INTRODUCTION:

Any pharmaceutical plant's primary objective is to consistently produce products of acceptable quality and quality at the lowest possible cost. Although validation studies in the pharmaceutical industry have been carried out for a long time, Validation is increasing due to the increased emphasis their industry has placed on the quality assurance program in recent years and is essential for an efficient production operation.

Validation is a concept originating in 1978 in the United States. Over the years, the concept of validation has been extended to cover a wide range of practices, from analytical methods used to control the quality of drugs and drug products to computerized clinical trial, labeling or process management systems.

Validation is based on, but not prescribed by, regulatory requirements and is best viewed as an important and integral part of CGMP. Validation simply means an evaluation of validity or an intervention to show effectiveness. Validation is a team effort involving people from different plant disciplines. This definition integrates the idea that there are the following conditions:

Quality, safety and efficacy are planned or integrated into the product. Quality can not be sufficiently guaranteed only by in-process and finished product inspection or monitoring at every level of the production process to ensure that the finished product meets all quality criteria, including requirements.

A drug product creation is a long-term process that involves drug discovery, laboratory testing, animal studies, clinical trials, and regulatory approval. System controls include raw material testing, system management and goals for the final product. The aim is to track and validate the production process's online and off-line output. Even after the manufacturing process has been validated to monitor its output, a well-written process control protocol is often needed to develop the current good manufacturing practice.

Validation for finished drugs is provided in 21 CFR parts 210 and 211, based primarily on FDA regulations describing the current good manufacturing practice (cGMP). The cGMP regulations require the design and control of production processes to ensure consistent and reliable compliance of in-process materials and the finished product. defined quality requirements. The cGMP regulations in parts 210 and 211 require process validation in both general and specific terms.

In the process of software development, validation is very important. To stop duplicating and inaccurate data entry into the database is beneficial. Software systems were typically introduced to make the company, shops and business easier to plan the job. Verification and validation define critical errors or defects in a software testing process that classified based on the level of severity in the application to be corrected.

History of Validation: [6]

Two FDA officials, Ted Byers and Bud Loftus, first suggested the idea of validation in the mid-1970s to enhance the safety of pharmaceuticals (Agalloco 1995). In direct reference to many issues in the sterility of the parenteral high volume market, it was proposed. The first testing activities centered on the processes involved in the production of these products, but spread quickly to the related pharmaceutical industry. The U.S.F.D.A. pioneered the testing of the method principle, but till 29th September 1978 the definition of process validation did not appear in any part of literature of U.S.F.D.A. no cGMP regulations talked anything about process validation.

Definitions: [7-9]

· European commission:

1991 –Validation-“Act of proving, in accordance of GMPs that Any” process actually leads to expected results.

2000 -'Documented evidence that the process operated in accordance with established parameters can effectively and reproducibly produce a medicinal product in accordance with its predetermined specifications and quality attributes. '

· US FDA Definition:

"Process validation provides documented evidence that provides a high degree of assurance that a specified process will consistently produce a product that meets its pre-determined specifications and quality features."

· ICH Definition:

"Process Validation is the means to ensure and provide documentary evidence that processes within their design parameters can produce a finished product of the required quality repeatedly and reliably."

· WHO Definition:

"The recorded act of proving that any method, process, equipment, material, operation or device actually results in the expected outcome."

Why Validation Is Required?[10]:

● The pharmaceutical industry uses expensive material, sophisticated facilities and equipment’s and highly qualified personals.

● Detailed study and managed batch testing of the manufacturing process is necessary in order to reduce the cost of failure and improve productivity.

● If it wouldn't be practical to use machinery that doesn't know if it will deliver the product we want, don't employ people with no guarantee that they can conduct or fail to perform process controls or tests to ensure that the product meets requirements.

● The effective use of these tools is crucial for the industry's ongoing success. The cost of failure of the product, rejects, reworks, recalls, grievances are the sufficient part of the total cost of production.

● Assurance of quality, cost reduction.

