The document summarizes the key aspects of validation presented in a seminar. It defines validation according to FDA and WHO as establishing evidence to consistently produce products meeting specifications. It discusses the types of validation including process, analytical method, and cleaning validation. It also describes the important components of a validation master plan such as scope, responsibilities, and timelines. The importance, types (prospective, concurrent, retrospective), and documentation of process validation are highlighted.

1. SEMINAR ON VALIDATION
PRESENTED BY:
Ranjeet singh
1st year M- Pharm

2. DEFINITION
According to the Food and Drug Administration (FDA), the
goal of validation is to:
“establish documented evidence which provides a high
degree of assurance that a specific process will consistently
produce a product meeting its predetermined specifications
and quality attributes.”
WHO: Defines Validation as an action of providing any
procedure, process, equipment, material, activity or system
actually leads to the expected results.

3. VALIDATION MASTER PLAN (VMP)
 Validation master plan (vmp) – it describes the basic
concept of over all site of validation programme
 The vmp addresses process validation, facility
qualification, Analytical method validation and cleaning
validation
 The validation master plan should provide an overview of
the entire validation operation, its organizational
structure, its content and planning.
 The main elements of it being them list/inventory of the
items to be validated and the planning schedule.

4.  The Validation Master Plan should be a summary document
and should therefore be brief, concise and clear.
 All validation activities relating to critical technical
operations, relevant to product and process controls within
a firm should be included in the validation master plan.
 It should comprise all prospective, concurrent and
retrospective validations as well as revalidation.
 It should not repeat information documented elsewhere
but should refer to existing documents such as policy
documents, SOP’s and validation protocols and reports.

5. The format and content should include:
 Introduction: validation policy, scope, location and schedule.
 Organizational structure: personnel responsibilities.
 Plant/process/product description: rational for inclusions or
exclusions and extent of validation.
 Specific process considerations that are critical and those requiring
extra attention.
 List of products/ processes/ systems to be validated, summarized in
a matrix format, validation approach.
 Re-validation activities, actual status and
 Key acceptance criteria.
 Documentation format.
 Reference to the required SOP’s.
 Time plans of each validation project and sub-project.

6. consideration
 Validation should thus be considered in the following
situations:
Totally new process
New equipment
Process and equipment which have been altered to suit
changing priorities

7. Importance of Validation
1. Assurance of quality
2. Time bound
3. Process optimization
4. Reduction of quality cost.
5. Minimal batch failures, improved efficiently and productivity.
6. Reduction in rejections.
7. Increased output.
8. Fewer complaints about process related failures.
9. Reduced testing in process and in finished goods.
10. More rapid and reliable start-up of new equipments
11. Easier maintenance of equipment.
12. Improved employee awareness of processes.
13. More rapid automation.

8. TYPES OF VALIDATION
 Process Validation
 Analytical method of validation
 Cleaning Validation

9. TYPES OF PROCESS VALIDATION
Prospective validation
 In prospective process validation, an experimental plan called the validation
protocol is executed (following completion of the qualification trials) before
the process is put into commercial use.
 This particular type of process validation is normally carried out in connection
with the introduction of new drug products and their manufacturing processes.
 The formalized process validation program should never be undertaken unless
and until the following operations and procedures have been completed
satisfactorily.
 1. The facilities and equipment in which the process validation is to be
conducted meet CGMP requirements (completion of installation qualification)
 2. The operators and supervising personnel who will be “running” the validation
batch have an understanding of the process and its requirements.

10.  3. The design, selection, and optimization of the formula have been
completed
 4. The qualification trials using pilot-laboratory batches have been
completed, in which the critical processing steps and process variables
have been identified, and the provisional operational control limits for
each critical test parameter have been provided
 5. Detailed technical information on the product and the manufacturing
process have been provided, including documented evidence of product
stability
 6. Finally, at least one qualification trial of a pilot-production batch has
been made and shows, upon scale-up, that there were no significant
deviations from the expected performance of the process
 The strategy selected for process validation should be simple and
straightforward.

11. Concurrent validation
 It is a type of prospective validation
 In-process monitoring of critical processing steps and end-product
testing of current production can provide documented evidence to show
that the manufacturing process is in a state of control.
 Concurrent validation may be conducted on previously validated
process.
 It is conducted at the initial stages of validation of a new process or
modified altered process, the distribution of goods is to be held up until
and unless all the data’s and results are validated and reviewed.
 Such validation documentation can be provided from the test
parameter and data sources disclosed in the section on retrospective
validation.

12. Test parameters Data source
Powder blend uniformity In process testing
Moisture content In process testing
Particle or granule size distribution In process testing
Weight variation In process testing
Tablet hardness In process testing
pH value In process testing
Color or clarity In process testing
Viscosity or density In process testing
Average unit potency End product testing
Content uniformity End product testing
Dissolution time End product testing
Weight variation End product testing

13.  Retrospective validation
 The retrospective validation option is chosen for established products
whose manufacturing processes are considered stable.
 It utilizes accumulated historical production, testing and control
charts, records of manufacturing procedures.
 Historical data must give all the information regarding whether the
product meets pre determined specifications or not.
 After complete satisfaction from historical data, the data is subjected
to statistical analysis and evaluation.
 Finally the process must be documented.

