This document discusses process validation for solid oral dosage forms such as tablets and capsules. It begins by defining process validation and outlining the types, including prospective, concurrent, and retrospective validation. For tablets, it covers validation of raw materials, analytical methods, equipment, and process parameters. For capsules, it discusses validation of the capsule composition, encapsulation process, and quality control tests. The conclusion emphasizes that validation ensures reproducibility and compliance.

2. CONTENT
1. Introduction
2. Types of process validation
3. Validation of tablet
4. Validation of capsule
5. Conclusion

3. INTRODUCTION
 Validation is one of the important steps in achieving and
maintaining the quality of the final product.
 If each step of production process is validated we can assure that
the final product is of the best quality.
 Validation of the individual steps of the processes is called the
process validation. Different dosage forms have different
validation protocols.
 Here this seminar concentrates on the process validation of solid
dosage forms.
 It gives in detail the validation of each step of the manufacturing
process of solid dosage forms

4. DEFINATION
 Validation is a key process for effective quality
assurance
 “Validation is establishing documented
evidence which provides a high degree of
assurances that a specific process or
equipment will consistently produce a product
or result meeting its predetermined
specifications and quality attributes

5.  Quality assurance: Validation checks the accuracy and
reliability of a system or a process to meet the predetermined
criteria. A successful validation provides high degree of
assurance that a consistent level of quality is maintained in
each unit of the finished product from one batch to another
batch.


6.  Economics: Due to successful validation, there
is a decrease in sampling and testing
procedures and there are less number of
product rejections and retesting. This leads to
cost-saving benefits.
 Compliance: For compliance to current good
manufacturing practices, validation is
essential.

7. TYPES OF PROCESS
VALIDATION
7
PROCESS
VALIDATION
RETROSPECTIVE
PROCESS
VALIDATION
PROSPECTIVE
PROCESS
VALIDATION
CONCRURRENT
PROCESS
VALIDATION

8. Types Of Process Validation
 Prospective validation: -
Conducted prior to market the product.
 Documented evidence which provides a high degree of assurances
that a specific process or equipment will consistently produce a
product meeting its predetermined specifications and quality
attributes.


9.  Concurrent validation:
Based on information generated during
actual implementation of the process.
 Establishing documented evidence that the
process is in a state of control during the
actual implementation of the process. This
normally performed by conducing in-
process testing.

10. Type of Process Validation
 Retrospective validation:
All the processes and subsystems should be validated
,which have been used for the production of batches of
numerical data of both process and the end product
testing of which are included in retrospective validation

11. PRODUCT VALIDATION
 Product validation involves following steps:
 Validation of raw materials and excipients.
 Analytical methods of validation.
 Equipment and facility validation .
 Process variables and limits.

12. VALIDATION OF RAW
MATERIALS AND EXCIPIENTS
 The validation process of solid dosage form begins with the
validation of raw materials , both API and excipients.
 Preformulation is one of the critical step to be validated in
product validation
 Physical characters such as drug and particle size can
affect material flow and blend uniformity.
 Chemical characters like impurities can effect stability of
drug.
 The hygroscopic nature is important in both handling and
reproducibility of the manufacturing process.

13. VALIDATION OF EXCIPIENTS
 Excipients can represent less then 1% of a tablet formula
 Factors to be aware of are
I. The grade and source of the excipients
II. Particle size and shape characteristics and
 Lot-to-lot variability
 Microcrystalline cellulose(MCC) used as diluents shows significant changes in the
chemical composition, crystalinity, particle size b/w different lots.
 Differences in particle size of MCC can effect wet granulation/blend uniformity
of tablet formulation.
 In direct compression formulations differences in particle size distribution b/w lots
can result in
 Non uniformity in initial mix
 Materials segregate during compression

14. ANALYTICAL METHODS
OF VALIDATION-
 Accuracy of method: Ability of a method to
measure the true value of a sample.
 Precision of method: Ability of a method to
estimate reproducibility of any given value.
 Specificity: Ability to accurately measure the
analyte in the presence of other components.
 Repeatability: Does the precision and
accuracy of the method change when
conducted numerous times on the same day
and repeated on a subsequent day?

