PROCESS VALIDATION For development of TABLETs

A Seminar On
PROCESS VALIDATION FOR DEVELOPMENT
OF TABLETS
Presented By:
Mr. Balu .S . Khandare
M. Pharm(PQA) Sem II
Roll No.523
Guided By:
Mr. P.B. Dudhe
(Assistant Professor)
Sinhgad College of Pharmacy, Vadgaon(Bk.), Pune-411041.
2017-2018

Mr.Balu.S.Khandare
 Contents
INTRODUCTION
DEFINITION
CONCEPT OF PROCESS VALIDATION
REASONS FOR PROCESS VALIDATION
IMPORTANCE OF PROCESS VALIDATION
TYPES OF PROCESS VALIDATION
STEPS INVOLVING IN VALIDATION
CASE STUDY
CONCLUSION
REFERENCES
210-Sep-18

Mr.Balu.S.Khandare
 Introduction
• Validation is a concept that has been evolving continuously
since its first formal appearance in the United States in 1978.
• The concept of validation has expanded through the years to
doing a wide range of activities from analytical methods
used for the quality control of the drug products.
• Process validation data provides high degree of assurance
that manufacturing process produces the product meeting its
predetermined specifications and quality attributes.
Nash, R.A. and Wachter, A.H., 2003. Pharmaceutical Process Validation, Vol. 129, An International 3rd Edition, Revised and Expanded.p.159
310-Sep-18

Mr.Balu.S.Khandare
To establish that the process equipment has the capability of
operating within required parameters for tablet manufacturing.
To demonstrate that controlling, monitoring, and measuring
equipment and instrumentation are capable of operating within the
parameters prescribed for the process equipment.
To monitor the validated process during routine operation. As
needed, requalify and recertify the equipment.
Objectives of Process Validation
Potdar , M. A ., Pharmaceutical Quality Assurance,(2007). nirali Prakashan, pp.6-7.
410-Sep-18

Mr.Balu.S.Khandare
“Process validation is defined as the collection & evaluation of data,
from the process design stage through commercial production,
which establishes scientific evidence that process is capable of
consistently delivering quality product.”
Definition
510-Sep-18

Mr.Balu.S.Khandare
 General Concept
Quality of product is derived from careful attention to number
of factors including selection of quality parts and materials such
as,
• Adequate product
• Process design
• Control of the process
• In-process and end product testing
610-Sep-18

Mr.Balu.S.Khandare
Quality assurance:
 Product quality cannot be assured for a process by routine
quality control testing because of the limitation of statistical
sampling.
 Validation changes the adequacy and reliability of a system or
process to meet predetermined criteria.
Economics:
 The direct economic benefit of validation is a reduction in the
cost associated with process monitoring, sampling and testing.
 In addition reduces product complaints and potential product
recalls would be minimized.
Compliance:
 Written procedures and process controls be established to assure
that the drug products have the “identity, strength, quality and
purity” .
 Reasons for Process Validations
Nash, R.A. and Wachter, A.H., 2003. Pharmaceutical Process Validation, Vol. 129, An International 3rd Edition, Revised and Expanded.p.159 710-Sep-18

Mr.Balu.S.Khandare
 Importance of Process Validation
The pharmaceutical industries are concerned about validation
because of the following importance.
 Assurance of quality
 Cost reduction
 Regulatory Compliance
 Process Optimization

Mr.Balu.S.Khandare
Assurance of Quality
• Consistent and Producible Quality • Minimize Product Liability Risk
• Minimize Complaints
World Health Organization, 2007. Quality assurance of pharmaceuticals: A compendium of guidelines and related materials. Good manufacturing practices and
inspection (Vol. 2). World Health Organization.
910-Sep-18

Mr.Balu.S.Khandare
COST REDUCTION
REDUCTION
OF
QUALITY
COSTS
Reduce unit cost of
tablet
 Fewer rejects
Fewer re-test
Maximize yields
 Fewer rework
Fewer wastage/scrap
1010-Sep-18

Mr.Balu.S.Khandare
Process Optimization
Process start-up time
Optimum batch size
Reduced processing timeDecreased downtimes
1110-Sep-18

