process analytical technique , pharmacy , quality assurance technique , QAT, Pharmaceutical quality, quality control.

1. PAT- PROCESS ANALYTICAL
TECHNIQUE
SALMAN LATIF
M PHARM QAT

2.  PAT is the system for designing, analyzing and
controlling the entire manufacturing process.
 It is kind of timely measurement used for critical
quality and performance of raw material and in
process material.
 Major area covered are:
1. Industrial Pharmacy.
2. Regulatory
3. Analysis
4. Manufacturing Science
5. Pharmacetical Engineering

3. DEFINITION
 System for designing, analyzing and controlling
manufacturing through timely measurement of
critical quality and performance attributes for raw and
in-process material with a goal of ensuring final
product quality.
 Quality cannot be tested in Final Product It
should be built in by design.
 It is scientific and risk based frame work.

4.  It helps manufacturing develop and implement
new efficient tools for use during pharmaceutical
development.
 There are two components:
Set of scientific principles and tools.
Strategy for regulatory
implementation that will
accommodate innovation

5. BACKGROUND
 Conventional manufacturing generally accomplished by
using batch process with laboratory testing conducted
on controlled samples to ensure quality to public.
 Today opportunities are available to improve the
efficiency of the pharmaceutical manufacturing and
quality assurance.
 Generally companies hesitate to implement new
technology because of scientific issues and sometimes
technology may be undesirable from public health
point of view.

6.  In future pharmacist will have prominent role in
health care sector.
 Industry will require cutting edge technology,
innovation, best engineering knowledge, good
quality management system to respond to
challenges.

7. PHARMACEUTICAL MANUFACTURING
DESIRES
1. Continuous and real time quality assurance.
2. Risk based regulatory approach.
3. Relevant regulatory policies.
4. Product quality and performance ensured through
design.
5. High level of understanding on how the
formulation and manufacturing process factors
affect product quality and performance.

8. GOALS
 Build quality into product.
 To enhance process safety.
 Reduce variation in process.
 Ensures understanding and control the manufacturing
process.
 Management of agency’s risk management and
quality system approach are incorporated into the
manufacturing of pharmaceutical while maintaining
product quality.
 Use latest scientific advances in manufacturing
technology.

9.  Resources are used effectively to reduce significant
health risk.
 The term “Analytical” in PAT- includes physical,
microbiological, mathematical and risk analysis
conducted in integrated manner.
 Goal is to understand and control manufacturing
process which is consistent with our current drug
quality system.
 Quality cannot be tested into final product it should
be built in or in design (QBD).

10.  QBD by understanding of :
1. Intended therapeutic objectives, patient population,
route of admin , pharmacology, toxicology and
pharmacokinetic character of drug.
2. Chemical, physical and bio-phramaceutics
characteristic of drug.
3. Selection of product components and packaging
based on drug attribute.
4. The design of manufacturing process using principle
of engineering, material science, QA to ensure
acceptable and reproducible product quality.

11. HOW PAT WORKS
ON-LINE TESTING/ IN-LINE TESTING.
DESIGNING OF PROCESS.
IDENTIFICATION OF CRITICAL CONTROL POINTS.
SELECTION OF SUITABLE PAT SYSTEM.
SELECTION OF PROCESS.

12. ADVANTAGES
1. Reduction in production time.
2. Prevent reprocessing and rejection.
3. Increase automation.
4. Improve operation safety.
5. Reduce human error in continuous process.
6. Controlling variability.
7. Continuous improvement.
8. Improving energy and material usage.

13. DISASVANTAGES
1. Requires efforts during design.
2. Specialized expert person required.
3. Maintenance cost Is high.
4. Costly.

14. PAT – TOOLS AND PRINCIPLE
 A manufacturing unit of operation is intended to modulate
certain process properties of material being processed to
ensure acceptable modulations.
 Consideration must be given to quality attributes of
incoming material and their process-ability for each unit
operation.
 Certain physical and chemical attributes are difficult to
characterize and has adverse effect causing variability.
 Eg: powder sampling procedures are prone to sampling
errors.

15.  Formulating design strategies exists that provide
robust process that are not affected by minor
differences in attribute of raw material.
 Based on the experience of a particular formulator
tests are performed offline after preparing and
collecting samples for analysis.
 Eg : content uniformity, moisture content,
dissolution, disintegration, colour, odor, taste etc.