Need of Pharmaceutical Validation:[11]

Validation is an integral part of quality assurance; it involves the systematic study of systems, facilities and processes to determine whether they are performing their intended functions properly and consistently as specified. A certified process is one that has been shown to provide a high degree of confidence that standardized batches will be produced that meet the requirements specified and have therefore been formally accepted. Validation does not enhance processes in itself, but ensures that the processes have been properly developed and are under control.

Scope of Validation:[12]

Pharmaceutical validation is a large area of work and it encompasses virtually every aspect of pharmaceutical processing activities, so identifying the validation scope becomes a very difficult task. Nonetheless, a thorough review of the pharmaceutical operations would suggest at least the following pharmaceutical validation areas;

· Analytical

· Instrument Calibration

· Process Utility services

· Raw materials

· Packaging materials

· Equipment

· Facilities

· Manufacturing operations

· Product Design

· Cleaning

· Operators

Responsible Authorities for Validation:[13, 14]

The Working Party on Validation is convened to identify progress, organize and eventually authorize the entire effort, including all the produced documentation. Normally the working party would include the following members of staff, Head of quality assurance.

· Head of engineering.

· Validation manager.

· Production manager.

· Specialist validation discipline: all areas.

Department /Designation	Responsibility
Manager Production	Responsible for manufacturing of batches and review of protocol and report.
Manager QC	Responsible for analysis of samples Collected
Executive QC	Responsible for samples collection and submission to QC
Manager Maintenance	Providing utilities and engineering Support
Executive Production	Responsible for preparation of protocol and manufacturing of validation batches
Manager QA	Responsible for protocol authorization and preparation of summary report.

Importance of Validation:[15,16]

· Assurance of quality

· Time bound

· Process optimization

· Reduction of quality cost

· Nominal mix-ups, and bottle necks

· Low batch errors, rapid development and efficiency

· Reduction in rejections

· Increased output

· Avoiding capital spending

· Fewer complaints about process related failures

· Reduced testing in process and in finished goods

· More rapid and reliable start-up of new equipment

· Easier scale-up form development work

· Easier maintenance of equipment

· Improved employee awareness of processes

· More rapid automation

· Government regulation (Compliance with validation requirements is necessary for obtaining approval to manufacture and to introduce new products)

Major Phases in Validation:[17,18]

The activities relating to validation studies may be classified into three:

Phase 1:

This is the Qualification Phase of Prevalidation, which includes all activities related to product research and development, formulation pilot batch tests, scale-up studies, transition of technology to commercial batches, establishing stability and storage conditions, and Handling of in-process and finished dosage forms, certification of equipment, qualification of installation, master product document, qualification of operation and process ability.

Phase 2:

This is the validation step of the cycle. It is designed to verify that all of the critical process parameter's defined limits are true and that even under the worst conditions acceptable products can be made.

Phase 3:

This is known as the Confirmation Maintenance Phase, including regular review of all process related documents, including confirmation of audit reports, to ensure that no adjustments, anomalies, defects and improvements have been made to the manufacturing process and that all standard operating procedures (SOPs), including change control procedures, are in place; They were followed. At this stage, the validation team of individuals representing all major departments also ensures that no changes / deviations have occurred that should have resulted in re-qualification and revalidation. A careful design and validation of systems and process controls can create a high degree of confidence that all lots or lots produced will fulfill their specifications. It is assumed that operations are carried out in accordance with the principle of good manufacturing practice (GMP) in general as well as in specific reference to the manufacture of sterile products throughout manufacturing and control.

Validation Steps:

The validation steps recommended in GMP guidelines can be summarized as follows:

· All studies should be performed as a pre-requisite in accordance with a comprehensive, pre-established protocol or series of protocols which, in effect, are subject to formal-change control procedures.

· All data generated during the course of studies should be formally reviewed and certified as evaluated against pre-determined criteria.

· There should be appropriate testing facilities, equipment, software and methodology available.

· Appropriate clean room facilities in both the "local" and the context setting should be available. There should be assurance that the clean room environment as specified should be properly installed, qualified and maintained by initial commissioning (qualification) and subsequently by implementing a re-testing program–in process equipment.

