Brought to you by

Process Analytical Technologies (PAT)

and Quality by Design (QbD)

Overview
2014

www.patandqbd.com

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Contents

3
Introduction
4
Key Benefits of PAT and QbD Implementation
6
3 Key Trends in PAT / QbD Implementation
7
Best Practice Ways to Overcome Common Challenges in PAT
8
Improving PAT Validation
9
Changes in PAT and QbD Investment and Implementation Inforgraphic

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introduction
80%

of companies plan to invest in

Quality by Design and PAT solutions,
do not have a fully established
process in place.

yet 72%

vBut what is the reason for this gap?c

59%

of people stated it was due to

internal lack of expertise.

For the past 11 years, Pharma IQs PAT & Quality By Design conference has been
bringing you the latest case studies to help show you the benefits of PAT and QbD
and how to effectively implement QbD into your company. This year in conjunction
with Pharma IQ we have brought together insights from leading experts in the
field.
In this eBook we explore 3 key trends in implementation, how to make a business
case for PAT and QbD implementation and best practice ways to overcome
common challenges in PAT.
We hope you enjoy reading.
Best regards
Andrea Charles
Editor
Pharma IQ
www.pharma-iq.com

www.patandqbd.com

Key Benefits of PAT and

QbD Implementation
Brett Cooper Research Fellow, MSD Development Laboratories, talks to
Pharma IQ, about the slower than anticipated industry uptake of PAT
and QbD, the key benefits of PAT and QbD implementation and the biggest
challenge pharma and bio companies face regarding the interpretation
of regulatory guidance. Cooper also discusses how to prove the business
case for PAT and QbD implementation. To listen to the interview in full
Making a Business Case for PAT and QbD Implementation:
Pharma IQ:
The SPA driven PAT and QbD initiative was launched almost ten years ago but there still remains
a substantial sector of the market that are not using PAT or QbD methods. Although companies
undoubtedly have much better understanding of what QbD is we still do not see many initiatives
taking place across the pharma industry. Why do you think the industry uptake has been slower t han
originally anticipated by the FDA?

b cooper:
I can think from the Merck point of view
that I guess once the FDA announced the
QbD initiatives and it started working on it
almost straight away. And I think that Merck
introduced QbD into one of its projects as part
of the trial that was going ahead initially. QbD
in that respect was sort of jumped into by
Merck to some degree. Although I guess the
big pharma companies such as Merck, there
obviously is some degree of alignment that
needs to take place before companies like that
can implement QbD throughout a project and
assess the impact of that. So I guess things like
management position on taking a stance on the

recommendations and then teams being formed

to work out how were going to implement those
sorts of procedures. And I guess the downstream
training and implementation of those processes
with the majority of staff in a large company
will take time. And I guess at least on a Merck
perspective we try to implement those processes
as quickly as possible. And then theres also the
impact of the development time lines that need to
be considered. So if you start with a new project
and start implementing QbD those projects can
take considerable time to get to the market or
get to review by the FDA.

Pharma IQ:
And what do you think is the biggest challenge pharma and bio companies face with regard to
interpretation of regulatory guidance?

b cooper:
In terms of regulatory guidance I guess that their
challenge would be more around the resource to
investigate that because a lot of those companies
will be smaller. For pharma and bio companies
especially, reading into the guidelines and
determining how to understand those may be
more problematic for the smaller companies.
But the larger companies I guess coming to an

agreement and discussing the guidance with the

regulatory authorities is another thing that needs
to occur. Sometimes I guess the big industries,
when we come to follow the guidances and
present those in a filing there can often be some
aspects which are seen as different by the FDA. It
depends on how the interpretation is set.

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Key Benefits of PAT and

QbD Implementation
Pharma IQ:
What are the key benefits of PAT and QbD implementation?

b cooper:
QbD obviously is designed to give you the
flexibility to change downstream. So if you can
demonstrate that you have a wide working
margin then you can maybe find ways to optimise
and improve your process downstream while
remaining within the QbD space that youve
designed. PAT is a pretty powerful tool and if you

link that with your processing machinery then

you can actually monitor the process. Maybe
come up with real time release of the process to
cut down on the amount of testing downstream
and also really link the PAT with the process to
ensure the quality of the material is optimised at
the end.