14.  Using either data-based computer systems or manual
methods, retrospective validation may be conducted in the
following manner
 1. Gather the numerical data from the completed batch
record and include assay values, end-product test results,
and in-process data.
 2. Organize these data in a chronological sequence
according to batch manufacturing data, using a spreadsheet
format.
 3. Include data from at least the last 20–30 manufactured
batches for analysis. If the number of batches is less than
20, then include all manufactured batches and commit to
obtain the required number for analysis.

15.  4. Trim the data by eliminating test results from
noncritical processing steps.
 5. Subject the resultant data to statistical analysis and
evaluation.
 6. Draw conclusions as to the state of control of the
manufacturing process based on the analysis of
retrospective validation data.
 7. Issue a report of your findings (documented evidence).

16.  Revalidation
 Whenever there occurs any deviation or change in any of
the critical process parameters, formulation, major
equipment, premises etc the process must be reviewed,
evaluated and revalidated.
 Process are required to be reviewed periodically at
scheduled intervals, whenever problem develops changes
are made immediately and revalidation are considered.
 Conditions requiring revalidation study & documentation
are listed as follows:
 1. Change in a critical component (usually refers to raw
materials).

17.  2. Change or replacement in an equipment.
 3. Change in a facility and/or plant (usually location or
site)
 4. Significant (usually order of magnitude) increase or
decrease in batch size.
 5. Sequential batches that fail to meet product and
process specification.

18. 2. ANALYTICAL METHOD OF
VALIDATION
 Definition : “The process by, which it is established, by
laboratory studies, that the performance characteristics
of the method meet the requirements for the intended
analytical application”.
 Analytical methods like chromatography, Spectroscopy,
XRD, Turbidometry, Nephalometry etc play an important
role in the new drug development and also evaluation of
existing product.

19. 3.CLEANING VALIDATION
 Definition: “A process of attaining and documenting
sufficient evidence to give reasonable assurance, given
the current state of Science and Technology, that the
cleaning process under consideration does, and / or will
do, what it purpoes to do.”
Objective..
 To minimize cross contamination.
 To determine efficiency of cleaning process.
 To do troubleshooting in case problem identified in the
cleaning process and give suggestions to improve the
process.

20. Validation of new process

21. DOCUMENTATION
 Documentation at each stage of the process validation
lifecycle is essential for effective communication in complex,
lengthy, and multidisciplinary projects.
 Documentation is important so that knowledge gained about
a product and process is accessible and comprehensible to
others involved in each stage of the lifecycle. Information
transparency and accessibility are fundamental tenets of the
scientific method.
 They are also essential to enabling organizational units
responsible and accountable for the process to make
informed, science based decisions that ultimately support the
release of a product to commerce

22. Validation Participants
 Validation is undertaken by one or more persons who are not
directly involved in the particular instance of training and
assessment being validated, and who collectively have:
 Vocational competencies and current industry skills relevant
to the assessment being validated
 Current knowledge and skills in vocational teaching and
learning
 The appropriate training and assessment qualification or
assessor skill set.
 Industry experts may be involved to ensure there is the
combination of expertise set out above.
 The following table summarises the participants involved in
any validation activities and the assigned responsibilities.
See Validation Work Instruction for more details.

25. Validation Procedure
 This procedure outlines the quality review process to confirm
that our assessment system consistently produces valid
assessment judgments. We have a schedule to validate each
training product ( qualification, skill set, unit of competency,
accredited short course and module) on our scope of
registration.
This procedure describes:
 who will lead and participate in the validation activities
 which training products will be the focus of the validation
 when assessment validation will occur
 how the outcomes of those activities will be documented
and acted upon.

26. VALIDATION PROTOCOL
 A written plan stating how validation will be conducted, including test
parameters, product characteristics, production and packaging
equipment, and decision points on what constitutes acceptable test
results.
 This document should give details of critical steps of the
manufacturing process that should be measured, the allowable range
of variability and the manner in which the system will be tested.
 The validation protocol provides a synopsis of what is hoped to be
accomplished.
 The protocol should list the selected process and control parameters,
state the number of batches to be included in the study, and specify
how the data, once assembled, will be treated for relevance. The date
of approval by the validation team should also be noted.
 In the case where a protocol is altered or modified after its approval,
appropriate reasoning for such a change must be documented.

27. The validation protocol should be numbered,
signed and dated, and should contain as a
minimum the following information:
 objectives, scope of coverage of the validation study validation
team membership, their qualifications and responsibilities
 type of validation: prospective, concurrent, retrospective,
revalidation
 number and selection of batches to be on the validation study
 a list of all equipment to be used; their normal and worst case
operating parameters
 outcome of IQ, OQ for critical equipment

28.  requirements for calibration of all measuring devices
 critical process parameters and their respective tolerances
 description of the processing steps: copy of the master documents for the
product
 sampling points, stages of sampling, methods of sampling, sampling plans
 statistical tools to be used in the analysis of data ,training requirements
for the processing operators
 validated test methods to be used in in-process testing and for the finished
product
 specifications for raw and packaging materials and test methods forms and
charts to be used for documenting results

29. REFERENCES
 Khushboo D. Singh; Review Article ; Overview of
Validation and Basic Concepts of Process Validation;
2014; page No. 178-190
 Sanford Bolton; pharmaceutical statistics; 3rd
edition,1997: Marcel Dekker , New York .
 Kaur H, Singh G, Seth N; Pharmaceutical Process
Validation: A Review. 2013; page No. 189-194.
 Fraderick J. Carleton, James P. Agalloco ; validation of
pharmaceutical processes; 2nd edition ,1998 New York ;
page No.259-257.