· The process, if aseptic, may be validated by means of "process simulation" studies if adequate attention has been paid to the above.

· The process should be revalidated at intervals; and there should be detailed documentation available to identify support and record the overall validation process.

Planning for Validation:

This should be prepared for all validation activities. In a validation master plan (VMP) or equivalent documents, the key elements of a validation program should be clearly defined and documented.

● The VMP should be a short, succinct and simple overview text.

● The VMP should contain data on at least the following:

1. Validation policy.

2. Organisational structure of validation activities.

3. Summary of facilities, systems, equipment and processes to be, validated.

4. Documentation format: The format to be used for protocols and reports.

5. Planning and scheduling.

6. Change control.

7. Reference to existing document.

8. Incase of large projects, it may be necessary to create separate validation master plans.

Types of Validation: [19,20]

1 Process validation

2 Cleaning validation

3 Equipment validation

4 Validation of analytical method.

1. PROCESS VALIDATION:

Dig: General View of Process validation.

Defination:

"Process validation provides documented evidence that provides a high level of assurance that a specific process will consistently produce a product that meets its predetermined specifications and quality characteristics."

It is beneficial to the manufacturer in many ways:

● This deepens process awareness, eliminates risk, avoids problems, and thus ensures the process runs smoothly.

● It decreases the risk of defect costs.

● It decreases the risk of regulatory non- compliance.

● A fully validated process may require fewer controls in the process and testing of the end product. In the following situations, validation should therefore be considered:

● Totally new process.

● Changed procedure and equipment to match changing goals.

● System in which the end-product evaluation is bad and the product quality measurement is inaccurate

Basic Concept of Process Validation

● Calibration, verification and maintenance of process equipment.

● Requalification or revalidation.

● Establishing specifications and performance characteristics.

● Qualification or validation of process and equipment.

● Testing the final product, using validated analytical methods, in order to meet specifications.

● Challenging, auditing, monitoring or sampling the recognised critical key steps of the process.

Objectives of Process Validation: [22,23]

● In addition to the specific machinery, the manufacturing process must be checked.

● The goal is to create a robust manufacturing process that consistently produces a minimally variable drug product that adheres to quality criteria of purity, identity and potency.

● In order to comply with standards, a testing plan for the manufacturing process should be drawn up and carried out by engineers. Generally the validation plan includes just one portion of the PQ.

● Like equipment validation, major changes will result in the need for subsequent revalidation after initial validation.

● In the end, process validation will ensure a robust product that is highly reproducible over time.

Advantages of Process Validation

● Expanded real time monitoring and adjustment of process.

● Enhanced ability to statistically evaluate process performance and product variables. e.g., individuals; mean; range; control limits.

● Enhanced data and evaluation capabilities and increased confidence about process reproducibility and product quality.

● Improved ability to set target parameters and control limits for routine production, correlating with validation results.

● Enhanced reporting capability.

Reason for Process Validation:

The possible reason for the validation of the process may include: new product or existing products as modified by SUPAC.

· Change in batch size.

· Change in equipment.

· Change in process existing products.

· Change in composition or components.

· Change in the critical control parameters.

· Change in vendor of API or critical excipient.

· Change in specification on input material.

· Abnormal trends in quality parameters of product through review during Annual Product Review (APR).

· Trend of Out of Specification (OOS) or Out of Trend (OOT) in consecutive batches.

Benefits of Process Validation [23]

· Consistent through output.

· Reduction in rejections and reworks.

· Reduction in utility cost.

· Avoidance of capital expenditures.

· Fewer complaints about process related failure.

· Reduced testing in process and finished goods.

· More rapid and accurate investigations into process deviation.

· More rapid and reliable start-up of new equipment.

· Easier scale-up from development work.

· Easier maintenance of equipment.

· Improve employee awareness of processes.

· More rapid automation.