Mr.Balu.S.Khandare
1210-Sep-18

Mr.Balu.S.Khandare
 The Types of process validation
1. Prospective validation
2. Retrospective validation
3. Concurrent validation
4. Revalidation

Mr.Balu.S.Khandare
Prospective validation
 The establishment of documented evidence that a system does
what it purports to do based on pre-planned protocol. This
validation is usually carried out prior to the introduction of new
drugs and their manufacturing process.
 This approach to validation is normally undertaken whenever a
new formula, process or facility must be validated before routine
pharmaceutical formulation commences.
QC + IPQC = PRODUCT QUALITY
BEFORE
PV + QC + IPQC = ASSURED PRODUCT QUALITY
NOW

Mr.Balu.S.Khandare
Retrospective validation
 The establishment of documented evidence that a system does
what it purports to do based on review and analysis of
historical data.
 This is achieved by the review of the historical manufacturing
testing data to prove that the process has always remained in
control.
FEATURES
Make good quality of
products
Use of
Historical data
RESTROSPECTIVE VALIDATION
1510-Sep-18

Mr.Balu.S.Khandare
Concurrent validation
 It is similar to prospective, except the operating firm will sell
the product during the qualification runs, to the public at its
market price.
 This validation involves in process monitoring of critical
control points and product testing.
1610-Sep-18

Mr.Balu.S.Khandare
Revalidation
It is the repetition of a validation process or a specific part of
it. This is carried out when there is any change or replacement in
formulation, equipment, plant or site location, batch size and in the
case of sequential batches that do not meet product and process
specifications.
1710-Sep-18

Mr.Balu.S.Khandare
• Developing process validation protocol
• Conduct installation qualification
• Conduct operational qualification
• Conduct performance qualification
• Analysed results and reach conclusion
Steps in Validating a Process
Alam , M.S. and Ahmad, J., 2013. Pharmaceutical technology transfer: an overview. International Journal of Pharmaceutical Sciences and Research, 4(7), p.2441.
18
10-Sep-18

Mr.Balu.S.Khandare
A document stating how process validation will be
conducted, including test parameters, product characteristics,
manufacturing equipment and decision points on what constitutes
acceptable test results.
1. General information
2. Objective
3. Background / Pre validation activities
4. List of equipment and their qualification status
5. Facilities qualification
6. Process flow chart
7. Manufacturing procedure narrative
8. List of critical processing parameters and critical excipients
9. Sampling, tests and specifications
10. Acceptance criteria.
Process Validation Protocol:
Alam , M.S. and Ahmad, J., 2013. Pharmaceutical technology transfer: an overview. International Journal of Pharmaceutical Sciences and Research, 4(7),
p.2441.
1910-Sep-18

Mr.Balu.S.Khandare
Qualification:
Action of proving and documenting that any premises, systems
and equipment are properly installed, work correctly and lead to
the expected results.
• Design qualification (DQ):
Documented evidence that the premises, supporting utilities,
equipment and processes have been designed in accordance with
the requirements of GMP.
• Installation qualification (IQ):
IQ is the documentary evidence which performs tests to ensure
that the installations such as machines, measuring devices, utilities
and manufacturing process are appropriately selected and correctly
installed and operate in accordance with established specifications.
2010-Sep-18

Mr.Balu.S.Khandare
• Performance qualification :
PQ is the documentary evidence which verifies that the equipment
or system operates constantly and gives reproducibility within defined
specification and parameters for prolonged periods.
• Process performance qualification:
Establishing documented evidence that the process is effective and
reproducible.
• Operational qualification (OQ):
OQ is the documentary evidence to verify that the equipment
operates in accordance with its design specifications.
2110-Sep-18

Mr.Balu.S.Khandare
Responsibilities
Technology
transfer
To prepare, review and approve the process validation protocol
and report.
R&D To provide necessary product information and technical support.
Production
Execution of manufacturing process during validation. Review and
approval of process validation protocol and report.
Analytical
development
To develop and perform analytical method validation.
Quality Control To analyse validation samples and review of analytical report.
Regulatory affairs To review protocol and report from regulatory perspective.
Quality assurance
To monitor the validation activity and sampling as per sampling
plan of protocol. Review and approval of process validation
protocol and report.
Kaur, H., Singh, G. and Seth, N., 2013. Pharmaceutical Process Validation: A Review. Journal of Drug Delivery and Therapeutics, 3(4), pp.189-194.
2210-Sep-18

