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Paras Virani1, 2*, Parul Jain3, Hasumati Raj2, Vineet Jain2
1Research Scholar 2014, Gujrat Technological University, Gujarat
2Department of Quality assurance, Shree Dhanvantary Pharmacy College, Kim, Surat, Gujarat
3Department of Quality assurance, Maliba Pharmacy College, Bardoli, Surat, Gujarat

Validation is an act of proving that any procedure, process, equipment, material, activity  or system performs as expected under given set of conditions and also give the required accuracy, precision, sensitivity, ruggedness. Validation parameter is used for establishing documented evidence which proves that performance characteristics of the method meet the requirements for the intended analytical applications. The goal of validation is to demonstrate that analytical results produced by the application of a particular method are fit for an intended purpose. In this review article we discussed about the validation and its important parameter.


PharmaTutor (ISSN: 2347 - 7881)

Volume 2, Issue 10

Received On: 22/07/2014; Accepted On: 30/07/2014; Published On: 01/10/2014

How to cite this article: P Virani, P Jain, R Hasumati, V Jain; Updated Review: Validation and Method Validation Parameters; PharmaTutor; 2014; 2(10); 27-37

Method validation is the process of demonstrating that an analytical method is suitable for its intended use, and involves conducting a variety of studies to evaluate method performance under defined conditions. Validation is required for herbal procedure, new process and reaction, new molecules, active ingredients, residues, impurity profiling and component of interest in different matrices. An analytical methodology consists of the techniques, method, procedure and protocol. This methodology includes the required data for a given analytical problem, required sensitivity, required accuracy, required range of analysis and required precision to the analyst.

The International Conference on Harmonization (ICH) of Technical Requirements for the Registration of Pharmaceuticals for Human Use[1] has developed a text on the validation of analytical procedures. The United States Food and Drug Administration (USFDA) have proposed guidelines on submitting samples and analytical data for methods validation.[2-5] The United States Pharmacopoeia (USP) has published specific guidelines for method validation for compound evaluation.[5]

The word validation was not mentioned in the current Good Manufacturing Practices (cGMP’s) of 1971, and precision and accuracy were stated as laboratory controls. The need for validation was implied only in the cGMP guideline of March 1979. It was done in two sections: (1) Section 211.165, where the word ‘validation’ was used and (2) section 211.194,[6] in which the proof of suitability,accuracy and reliability was made compulsory for regulatory submissions.

A review on validation of bioanalytical methods was published by Karnes et al. in 1991 which was intended to provide guidance for bioanalytical chemists .[7]One year later, Shah et al. published their report on the conference on "Analytical Methods Validation: Bioavailability, Bioequivalence and Pharmacokinetic Studies" held in Washington in 1990 (Conference Report). During this conference, consensus was reached on which parameters of bioanalytical methods should be evaluated, and some acceptance criteria were established.[8]  In the following years, this report was actually used as guidance by bioanalysts And also US FDA Technical Review Guide gives Validation of Chromatographic Methods prepare by Center for Drug Evaluation and Research (CDER) in 1993.[9] That give fully authorized guideline for validation of chromatographic methods.Despite the fact, however,  that some principle questions had been answered during this conference, no specific recommendations on practical issues like experimental designs or statistical evaluation had been made. In 1994, Hartmann et al. analyzed the Conference Report performing statistical experiments on the established acceptance criteria for accuracy and precision.[10]  Based on their results they questioned the suitability of these criteria for practical application. From 1995 to 1997, application issues like experimental designs and statistical methods for bioanalytical method validation were discussed in a number of publications of Dadgar et al[11], Wieling et al[12], Bressolle et al[13]. andCauson[14]. An excellent review on validation of bioanalytical chromatographic methods has been published by Hartmann et al. in 1998, in which theoretical and practical issues were discussed in detail. Finally, in an update conference of the Washington conference,[15] experiences and progress since the first conference have been discussed. The results were again published by Shah et al. in a report (Conference Report II) .[16] which has also been used as a template for their own guidelines by the U.S. Food and Drug Administration (FDA). Besides, it should be mentioned that some journals like Journal of Chromatography B or Clinical Chemistry have established their own criteria for validation.[17] Two other documents that seem to be important in this context have been developed by the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) and approved by the regulatory agencies of the European Union, the United States of America and Japan. Despite the fact, that these were focussed on analytical methods for pharmaceutical products rather than bioanalysis, they still contain helpful guidance on some principal questions and definitions in the field of analytical method validation. the first document, approved in 1994[18], concentrated on the theoretical background and definitions, the second, approved in 1996, on methodology and practical issues [19]. both can be downloaded from the ich homepage free of charge (ich.org). validation of analytical methods – strategies & importanceravichandran v,  shalini s, sundram k. m and harishrajak in 2010.In few time before gives  validation and peer review of u.s. environmental protection agency chemical  methods of analysis in 2005,[20] After that validation  a critical parameter for quality control of pharmaceuticals tangripranshu, rawatprakashsingh, jakhmolavikash, lakshmayya in 2012,[21]  method development and validation- a review article by sudha t, krishanakanth v, nukalapooran in 2012. Guidance for IndustryGuideline for Analytical Procedures and Methods Validation for Drugs and Biologics by FDA and CDER in 2014.[22]

