Rajpal et al Journal of Drug Delivery & Therapeutics.

2016; 6(4):79-87 79

Available online on 15.07.2016 at http://jddtonline.info

Journal of Drug Delivery and Therapeutics
An International Peer Reviewed Journal
Open access to Pharmaceutical and Medical research
© 2016, publisher and licensee JDDT, This is an Open Access article which permits unrestricted noncommercial use, provided the original
work is properly cited

REVIEW ARTICLE

BASIC CONCEPT OF PROCESS VALIDATION IN SOLID DOSAGE FORM (TABLET):

A REVIEW
Rajpal Govind,* Arya Rajeshwar Kamal Kant, Kunwar Nitin
Department of Pharmaceutical Sciences, Bhimtal Campus, Kumaun University Nainital, India
*Email of corresponding Author: [email protected]
Received 02 June 2016; Review Completed 30 June 2016; Accepted 30 June 2016, Available online 15 July 2016

ABSTRACT
Process validation is an essential component for the safety of drug product and also to maintain the quality of the product. Process
validation is the fundamental component for assuring the quality system used by pharmaceutical industries. Process validation is
the key element to assure the identity, purity, safety, efficacy and also maintaining the quality of final product. The Process
validation precisely focused on the aim, method of analysis, and knowledge. The Process validation establishes the flexibilities and
limitations which are faced during the manufacturing process; the variables are controlled for attaining the desired attributes,
which assures a consistency in quality of product throughout the product life. In this article an overview is given on process
validation with special reference to tablet.
Key-words: Process validation, good manufacturing practices (GMP), Critical Process Parameter

INTRODUCTION
The main aim of the designing a dosage form is to get approval from various regulatory bodies like USFDA
the predictable medicinal responses of the drug from and CGMPs, Validation can be for a process,
the dosage form. The product should be a quality equipment and analytical method.
product, the quality assessment is the most important
When we validate a set of all individual step of
part for any product, the product should confirm all the
manufacturing, this is known process validation.
criteria given in the pharmacopoeia; it should be
Process validation is assuring and documenting the
reproducible when manufactured in large scale. For the
process within their specified and designed criteria,
assurance of quality, there a lot of features are required,
therefore the manufactured product will meet its
which are related to chemical and physical stability of
predetermined criteria and quality attributes with
drug and formulation, preservation from microbial
reproducible and constant result2. In 1970’s FDA
contamination, content uniformity of drug and should
officials Ted Byers and Bud Loftus have given the
be well accepted by the physicians and patients1.
concept of validation for improving the quality of
Building quality in the product is a most convincing
pharmaceuticals. In present scenario, validation is the
concept, rather than testing the final product, quality
prerequisite for pharmaceutical industry which is much
cannot be assured by testing in-process or finished
talked subject and done by almost all pharmaceutical
product,2 therefore each and every step of product
companies.
manufacturing should be controlled to achieve the
predetermined design and quality attributes including A tablet comes under solid dosage forms. The
specification. Therefore each and every step should be manufacturing of solid dosage forms involves
performed and validated. extensive powder handling. A series of unit operation
are involved in manufacturing of tablet which include
Validation is essential part of good manufacturing
powder blending for content uniformity and converted
practices (GMP). Validation is therefore, an element of
into solid mass form either through wet granulation or
quality assurance which confirms the quality of
direct compression. Various unit operation are used
product, equipment, manufacturing steps, and
which include weighing, sieving, dry mixing/blending,
analytical test procedures.3 From the economic point of
wet mixing drying milling and sieving, blending,
view validation is very important it helps in decreasing
compression coating and packing. Therefore a lot of
the rejection and retesting, which minimized the waste
error may arise in each step, for minimizing those
and cost. Validation is prerequisite for product
errors, the process should be validated.