15. ANALYTICAL METHOD
VALIDATION
 Reproducibility: Repeat the precision and
accuracy studies within the same lab using the
same instrument but different analysts to
challenge the reproducibility of the method.
 Precision: How will different instruments
within the same lab run by the same analyst
affect the accuracy and precision of the
method.
 Ruggedness: Will the precision and accuracy
of the method be same between the
development and quality control lab

16. EQUIPMENT VALIDATION

17. EQUIPMENT VALIDATION
 This can be divided into
1. Design qualification
2. Installation qualification
3. Operation qualification
4. Performance qualification
5. Maintaince (calibration, cleaning, repair) qualification

18. QUALIFICATION AND PROCESS VALIDATION
Design or Development of Equipment, System, or Product
Installation Qualification
Operational Qualification
Process Performance Qualification
or Process Validation
Change Control

19. PHASES OF VALIDATION-
 Design qualification (DQ): Documented
verification of the design of equipment and
manufacturing facilities.
 Installation qualification (IQ): Documented
verification of the system design and adherence
to manufacturer’s recommendations.
 Operational qualification (OQ): Documented
verification of equipment or system
performance in the target operating range.

20. PROCESS PERFORMANCE
QUALIFICATION (PQ):
 Documented verification that equipment
system operates as expected under routine
production conditions.
 The operation is reproducible, reliable and in a
state of control .

21. EQUIPMENT VALIDATION
Design and
development of
equipment system,
or product
Installation
qualification
Operational
qualification
Process
performance
qualification
Change control

22. VALIDATION PROCESS FLOW
CHART
Revalidation
Validation Report and Sign-Off
Data Analysis
Protocol Execution
Validation Protocol- Review and Approval
Validation Protocol – Preparation
Pre-Validation Activities
22

24. CAPSULE COMPOSITION-
 Capsule shell provide :
 The reason for the presence of each ingredient in the
capsule formulae.
 Justify the level and grade of each ingredient .
 Explain the selection of the capsule size and shape
 Discuss the need for capsule identification(color).

25.  Capsule shell contents-
 Establish the compatibility of the capsule shell and the
capsule contents.
 Determine the hygroscopic nature of the capsule
formulation
 For example : A hygroscopic formulation(API
/excipients)can pull water from the capsule shell, which
could effect the API stability.

26. PROCESS EVALUATION AND
SELECTION
 The process to manufacture the contents of a
hard gelatin capsule is the same as the tablet.
 It may required only a blending step, such as a
direct compression tablet, or several unit
operations, such as a wet granulation tablet
(e.g. mixing, wet milling, drying, dry milling
and blending).
 In either case, the materials are then
encapsulated in a capsule shell.

27. ENCAPSULATION SPEED
 The formulation should be encapsulated at a wide
range of speeds to determine the operating range of the
encapsulation.

28. ENCAPSULATION
 Encapsulation is a critical step in the
production of capsules, similar to the
compression for tablet dosage forms.
 The materials to be encapsulated will need to
have good flow properties and a consistent
density.

29. QUALITY CONTROL TESTS
ARE DIVIDED INTO
 PHYSICAL TEST
 Disintegration test
 Weight variation
 CHEMICAL TEST
 Dissolution test
 Assay
 Content uniformity
 Stability testing Moisture permeation test

30. CONCLUSION
 Solid dosage form validation should be part of
comprehensive validation program within an
industry.
 The multidisplinary validation team must identify
the product and process characteristics that must
be studied and incorporate specific validation tests
to ensure that product will meet all quality,
manufacturing and regulatory requirements.
 Continuous awareness of validation will produce
reproducibility.

31. REFERENCES
1. http//www.pharmainfo.net/reviews/guidelines-general-
principles-validation-solid-dosage.
2. www.google.com
3. Mervyn.J, Venketachallam.V.V, Hard gelatin capsules A
formulation design perspective and evaluation, Int J of
Chem and Pharma Sci,2014;5(3):129-135.
4. Elsie.J, Review article:An Overview of Pharmaceutical
Validation and Process Controls in Drug Development
Tropical J of Pharm Res, 2002; 1 (2):115-122.

32. 5. Lakshmana P, Suriyaprakash.T,Concepts of Process Validation in
Solid Dosage Form Capsule,An Overview,2012;(1):1-12.
6. Aleem.H, Zhao.Y, Lord.S, Pharmaceutical process validation: an
overview. J of Process Mech Engg,2013;(217):141-51.
7. Ahir KB, Singh KD, Yadav SP, Patel HS, Poyahari CB (2014)
Overview of Validation and Basic Concepts of Process
Validation. Scholars Academic Journal of Pharmacy 3: 178-190.
8. www.pischeme.org
9. www.fda.gov/cder/guidance/pv.html.