Pharma IQ:
How do you think companies can improve the business case for PAT and QbD implementation?

b cooper:
I guess by trial and implementation of
those processes and then evaluating how
those processes have gone. I guess the
bigger companies where when you have
multiple projects going forward and you start
implementing your PAT and QbD processes and
you start comparing those with prior processes
you can sort of track how things are going and
how the costs can be potentially reduced. Some

procedures where you implement QbD strategies

or designs or procedures that are already in
place where there are maybe some issues or
batches that potentially arent processing so well,
you can almost see an immediate change if you
track the processes during the manufacture.
So theres sometimes an immediate win by
implementing those processes that can be
achieved.

http://www.pharma-iq.com/pre-clinical-discovery-and-development/articles/key-benefits-of-patand-qbd-implementation/

www.patandqbd.com

3 Key Trends in PAT / QbD

Implementation
In 2013 Peter Boogaard, Founder of Industrial Lab Automation and
Director at Vialis AG gave a workshop at the 10th anniversary Pat &
Quality by Design Conference. He gives an overview of the top takeaways
from the event.
Last years program included many case studies and general trends in
the QbD and PAT adoption, but there were three particular topics that
triggered his attention.

1
Driving the need for constant product innovations
in a legislation-complex industry remains a
challenge in the life sciences industry. Quality
should be built into the design throughout the
specification, design and verification process. The
consumer demand becomes more sophisticated,
in both the innovative pharma and generics side
if the industry. During breakout discussions at
the conference, it was obvious that the drivers

for both pharma segments are different. The

traditional pharma industry is focusing on new
product innovation while the generic industry
is concentrating on optimizing production to
reduce costs with manageable predictive quality.
It seems implementing QbD within the generic
industry has many similarities with other
industries such as consumer packaged goods
and electronics.

2
It may seem a boring topic these days, but the
need for standardisation in our industry has
never been higher. Forums like this conference
presents a valuable opportunity for so many
people from different regions, job functions
and seniority to come together to discuss
how the industry can evolve these and make
it happen. Both John Purves, former head of
EMA and Lawrence Yu, Deputy Director of the

FDA, presented the notion that regulators are

more familiar with QbD than some years ago.
Instead of discussion why QbD, the focus was
centred on how can we make it happen. A
point of attention was raised for standardisation
in nomenclature and naming convention to
avoid miscommunication across industry and
regulators.

3
The term QbD and PAT are becoming mainstream
in our industry, however recent research from
Pharma IQ showed that 68% of individuals
surveyed are in the early stages of implementing
QbD and lack the expertise to fully implement
into all processes. Quality should be built into
the design throughout the specification, design,

and verification process. There is still a lot

of education to be done across the different
disciplines within organizations. The ICH Q10
guidelines clearly defines that a modern quality
system assures science and risk-based drug
manufacturing and quality decisions throughout
the lifecycle.

http://www.pharma-iq.com/manufacturing/articles/3-key-trends-in-pat-qbd-implementation/

www.patandqbd.com

Best Practice Ways

to Overcome Common
Challenges in PAT
Rakhi Baj, Technical Project Leader at Abbott Diagnostics, joins Pharma
IQ to offer some best practice ways to overcome common challenges in
PAT. To listen to the podcast now go to Inside Tips on Making Progress
in PAT.
Pharma IQ:
What do you think are the major challenges that hinder the progress of increased process
understanding and control?

R Baj
One of the key challenges that I come across
quite often is a lack of understanding of the
actual tools. People are inherently wary of
mathematics and statistics and they get the
perception that theyre really difficult and that
really it should be left up to the statisticians
to work away in the corner and come up with
the answer. But I think both scientists and
statisticians need to work together to get a

better understanding of the process; what are

the issues; where are the bottlenecks, and
then decide on the best approach. I think its
really important for statisticians to get a better
understanding of the process and for scientists to
get a better understanding of statistics, and that
way the two groups can decide on the best tools
to use for that specific area.

