Factores de Sucesso na Implementação de Tecnologias PATmittic.gobex.es/upload/web/publico/03_uid2.Success_Factors_PAT_2… · Adapted from A.Hussain (FDA) Presentation at Pittcon

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Factores de Sucesso na Implementação de Tecnologias PAT

tune (verb)adapt, adjust, conform, fix, integrate, modulate, regulate, tighten, bring into harmony


Originating from our own track-record

Large Multinational Companies

World-class CMO Companies

Innovator SMEs

Regulatory Agencies




The PAT Team

Diverse knowledgeable people (diverse team)

QA, QC and Production Management on-board

upper management support

control engineers – sensor, sampling, DAQ

statisticians and computer-nerds are to be avoided

put together a team of good, competent, hard-working people

don’t underestimate the importance of having expertise in

chemometrics and multivariate process control on board

A PAT-champion in upper management


Goals Activities Team &

Hierarchy Project Management &

Work Flow Financing & BudgetClients & Internal Dependencies Action

Plan Short & Long-Term

PAT Team Governance


Before you Start

Check the quality and quantity of your process operating data

and the associated lab (QC) data

Check again that your QC has their protocols validated

Ensure good comunication among all involved

clear understanding of gools by all parties involved

good comunication: QA – QC – Production

Have and enforce all the time realistic expectations

reduce expectations of your “end-users” when necessary


Equipment

Type of AnalysisAt-line

in-line

on-line (in-situ)

Multiple Instruments vs Centralized EquipmentMultiple probes in one instrument

Dedicated instrument

SamplingMay become more complex than all the rest

Make sure you design and then measure your sampling system withyour process dynamics in mind (sample transport delays).


Project Development

Define project comprehensively

start-small (less ambitious)

don’t fancy people with your PAT/QbD tools(viz., chemometrics)

Don’t believe in your first results ever

Check & double-check – keep a critical attitude all the time

Use proper statistics in calibration development & validation

Don’t throw away “outliers” (abhnormal data)

Keep as close as possible to the industrial people

don’t get to attached to scaled-down or lab experiments

move ASAP to or even start right away at the industrial problem

Don’t underestimate the time (or effort) needed to get things working (1sttime) and then to keep things running after that.


Adapted from A.Hussain (FDA) Presentation at Pittcon 2002

Marketed “robust” products.

PAT to improve efficiency (minimal

improvement in quality assurance).

Cost reductions associated with QC.

Marketed products needing improvement.

Step wise PAT approach: first improve product

quality, then concentrate on process efficiency !

QC cost reductions, but major profit increases.

New products

same PATs used throughout development,

scale-up & full scale production.

Faster process and product R&D cycles.

A

B

C

without PAT with PAT

PAT Implementation Scenarios


PAT “Clients”

Quality Control Labs

Production Plants

Process Development Labs


Governance

A

B

C


Quality Control

Production

Process Development


Quality Control

PAT Team

QC Labin a specific

site

– Supplier – Client

Risk VERY LOW

Investment LOW

Return MEDIUM/LOW, might not even justify computation of ROI

Goal QC cost reduction

Example faster & cheaper IPCs and guided sampling towards end-point QC


Production

PAT Team

Production Linein a specific

site

– Supplier – Client – Solution Owner

Risk LOW/MEDIUM

Investment MEDIUM

Return HIGH

Goal Significant Productivity & Consistency Increases

Example Yield optimization, cycle time reduction, variability reduction, etc


Process Development

– Supplier – Client

PAT TeamR&D

Risk MEDIUM

Investment MEDIUM/HIGH

Return VERY HIGH

Goal Faster-Better-(Cheaper) Time-to-Market

Example Quality by Process Design


Implementation & ROI

Building a QbD/PAT Cultureestablishing in-house programs, teams and implementation issues

Business Incentives of QbD & PAT Implementationreturn on investment (ROI)


Typical ROI of PAT Implementations

For Type-A implementations ca. € 50 000 / parameter / year.

For Type-B implementations half of the optimization margin istipically within reach of PAT for improvement (€ 0.5 – 5million/year) depending on type of industry (pharma /biopharma), product unit value, market, regulatory status,.

ROI of Type C implementations is 1 to 2 orders of magnitude hiherthan Type B.

These figures have been obtained by us on several (> 50) industrialPAT projects and also reported by others.


