing the various work orders?
Do we have documentation forall the contractors that we
may use to do maintenance?
Have we done walkthroughs on a,on on a regular basis to ensure

(08:54):
everything is well organized and,and and presents itself well?
And in many cases it's good to getsort of an outside Perspective so many
times the quality assurance organizationwill be involved to, to kind of help
with identifying areas, improvementof improvement, and then kind of

(09:19):
acting as inspectors or auditors, if youwill, in the preparation, in, in the
identification of areas for improvement.
And then ultimately theremediation activities.
As well as you know, that afinal determination, okay.
That yes, this, this areaappears to be ready.
We can check the box andsay we're, we're ready here.

James C. Taylor (09:43):
Okay?
Now what are the risks?
What are you taking a chance onif you aren't prepared adequately?

Vince Narbut (09:53):
Well, James, the main risk is that you risk the timely
approval of your license application.
So

James C. Taylor (10:01):
kind of important.

Vince Narbut (10:02):
Yeah, yeah.
Absolutely.
If the, if the facility is not ready or,or one or more, the areas are not ready.
And you go through the inspectionprocess and the inspection
does not prove successful.
It's quite possible that youcould receive a complete response
letter for your application.
In which case, the productis not approved due to.

(10:26):
Problematic areas at the manufacturingfacility and those items will
need to be remediated and, orfixed whatever have you before.
Probably another inspectionand, and then approval.
Subsequent to, to successfuland acceptable reinspection.
So the, the main risk is that yourproduct approval is is delayed.

(10:52):
On the others you know,a secondary risk, which

James C. Taylor (10:56):
mm-hmm.

Vince Narbut (10:56):
Is not inconsequential over the long run.
Is that you've created a, a poor firstimpression with FDA and, and that
doesn't set you up well for the future.
Ultimately FDA is gonna bevisiting a commercial manufacturer,
usually on a biannual basis.
And, and they determine how oftenthey need to inspect facilities and

(11:20):
whether they need to go every twoyears or not a lot based on what they
see when they visit the facility.
So if you've given a poor impressionon your first time out, that doesn't
set you up for success going forward.
So it's an important aspect to, toconsider is, is you really want to
put your best foot forward, especiallyin a pre-approval inspection and,

(11:41):
and and have a successful outcome.

James C. Taylor (11:45):
I would think that wanting the regulatory
agency to, you know, like youwould be a, a good thing to do.
You know, not, this is kind of, thisis outside of my area expertise, but
I, I just have a feeling that havingthem not be annoyed is helpful.

Vince Narbut (12:05):
Yeah.
Yeah.
Absolutely.

James C. Taylor (12:08):
All right, so now what can we, Biologics
Consulting help companies do toprepare to be commercially ready?

Vince Narbut (12:17):
Okay.
Well James BC or Biologics Consultinghas been involved with a number of
companies over the years in the timethat I've been with the company where
we help companies in their overallcommercial readiness preparations.
And that can involve one or moreconsultants helping in a specific area.

(12:40):
It can involve us coming in anddoing an overall gap assessment
or, or a mock inspection.
Sometimes multiple people for a weekwhere we kind of do a deep dive in
all areas to try to identify as manyareas of improvement as possible.

(13:01):
And so we can, we can, you know,be involved on that side of things.
We can also be involved in, incoming up with solutions and, and
recommendations for improvement.
And then we can also be part of theactual improvement plans where we help
with remediation activities, writingSOPs, whatever the case may be.

(13:26):
We have consultants with with theexpertise in, in all the general areas
of GMP and facility preparedness.
So on the facilities and theengineering side, on the production
side, on the quality control andlaboratory control side, on the quality
assurance and quality systems side.

(13:48):
So we have, we have folks thatcan help with all those things.
And we can help in a holisticway sort of in all aspects.
Or we can kind of help in veryspecific areas where a company
may know they need some help.

James C. Taylor (14:01):
All right, Vince, and if people have more questions,
they can feel free to contact you.
Yes.

Vince Narbut (14:08):
Oh, absolutely.
Yeah.
So we do this quite regularly.
I'd say it's it's one of our morefrequent repeat type of activities
that we do with with clients o overthe years as they, as they gear up and
prepare for pre-approval inspections.
We've done these withrelatively large companies.

(14:29):
We've done it with contract manufacturingcompanies you know, we'll call it
traditional biotech type protein andmonoclonal antibody manufacturers.

James C. Taylor (14:39):
Mm-hmm.

Vince Narbut (14:39):
And then, you know, most recently we're helping companies
with with portfolios in, in celland gene therapy areas as well.
So we've helped all those
folks.

James C. Taylor (14:50):
Well, cool, and thank you, Vince, for coming
in talking to us about this.
And folks, if you'd like more information,you can just email Vince or any of us
here at [e-mail].
We'll route it to whoeveryou need to talk to.
That's insight at biologicsconsulting dot com.
Also, we'd love it if you'd like,subscribe to rate and review our show.

(15:14):
The executive producer of InsightBiologics is Kris Kraihanzel.
This episode was producedand edited by me, James C.
Taylor.
The technical supervisor is Jeff Wease.
The Insight and Biologicstheme is by Tom Rory Parsons.
I am James C.
Taylor, and thank you forjoining us, and please come back
for more Insight at Biologics.