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Rajpal et al Journal of Drug Delivery & Therapeutics. 2016; 6(4):79-87 80

Definition of validation: Action of proving in 2. In general practice in pharmaceutical industries

accordance with the principles of Good Manufacturing first three batches which meet the set specification
Practice, that any procedure, process equipment, of product quality considered for prospective
material, activity, or system actually leads to the validation before marketing.
expected result4.
3. The process should include identification and
USFDA defined process validation as “A documented evaluation of individual steps, identification of
evidence which provides high degree of assurance that critical situations, design of trial plans and set of
a specific process will consistently produce a product priorities, performance of trial, recording result,
meeting its predetermined specification and quality assessment and evaluation of observed results.
characteristics”5.
Concurrent validation: A process can be monitored
We can perform the process validation:- by monitoring processing steps of a finished product or
the process validation is done in ongoing process. In
1. For new product in which trail batch, development
different batches the quality of product may vary.
batch are manufactured.
Some of the conditions are given here:
2. Products produced at the sending site or
1. If a prevalidated process is transferred to a third
transferred product
party contract manufacturer or shifting to any other
3. The original product before revalidation. manufacturing unit.
Why process validation is required? 6,7 2. If a product of different strength from a
prevalidated batch having the same ratio of
The process validation is very essential for
active/inactive ingredient is to be changed.
pharmaceutical industry. There are various reasons for
performing process validation, which include: 3. If a small volume batch is needed for production or
on market demand.
1. For New product or existing products if there are
any changes as per SUPAC. 4. In case of urgent supply is needed due to shortage.
2. If the manufacturing site is changed.
5. If there any deviation is arises the justification
3. If the batch size, equipment and the manufacturing
should be documented approved by validation team.
process of existing products is to be changed.
4. If the composition or components and critical 6. If any adverse reaction is seen in concurrent
control parameters are to be changed. validation a proper plan for handling of the marketed
5. If the vendor of API or critical excipient is to be product should be there.
changed.
7. The 3 consecutive batches are acceptable for study.
6. If the quality parameters shows any abnormality in
Annual Product Review (APR). Retrospective validation: Retrospective validation is
7. If there is trend of OOS or OOT is observed in next performed for a product already in the market, and it is
batches. based on the historical data to establish a process
validation. This may be performed for the old product
TYPES OF PROCESS VALIDATION 8,9
which was not prevalidated by the manufacturer earlier
1. Prospective validation and now to be validated to confirm the requirements of
2. Concurrent validation regulatory bodies. Some of the necessary components
3. Retrospective validation are given below:
4. Revalidation
a) Batch size/strength/manufacturing year/period.
Prospective validation
b) MMR and BPR documents.
The Prospective validation is executed before
c) A complete list of deviations and its rectification
commercialization of product, it is performed before or
measures and changes to manufacturing
during the development of either a new product or in
documents.
changing production process, the risk and errors that
may arise during production are check out, these d) Stability testing data of different batches.
changes may have a significant effect on the properties
e) All analytical method to be used.
of the product. It is a predetermined scientific approach
having a validation protocol which include steps of In retrospective validation 20 batches should be
process development, sampling plan, batch record, considered, if the batches are more than 20, the data
specifications for API/ excipient/packaging material, obtained from at least 20 last consecutive batches must
pilot runs, transfer of technology from scale-up to be taken and if batches are less than 20 all batches are
commercialized batch, list of all processes to be taken. This validation is rarely used nowadays because
performed with environmental controls like any existing product is not subjected to the prospective
temperature and humidity.8 validation. This is performed only for the audit
purpose. Rejected batches are not included in this
1. The validation batch size should be up to 10times
validation.
of the representative development batch.

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Rajpal et al Journal of Drug Delivery & Therapeutics. 2016; 6(4):79-87 81

