Drivers for Continuous

Tablet Manufacturing
in Pharmaceutical
Industry
Satu Lakio
PhD (pharm.), Adj. Prof.
Industrialisation and
product life cycle management
Orion Pharma

29th Annual Symposium of the Finnish Society of Physical Pharmacy, 8.-9.2.2018

 Disclaimer

These slides are intended for educational purposes only and for the personal use of the audience. These
slides are not intended for wider distribution outside the intended purpose without presenter approval.

The content of this slide deck is accurate to the best of the presenter’s knowledge at the time of
production. The views and opinions expressed in this presentation are those of the author and do not
necessarily reflect the official policy or position of Orion Pharma or any of its officers.
Agenda

● Orion today
● Modernizing pharmaceuticals manufacturing
● What is continuous tablet manufacturing?
● Benefits of continuous manufacturing
● Challenges and hot-topics

Satu Lakio / Orion Pharma 3

 Orion today Orion is developing, manufacturing and
marketing pharmaceuticals and diagnostic tests

Sales split by market area

Net sales 1 074 MEUR
Operating profit 315 MEUR
13%
32%
8%
Personnell 3 446

R&D investments
118 MEUR
31%
16%
6 production sites in
Finland Finland
Scandinavia
Orion Headquarters, Espoo Finland Other Europe
Own sales unit in North America
26 European countries
ROW

Year 2016

Satu Lakio / Orion Pharma

Our businesses
Proprietary Products
In-house developed drugs
● CNS, oncology, respiratory
Animal Health
Medicine and well-being products for
animals
● Utilises the R&D of proprietary
products to develop new medicines for
animals
Contract Manufacturing
Production for other
pharmaceutical companies
Specialty Products
Generic prescription drugs, OTC and
non-medicinal products
Fermion
● APIs to Orion’s proprietary
products
● Generic APIs
● Contract development for
pharmaceutical companies
Orion Diagnostica
Diagnostic tests and test
solutions
Satu Lakio / Orion Pharma
Background
Evolving business needs of the
● More than 100 billion tablets manufactured / year
pharmaceutical industry
● Megatrends
– Personalized medicines, individual dosing
– Shift from blockbusters to niche products Accelerated
Cost pressures
Changing
development markets
● Global R&D expenditure expected to be $160B in 2020
– Only 12% of molecules that enter to Phase II will reach
market More, lower
– Dramatically higher clinical trials costs and timelines Breakthrough Reduce
volume
– Molecules are more challenging (poorly soluble,
therapy inventory
products
macromolecules, etc.)
● Challenges & opportunities
– Changing market demands, drug shortages
– Expiring patents/IP, rising generics competition Reduce Access to
– Healthcare costs are rising Oncology development emerging
– Demand for green(er) technology costs markets

● Regulatory push: Process understanding and

predictability, quality aspects Uniformly high quality and supply reliability

Ref. Arden house conference on continuous manufacturing, 2015

Satu Lakio / Orion Pharma February 16, 2018 6

 Modernizing Pharmaceutical Manufacturing

“If we used a time machine to transport a

pharmaceutical scientist from the 1960s into
a current pharmaceutical production plant of
today, it might be surprising to learn that they
would already be very familiar with most of
the processes and production techniques being
used.” (Lawrence Yu, FDA)
”The pharmaceutical industry is going through a
period of dramatic change, and incremental
improvement to the decades-old batch
manufacturing paradigm is no longer sufficient”
(P. Nixon, VP and Head of Development Americas, Pfizer)

”The pharmaceutical industry is going through a period of dramatic change, and incremental improvement to the decades-old
batch manufacturing paradigm is no longer sufficient”
 Need for modernizing  Continuous manufacturing
-Philip Nixon, VP and Head of Development Americas in Pfizer Essential Health

pharmaceuticals manufacturing
Satu Lakio / Orion Pharma
Batch vs Continuous Manufacturing

Continuous manufacturing is a production

method used to manufacture, produce, or
process materials without interruption

• One room
• Automatic material handling and transportation
• Real-time analytics; Process Analytical Technology (PAT)

• Multiple rooms
• Manual material handling and transportation Mu
• Time and resource consuming
• Analytics done post processing

Satu Lakio / Orion Pharma

Continuous Direct Compression (CDC)
TEVA
University of
Eastern Finland
GEA CDC-50
Glatt

Satu Lakio / Orion Pharma

Continuous Wet Granulation
Hovione Pfizer (POD)

ConsiGma25 by GEA

Satu Lakio / Orion Pharma

Continuous Manufacturing provides many benefits
Continuous flow of material instead Shorter production lead times, more
of step-by-step processing
flexible manufacture

No scale up and tech. transfers

Shorter development times

Smaller footprint, decreased waste,

energy consumption and raw Reduced costs and environmental burden
materials

Better process understanding by in Enhanced process robustness and

line monitoring (PAT, QbD)
product quality

Potential for real-time release (RTR)

Mu Reduced analytical costs

To keep the competitiveness in future! Satu Lakio / Orion Pharma

Increased process understanding…
 Better and more consistent quality

Input variable Process Output

Batch Fixed
Black Box

Input space Processing Product space

Control loop

Continuous Steady

 Potential for real-time release

Satu Lakio / Orion Pharma 12
RTD = residence time distribution
Real time release testing, RTRT

● Provides increased assurance of quality

– More data and better understanding
● Increased manufacturing flexibility and
efficiency
– Shorter cycle time
– Reduced inventory
– Reduction in ‘at release’ testing
– Reduction of manufacturing cost
● Allows leveraging of enhanced process
understanding
– Corrective actions may be implemented in
real time  amount of waste decreases
Ref. Moore, FDA, 2011

Satu Lakio / Orion Pharma 13

Presenter / Department 16 February 2018 14
Business case for pharmaceutical industry
● Depends highly on focus
– NCEs
and/or
– Existing products

Satu Lakio / Orion Pharma 15

Challenges and hot topics
● Cleaning & change over time
● Data real-time handling
● Control strategy
● Achieving “CM mind-set”
● Lack of experience
● Regulatory uncertainty

● Significant investments
– Standardization of equipment and interfaces

Satu Lakio / Orion Pharma

 Take home message

The “Continuous” Age Has Begun