1. Process analytical technology (PAT) aims to improve understanding and control of pharmaceutical manufacturing processes through measurement of critical quality parameters during processing. 2. Conventional batch processing relies on final testing of samples, which risks discarding good batches if samples fail tests. PAT allows for continuous monitoring and adjustment to ensure consistent quality throughout production. 3. Key aspects of PAT include incorporating advanced sensors and instruments for online and inline measurements of critical attributes, linking these measurements to product quality through multivariate models, and using the enhanced process understanding to design control strategies and quality into the process from the start.

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Esha Bhavin Shah
Assistant Professor
Department of Pharmaceutical Chemistry and
Quality Assurance
Babaria Institute of Pharmacy
Bits Edu Campus
Email: eshahshah.bip@bitseducampus.ac.in

2. What is PAT??
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Shifting from validation to continuous
verification !!
Replacing the photograph with a
continuous video.
Esha B. Shah

4. Conventional pharmaceutical manufacturing is generally accomplished
using batch processing with final laboratory testing conducted on
representative samples to ensure quality of the product.
The problem with this type of approach is that if at final testing, the
product fails to pass the quality specifications ,the whole batch has to be
discarded incurring a huge loss.
 If a particular representative sample is not upto the quality
specification but the overall batch is good, in that case also the whole
batch will be discarded based on the result of the sample.
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5.  It may also happen that the representative samples passes the test
but the overall batch is of low quality and based on the result of the
test sample, product is released, only to be recalledlater from
the market.
Continued..
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6. PAT is an important part of a much broader and
risk based paradigm introduced by 21st century
current good manufacturing practices.
FDA has adopted a paradigm shift in its thinking as
it has made QbD compulsory.
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7. A system for :
Designing, analyzing,& controlling manufacturing
Timely measurements (i.e. during processing)
Critical quality and performance attributes
Raw and in-process materials
Processes
“Analytical” includes
integrated chemical ,physical,microbiological,mathematical
and risk analysis.
“TECHNOLOGY”=Innovation
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8. According to the FDA’s guideline, PAT can be defined as a
system for designing, analyzing, & controlling pharmaceutical
Manufacturing through the measurement of critical quality
and performance parameters.
The measurements performed on raw and in process
materials or process Parameters are intended to enhance
final product quality.
Focus of PAT is understanding and controlling the
manufacturing process.
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9. A process is well understood when:
all critical sources of variability are identified and
explained
variability is managed by the process
product quality attributes can be accurately and
reliably predicted.
Accurate and Reliable predictions reflect process
understanding
Process Understanding inversely proportional to risk.
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10. The goal of PAT is to enhance understanding and control of the manufacturing
process.
Allows more focus to be placed on relevant multi-factorial
relationships
- provides a basis for identifying and understanding relationships
among various critical formulation and process factors and for
developing effective risk mitigation strategies (e.g., product
specifications, process controls, training)
Quality cannot be tested into
products; it should be built-in
or should be by design.
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11. Aims to improve the understanding and control
of manufacturing processes
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12. Industrial pharmacy &
Pharmaceutical engineering
Regulatory reform
Process analytical chemistry Manufacturing Science
Multidisciplinary components of PAT in
Pharmaceutical manufacturing
PAT
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13.  PAC describes the science and technology associated with
displacement of laboratory-based measurements with sensors and
instrumentation positioned closer to the site of operation.
 5 eras of PAC:
Off line
At line
Online
Inline, and
Noninvasive
This describes the evolution of sensor technologies.
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PAT Sensors
Esha B. Shah

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15.  NIR spectroscopy enables simultaneous measurement of chemical
compounds and physical properties. Designed for process control, the
Sartorius PMD500 allows easy and flexible installation. For complex
analysis, the system sets a new standard using a unique combination
of NIR with UV-VIS and CCD imaging modules.
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16. PAT-7200 water proof pH/mV/conductivity/TDS/Salt/Temp pen
tester will measure liquid’s acidity and alkalinity, potential of
hydrogen commonly known as pH. pH is one of the most common
parameter measured and tested in a variety of industries ranging
from water and wastewater treatment, mining and mineral
processing, environmental monitoring, chemical production,
agriculture research and chemical production, life sciences
research, biochemical and pharmaceutical research, electronics
production to food processing.
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17. PAT
QbD
21st century
GMP’s
Goal:
Well controlled product
ICH: Q8 , Q9, Q10,Q11
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18. QbD (Quality by Design) means that product and
process performance characteristics are scientifically designed to
meet specific objectives, not merely empirically derived from
performance of test batches, by utilization of increasingly
sophisticated instruments and measurements.
PAT provides:
•Increased information on the process
•Continuous learning
•Identification of sources of variability
•Increased understanding of which process variables effect
critical product parameters
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19. PAT Evolution in Pharmaceutical
Manufacturing
Process Understanding
Quality By Design
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20. PROCESS UNDERSTANDING
As per PAT guidance, a process is considered well understood when:
1. All critical sources of variability are identified and explained.
2. Variability is managed by the process
3. Product quality attributes can be studied accurately & reliably
over the design space established for the materials used, process
parameters,manufacturing,environmental etc.
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21. Formulation & Process
Design
(CRITICAL ATTRIBUTES)
PAT sensor data
(e.g NIR)
Drug Product Performance
Attribute(e.g. Dissolution)
correlation
(e.g. calibration model)
PAT method
understanding
Causal link
Causal link
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Design space & Quality by Design
Process
Product Performance
Design space PAT
PAT provides Continuous “real
time” assurance of quality.
Design space sets boundaries for the
formulation & process variables so that
product quality & performance is
achieved.
Esha B. Shah

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Implications of PAT
Implications on Regulatory benefits
Implications on QA approach
Implications on industry benefits
Implications on process understanding
Impact on production related QA/QC
Esha B. Shah

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References:
1.Guidance for Industry. PAT — A Framework for Innovative Pharmaceutical
Development, Manufacturing, and Quality Assurance.
http://www.fda.gov/cder/guidance/6419fnl.htm
2.Weinberg Sandy “Process Analytical Technology-An Emergent Biomedical
Regulatory Methodology “
3.Schneidir Ray “Achieving Process Understanding –The foundation of strategic PAT
programmer”
4.Hussain Ajaz “The desired state :PAT and road to Enlightment”
5.Mollan Matthew and Lodaya Mayur “Continuous Processing In Pharmaceutical
Manufacturing”
6.Cox Shayne “Pharmaceutical Manufacturing Handbook Regulation and Quality”
7.Agalloco James and Carleton Fredrik “Validation of pharmaceutical Processes”.
8.“Pharmaceutical Quality Assurance & Management” Chapter 12,Pg 502-523
Esha B. Shah

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PLAN!
DESIGN!
MANAGE!
INCORPORATE NEW
TECHNOLOGICAL
INNOVATIONS!
CONTINOUS IMPROVEMENT!
Esha B. Shah

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