Types of Process Validation: [19,20]

1. Prospective Validation:

Before the distribution of either a new product or a product made under a modified manufacturing process, where the modifications are significant and may affect the characteristics of the product. It is a pre-planned scientific approach which involves the initial stages of development of formulation, process development, process requirements, the development of sampling plans for in-process experiments, The creation of batch documents, the description of requirements for raw materials, the completion of pilot runs, the transition of technology from scale-up batches to commercial batches, the listing of major processes and environmental controls. The validation protocol will be performed in Prospective Validation before the process is placed into commercial use. It is generally considered appropriate that within the finally accepted parameters three consecutive batches / runs will constitute a proper validation of the process, giving the product of the desired quality. It is a pre-market check on the three consumer stocks.

2. Concurrent Validation:

A Process where current batches of production are used to monitor parameters of processing. It provides limited assurance regarding the consistency of quality from batch to batch from the current batch being studied.

3. Under certain conditions, concurrent validation may be the practical approach. Examples of this might be when:

● A Previous approved process shall be moved to the contract manufacturer of a third party or to another location.

● The drug is a different intensity of a product previously tested with the same active / inactive ingredient ratio.

● The number of lots evaluated under the Retrospective Validation was not sufficient to obtain a high degree of assurance demonstrating full control of the process.

● The number of lots produced is limited.

● Process with low volume of output per lot and demand on the market.

● The manufacturing process is urgently needed due to lack of supply or shortage of drugs.

● Concurrent validation shall be valid in all cases referred to above, provided that the following conditions are appropriate.

● Pre-approved protocol for reasonable validation at the same time.

● A deviation shall be justified and accepted by the owner / Head-QMS of the plant head / head process.

● Based on developmental / scale up / test sets, product actions and history shall be checked.

● If any adverse reactions are detected during the concurrent validation process, a detailed protocol shall be designed for the handling of the advertised product.

● Concurrent validation batches are collected in the report and all core disciplines are accepted.

3. Retrospective Validation:

Based on extensive data collected over several lots and over time, it is performed for a product already being advertised. Retrospective Validation may be used for older products that were not validated by the manufacturer at the time they were first marketed and are now to be validated to confirm the requirements of Section 2, Part C of the Food and Drugs Act Regulation. Retrospective Validation is only suitable for well-established comprehensive processes and will be unacceptable if recent changes have been made to the product composition, operating procedures, equipment and facilities18 Some of the essential elements for retrospective validation are:

● Batches manufactured for a defined period (minimum of 10 last consecutive batches).

● Number of lots released per year.

● Batch size/strength/manufacturer/year/period.

● Master manufacturing/packaging documents.

● List of process deviations, corrective actions and changes to manufacturing documents.

● Data for stability testing for several batches.

● Trend analysis including those for quality related complaints.

4. Process Re-Validation:

Required If any of the critical process parameters, composition, primary packaging elements, supplier of raw materials, major equipment or premises are modified. In addition, failure to meet product and process requirements in lots will entail re-validation of the process.

● In certain cases, re-validation is appropriate. Some of the expected or unplanned changes that may need re-validation are the following examples: changes in raw materials (physical properties such as density, viscosity, distribution of particle size and moisture, etc., which may affect the process or product).

● Changes in the source of active raw material manufacturer.

● Changes in packaging material (primary container/closure system).

● Changes in the process (e.g., mixing time, drying temperatures and batch size).

● Changes in the equipment (e.g. addition of automatic detection system).

● Changes in equipment requiring "like for like" replacement of equipment would not normally require a revalidation except for this new equipment.

● Must be qualified.

● Changes in the plant/facility.

● Variations revealed by trend analysis.

Phases in Process Validation [24, 25]

The activities relating to validation studies may be classified into three:

Phase 1: Pre-Validation Qualification Phase:

This process includes all activities related to product research and development, formulation pilot batch tests, scale-up studies, technology transfer to commercial batches, stability conditions and storage, and Handling of in-process and finished dosage forms, certification of equipment, master development document for installation approval, operational qualification and process ability.

Phase 2: Process Validation Phase:

It is designed to verify the validity and satisfaction of all established critical process parameter limits. Even under the worst conditions, goods can be generated.