Re-Validation: The need of re-validation is arises assurance is obtained during the routine production
when there is any critical process parameter, which is remains in a state of control.
formulation, packaging material, excipient, equipment
Second approach is recommended by ICH; according
and building is changed. If the product get failed to
to ICH guideline three things are considered, which
meet the specifications in batches, this require re-
include Pharmaceutical development (ICH Q8 (R2),
validation. Re-Validation becomes essential in some
Quality Risk Management (ICH Q9) and
condition; there few conditions are given below where
Pharmaceutical Quality System (ICH Q10).
re-validation is required.
According to ICH guideline the pharmaceutical
1. In case raw materials to be changed
development is done. During the development of a
(physicochemical properties that may affect the
product and its manufacturing process, information is
process or product).
generated from the scientific approaches and quality
2. In case the vendor of API/excipient/ packaging risk management. Pharmaceutical development (ICH
materials is to be changed. Q8) is done for the marketing application and can be
updated to support new information obtained over the
3. In case the packaging material is to be changed
lifecycle of a product. A complete knowledge of
(primary container/closure system).
product and manufacturing process is obtained for
4. In case the process variables are (e.g., mixing time, reviewers and inspectors. Pharmaceutical and
drying temp. and batch size) to be changed. manufacturing sciences give an idea about regulatory
flexibility. The regulatory flexibility is based on
5. If the equipment is to be changed (e.g. addition of
relevant scientific information. It is programmed that
automatic detection system).
the manufacturing process should provide a quality
6. If the plant/facility is to be changed. product with consistency in performance as determined
previously. The information which is obtained from
7. Variations revealed by trend analysis (e.g. process development studies and experiences, gives the
drifts). scientific understanding for establishing designing
APPROACHES FOR PROCESS VALIDATION space, criteria, and process controls. This Information
9.10.11,12 may be a used for the quality risk management (ICH
Q9). The quality cannot be tested into products.
In process validation a series of unit operations are Quality should be built in by design. The changes in
conducted throughout the lifecycle of the product and formulation and manufacturing process, at the time of
process. There different approaches are used in process development and lifecycle management may be used to
validation recommended by USFDA, ICH and CPV. get information and can be used to establish in space
There are three stages are recommended by USFDA in designing. From the experiments and unexpected
process validation.9 results, the relevant information is obtained which
Stage 1–Process Design: In process design the should be included. According to this guideline, to
manufacturing process for commercialization is understand the role and impact of attributes and
defined on the basis of previous knowledge of parameter on product or in- process material, all
development and scale-up activities. attributes and parameter should be checked and re-
evaluated to make new information. Those attributes
Stage 2–Process Qualification: In process tell about the degree of control on risk to the process
qualification the capability of producing reproducible and output, the higher degree of control is appropriate
results on commercialization of manufacturing process for attributes that pose higher risk. Pharmaceutical
is determined by evaluating process design. Quality System ICH (Q10) is the management
Stage 3–Continued Process Verification: In responsibility; it is used to prepare quality policy,
continuous process verification the concurrent quality planning and resource management.

ICH Q10
Pharmaceutical
Quality System

ICHQ8 ICH Q9
Pharmaceutical Quality Risk
Development Management

Figure 1: showing relationship between Q8, Q9 and Q10

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Rajpal et al Journal of Drug Delivery & Therapeutics. 2016; 6(4):79-87 82

Continuous Process Verification is an alternative and their respective control limits which will also
approach to the traditional validation, where the affect the quality and consistency of product
manufacturing process is continuously monitored and (outcomes/attribute). A brief discussion on fish bone
tested, this is science and risk based on real time diagram and constrain analysis will be relevant here.
approach to verify and demonstrate that a process that
operates within the predefined specified parameters
consistently produce material which meet all its critical 1. Fish bone diagram9
quality attributes and quality strategy requirements. It
Let us consider a tablet manufacturing process, all the
is recommended that the industry should perform
suitable in-line or at-line controls and the performance steps are as follows:
and quality of product monitored regularly. 1. Preblending (Mixing of API and excipient)
1. The quality attributes of raw material or in-process 2. Granulation
and finished material should be collected,
including verification of attributes, parameters, 3. Drying
and end point, the CQA and the critical process 4. Milling
parameters should be assessed.
5. Blending
2. Process analytical technology application like NIR
spectroscopy with or without feedback loop(e.g. 6. Compression
end point determination, blend uniformity, granule Step1: Preblending: The factor could influence the
surface area, assay) and multiple statistical process preblending processes are:
control can also view for continuous process
verification validation a) Speed of Propeller/blades

