3 validation - an overview

8/2/2019 3 Validation - An Overview

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VALIDATION

AN OVERVIEW

Fiona OSullivan


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What is Validation?

The documented act of proving that any procedure, process,equipment, material, activity or system actually leads to the

expected results

W.H.O


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Content Evolution of Validation

Regulations, Guidelines Definitions

Why Validate?

Commissioning, Qualification, Validation

Lifecycle Approach to Validation

Validation Documentation

Validation Related Programmes

Effective Validation, how much validation and benefits of

validation


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Evolution of Validation

In 1971 the first edition of the British Guide to Good

Pharmaceutical Manufacturing Practice stated:

Procedures should undergo a regular critical appraisal to

ensure that they are, and remain, capable of achieving the

results they are intended to achieve


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Evolution of Validation

The 1983 edition of the UK GMP Guide defined validation

as;

The action of proving that any material, process, procedure,

activity, equipment or mechanism used in the manufacture

or control, can, will and does achieve the desired andintended result


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Evolution of Validation Prior mid 1970s validation only applied to analytical testing

methods

Mid 1970 with introduction of GMP rules in US and Europe

wide spread validation began

1977: Sterilisation Validation

1979: Aseptic Processing Validation


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Evolution of Validation 1981: Water Treatment Validation

1983: Nonaseptic Processing- FDA issued draft guidelines

on General Principles of Process Validation - finalised in

May 1987

Late 80s/early 90s

- Cleaning Validation

- Equipment Qualification - FAT,

commissioning and qualification


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Regulations

Code of Federal Regulation

www.fda.gov/cder/dmpq/cgmpregs.htm

EU Guide to GMP Vol 4.

-Annex 15 Qualification and Validation, July 2001

http://pharmacos.eudra.org/F2/eudralex/vol-4/home.htm


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Guideline Documents Recommendations on Validation Master Plan, Installation

and Operational Qualification, Non Sterile ProcessValidation and Cleaning Validation, PIC/S, July 2004

Recommendation on the Validation of Aseptic Processes,

PIC/S, July 2001

Guideline on the General Principles of Process Validation,

FDA, May 1987

Guide to Inspection Validation of Cleaning Processes, FDA,

July 1993


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Regulations versus Guidelines Regulations state what must be done and do not stipulate

how to do it

Guides and guidelines are written and made effective at any

time without public notices or hearings and are not legally

binding

Many group have come together to write guidelines for

Validation in the past 20 years

Industry standards and practices


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European definition

Documented evidence that the process, operated within

established parameters, can perform effectively andreproducibly to produce a medicinal product meeting its

predetermined specifications and quality attributes

EU Guide to GMP, Annex 15, July 2001


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US definition

Process Validation is establishing documented evidencewhich provides a high degree of assurance that a specifiedprocess will consistently produce a product meeting its

pre-determined specifications and quality characteristics

US Food and Drug Administration, 1987


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Why Validate? Essential element of Quality Assurance. QC testing has too

many limitations

Regulatory requirement

Improves equipment & process knowledge

Enables continuous improvement

Should reduce the risk of complaints and recalls


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Why Validate? A regulatory exercise & good business practice

Products must be safe and effective. The validation

process from research laboratory to commercial

manufacturing is critical in assuring this claim

A basic premise in the pharmaceutical industry - quality

cannot be tested into the product. It must be built into the

product and any method, device or system associated with

its production

Validation - logical avenue to achieve this


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What does Validation apply to?

VALIDATION

EQUIPMENT FACILITIES UTILITIESCONTROL

SYSTEMS

PROCESS &

CLEANING


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Terminology Commissioning

Qualification

Validation


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Purpose of Qualification

to provide assurance that they (systems) have been

properly designed, installed and tested according to pre-

determined acceptance criteria, based on assessment of

those installation and operational characteristics, and

parameters with potential product quality impact

ISPE Baseline Pharmaceutical Engineering Guide


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Commissioning defined as.

A well planned, documented and managed engineering

approach to the start-up and turn over of facilities, systemsand equipment to the end-user that results in a safe and

functional environment that meets established design

requirements

ISPE Baseline Pharmaceutical Engineering Guide


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Terminology FAT Factory Acceptance Testing

SAT Site Acceptance Testing

Commissioning

IQ - Installation Qualification

OQ - Operational Qualification

PQ - Performance Qualification


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Definitions

Factory Acceptance Testing (FAT)

Testing performed at the vendor site to demonstrate that the

system functions in accordance with the user requirements

Site Acceptance Testing (SAT)

Testing performed at the production site to demonstrate that thesystem functions in accordance with the user requirements


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Definitions

Installation Qualification (IQ)