Mr.Balu.S.Khandare
PQ
OQ
IQ
User
Specification
Functional
Specification
Design
Specification
D
E
S
I
G
N
Q
U
A
L
I
F
I
C
A
T
I
O
N
Is based on
Is based on
Implementation of QUALITY
Validation V-model
Is based on
Alam , M.S. and Ahmad, J., 2013. Pharmaceutical technology transfer: an overview. International Journal of Pharmaceutical Sciences and Research, 4(7), p.2441. 2310-Sep-18

Mr.Balu.S.Khandare
STAGES OF PROCESS VALIDATION
2410-Sep-18

Mr.Balu.S.Khandare
Process design:
To ‘design a process suitable for routine commercial
manufacturing that can consistently deliver a product that meets its
critical quality attributes (CQAs)'.
The guidance again makes reference to ICH Q10 in Pharmaceutical
Quality Systems .
Process qualification:
(a) Design of a facility , qualification of utilities and equipment-
‘Activities undertaken to demonstrate that utilities and pieces of
equipment are suitable for their intended use and perform properly is
referred to in this guidance as qualification’.
(b) Performance qualification-
‘Confirm the process design and demonstrate that the commercial
manufacturing process performs as expected’.
2510-Sep-18

Mr.Balu.S.Khandare
Continuous process verification:
“Continually assure that the process remains in a state of control
(the validated state) during commercial manufacture.”
This will require robust systems for detecting unplanned
departures from the designed process and a strong statistically
trended data which is reviewed in a timely manner by trained
personnel.
2610-Sep-18

Mr.Balu.S.Khandare
Process overview:
Jena, S., Arjun, G., Kumar, D.S., Vinod, K.R. and Banji, D., 2010. Industrial process validation of solid dosage forms-An overview. Int J Pharm Sci
Rev Res, 4(2), pp.145-54.
2710-Sep-18
Dispensing

Mr.Balu.S.Khandare
1
35
4
2
6
TABLET
PROCESS FLOW
CHART
Jena, S., Arjun, G., Kumar, D.S., Vinod, K.R. and Banji, D., 2010. Industrial process validation of solid dosage forms-An overview. Int J Pharm Sci Rev Res, 4(2),
pp.145-54.
2810-Sep-18

Mr.Balu.S.Khandare
 Some parameter are to be checked in process
validation for development of tablets.
• Blending
• Compression
• Coating
• Appearance
• Group weight
variation
• Individual weight
variation
• Thickness
• Hardness
• Friability
• Disintegration
• Content Uniformity RSD
• Dissolution
Gupta, S., Saini, S., Singh, G. and Rana, A.C., 2012. Industrial Process validation of tablet dosage form: An overview. International Research Journal of Pharmacy, 3(3). 2910-Sep-18

Mr.Balu.S.Khandare
Gupta, S., Saini, S., Singh, G. and Rana, A.C., 2012. Industrial Process validation of tablet dosage form: An overview. International Research Journal of Pharmacy, 3(3).
3010-Sep-18

Mr.Balu.S.Khandare
Nifedipine Film Coated Tablet
 Case Study – Nifedipine Film Coated Tablet
dimethyl 2,6-dimethyl-4-(2-
nitrophenyl)-1,4-dihydropyridine-3,5-
dicarboxylate
Calcium ion influx inhibitor (slow-channel blocker
or calcium ion antagonist) which inhibits the
transmembrane influx of calcium ions into
vascular smooth muscle and cardiac muscle.
Structure
Chemical Name
Category
Patel, N., Vaghasiya, J., Patel, P. and Panchal, K., 2013. Process Validation of Nifedipine Film Coated Tablet. Pharmagene, 1(2), pp.25-31.
3110-Sep-18