Identification of Critical Process Parameter9 b) Load in the mass mixer

The critical process parameters are identified with the c) Total mixing Time
help of process capability. Process capability is defined Step 2- Granulation: The factors which could
as the studies to determine critical process parameters influence the granulation process are:
or operating variables which influences the process
output and also the range of numerical data. These a) Load of mixture
studies result in acceptable output. For manufacturing b) Rate of oscillation/ rotation
of any dosage form certain process is used and some
process capability qualification is considered as given c) Speed
below: d) Time
1. Specification, testing methods and acceptance Step 3: Drying: The factors which could influence the
criteria related to raw materials drying are:
2. The basic rational for using excipients a) Temp
3. Quantitative formula of final product b) Size for drying
4. Specification, testing methods and acceptance c) Time for drying
criteria related finished product
Step 4: Milling: The factors which could influence the
5. Details of instrument and apparatus to be used for Milling are:
preparing a batch size in 10time multiplication.
a) Mesh size of screen
6. The stability reports of finished product.
b) Speed of oscillation/rotation
7. Process Flow diagram showing details of each
stage in logical manner with excipient added, Step5: Mixing/ lubrication
control variable, major equipment and test a) Load in blender
parameters for each process variable.
b) Speed of rotation
For finding out the critical process parameters the
study of process characterization and process ranging c) Time
with performance qualification is done. In process Compression
characterization different methods are used to find out
critical parameter process or test parameter include a) Force of die
cause and effect shown by fish bone diagram,
b) Speed of machine
constraint analysis Pareto principle etc, process ranging
is the study to find out critical process or test parameter All the factors can be shown by fish bone diagram

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Rajpal et al Journal of Drug Delivery & Therapeutics. 2016; 6(4):79-87 83

Pre-blending Drying Blending

speed- - load -temp - load -speed

time - - size - time -time
time- -speed force-

Granulation Sizing Compression

Figure 2: Process flow diagram for process validation of tablet

This diagram shows the relationship and method is made available to the plant or not before
interrelationship which may exist between various performing validation testing and routine testing; with
process variable and single response i.e. product QC/QA. The designee also prepares the production
attributes. The centre line of fish bone diagram is records of Commercial/ exhibit batch, including control
composite of all factors which may affect the quality and operational limits and plan for process control
and consistency of all finished product. The branches of based on development report. Then process validation is
central line show the influence of process steps. The conducted after validating the facilities, utilities, and
process variables for each step which can cause the equipment, and laboratory test methods and released for
variation in the final product have been shown as process validation activities. Where compendia method
subbranches. When the experimentation is done the is used only limited analytical method validation shall
variables are varied within the operational range and the be conducted. The specifications of raw materials and
results are evaluated, if the result have no significant packaging materials should be approved by QC and
deviation the variable are called non critical. vendor. The equipments and instruments should be
calibrated. All the SOPs should be placed properly. The
(ii) Constraint Analysis: If we dealing with various
training should be given to the worker regarding the
variables, problems can arise there, constraints analysis
equipments, operations, manufacturing instruction and
aimed at limiting the operational range of each process
sampling plan.
variable and or specification limits.
Steps in Process Validation13
The constraint analysis the information obtained from
previous work and experiment regarding the process, Step 1: Identification of critical parameters of major
equipment, raw material and packaging vendors or the processes to be validated.
published literature is used. 9
Step 2: Identify the methodology, processes, and piece
(iii) The Pareto Principle: Pareto has given a 20-80 of equipment that will be used in the manufacture of the
rule according which 80% of variation in a statistical products.
sample is caused by 20% input variable. Means if we
Step 3: Identify the potentially relevant and critical
get 80% deviation in final result this is caused by only
process variables.
20% of process variables.9
Step 4: Conduct process validation experiments.
PREREQUISITE OF PROCESS VALIDATION 7
Step 5: Review product performance against the
Prior to initiating validation studies, and it is necessary
proposed specification. After describing the quality
to assure that the equipment to be used in validation is
features, which must be achieved in the product and the
functioning properly and working within the given
minimum acceptable values of each feature, the
range. The equipment should comply the qualification,
specifications developed for the product should be
according to WHO GMP. The validation qualification
reviewed.
should be established and documented. The process
development designer reviews the design qualification Step 6: Monitor and review the results of the validation
(DQ) of premises, utilities and process according to experiments. Validation report will be prepared.
GMP. He also reviews weather the utilities and Optimized values of process variables will be assigned
equipment are installed according to Installation based on those validations experiments for subsequent
qualification IQ and performing according to their running production which will give the confidence that
performance qualification (PQ) or operating according the each unit operations/sub processes will lead to
to their operational qualification (OQ). He also reviews produce products of pre-defined quality consistently
the reports of product development, pilot scale, scale up over time.
batch, the proposed master formula of product to be
manufactured. He also confirms that the analytical

