INTRODUCTION:

Analysis is important for any product, and it is important for medicine because it involves life¹. An analytical chemistry is a branch of science that uses advanced technology in determining composition by way of analysis². An analytical chemistry is the analysis of the classification, measurement and identification of chemical additives of herbal and synthetic compounds composed of one or more compounds or features. Analytical chemistry is divided into two distinct classes, qualitative evaluation that mean chemical-related additives are present in the sample, and quantitative evaluation measure the amount of fine particles or compounds within an object, i.e. a sample³. Drug development is a long-term process that includes drug discovery, laboratory testing, veterinary research, clinical trials, and accreditation. Many regulatory agencies, such as the United States Food and Drug Administration (FDA), require that a drug product be tested for its potency, strength, quality, purity, and stability before it can be released for use, in order to improve its effectiveness. and safety. As a result, drug validation and process control are essential, despite any potential problems⁴.

Analytical Method Development:

If no specific methods are available, new methods are developed to test the product of the novel. In order to investigate the existence of novel pharmaceutical or non-pharmaceutical product approaches they are being developed to reduce the amount without time for high accuracy and strength. These techniques have been developed and are working with the original functionality. Alternative methods are developed and used to change the current process within the laboratory information for comparison with all accessible and accessible disadvantages.

Fig. 1: Life cycle of the analytical method ⁵

Steps for developing a method:

Various steps are involved in the development of an analytical method are as follows

· Characterization of analyte and standard: All known known data related to the analyte and its structure meaning that it refers to physical and chemical properties such as melting, optical isomerism, etc., are collected.

A normal analyte equals 100% purity obtained. The required arrangement will be created for the appropriate storage area (refrigerator, desiccators, and refrigerator).

In the sample matrix, where multiple components are to be measured the number of elements that are accurately identified presenting information and the level of achievement are calculated. Techniques such as spectroscopy (UV-Visible, FTIR, atomic absorption spectroscopy, etc.), fluid-based chromatography and gas chromatography etc., however, are almost always associated with sample stability^3.

· The need for a strategy: The need for an analytical approach is essential for building an analytical fig. of benefit such as line, selection, specification, width, accuracy, accuracy, LOD, LOQ etc. will be disclosed ³.

· Literature research and previous methods: All medical literature related data is updated due to its physical and chemical properties, production, melting and validation methods based on relevant literature, journals, united states pharmacopeia / national formula (USP/NF), official agricultural chemical association (AOAC) and the American testing and building materials organization (ASTM) are published and it is much easier to look at automated Chemical Abstracts Service computer manuals³.

· Selecting the method: Using data obtained from the document, the method changes as the method is adjusted where necessary. In some cases, it is important to find additional tools to create, modify or replicate and to validate existing analysis and evaluation processes.

· If no appropriate previous methods are available to investigate the analyst will be evaluated³.

· Appropriate tool and initial studies: Inclusion (IQ), operational suitability (OQ), and operational suitability (PQ) of a tool that complies with the standard research methodology are assessed by the appropriate set of tools ^3.

· Enhancement: During an upgrade, when the parameter is changed in time, and the set of conditions are separated, before applying the trial and error method. This work is necessary to achieve it based on a systematic scientific approach to all the required points and written in relation to dead conclusions^3.

· Proper documentation of analytical fig. of merits: A definite determined analysis fig. of benefit including LOD, LOQ, cost, line and timing of testing and sample planning, etc. it is also recorded

· Strategic analysis of a real sample: The solution solution requires a straightforward, complete knowledge of the great interest of the tree without all the different parts of the matrix ³.

· Percentage rate for actual sample detection and sample quantitative analysis: Percentage for the sample of a spiked, real standard drug into a grid sample that includes no analysis analyzes. Improvements in recovery from recovery to testing should have emerged. It is not always necessary to obtain a 100% refund so far as the results can be reproduced to be seen with a high degree of validity ^3.

Validation:

Validation is an important part of quality assurance; involves a systematic study of the programs, resources and processes aimed at determining whether they perform their intended functions adequately and consistently as specified. The proven process is the one that has been shown to provide the highest level of assurance that the same collections to be produced meet the required conditions and are therefore officially accredited. Self-certification does not improve processes but ensures that processes are well developed and under control ^[6]. If any new production method or preparation method is adopted, steps must be taken to demonstrate its suitability for standard processing. The specified process must be demonstrated to produce a product that meets the required quality. At this stage, the extent to which deviations from the selected parameters can affect the quality of the product should also be considered. Once certain processes or products have been verified during the development phase, it is not always necessary to re-verify the entire process or product once the same equipment is used or the same products are already produced, as long as the final product complies with the internal controls as well. final product details. There should be a clear distinction between internal control and Validation. In production, tests are performed each time with each group using specifications and methods designed during the development phase. The aim is to monitor the process continuously ^7.