Mr.Balu.S.Khandare
Materials and Method; Table 1&2
10-Sep-18 Patel, N., Vaghasiya, J., Patel, P. and Panchal, K., 2013. Process Validation of Nifedipine Film Coated Tablet. Pharmagene, 1(2), pp.25-31. 32

Mr.Balu.S.Khandare
Dry mixing
Blender RPM : 80 RPM
Blender load : 34.875 kg
Variables Considerable For Study : Blending Time
Time Intervals Studied : 18, 20 & 23 Min
Acceptance Criteria : 100±15% (RSD NMT 6.0%)
Measured Response : Content Uniformity And RSD
Batches Taken For Study : A, B & C
3310-Sep-18

Mr.Balu.S.Khandare
Table 3: Dry mixing process results
3410-Sep-18

Mr.Balu.S.Khandare
Fluidized Bed Dryer
Table 4: Drying stage results
Patel, N., Vaghasiya, J., Patel, P. and Panchal, K., 2013. Process Validation of Nifedipine Film Coated Tablet. Pharmagene, 1(2), pp.25-31. 3510-Sep-18

Mr.Balu.S.Khandare
Table 5: Results of compression process
3610-Sep-18

Mr.Balu.S.Khandare
Table 6:Results of coating stage
3710-Sep-18

Mr.Balu.S.Khandare
 Result
• The concurrent process validation of Nifedipine film coated
tablet has been performed for three batches (batch A, batch B,
batch C) and all the parameters and results were found within
the acceptance limit.
• Based on the results of the validation data for three batches, it
was concluded that the manufacturing process used for
formulation of Nifedipine film coated tablet will consistently
producing the stable product meeting its predetermined
specifications and quality attributes.
.
3810-Sep-18

Mr.Balu.S.Khandare
 Conclusion
• Process Validation is the commonest word in the areas of drug
development, for manufacturing and specification of finished
products of tablets.
• It also renders reduction in the cost linked with process
monitoring, sampling and testing of tablets.
• Pharmaceutical process validation and process control variables
of tablets manufacturing processes in industry and it is the full
fledged quality attributing tool for the pharmaceutical
industries.
• Nowadays Validation is the art of designing and practicing the
designed steps together with the documentation in
pharmaceutical industry .
• Process validation in solid dosage form is a systematic approach in
identifying, measuring, evaluating, documenting and re-evaluating
the critical steps in the pharmaceutical solid dosage form
(TABLETS).
3910-Sep-18

Mr.Balu.S.Khandare
• Alam , M.S. and Ahmad, J., 2013. Pharmaceutical
technology transfer: an overview. International Journal of
Pharmaceutical Sciences and Research, 4(7), p.2441.
• Patel, N., Vaghasiya, J., Patel, P. and Panchal, K., 2013.
Process Validation of Nifedipine Film Coated
Tablet. Pharmagene, 1(2), pp.25-31.
 References
• Nash, R.A. and Wachter, A.H., 2003. Pharmaceutical Process
Validation, Vol. 129, An International 3rd Edition, Revised
and Expanded.p.159
• Potdar , M. A ., Pharmaceutical Quality Assurance,(2007). nirali
Prakashan, pp.6-7.
4010-Sep-18

Mr.Balu.S.Khandare
• Jena, S., Arjun, G., Kumar, D.S., Vinod, K.R. and Banji, D.,
2010. Industrial process validation of solid dosage forms-An
overview. Int J Pharm Sci Rev Res, 4(2), pp.145-54.
• Gupta, S., Saini, S., Singh, G. and Rana, A.C., 2012.
Industrial Process validation of tablet dosage form: An
overview. International Research Journal of Pharmacy, 3(3).
• Kaur, H., Singh, G. and Seth, N., 2013. Pharmaceutical
Process Validation: A Review. Journal of Drug Delivery and
Therapeutics, 3(4), pp.189-194.
• World Health Organization, 2007. Quality assurance of
pharmaceuticals: A compendium of guidelines and related
materials. Good manufacturing practices and inspection (Vol.
2). World Health Organization.
4110-Sep-18

Mr.Balu.S.Khandare
Thank You
Save the environment …..Go green!!!
10-09-2018 42

PROCESS VALIDATION For development of TABLETs

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