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Rajpal et al Journal of Drug Delivery & Therapeutics. 2016; 6(4):79-87 84

Validation Protocol 9 schedules, process variable, change control, analytical

method to be used, acceptance criteria, references and
For performing the process validations the detailed
validation option (prospective, concurrent and
protocols are required for ensuring that the process is
retrospective validations as well as revalidation). The
been adequately validated. The protocol should contain
information not to be repeated documented elsewhere
the following components:
but should refer to existing documents such as policy
1. The purpose and scope of the validation. documents, SOP’s and validation protocols and reports.
2. Validation team with their qualifications and
The format and content should include:
responsibilities.
3. Type of validation: Prospective, Concurrent, 1. Introduction: Scope of validation,
Retrospective, Re-validation.
2. Validation policies of manufacturer, aimed to
4. Total Number batches should be validated.
implementation of GMP requirement in the country
5. A complete list of equipments and apparatus to be
where the plant is located or countries where the
used; with their parameters.
product is to be exported.
6. Installation Qualification and Operation
Qualification of equipments. 3. Organizational structure of all activities including
7. The calibration criteria for all instruments. personnel responsibility, validation protocol, validation
8. All possible critical process parameters with their work, document preparation, reports, approval at every
criteria. step and training.
9. All the process variables/ attributes with their risk
4. Extent of validation required (IQ,OQ and or PQ)
and management should be given.
10. Production related all processing details should be 5. Re-validation frequencies
clearly described in the form of master documents.
11. Sampling schedule with all details of sampling 6. Summary of facilities, list of equipments and
points, methods and sampling plans. complete description of process.
12. Statistical tools to be used in the analysis of data. 7. Complete description of product
13. Training schedule for operators.
14. Validated test methods to be used in in-process 8. Specific process considerations that are critical and
testing and for the finished product. those requiring extra attention.
15. Specifications for raw and packaging materials and 9. Re-validation activities, actual status and future
test methods. planning.
16. All performs for documenting the results,
conclusions and for approval of study results 10. Method of analysis and acceptance criteria
should be given. 11. Documentation format.
12. References existing document
Organization for validation and its duties 13. List of all relevant SOPs.
Validation is responsibility of an organization, various 14. Time plans of each validation project and sub-
department are engaged in this organization the team project.
member are selected from R and D, production, QC,
QA engineering and validation expert who can head this
organization. The job of his team/organization is Sampling Schedule for Validation 14,15
preparation of V M P, designing and implementation of
validation procedures as per validation protocol, For validation, a detailed sampling Schedule or plan is
coordination with equipment vendors and assist in required, which contain an idea about the sampling
process fabrication and prepare appropriate reports for pattern, sampling time, method of analysis and also the
approvals, identification of turnover of validated monitory method.
systems and process, preparation of project schedules a) This plan contains a detail about sampling point,
and implement protocols for validation, development of total no. of sample to be taken; sampling frequency
test method, conducting calibration on validation test at every unit operation, these are decided on basis
equipments and processes and also preparation of of properties of product and equipments used in
reports to submit to management. validation.
b) Appropriate no. the samples should be there.
Validation Master Plan13 c) At least 3 samples from each sampling point should
The WHO GMP explains that all the content of be withdrawn for the statistical confidence of
validation program should be clearly mentioned and quality both within a batch and between batches.
documented in validation master plans, it is an d) In case of blend sample on case to case basis,
internally approved plan, which include validation sampling size can be increased from 1to10 time As
policies, structure of organization, summary of facilities per USFDA, which provided on scientifically
like list of equipments to be used, steps used in justified.
validation, formats for documentation, sampling

