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VALIDATION OF PHARMACEUTICAL PROCESSES

Presented By..

Mr. Rahul S. DalviM. Pharm. (SEM – I)Dept. of Pharmaceutics

Guided By..

Dr. A. J. ShindeAsso. Professor of Pharmaceutics

BHARATI VIDYAPEETH COLLEGE OF PHARMACY, KOLHAPUR

2015-2016

Date: 02/12/2015

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Contents : Introduction

Need of Validation

Scope of Validation

Documentation of Validation

Validation Master Plan

Types of Validation Process Validation Cleaning Validation Equipment Validation Validation of Analytical method

Conclusion

References

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Introduction The concept of validation was first proposed by Food and Drug

Administration(FDA) officials, Ted Byers and Bud Loftus, in the

mid 1970s in order to improve the quality of pharmaceuticals.

Validation is "Establishing documented evidence that provides a

high degree of assurance that a specific process will consistently

produce a product meeting its pre-determined specifications and

quality attributes.

This is to maintain and assure a higher degree of quality of food

and drug products.

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Need for validation Customer satisfaction

Customer mandated

Product liability

Control production cost

The development of the next generation

Safety

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Scope of validationAnalytical Test Methods

Instrument Calibrations

Process Utility Services

Raw Material

Equipment

Facilities

Product Design

Cleaning

Operators

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Documentation of ValidationThe validation activity cannot be completed without proper

documentation of each and every minute activity with utmost details.

Documentation of validation is generally different types such as:

Validation Master Plan(VMP)

Validation Protocol(VP)

Validation Reports(VR)

Standard Operating Procedure(SOP)

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Advantages :

It gives idea about future performed: What activities are to be performed?

Who is going to perform these activities?

When the activities should start and when

they should get over?

What documents will be generated?

What the policy on revalidation?

Validation master plan

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V.M.P. includes.. Premises

Processes

Products

Format for protocol and other documentation

List of relevant SOPs

Planning and scheduling

Location

Estimation of staffing requirements

A time plan of the project

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Guidelines on Preparing V.M.P. V.M.P. write on A4 size paper.

File in a presentable form.

Have sufficient explanatory drawings.

Clearly divide the V.M.P. in different form.

It must be dated and signed properly by authorized

persons.

If found any step inappropriate is discuss this the

F.D.A. people in advance.

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Types of Validation The major types of Validation : Process validation

Cleaning validation

Equipment validation

Validation of analytical methods

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Process validation Definition As per FDA Nov.2008,‘The collection of data from the process

design stage throughout production,which establishes scientific

evidence that a process is capable of consistently delivering quality

products.

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Process validation life cycle:

Stage 1. Process design

Stage 2. Process qualification

Stage 3. Continued process verification

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Types of Process validation:

Prospective validation.

Retrospective validation.

Concurrent validation.

Revalidation.

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Process validation Flow chart:

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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.

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Source of contamination: Cross contamination product of one product into another.

Product contamination by a foreign material.

Microbial contamination.

Cleaning methods: Manual cleaning method.

Semi automated procedures.

Fully automated procedures.

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Factors Influencing Cleaning validation : Product.

Equipment.

Facilities.

Cleaning methods.

Cleaning agents.

Sampling.

Testing, Limits, and acceptance criteria.

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Cleaning validation Flow chart :

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Equipment Validation

Definition As per FDA, May 1987,‘Action of proving that any

equipment works correctly and leads to the expected result is

equipment qualification.

It is not a single step activity but instead result from many

discrete activities.

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Steps involved.. User requirement specification

Design qualification

Installation qualifications

Operational qualifications

Performance qualification

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Process flow chart :

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Validation of analytical methods

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”.

Accuracy :

“The closeness of test results obtained by that method to the true value. This

accuracy should be established across its range.”

Precision:

“The degree of agreement among individual test results when the method is

applied repeatedly to multiple sampling of a homogenous sample.”

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Specificity :

“The ability to assess unequivocally the analyte in the presence of

components that may be expected to be present, such as impurities

degradation products and matrix components.”

Limit of Quantitation :

“A characteristic of quantitative assays for low levels of compounds in

sample matrices such as impurities in bulk substances and degradation

products in finished pharmaceuticals. It is the lowest amount of analyte in

a sample that can be determined with acceptable precision and accuracy

under the stated experimental conditions.”

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Range :

“Interval between the upper and lower of analyte (including these levels) that

have been demonstrated to be determined with a suitable level of precision ,

accuracy and linearity using the method as written. The range is normally

expressed in the same units as test results. ( e.g. Percentage , parts per

million, etc.) obtained by the analytical method.”

Ruggedness:

The degree of reproducibility of test results obtained by the analysis of the

same sample under a variety of conditions such as different laboratories,

different analysts, different instruments , different lots of reagents, different

elapsed assay times, different assay temperatures, different days, etc.”

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Robustness:

"A measure of its capacity to remain unaffected by small but deliberate

variations in method parameters and provides an indication of its reliability

during normal usage.”

Linearity :

“Its ability to elicit tests that are directly or by a well defined mathematical

transformations proportional to the concentration of analyte in samples

within a given range.”

Limit of Detection :

The lowest amount of analyte in a sample that can be detected but not

necessarily quantitated, under the stated experimental conditions.”

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Conclusion Validation has been proven assurance for the process efficiency and

sturdiness and it is the full fledged quality attributing tool for the

pharmaceutical industries.

Validation is the commonest word in the areas of drug development,

manufacturing and specification of finished products. It also renders

reduction in the cost linked with process monitoring, sampling and

testing.

Apart from all the consistency and reliability of a validated process

to produce a quality product is the very important for an industry.

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References1. Fundamental of quality assurance techniques..by Ramesh Sawant and

Sandip Hapse,First edition Dec 2011, Career publications.

2. Pharmaceutical Quality Assurance..by Manohar Potdar,Second edition Dec

2007,Nirali Prakashan.

3. IJRPC 2011 ‘An overview of pharmaceutical validation: quality

assurance view point’ by Nandhakumar et al.

4. TJPR Review Article ‘An Overview of Pharmaceutical Validation and

Process Controls in Drug Development’ Elsie Jatto and Augustine

O.Okhamafe

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