PERSPECTIVE

FRAMEWORK

THINKING

PROCESS

DISCIPLINE VOCABULARY

SET OF

TOOLS

AN ABILITY WAY

OF

THINKING

CIRCULAR

PAT is about Systems Thinking

being systemic, strategic and holisticPAT must be in place early in process development and throughout process &

product life-cycle


©J.C

. M

enezes,

2000

Monitoring

Control

Supervision

Diagnosis

PAT Multiple Benefits


better process characterization & process understanding,

potentialy shorter development & scale-up cycles,

consistent process operation, reducing product variability,

increased productivity with faster monitoring techniques,

increased frequency of analysis for each critical step (product)

achieving higher safety & quality levels for whole process (end-

product),

better use of available production equipment, reduction of

inventory of in-processing products

Process Analytical Technologies


©J.C

. M

enezes,

2000

Monitoring

Control

Supervision

Diagnosis

Processing Industries: Strong in Control


A

B

C

process with PAT

process without PAT

QC efficiency gains through cheaper and simpler on-line or

at-line measurements by shift-personnel. Minimal QA

improvements.

Gains in QA with significant reduction in off-spec products

and product reworks, major productivity improvements.

Significantly faster process and product R&D cycles (“time

to market”), very efficient and creative process designs

(“near real-time product release”) and process operation

paradigms.

PAT Implementation Scenarios


Scenario A: PAT as QC Tools


Near-Infrared & Mid-Infrared EquipmentDiffuse Reflectance, Transmittance, Transflectance, Attenuated Total Reflectance

Process Analytical Chemistry

In-Process QC


FASTER more rapidly (secs) for equal accuracy

BETTER simpler sample presentation

no sample preparation, automatic analysis & reporting

CHEAPER no reagents, no dedicated CQ personel

shift personel handle analysis and measurement feedback

to the process

NIR analyses are generally, 5 to 20 times cheaper and/or faster than reference

methods, for the same accuracy & precision

exact figures depend on type of analysis (identification or quantification) and the

replaced analytical reference method.

NIR Analytical Benefits


Cost x Investment

Profit x Value


Scenario B: PAT in Process Improvement


A Batch Process


Direct Benefits - COST REDUCTIONS

In-Process Quality Control ………. > € 40,000 / y

Raw-Mat Qualification ………. > € 6,000 / y____________________

TOTAL ca. € 50,000 / y

Indirect Benefits - PRODUCTIVITY INCREASES

ca. 20 times greater : ca. € 1,000,000 / year

1. Improved process understanding

2. Improved process operation

3. Improved QA (following FDA’s tendency)

4. Freeing QC for end-product certification

Economic Evaluation for one PAT Implementation


Scenario C: PAT and Time-to Market


Faster Time to Market


Batches - Samples - Parameters

Transferring from #1 to #2

PAT – Analysis with multi-parametric sensors– On-line processing of data obtained– re-evaluation of transfer criteria

#1

#2


Time 0

industrial

lab

Scaled-Down Experiments (1:1000)

after ensuring comparability of scale-down results

different operating recipes

were used in designed (DOE)

LAB experiments

INCREASING

PROCESS

UNDERSTANDING

OPTIMAL

PROCESS

RECIPES


QbD/PAT: Faster PD & MAN

Improve Process & Product Target

Compliance

Prototype New Processes Faster

Design More Robust Product Formulations


QbD/PAT Implementation Scenarios

Adapted from A.Hussain (FDA) Presentation at Pittcon 2002

Marketed “robust” products.

PAT to improve efficiency (minimal

improvement in quality assurance).

Cost reductions associated with QC.

Marketed products needing improvement.

Step wise PAT approach: first improve product

quality, then concentrate on process efficiency !

QC cost reductions, but major profit increases.

New products

same PATs used throughout development,

scale-up & full scale production.

Faster process and product R&D cycles.

A

B

C



QbD/PAT: The value proposition

Half of the quality losses are within reach of PAT for improvement.

These can amount to € 0.5 – 5 million/year depending on type of

industry, product unit value, market, regulatory status, etc

These figures have been reported and have been obtained by us on

several (> 20) industrial PAT applications already deployed.

Typical figures for the optimization margin captured by PAT are in the

range € 1-2 million / year per PAT application.


Summing Up

QbD & PATs were born in the 21st century for this century’s

industries

QbD & PATs are changing process validation, regulatory

submission & inspection (QC & QA)

QbD & PATs are an important economic opportunity at times

of increased competition (e.g., time to the market &

competitive processes)


THANK YOU, any questions ?

Chief Business Development ManagerJoão E Machado, 4Tune Engineering Ltd

[email protected]

4Tune Engineering LtdAv. Antonio Augusto Aguiar 108, 4th floor1050-019 Lisbon, Portugalwww.4TuneEngineering.com

Tel. (+351) 21 606 2788 Fax (+351) 21 606 2790

better processes, better products ©

Documents

Factores de Sucesso na Implementação de Tecnologias PATmittic.gobex.es/upload/web/publico/03_uid2.Success_Factors_PAT_2… · Adapted from A.Hussain (FDA) Presentation at Pittcon