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Rajpal et al Journal of Drug Delivery & Therapeutics. 2016; 6(4):79-87 85

e) The location from where the samples to be prepared on basis the results obtained from study
withdrawn from any equipment should be clearly conducted as per approved validation protocol.
indicated with the help of diagram.
Basic Steps for validation and acceptance criteria for
Acceptance Criteria tablet16
The acceptance criteria are the parameter that clearly While performing the validation of tablet dosage form
defines the activity and limits of acceptance. The we have to first know all the steps, equipment,
acceptance criteria are the specification given in official apparatus used with their process variables, assessment
books like IP/USP. The test results obtained from parameter and acceptance criteria involved in
validation studies evaluated against the acceptance validation. The all above stated things are performed
criteria or specifications, the conformance is discussed accordingly and the data are recorded. Here all possible
to support the validation activities. The all results are processing steps, assessment parameter and acceptance
evaluated for consistency and reproducibility and meet criteria are given in tabular form to understand how the
with predetermined attributes. A validation report is validation is performed.

Table 1: Steps involved in validation and acceptance criteria for tablet

S. Steps Control variable Assessment parameter Acceptance criteria

N.
1 Shifting Mesh size 1.Material retention Entire material should pass
2. Sieve integrity (before and after) through specified mesh
Sieve should be intact
without any damage
2 Dry Mixing Time Blend uniformity The individual result
Mass mixture/ should be in the limit as
RMG specified in monograph
Impeller/chopper speed Slow/medium/high For information only
3 Binder Mixing time Check the Consistency Color of For information only
Preparation Temp. Solvent used binder
4 Binder Addition Mixing time, Impeller Check the consistency of wet mass For information only
speed
5 Granulation Mixing time Slow/medium/high For information only
Mass mixture or Impeller speed Slow/medium/high For information only
RMG Impeller load For information only
6 Wet Milling Time, speed, load Sieve integrity (before and after) Sieve should be intact
Multi-mill without any damage
7 Drying Time and Temp. Inlet/outlet/ Temp./LOD Moisture content
Tray dryer/FBD
8 Sifting And Mesh size Particles size Sieve should be intact
Milling without any damage
9 Lubrication Time and Speed Blend uniformity, Bulk density, As specified in reference
(Slow/medium/high) tapped density, Hausner ratio, book (IP/USP)
Compressiblity index, assay
10 Compression Speed pressure Av. Wt , Thickness, Hardness, D.T As specified in reference
Slow/medium/high Friability, assay, Dissolution book (IP/USP)
11 Packing Forming pressure, Leak test, Label matter, Stereo, As per specification
Sealing Temp, Forming impression, Defected
Temp, Machine speed Yield at packaging stage

Failure and Deviation 11 Suspension of the process validation exercise until

further technical evaluation and/or development has
In process validation test has been performed to
been carried out, sampling regime, analytical procedure
determine failure and deviation. There should not any
and process validation acceptance criteria can be
case of failure. The procedure should cover all the
changed.
possible areas of potential failure. The validation study
gives an idea on the action to be done, recording its Final Process Validation Report 15
justification and recommendations. This decision
A document in which the records, results and
consider: if the analytical results are not within limit,
evaluation of a completed validation programmer are
retesting is required. The operation parameters, process
assembled and summarized. It may also contain
steps, equipment, procedure may be changed.