Documented verification that all aspects of a facility utility or

equipment that can affect product quality adhere to approved

specifications and are installed correctly

Operational Qualification (OQ)

Documented verification that all aspects of a facility utility or

equipment that can affect product quality operate as intended

throughout all anticipated ranges


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Definitions continued

Performance Qualification

Documented verification that the system as a whole performs its

intended functions reliably and reproducibly


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Lifecycle Approach to ValidationPROCESS REQUIREMENTS

& PRODUCT

SPECIFICATIONS

USER REQUIREMENTS &

SPECIFICATIONS

FUNCTIONAL

SPECIFICATIONS

DETAILED DESIGN DESIGN

QUALIFICATION

CONSTRUCTION /

FABRICATIONS

OPERATIONAL

QUALIFICATION

INSTALLATION

QUALIFICATION

FACTORY ACCEPTANCE

TESTING

PERFORMANCE

QUALIFICATION

PROCESS & CLEANING

VALIDATION

SAT / COMMISSIONING


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Project Plan


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Validation Process Validation

Cleaning Validation

Analytical Method Validation

Control/Computer System Validation


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Process Validation Terminology Prospective

Concurrent

Retrospective


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Validation Terminology Prospective Validation

Validation conducted prior to the distribution of either a newproduct or a product made under revised manufacturing processwhere the revisions may affect the products characteristics

Concurrent ValidationValidation during routine production

Retrospective ValidationValidation of a process for a product already in distribution

based upon accumulated production, testing and control data


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An ExampleValidation of a Sterile Product

Manufacturing operations

mixing/blending

heating/cooling..

Sterilisation operations

aseptic process

terminal sterile filtration

steam, dry heat, ETO etc.

Environmental control systems

clean room

LAFs


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Validation of a Sterile Product Personnel Monitoring

Validation of aseptic process

Process Simulation/Media Fill

Market container/closure sterilisation

Autoclave validation

sterilisation tunnel

Equipment sterilisation

Disinfection etc..etc


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Validation Documentation Validation Master Plan (VMP)

Validation protocol

Equipment, systems & services files for qualification

Validation SOPs & procedures

Validation raw data

Validation Summary Reports

Validation approvals


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Validation Master Plan A validation master plan (VMP) should provide information

on the way a company organises its validation work

The purpose of a VMP is to:

- briefly describe why, what, by whom, how and when the

validation is to be carried out- provide up to date information about the state of affairs

relating to the validation

- demonstrate the company commitment to carry out

adequate validation


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Advantages of a VMPA VMP ensures:

-management know what the validation program involves

with respect to time, people and money and understand the

necessity for the programme

- the prevention of wasting resources on ineffective or

unnecessary validation

-members of the validation team know their tasks andresponsibilities


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Suggested Content for VMP Introduction including company business and structure

Facility description and design including Plant Layout and

area plans

Process description

Process control

Services and utilities Systems/equipment/utilities/process to be validated

Validation schedule

Support programmes

Management structure

Approval by key personnel


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When should Plan be written Ideally prior to commencing any validation for existing

facilities

For new facilities during construction

Revise as appropriate


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VMP Inputs Corporate or Company Policy

GMP

Regulatory Requirements

Market Requirements


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Validation protocols Introduction

Purpose/Objective

Description of process, system or equipment

Documentation prerequisites prior to validation

Scope

Procedure & evaluation Acceptance criteria

Responsibility

Approval & follow up required


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Scope of Validation How many consecutive runs?

3 consecutive runs

Frequency of validation

Extent of validation?

For Process Validation

- all products ?

- all manufacturing operations?

Sound scientific rationale for strategy used


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Revalidation Policy Regular review of systems, equipment and processes

Revalidation policy of 3-5 years

Change control review of requirement to revalidate

following change


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Validation Related Programmes Equipment calibration

Process development

Equipment qualification

Change control


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Effective Validation requires.. Validation Master Plan

Good Validation Team

Training all relevant personnel in validation requirements

Company commitment & resources

Good protocols, reports, records and follow through

Good communication


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How much Validation? How much validation is too much?

Satisfy regulatory authorities

Industry trends and guidelines

Value of work


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How much Validation? Logic, common sense and sound scientific rationale

Company has responsibility to define appropriate level of

validation based on judgement, experience and regulatory

requirements

Risk assessment- investigate and evaluate risks


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Benefits of Validation Questioning approach to equipment/systems/utilities/process

Understanding how process works

Highlights potential weaknesses

Allows corrective action to be taken

Foundation for monitoring and in-process control


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Benefits of Validation Reliable and consistent performance

Easy measurement and control of quality

Encourages communication between people

Reduce level of testing