Phase 3: Validation Maintenance Phase:

It requires frequent review of all process-related documents, including clarification of audit reports, to ensure that no modifications, anomalies and manufacturing process adjustments have occurred and that all standard operating procedures (SOPs) have been implemented, including improvements in control procedures. At this point, the validation team of individuals from all major departments also ensures that no changes / deviations have occurred that should have resulted in re-qualification and revalidation. A careful design and testing of systems and process controls will establish a high degree of confidence that all lots or lots created will fulfill their requirements. It is assumed that operations are carried out in accordance with the principle of good manufacturing practice (GMP) in general as well as in specific reference to the manufacture of sterile products throughout the production and control.

APPROCHES OF VALIDATION: [26,27,28]:

There are two basic approaches to the validation of the process itself (apart from the certification of the equipment used in manufacturing, the control calibration should be carried out in two stages:

1. Component Operational Qualification, What a large part of the calibration can be considered.

2. System Operational Qualification, to determine if the entire system operates as an integrated whole.

Process Performance Qualification (PQ):

This verifies that the system is repeatable and is consistently producing a quality product11.

By sufficient success lists and associated documents, these exercises ensure proper commissioning of facilities, ancillary systems and sub-systems. The end result is that all future operations will be successful and within the operating limits prescribed. Protocols, protocols, procedures, requirements and acceptance criteria for test results are provided at various stages in a validation exercise. All of these must be checked, confirmed, and approved. Representatives from the technical disciplines would be required, of example, engineering, research and development, production, quality control and quality assurance are actively involved in these undertakings with final authorisation from a validation committee or representative of qualityassurance18. Measuring instruments, environmental factors assessment, etc.). These are the experimental approach and the approach based on the analysis of historical data.

The experimental approach, which is applicable to both prospective and concurrent validation, may involve:

· Extensive product testing,

· Simulation process trials,

· Challenge/worst case trials, and

· Control of process parameters

(mostly physical).

One of the most realistic types of process validation, particularly for non-sterile products, is the product's final testing to a greater extent than is needed in routine quality control. It may entail comprehensive sampling, far beyond what is needed in standard quality control and specifications, and often only for some parameters. For example, to determine unit dose uniformity, several hundred tablets per batch may be weighed. The results are then statistically treated to verify the distribution's normality and determine the standard deviation from the average weight. Confidence limits are also estimated for individual outcomes and batch homogeneity. Strong assurance is provided that samples taken at random comply with regulatory requirements if the confidence limits are in the specifications of the compendia.

No experiments are carried out in retrospective validation in the approach based on the analysis of historical data, but instead all available historical data relating to a number of lots are combined and analyzed together; Where production proceeds smoothly during the period preceding validation and data are combined and statistically treated during process inspection and final product testing. The results, including the outcome of studies of process capacity, trend analysis, etc., will indicate whether or not the process is under control.

Strategy for The Validation of Methods: [29]:

Throughout laboratory experiments, the validity of a particular method should be demonstrated using samples or criteria that are identical to regularly studied unknown samples. A validation protocol, ideally written in a step-by-step instruction format, should be used for planning and implementation. This suggested technique assumes the selection of the instrument and the production of the process. It meets standards such as ease of use; ability to be automated and operated by computer systems; cost per analysis; sample by put; turnaround time; and specifications for the environment, health and safety.

1. Develop a validation protocol, an operating procedure or a validation master plan for the validation.

2. For a specific validation project define owners and responsibilities

3. Develop a validation project plan

4. Define the application, purpose and scope of the method

5. Define the performance parameters and acceptance criteria

6. Define validation experiments

7. Verify relevant performance characteristics of equipment

8. Qualify materials, e.g. standards and reagents for purity, accurate amounts and sufficient stability.

9. Perform pre-validation experiments

10. Adjust method parameters or/and acceptance criteria if necessary

11. Perform full internal (and external) validation experiments

12. Develop SOPs for executing the method in the routine

13. Define criteria for revalidation

14. Define type and frequency of system suitability tests and/or analytical quality control (AQC) checks for the routine

15. Document validation experiments and results in the validation report www.intechopen.

VALIDATION PROTOCOL:

The validation protocol should be numbered, signed and dated, and should contain as a minimum the following information:

1. Title

2. Objective & Scope

3. Responsibility

4. Protocol Approval

5. Validation Team

6. Product Composition

7. Process Flow Chart

8. Manufacturing Process

9. Review of Equipments / Utilities

10. Review of Raw Materials and Packing Materials Review of Analytical and Batch Manufacturing Records

11. Review of Batch Quantities for Validation (Raw Materials)

12. Review of Batch Quantities for Validation (Packing Materials)

13. HSE Requirements

14. Review of Process Parameters Validation Procedure

15. Sampling Location

16. Documentation

17. Acceptance Criteria

18. Summary

19. Conclusion

Parameters for Method Validation: [30,31, 32]

The various validation parameters are;

1. Accuracy

2. Precision (repeatability and reproducibility)

3. Linearity

4. Range

5. Limit of detection (LOD)

6. Limit of Quantitation (LOQ)

7. Selectivity/ specificity

8. Robustness

9. Ruggedness

10. System Suitability Studies

1. Accuracy:

Defination:

The accuracy of the analytical technique reflects the connection between the value accepted either as a standard true value or as an agreed reference value and the observed value.

Accuracy over the specified range of the analytical procedure should be established.

Accuracy should be assessed using at least 9 determinations over at least 3 concentration levels covering the specified range (e.g., 3 concentrations/3 replicates each of the total analytical procedure). Accuracy should be reported by assaying the known added analyte amount in the sample as a percentage recovery or as the difference between the mean and the accepted true value along with the intervals of confidence.

2. Precision: Defination:

The accuracy of the analytical method represents the closeness of agreement (degree of scatter) between a series of measurements obtained from multiple sampling of the same homogeneous sample under the conditions defined.

Precision may be considered at three levels:

a) Repeatability,

b) Intermediate precision and

c) Reproducibility.

Precise use of homogeneous, appropriate samples should be investigated. Furthermore, if a homogeneous sample can not be obtained, it can be tested using samples that are chemically formulated or a sample solution. An analytical procedure's precision is usually expressed as the variance, standard deviation, or variation coefficient of a sequence of measurements.

a. Repeatability:

Repeatability expresses the precision over a short interval of time under the same operating conditions. Repeatability is also called precision intra-assay.

Repeatability should be tested with the following:

a) at least 9 determinations covering the defined procedure spectrum (e.g., 3 concentrations/3 replicates each); or (b) at least 6 determinations at 100% of the test concentration.

b. Intermediate precision:

Intermediate precision Expresses differences within the laboratory: different days, different researchers, different equipment, etc. Depending on the circumstances under which the technique is meant to be used, the degree to which intermediate precision should be calculated. The applicant will assess the impact of random events on the analytical procedure's precision. Typical differences are days, experts, machinery, etc. to be observed. Studying such effects on an individual basis is not considered necessary. It is advised to use an experimental design (matrix).

c. Reproducibility:

Reproducibility expresses Laboratory precision (collaborative research, usually applied to technique standardization). Reproductivity is measured through an inter-laboratory analysis. Reproducibility should be required for the inclusion of procedures in pharmacopoeias, for example, in the case of standardization of an analytical method. Such details do not form part of the checklist of marketing authorisation.

Recommended Data:

For each form of precision examined, the standard deviation, relative standard deviation (variation coefficient) and confidence interval should be stated.

3. Specificity (Selectivity):

Defination:

Specificity is the ability to test the analyte unambiguously in the presence of components that may be known to be present. These may typically include impurities, degradants, matrix, etc. Other supporting analyticalprocedure(s) can compensate for the lack of specificity of an individual analytical procedure.

4. Linearity: Defination:

The an analytical procedure's linearity is its capacity (with in a given range) to produce test results that are directly proportional to the concentration (amount) of the sample.

Linearity should be measured as a function of analyte concentration or content by visual inspection of a plot of signals. If a linear relationship exists, test results should be evaluated using appropriate statistical methods, e.g. by calculating a regression line using the least square method. It is appropriate to apply the correlation coefficient, y-intercept, regression line slope and square residual sum. It is important to include a plot of data. Therefore, it may also be useful to assess the variance of the actual data points from the regression line to test linearity. For the establishment of linearity, a minimum of 5 concentrations is recommended.