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Rajpal et al Journal of Drug Delivery & Therapeutics. 2016; 6(4):79-87 86

proposal for improvement of process. At the preventive maintenance, calibration and sanitation cost.
conclusion of validation activities, a final report should The Appraisal cost include inspection of raw material
be prepared. This report should summarize and in-process material, finished product and stability
reference all protocols and results. It should derive testing, the internal failure cost include re-inspection,
conclusions regarding the validation status of the retesting, rework, and rejection and external failure
process and necessary recommendation for routine cost include recall, complaints and return due to quality
process. The final report should be reviewed and issue. Validation leads to the optimization of processes
approved by the validation team and appropriate and results in minimization of those expenses.
management. Reduction in rejections and reworks. Reduction in
utility cost. Avoidance of capital expenditures.
APPLICATION OF PROCESS VALIDATION
4. Reproducibility
Validation is basically good business practice. It helps
in following:- The product obtained from process validation shows
reproducibility in quality, purity, strength and also
1. Regulatory Requirement
shows consistency in results.
Validation is regulatory requirement for the cGMPs
5. Easier scale-up from development work.
and USFDA all over the world. The cGMP basically
serve as guidelines but do not provide step-by-step 6. Easier maintenance of equipment.
directions on how to achieve them. However, the
7. Improve employee awareness of processes.
validation master plan and associated SPOs exactly
responsibilities: who, when, where, and how much is 8. More rapid automation.
sufficient to demonstrate. Improve employee
awareness of processes. CONCLUSION
Validation is not only for a regulatory requirement of
2. Quality Assurance
cGMP or audits across the world, but it also improve
Validation provides confidence in the quality of whole process by which an industry save time, wastage
product of products manufactured as the over quality of of investment. The process validation not only
a particular process cannot be established due to the improves process but it also assured that the process
limited sample size. Validation leads to less will be performed in prescribed pattern and which is
troubleshooting with routine production. As a result it been controlled to attain and manage the quality of
reduces the number of customer complaints and drug final product. Process validation is systematic approach
recalls. in identifying, measuring, evaluation; documenting and
revalidating the critical steps in pharmaceutical
3. Cost Cutting Tool
dosages form (tablet), with control assure consistency
Validation is a tool for cutting the cost; it is comprised in the quality of final product. With the help of this
of preventive, appraisal, internal failure external review one can conduct the process validation and one
failure. The preventive cost includes quality planning, can know basic about the process validation of in an
vendor approval, training, documentation and industry.

REFERENCES
1. Aulton M E, Pharmaceutics, The Science of Dosage Form 9. Sharma P P, Validation In Pharmaceutical Industry, 2nd
Design, International edition, second edition, Churchill Edition, Vandana Publication, 2013
Livingston (Elsevier), 2006. 10. www.nsf-dba.com
2. Nash R A, Wachter A H, Pharmaceutical Process Validation, 11. www.ich.org
Third Edition, vol 129, Marcel Dekker, Inc., New York, 12. www.pharmatech.com
2003;159-180. 13. Potdar M, cGMP for pharmaceuticals, Pharma Med Press
3. Michael L, Pharmaceutical Process Scale-Up, Marcel Dekker, reprint, 2012.
Inc., New York, 2002, 313. 14. Parajuli RR, Shrestha S, Lamichane S, Pokhrel P, A review on
4. Quality Assurance of Pharmaceuticals: A Compendium of pharmaceutical process validation of solid dosage form
Guidelines And Related Materials Vol 2, 2nd updated edition [tablets], Journal of Drug Delivery and Therapeutics. 2015;
105. 5(6): 1-7
5. U.S. Food and Drug Administration. Guideline on General 15. Satyabrata J, Arjun G, Ravipati A K, Industrial Process
Principles of Process Validation; U.S.FDA: Rockville, M D, Validation of Solid Dosage Forms – An Overview Int. J.
May, 1987. Pharma Sci Rev And Res, 2010, 4(2), 145-148.
6. Chirarutsami W, Process Validation of Sterile Liquid 16. Bhattacharjee D, Maity S, Manna A, Industrial Application of
Products, 2006. Process Validation in the Development and Scale-Up of
7. M D Shoaib, Pharmaceutical Process Validation: An Pharmaceutical Tablet Dosage Form of a Low Dose
Overview, Journal of Advanced Pharmacy Education and Containing Drug and a High Dose Containing Drug, J P S T,
Research, 2012, 2 (4) 189-191. 2011, 3(3), 570-573.
8. Kaur H, Singh G, Seth N, Pharmaceutical Process Validation: A 17. Agalloco J, Frederick J. Carleton, Validation of
Review, Journal of Drug Delivery and Therapeutics. 2013; Pharmaceutical Processes, Third Edition, Informa Healthcare
3(4):189-194 USA, Inc., New York, 2008, 403-416.