Pharma IQ:
So, expanding on this, do these challenges differ when working in the diagnostics field, and if so, how?

R Baj
Not really. The challenges stay the same, but the
processes are different, but I do believe that with
increased communication and working across

the functional groups, a better understanding of

the process can be achieved, and therefore better
control.

Pharma IQ:
Finally, what are the key tools and techniques that you personally find the most effective in your work?

R Baj
In terms of the statistics tools we use a lot of
control charts and host capability type tools
and indices, and in terms of the non-stats tools,
things like process flow diagrams and Ishikawa

fishbone diagrams work really well. Were big

fans of fast jump and mini tab as well in terms of
statistical software packages and we use them
quite a lot in everyday activities.

http://www.pharma-iq.com/manufacturing/articles/best-practice-ways-to-overcome-common-challenges-i/

www.patandqbd.com

Improving PAT Validation

Qualification of
equipment and validation
of analytical methods
are critical components
for the implementation
of process analytical
technology (PAT).

Martin Warman,
Scientific Fellow, Analytical
Development at Vertex
Pharmaceuticals, joins
Andrea Charles from Pharma
IQ, to discuss the effects of
apply PAT to pharmaceutical
manufacturing and how to
successfully validate PAT
methods.

Warman also shares

his insights on
how to select the
right partner in the
validation process.

Listen to Martins
podcast here
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Changes in Investment and

Implementation: 2010-2012
80% said they plan to invest in Quality by Design and PAT solutions. With budgets being cut and margins becoming tighter, QbD
and PAT are becoming more and more critical for the pharmaceutical industry. In preparation for the 10th Annual PAT and QbD
conference, Pharma IQ has analysed the change in investment levels over the last 3 years.

Knowledge and expertise in the field of

QbD is up 13% since 2011

50% say lack of knowledge and expertise is

In 2011, 42% said the

ability to demonstrate ROI
was the biggest barrier to
investing in QbD and PAT
solutions

In 2012, the main

solutions that
end-users invested
in were:

the biggest reason for not implementing QbD

4
5

What are the key

reasons for not
implementing QbD?

62% say they use conferences and

events to find out about solutions
and services in this space:

PAT hardware 34%

QbD software 15%
QbD expertise and consultants 30%

2010

42% ability to
demonstrate ROI

2011

40% integration

with current practices

lack of
2012 59%
internal expertise

18th-20th March 2013

London, UK
www.patandqbd.com

Data management solutions 21%

2012 80%
2011 44%
88% believe QbD practices 7
will become mandatory in the
innovative pharma industry as it
has done with generics

% of those planning to
invest in QbD and PAT in
the next 12 months

Changes in of QbD and PAT implementation over the last 3 years

No plans for implementation

In early stages of
implementation

5%

13%

Interested in learning
more but not done yet

5%

20%
25%

34%

14%

28%

21%

Established QbD
implementation

32%

2010

18th - 20th March 2013, London, UK

www.patandqbd.com

50%

2011

53%

2012

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Maximise cost efficiency, improve quality

and cut waste through Quality by design
24 - 25 March, 2014 - London, UK
Key
topics include:
v What the regulators expect from filings and how this can
be achieved, with key updates on current regulatory
requirements along with results from the latest FDA/EMA
parallel pilot study
v How to implement the most effective QbD process in order
to maximise profit and case studies from leaders in the
industry on how this has been done
v The future of QbD in Biologics: overcoming the problems of
heterogeneity and data variation
v The implementation of QbD in the generic industry:
how the industry are coping with the mandatory
requirement
v Latest advances in PAT technology and the best
implementation practice of these techniques
v Moving from batch manufacturing to continuous
manufacturing, how to effective implement this, how this
will aid quality by design and overcoming the problem of
defining a batch

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