Table 1: Important stages in validation ⁸

Stage 1	Stage 2	Stage 3
It include pre-validation qualification stage.	It involves process validation phase.	It is also called the validation maintenance stage.
It coves all exercises identifying with product studies and improvement, formulation pilot batch testing, scale-up research, exchange of innovation to business scale groups, setting up stability conditions, and managing of in-process, finished pharmaceutical formulations, qualification of equipment, master documents, and process limit.	It is intended to check that every installed limit of the vital process parameter is substantial and the satisfactory products can be created even below the worst situation.	it requires constant review of all procedure related archives, including validation of the review reports, to guarantee that there have been no modifications, departure, failures, and alteration to the production procedure and that all standard operating procedures (SOPs), involving change control procedures, had been observed. At this phase, the approval team involving people representing all essential departments also guarantees that there have been no modifications/deviations that ought to have brought about requalification and revalidation.

Figure 2: Types of validation ⁹

Equipment Qualification:

The main idea of authorization is to provide an unconventional form of reported evidence that the material and process are compliant with the written standard. The level is controlled by the complexity of the system or equipment. Validation should provide the necessary data and evaluation method required to ensure that the framework and procedure meet the prescribed requirements. Equipment Validation includes the following:

Installation Qualification (IQ): It is a written confirmation that all aspects of the facility, service or equipment that may affect product quality comply with authorized specifications and are properly installed. ^10.

Installation qualification points include

• Equipment design feature (i.e. material of construction cleanability, etc.)

• Installation conditions (writing, utility, functionality, etc.)

• Calibration, preventative maintenance, cleansing schedules.

• Safety features.

• Supplier documentation, prints, drawings and manuals.

• Environment conditions (such as clean room requirements, humidity, and temperature ^11.

Operational qualification (OQ): Written confirmation that all aspects of the facility, service or equipment that may affect product quality are working out to target all expected categories^{. 12.}

Operation Qualification points include

• Process control limits (time, temperature, pressure, line speed, setup conditions, etc)

• Software parameters

• Raw material specifications

• Process operating procedures.

• Material handling requirements.

• Process change control

Performance Qualification (PQ): It is a documented Validation that all aspects of a facility, utility or equipment perform as intended in meeting predetermined acceptance criteria

Performance Qualification points include

• Actual product and process parameters and procedure established in OQ.

• Acceptability of the product.

• Assurance of process capability as established in OQ.

• Process repeatability, long term process stability

Process Validation:

“Process Validation is defined as data collection and testing, starting from the process of designing a process across production, establishing scientific evidence that the process is capable of delivering quality products continuously ^”13. Process Validation should ensure that the control strategy is sufficient to support the process structure and product quality. Validation should include all the energy produced and all the production sites used to produce products on the market^14.

Types of process Validation:

Prospective Validation: It is defined as the most reported system that the device does what it has shown to do based on pre-programmed protocols. This Validation is usually done earlier in order to distribute both a new item and an item made under the revised production process^15.

Prospective validation should include, however, not limited to the following:

· A brief description of the process.

· Summary of important processing steps to be investigated.

· List of goods / services to be used (including rating, monitoring / recording) and their measurement status.

· You have completed the specification of the product to be released.

· List of analysis methods, as appropriate.

· Proposed in-process controls with acceptance conditions.

· Additional tests to be performed, in terms of acceptance and confirmation of analysis, as appropriate.

· Sample system.

· Methods for recording and evaluating results.

· Duties and responsibilities.

· Proposed timeline¹⁶

Concurrent Validation: Similar to possible Validation without a valid firm, it will provide the product at the time of learning, to the public at its market cost, and moreover as a back guarantee. This type of Validation includes the consideration of key processing steps and product output. This assists production and reported evidence to show that the production process is in a controlled state^15.

This Validation includes in-process monitoring of important processing steps and product testing. This facilitates production and documentary evidence to show that the production process is in a controlled state.

· In rare cases if it may be acceptable not to complete the Validation process before normal production begins.

· One-time Validation decision must be approved, in writing and approved by authorized personnel.

· Documentation requirements for simultaneous Validation are the same as specified for future Validation¹⁶

Retrospective Validation: It is characterized by the reported established assurance that the system does what it is supposed to do in the research and investigation of historical data. This is achieved by a production information test to show that the process has been in control. This is the kind of process approval that is already being distributed. Reversible Validation is sufficient for well-established processes and will be invalid in the event of current changes between product design, operating systems or device^15.

Some of the key elements of retrospective Validation are:

· Collections are made for a fixed period (minimum of the last 10 consecutive times).

· Number of votes issued annually.

· Collection size/power/manufacturer/year/period.

· Professional production / packaging documents.

· Current details of finished products/finished products.

· List of deviation processes, corrective measures and changes in production documents.

· The stability data of several clusters.^16.