© 2011-16, JDDT. All Rights Reserved ISSN: 2250-1177 CODEN (USA): JDDTAO
Rajpal et al Journal of Drug Delivery & Therapeutics. 2016; 6(4):79-87 87
18. Gupta G D, Garg R, Aggrwal S. Guidelines on General 27. Validation Master Plan Installation and Operational
Principles of Validation: Solid Liquid and Sterile Dosage Qualification – Pharmaceutical Inspection Convention;
Forms, 2008; 6(1):28-33. Pharmaceutical Inspection Co-Operation Scheme; PI 006 – 2;
19. Guidance for Industry: Process Validation: General Principles July, 2004.
and Practices. U.S. Department of Health and Human 28. Kathiresan K, Moorthi C, Prathyusha Y, Gade B. R, Reddy B.
Services, Food and Drug Administration, Centre for Drug K, Manavalan R, An overview of pharmaceutical validation;
Evaluation and Research (CDER), Centre for Biologics Research Journal of Pharmaceutical, Biological and Chemical
Evaluation and Research (CBER), Centre for Veterinary Sciences, RJPBCS, 2010, 1(4), 1026.
Medicine (CVM), 2011. 29. FDA’s guidance for industry, Quality Systems Approach to
20. Oechslein C, Lazar M S – Process Validation from view Pharmaceutical Current Good Manufacturing Practice
report of the FDA, Maas & Peither AG – GMP Publishing, Regulations, 4. Health Canada / Health Products and Food
LOGFILE, 3, 2012. Branch Inspectorate Validation Guidelines for Pharmaceutical
21. Quality Management System – Process Validation Guidance Dosage Forms (GUI – 0029) /December, 2009.
GHTF/SG3/N99-10, 2nd Edition, 2004. 30. Recommendations on Validation Master Plan, Installation and
22. Patel R C, Bhuva C K, Singh R P, Dadhich A, Sharma A, Operational Qualification, Non-Sterile Process Validation,
Pharmaceutical Process Validation, Pharmatutor – ART – Cleaning Validation, PIC/S September, Review Article I J P
1053. R N K, 2007.
23. Guidance on Process Validation: Rev 1- 31. ASTM E2476-09 Standard Guide for Risk Assessment and
EMA/CHMP/CVMP/QWP/7027/2012. 8. Health Canada / Risk Control as it Impacts the Design, Development, and
Health Products and Food Branch Inspectorate Validation Operation of PAT Processes for Pharmaceutical Manufacture.
Guidelines for Pharmaceutical Dosage Forms (GUI – 0029) / 32. ASTM E2281-03 Standard Practice for Process and
2009. Measurement Capability Indices, 11,
24. Guidelines for Process Validation of Pharmaceutical Dosage 33. ASTM E2500-07 Standard Guide for Specification, Design,
Form – Saudi Food & Drug Authority; Version 2; 1992. and Verification of Pharmaceutical and Biopharmaceutical
25. Guide to Inspections of Oral Solid Dosage Forms pre/post Manufacturing Systems and Equipment.
Approval Issue for Development and Validation; issue (1/94); 34. ASTM E2709-10 Standard Practice for Demonstrating
January, 2010. Capability to Comply with a Lot Acceptance Procedure.
26. Note for Guidance on Process Validation – The Europe 35. ASTM E2474-06 Standard Practice for Pharmaceutical
Agency From Evaluation of Medicinal Products; Process Design Utilizing Process Analytical Technology.
CPMP/QWP/848/96; EMEA/CVMP/598/99;

How to cite this article:

Rajpal G, Arya RKK, Kunwar N, Basic concept of process validation in solid dosage form (tablet): a
review, Journal of Drug Delivery & Therapeutics. 2016; 6(4):79-87

© 2011-16, JDDT. All Rights Reserved ISSN: 2250-1177 CODEN (USA): JDDTAO