Process Analytical Technologies Process Analytical Technologies Subcommittee Subcommittee Product and Process Development: Product and Process Development: An Industry Perspective An Industry Perspective David Rudd PhD David Rudd PhD Process Technology Process Technology GlaxoSmithKline Research and GlaxoSmithKline Research and Development, UK Development, UK
Transcript
Slide 1
Process Analytical Technologies Subcommittee Product and
Process Development: An Industry Perspective David Rudd PhD Process
Technology GlaxoSmithKline Research and Development, UK
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2 Source: UK Department of Trade and Industry UK manufacturing
profitability by sector (1995 to 1999)
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3 Manufacturing process Process feed Process output Store or
hold Current manufacturing philosophy
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4 Manufacturing process Process control Process feed Process
output Closed loop control (process parameters only) Store or hold
Temperature Time Pressure etc. Current control philosophy
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5 Manufacturing process Policing function Off-line (lab-based)
review of product quality parameters Process control Process feed
Process output Closed loop control (process parameters only) Store
or hold Temperature Time Pressure etc. Current control
philosophy
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6 Guaranteed product quality Avoidance of delay Optimal
utilization of resource Minimization or elimination of waste
Movement towards continuous processing Business case for
improvement
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7 Optimized process Scaleable process Ease of technology
transfer Well-characterized (well-understood) process Reliable and
robust process Product and process development objectives
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8 Provision of manufacturing and monitoring equipment and
technical expertise Development of process understanding
Identification of critical process parameters Implementation of
critical process controls Decision-making basis for process
feedback R&D responsibilities - in conjunction with
Manufacturing
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9 Tablet manufacturing process Dispensing and sieving
Dispensing and sieving Blending Blending Granulation and milling
Granulation and milling Drying Drying Compression Compression Film
coating Film coating
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10 Homogeneity of powder blend (on-line NIR, at-line HPLC or
UV-visible and/or imaging techniques) Homogeneity of powder blend
(on-line NIR, at-line HPLC or UV-visible and/or imaging techniques)
Moisture content (on- line near infra-red and/or ERH probes)
Moisture content (on- line near infra-red and/or ERH probes)
Blending
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11 Concentration of analyte versus time Near infra-red
monitoring of powder blend process
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12 Replication of spectra (moving block of 12 samples) Near
infra-red monitoring of powder blend process
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13 Powder blend imaging using spectroscopy
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14 Powder blend dynamics
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15 Granulation end-point Granulation end-point Flow
characteristics, bulk density etc Flow characteristics, bulk
density etc Homegeneity of granule Homegeneity of granule Moisture
content Moisture content Particle size Particle size Granulation
and milling
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16 Power consumption curve during granulation
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17 2 5 8 11 258 Karl Fischer value (%w/w) NIR predicted 0 200
400 600 800 0200400600800 Particle size (sieve analysis) in microns
NIR predicted Near infra-red monitoring of granulation process
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Acoustic monitoring of high shear granulation process
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Machine off Dry mixing Wet massing Liquid addition (wet
granulation) Acoustic emission produced during granulation
process
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20 Actual versus predicted Mass Median particle size
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21 Actual versus predicted Flowability Index
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22 Actual versus predicted maximum crushing strength
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23 Effect of scale on acoustic signature of a granulation
process
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24 Stages of the product manufacturing process can be
characterized and then described based on the use of a variety of
diverse measurement techniques This multi-dimensional profile can
then be used to produce a process signature which, in turn, offers
a means of ensuring process reproducibility and robustness The
process signature may also be viewed as an end-point to work
towards during scale-up or after equipment changes or site changes,
for example Process signature
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25 Perhaps the concept of the process signature equates to the
establishment of a process specification - that is, a series of
requirements which need to be met if the process is to be
considered under control? Just as parametric release implies the
removal of critical end-product testing, perhaps the natural
corollary is to transfer the critical specification from the
product to the process? Process specification
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26 Manufacturing process Control function On-line monitoring of
critical process parameters Process control Process feed Process
output Closed loop control (process parameters only) Temperature
Time Pressure etc. Future control philosophy
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27 To Granulator Continuous dry blender Mass flow Excipient A
Mass flow Excipient B Mass flow Active Mass flow PAT Blend speed
Control philosophy PAT (NIR, process imaging etc) monitors
composition and blend uniformity Feedback controls mass flow in or
out and modifies blend speed, if necessary Key Mass flow control
Instrumentation Material flow Process control loop Physical control
loop Continuous blending process
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28 Development of novel analytical monitoring techniques (or
novel applications of existing techniques) appropriate for the type
of measurements required Emphasis on indicators of change rather
than necessarily quantitative measurement New data processing
methods required (data reduction and/or combinations of data from
diverse sources) Implications and new research areas
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29 Development scale = Manufacturing scale? Establish
relationship between traditional end-product quality parameters
(release and end-of-life specification for finished product) and
key process measurements Demonstrate predictive capability of in-
process measurements Development of process specification
Implications during product and process development
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30 Process Analytical Technology (PAT) is seen as a means of
improving existing manufacturing process monitoring and control
strategies The most significant advantages are to be gained by
moving towards true process understanding (gained during process
development) which, in turn, offers the opportunity of Quality by
Design manufacturing methods and parametric release concepts PAT is
vital if the pharmaceutical manufacturing industry is ever to
embrace continuous processing Final thoughts