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VALIDATION

INTRODUCTION :
Validation is an essential and integral part of GMP. Validation provide the good
quality product and the equipment . Validation give the surety that equipment having
the good qualification like design, operation, installation, and performance
qualification which have pre-determined. Validation data should be generated for the
all types of the product and the equipment to demonstrate the adequacy of the

manufacturing process
Validation is an established documented evidence which provides high degree
of assurance that a specific equipment, process, method or system will
consistently

produce

results

meeting

their

specifications

and

quality

characteristics. Or It is the assurance of reproducibility of results, with


documented evidence.
These principles may be stated as:
quality, safety and efficacy must be designed and built into the product;
quality cannot be inspected or tested into the finished product; and each step of the
manufacturing process must be controlled to maximize the probability that the
finished product meets all quality and design specifications.
Validation of processes and systems is fundamental to achieving these goals.
It is by design and validation of both process and process controls that a manufacturer
can establish confidence that all manufactured products from successive lots will be
acceptable.
The documentation associated with validation includes:
A quality manual
Standard Operating Procedures (SOPs)
Specifications
Validation Master Plan (VMP)
validation and qualification protocols
validation and qualification reports
The implementation of validation work requires considerable resources in terms of:
-time: generally validation work is submitted to rigorous time schedules;
-finance: validation studies require time of highly specialized personnel and expensive
technology;
-personnel: collaboration of experts of various disciplines.

Importance of Validation: - :

Increased throughput.
Reduction in Rejections & Reworking.
Reduction in Utility Cost.
Avoidance of Capital Expenditure.
Fewer complain about Process-related failures.
Reduced testing in-process & in finished goods.
More Rapid & Reliable start-up of new equipment.
Easier Scale-up from development work.
Easier Maintenance of equipment.
Improved Employee awareness of process.
More Rapid Automation.

Types of Validation:Prospective Validation (Also Called Premarket Validation)


Retrospective Validation
Concurrent Validation
Re-Validation
Prospective validation:

Is carried out during the development stage by means of a risk analysis of the

production process.
Process is broken down into individual steps which are then evaluated on the basis of

past experience to determine whether they might lead to critical situations.


When possible critical situations are identified, the risk is evaluated, the potential
causes are investigated and assessed for probability and extent, the trial plans are

drawn up, and the priorities set.


The trials are then performed and evaluated, and an overall assessment is made. If, at

the end, the results are acceptable, the process is satisfactory.


Unsatisfactory processes must be modified and improved until a validation exercise

proves them to be satisfactory.


This form of validation is essential in order to limit the risk of errors occurring on the
production scale

Concurrent validation:

Is carried out during normal production.


This method is effective only if the development stage has resulted in a proper

understanding of the fundamentals of the process.


The first three production-scale batches must be monitored as comprehensively as
possible. The nature and specifications of subsequent in-process and final tests are
based on the evaluation of the results of such monitoring.

Concurrent validation together with a trend analysis including stability should be


carried out to an appropriate extent throughout the life of the product.

Retrospective validation:
Involves the examination of past experience of production on the assumption that
composition, procedures and equipment remain unchanged. such experience and the results
of in-process and final control tests are then evaluated. Recorded difficulties and failures in
production are analyzed to determine the limits of process parameters. A trend analysis may
be conducted to determine the extent to which the process parameters are within the
permissible range.
Retrospective validation is obviously not a quality assurance measure in itself, and should
never be applied to new processes or products. It may be considered in special circumstances
only. E.g. when validation requirements are first introduced in a company. Retrospective
validation may then be useful in establishing the priorities for the validation program. If the
results of a retrospective validation are positive, this indicates that the process is not in need
of immediate attention and may be validated in accordance with the normal schedule.
Revalidation:
Revalidation must be performed on introduction of any changes affecting a manufacturing
and/or standard procedure having a bearing on the established product performance
characteristics. Such changes may include those in starting material, packaging material,
manufacturing processes, equipment, in-process controls, manufacturing areas, or support
systems (water, steam, etc.). Is needed to ensure that changes in the process and/or in the
process environment, whether intentional or unintentional, do not adversely affect process
characteristics and product quality.
Revalidation may be divided into two broad categories:
1] Revalidation after any change having a bearing on product quality.
2] Periodic revalidation carried out at scheduled intervals
Typical changes, which require revalidation, includes:
1) Changes in the starting material(s). Changes in the physical properties, such as density,
viscosity, and particle size distribution, and crystal type and modification, of the active
ingredients or excipients may affect the mechanical properties of the material; as a
consequence, they may adversely affect the process or the product.

2) Changes in the packaging material, e.g. replacing plastics by glass, may require changes in
the packaging procedure and therefore affect product stability.
3) Changes in the process, e.g. changes in mixing time, drying temperature and cooling
regime, may affect subsequent process steps and product quality.
4) Changes in equipment, including measuring instruments, may affect both the process and
the product; repair and maintenance work, such as the replacement of major equipment
components, may affect the process.
5) Changes in the production area and support system, e.g. the rearrangement of
manufacturing areas and/or support systems, may result in changes in the process. The repair
and maintenance of support systems, such as ventilation, may change the environmental
conditions and, as a consequence, revalidation/requalification may be necessary, mainly in
the manufacture of sterile products.
6) Unexpected changes and deviations may be observed during self-inspection or audit, or
during the continuous trend analysis of process data.
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 protocol 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.
Validation Master Plan: :
Validation in general requires meticulous preparation and careful planning of the various
steps in the process. In addition, all work should be carried out in a structured way
according to formally authorized SOP. All observations must be documented and where
possible must be recorded as actual numerical results.

A validation master plan is a document that summarises the companys overall


philosophy, intentions and approaches to be used for establishing performance adequacy.
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 the
list/inventory of the items to be validated and the planning schedule.
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. The Validation Master Plan should be brief, concise and clear. It should not
repeat information documented elsewhere but should refer to existing documents such as
policy documents, SOPs and validation protocols and reports
The format and content should include: :
1. Introduction: validation policy, scope, location and schedule
2. Organizational structure: personnel responsibilities
3. Plant/ Process /Product description: rational for inclusions or exclusions and extent of
validation
4. Specific process considerations that are critical and those requiring extra attention
5. List of products/ processes/ systems to be validated, summarized in a matrix format,
validation approach
6. Re-validation activities, actual status and future planning
7. Key acceptance criteria
8. Documentation format
9. Reference to the required SOPs
10. Time plans of each validation project and sub-project.
Various areas of Validation: :
Various areas of Validation: Pharmaceutical Development. Facilities, Equipment & Services.
Process. Raw Material. Cleaning. Analytical Method. Packaging Components. Medical
Devices. Computer System. Laboratory Control