5. Range: Defination:

The range of the analytical procedure is the interval between the upper and lower concentration (amounts) of the analyte in the sample (including those concentrations) for which it has been shown that the analytical procedure has an acceptable l The following minimum defined ranges should be considered: for the testing of a drug substance or a finished (food) product: usually between 80 and 120% of the test concentration; level of accuracy, precision and linearity.

For material uniformity: covering a minimum of 70 to 130% of the test concentration, unless a broader, more acceptable range is required, based on the nature of the dosage type (e.g. metered dose inhalers); for Dissolution Testing: + /-20% over the specified range.

6. Detection Limit (LOD): Defination:

The detection limit of an individual analytical Procedure is the lowest amount of analyte in a sample that can be measured but not generally quantitated as an accurate measure. Based on whether the technique is a non-instrumental or instrumental, multiple methods are possible to determine the detection cap. It may be appropriate to use strategies other than those mentioned below.

· Based on Visual Evaluation

· Based on Signal-to-Noise

· Based on the Standard Deviation of the Response and the Slope The detection limit (DL) may be expressed as:

DL=3.3 σ/S

Where σ = the standard deviation of the response,

S = the slope of the calibration curve.

The slope S may be estimated from the calibration curve of the analyte.

7. Quantitation Limit (LOQ):

Defination:

The quantitation limit of an individual analytical procedure is the lowest amount of analyte in a sample that can be determined quantitatively with adequate accuracy and precision. The quantitation limit is a parameter of quantitative assays for low compound levels in sample matrices and is used to determine impurities and/or degradation products in particular. Based on whether the technique is a non-instrumental or instrumental, multiple methods are possible to determine the quantitation limit. It may be appropriate to use strategies other than those mentioned below.

· Based on Visual Evaluation

· Based on Signal-to-Noise Approach

· Based on the Standard Deviation of the Response and the Slope

The quantitation limit (QL) may be expressed as:

QL=10/S

Where σ = the standard deviation of the response,

S = the slope of the calibration curve.

The slope S may be estimated from the calibration curve of the analyte.

8. Robustness: Defination:

The robustness of an analytical procedure is a measure of its ability to remain unaffected by minor yet deliberate changes in the parameters of the system and shows its efficiency during regular use. during the development phase, the robustness evaluation should be considered and depends on the type of procedure being studied. The reliability of an experiment should be shown with respect to intentional differences in system parameters. Examples of typical variations are: Stability of analytical solutions; Extraction time.

In the case of liquid chromatography:

examples of typical variations are:

· Influence of variations of pH in a mobile phase;

· Influence of variations in mobile phase composition;

· Different columns (different lots and/or suppliers);

· Temperature; Flow rate.

In the case of gas-chromatography:

examples of typical variations are:

· Different columns

· Temperature; flow rate.

9. Ruggedness:

Defination:

Ruggedness is Measurement of reproducibility test results under conditions that are normally expected from laboratory to laboratory and from analyst to analyst.An analytical method's roughness is the degree of reproducibility of test results obtained by examining the same samples under a variety of conditions, such as; various laboratories, researchers, equipment, reagents, temperature, time etc.

10. System Suitability Testing:

An integral part of many scientific procedures is machine suitability testing. The tests are based on the concept that the equipment to be analyzed, electronics, analytical operations and samples are an integral system that can be evaluated as such. Test for suitability of the system The criteria to be set for a specific procedure depend on the type of procedure to be validated. For more detail, see Pharmacopoeias.

CONCLUSION:

Pharmaceutical Process Validation is the most important and recognized parameters of cGMP. The validation is an important technique in now a-days because it provides the good quality of the products in pharmaceuticals. Process validation involves a series of activities taking place over the life cycle of the product and process.

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Received on 13.01.2020 Modified on 08.02.2020

Res. J. Pharma. Dosage Forms and Tech.2020; 12(1): 17-26.

DOI: 10.5958/0975-4377.2020.00004.X