16.  PAT tool are available that enables
scientific and risk management in
manufacturing and analysis.
 These tools when used in a system can
provide effective and efficient means for
acquiring information to facilitate process
understanding and risk management.
 Tools include…..

17. 1. MULTIVARIATED DATA ACQUISITION
AND ANALYSIS.
 Physical, chemical and biological analysis of
pharmaceutical product is a complex and multi-factorial
design.
 There are many different development strategies that
can be used to identify optimal formulation and process
condition.
 It includes:
1. Process analyzer.
2. Process monitoring.
3. Continuous improvement.

18. 2. PROCESS UNDERSTANDING
 A process is generally considered well understood when:
1. All critical sources of variability are identified and
explained.
2. Variability is managed by the process.
3. Product quality attribute can be accurately and reliable
predicted over the range of acceptance.
 Criteria established for materials used, process,
parameters and manufacturing environmental and
other condition.

19.  The ability to predict reflect a high degree of process
understanding.
 Although retrospective process capability data are
indicative of a state of control these alone may be
insufficient to gauge or communicate process
understanding.
 The emphasis on process understanding provides a
range of option for qualifying and justifying new
technologies such as modern on-line process analyzers
intended to measure and control physical or chemical
attributes of materials to achieve real time release.

20.  Eg: If process knowledge is not shared or
communicated when proposing new process
analyzers, the test to test comparison between on
line process analyzer (Eg: NIR Spectroscopy for
content uniformity) and a conventional test method
(Eg: A wet chemical test) on collected sample may be
the only available option.
 In some cases this approach may be to burdensome
and may discourage the use of some new
technologies (Eg: Use of acoustic measurement
patterns/ signature for process controls).

21.  An emphasis on process knowledge can provide
less burdensome approaches for validating new
technologies for their intended use.

22. 3. RISK BASED APPROACH
 Within an established quality system and for a
particular manufacturing process one would expect
on inverse relationship between the level of process
understanding and the risk of producing a poor
quality product.
 Level of inderstanding 

23.  For process that are well understood ,
opportunity exists to develop less restrictive
regulatory approaches to manage changes.
 This a focus on risk understanding can facilitate
risk based regulatory decision and innovation.
 This is currently under discussion as a part of the
broad FDA risk - based initiatives.

24. 4. Integrated System Approach
 The past pace of innovation in today’s information age
necessitates integrated system thinking for evaluating and
timely application of efficient tools and system that satisfy the
needs of patients and the industry.
 Many of the advance that have occurred and are anticipated
to occur are bringing the development, manufacturing, quality
assurance and information/ knowledge management function
so closely together that these four areas should be
coordinated in an integrated manner.

25.  Therefore, upper management support for
these initiatives is critical for successful
implementation.

26. 5. Real Time Release
 Real time release is the ability to evaluate and
ensures the acceptable quality of in-process and
final product based on process analytical data.
 Typically the PAT components of real time release
can include a validation combination of assed
material attributes (in-process product at final
process stage), process control, process end-point
and other critical process parameters.

27.  Material attributes can be assessed using direct or indirect
(Eg: Correlated) process analytical method.
 The combined process analytical measurements and other
test data gathered during the manufacturing process can
serve the basis for real time release of the final product and
would demonstrate that each batch confirms to establish
regulatory quality attributes.
 We consider real time release testing to be an example of
alternative analytical procedure for final product release.

28. PAT Regulatory Approach
 One goal of this guidance is to tailor the agency’s
usual regulatory scrutiny to meet the needs of PAT
based on innovation that :
1. Improve the scientific basis for establishing
regulatory specification.
2. Promote continuous improvement.
3. Improve manufacturing while maintaining and
improving the current level of product quality
assurance.

29.  To be able to do this manufacturers
should commun icate important scientific
knowledge to the agency and resolve
related technical issues in a timely manner.
 Our goal is to facilitate a flexible
regulatory assessment involving multiple
agency offices with varied responsibilities.

30. PAT Regulatory Guidance
 Regulatory agencies like US-FDA, ICH,ASTM etc.
who has been active in the areas of PAT in the
development of standards for use of PAT in
pharmaceutical industry internationally in their
standards committee E55.
 US-FDA was published PAT final guidance in SEP
2004.