1. The company's overall policy, intentions, and approach to validation, including the validation of production processes, cleaning procedures, analytical methods, in-process control test procedures, computerized systems, and persons responsible for design, review, approval and documentation of each validation phase, should be documented.

2. The critical parameters/attributes should normally be identified during the development stage or from historical data, and the ranges necessary for the reproducible operation should be defined. This should include:
- Defining the Medicinal Product/Drug in terms of its critical product attributes;
- Identifying process parameters that could affect the critical quality attributes of the Medicinal Product/Drug;
- Determining the range for each critical process parameter expected to be used during routine manufacturing and process control

3. Validation should extend to those operations determined to be critical to the quality and purity of the Medicinal Product/Drug.

the four most common types of analytical procedures:
1. Identification tests
2. Quantitative tests for impurities content
3. Limit tests for the control of impurities
4. Quantitative tests of the active moiety in samples of drug substance or drug product or other selected component in the drug product.

The biggest advantage of validation is that it builds a degree of confidence, not only for the developer but also to the user. Although the validation exercise may appear costly and time consuming, it results inexpensive, eliminates frustrating repetitions and leads to better time management in the end. Minor changes in the conditions such as reagent supplier or grade, analytical setup are unavoidable due to obvious reasons but the method validation absorbs the shock of such conditions and pays for more than invested on the process.

The most compelling reasons to optimize and validate pharmaceutical productions and supporting processes are quality assurance and cost reduction .the basic principles of quality assurance has as their goal and the production of articles that are fit for their intended use.10 These principles are Quality, safety, and effectiveness must be designed and built in to the product, quality cannot be inspected or tested in the finished products and each step of the manufacturing process must be controlled to maximize the probability that the finished product meets all quality and design specification. The relationship of quality assurance and process validation[23] goes well beyond the responsibility of any quality assurance functions, nevertheless it is fair to say that process validation is a quality assurance tool because it is establishes a quality standard for the specific process.


Equipment validation is usually carried out by conducting the following activities, individually or combined:
- Design Qualification (DQ): documented verification that the proposed design of the facilities, equipment,or systems is suitable for the intended purpose.
- Installation Qualification (IQ): documented verification that the equipment or systems, as installed ormodified, comply with the approved design, the manufacturer’s recommendations and/or user requirements.
- Operational Qualification (OQ): documented verification that the equipment or systems, as installed ormodified, perform as intended throughout the anticipated operating ranges.
- Performance Qualification (PQ): documented verification that the equipment and ancillary systems, asconnected together, can perform effectively and reproducibly based on the approved process method andspecifications.


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