Revalidation: Re-Validation provides evidence that changes in process, as well as the nature of the process presented do not adversely affect process features and product quality. Organizations, resources, equipment and methods that include cleaning, should be inspected periodically to ensure they remain functional. Where no significant changes have been made to the approved environment, reviewed evidence that institutions, organizations, tools and processes that meet the recommended requirements meet the need for renewal.

Re-Validation is required in certain circumstances. Some of the changes that need to be confirmed are as follows:

· Changes in immature substances (body structures such as density, viscosity, particle size distribution and humidity, etc., which may affect the process or product).

· Changes in the raw material manufacturer's source.

· Changes in packaging materials (first container / closing plan).

· Changes in the system (e.g., mixing time, setting temperature and batch size).

· Changes in equipment (eg, automatic detection system addition). Equipment changes that include modification of equipment in a “similar” way will usually not need to be re-validated unless the new item must have a qualification.

· Changes in industry / institution.

· The decision not to undergo a re-certification course must be fully documented and in writing.¹⁶

Analytical Method validation:

1) Accuracy: The accuracy of the analysis process reflects the proximity of the agreement between the received value of the reference value and the acquired value. This is sometimes called trueness¹⁷.

2) Precision: The precision of the analysis process reveals the proximity of the agreement (scatter rate) between a series of measurements obtained from multiple samples of the same sample under specified conditions.

Precision can be considered at three levels: repeatability, intermediate precision and reproducibility. The precision of the analysis process is often expressed as variance, standard deviation or coefficient of variation in a series of measurements¹⁷.

Precision can be considered at 3 levels:

· Repeatability: also known as intra-assay precision, it expresses the precision of a test performed under similar operating conditions over a short period of time. A minimum of six replicates of a similar or consistent sample ready for 100% check are required ¹⁸.

· Intermediate precision: This term refers to the accuracy of research laboratories on different days, with different analysts, and with different instruments and equipment. Two analysts, each preparing six sample solutions according to the technique

· Reproducibility: This term refers to the consistency of results obtained from different analytical laboratories. According to the analytical technique, each research centre set up a total of six sample solutions ¹⁸.

3) Specificity: The ability to assess the analyte definitively in the presence of components that may be present is known as specificity. Impurities, degradants, matrix, and other substances are examples of these. An individual analytical procedure's lack of specificity may be mitigated by additional supporting analytical procedure(s).

4) Limit of detection (LOD): An particular analytical procedure's detection limit is the smallest amount of analyte in a sample that can be detected but not necessarily quantified as an exact value ¹⁷.

LOD can be expressed as LOD = 3.3SD/S

Where,

SD = standard deviation of response

S = slope of calibration curve

5) Limit Of Quantitation (LOQ): A specific analytical procedure's quantitation limit is the smallest amount of analyte in a sample that can be quantitatively measured with sufficient precision and accuracy. The quantitation limit is a parameter in quantitative tests for low amounts of substances in sample matrices, and it is used to determine impurities and/or degradation products in particular ¹⁷.

LOQ can be expressed as LOQ = 10SD/S

Where,

SD = standard deviation of response

S = slope of calibration curve.

6) Linearity: The line of the analysis process is its ability (within a given range) to obtain experimental results directly proportional to the concentration (value) of the analyte in the sample.

7) Range: The scope of the process of analyzing the interval between the high and low concentrations (values) of the analyte in the sample (including this focus) has been shown by which the analysis process has the right level of accuracy, accuracy. and line.

8) Robustness: The rigidity of the process of analyzing the measure of its resilience is relatively small, but the deliberate variability in method parameters and provides an indication of its reliability during normal use ¹⁷.

9) System compatibility parameters: System suitability tests are used to assess the sensitivity, correction, and dynamics of the chromatographic system are appropriate for analysis. The most commonly used features of a system fit are the tailing factor, no. of theoretical plate, retention time, resolution, etc. ²⁰

Table 2: Acceptance criteria (limits) of system suitability parameters are shown in the following ²¹

Parameter name	Resolution	Relative retention	Tailing factor	Number of theoretical plate	RSD
Acceptance criteria	˃1.5	˃1	˂2	˃2000	˂2

CONCLUSION:

This article explains what validation is, the many forms of validation, why it is important, how to build a method, and how to carry out the validation procedure to show that the methodology can be used for the intended purpose. All validation parameters are thoroughly described with examples of specific pharmaceuticals, including linearity, LOQ, LOD, range, specificity, robustness, ruggedness, and system suitability. Validation is a technique used in the pharmaceutical industry to ensure that quality is built into the procedures that support product development and production.

ACKNOWLEDGMENT:

I would like to express my sincere thanks to Mr. Someshwar Mankar and Dr. Santosh Dighe for their valuable guidance and support for this review work.

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Received on 19.01.2022 Modified on 31.01.2022

Research J. Science and Tech. 2022; 14(1):77-83.

DOI: 10.52711/2349-2988.2022.00012