VALIDATION

1. Purpose

This document covers the process for VALIDATION of processes, products, software and sterilization and sterile barrier systems  in compliance of ISO13485.

 2. Approval

(Version at end of page)

Signed V16  AA  19.08.2021  Approved 25.05.2022 SCR (RP)

3. Scope

The process covers all documents and process and products as defined in the SOP

4. Responsibilities

Approval & Changes:: Author of the document, Alexis Arhondonis, medicines; RP SC Rudolph-Shortt

5. Definitions

Protocol - the defined plan for the scope, responsibilities, activities and records of the validation 

Software consists of information and is generally intangible and can be in the form of approaches, transactions or procedures.

Hardware is generally tangible and its amount is a countable characteristic. Processed materials are generally tangible and their amount is a continuous characteristic. Hardware and processed materials often are referred to as goods.

Installation Qualification (IQ) : The installation qualification demonstrates that the sterilization equipment and any ancillary items have been supplied and installed in accordance with their specification.

Operational Qualification (OQ) : The operational qualification demonstrates that the installed equipment is capable of delivering the specified process within defined tolerances.

Performance Qualification ( PQ) : The performance qualification demonstrates that the equipment consistently operates in accordance with predetermined criteria and that the process produces product or output to the required specification

Qualification - Action of proving that any equipment works correctly and actually leads to the expected results.The word validation is sometimes widened to incorporate the concept of qualification.

Calibration - Activity of verifying the accuracy of a test equipment to SI standards and /or bring the test equipment back to accuracy

Verification - checking compliance to a requirement or specification

Validation -  Action of proving, in accordance with the principles of Good Manufacturing Practice, that any procedure, process, equipment, material, activity or system actually leads to the expected results (see also qualification).

Validation Master Plan (Pharmacy) -  validation master plan (VMP) outlines the principles involved in the qualification of a facility, defining the areas and systems to be validated, and provides a written program for achieving and maintaining a qualified facility 

6. Abbreviations

SOP – Standard Operating Procedure

QMS – Quality Management System

PARA - Preventive Action Risk Assessment

NCCA - Non Conformance Corrective Action

SHEQ - Safety, Health, Environment and Quality

7. References

ISO13485 clauses 4.1.6 & 7.5.6 & 7.6

PROCEDURE FOR PREVENTIVE AND CORRECTIVE ACTION AND HANDLING OF NONCONFORMING PRODUCT

8. Procedure

ONLY software validation is applicable for medical devices

Validation, Qualification & Calibration (refer infrastructure) and Verification are followed in product realization

Validation Procedure:

Validation studies should reinforce Good Manufacturing Practice and be conducted in accordance with defined procedures. Results and conclusions should be recorded.

When any new manufacturing formulation or method of preparation is adopted, steps should be taken to demonstrate its suitability for routine processing. The defined process, using the materials and equipment specified, should be shown to yield a product consistently of the required quality.

Significant amendments to the manufacturing process, including any change in equipment or materials, which may affect product quality and/or the reproducibility of the process should be validated.

Processes and procedures should undergo periodic critical re-validation to ensure that they remain capable of achieving the intended results.

Responsibilities are defined in the protocol

Validation Process and Procedures:

Validation Master Plan (Pharmacy)

VALIDATION MASTER PLAN (Pharmacy)

8.1 Responsibilities

The Initiator is responsible for ensuring the protocol is followed.

All department representatives for departments involved are responsible for ensuring that relevant details and/or data required in the Protocol Procedure are documented, signed and completed

8.2 Types of Validations

Protocols, not limited to or as applicable, are to be drawn up for the following :

Storage temperature mapping and Travel

Process Validations - Change Control

- New Products

- Reformulation

Cleaning Validations - All Machines  (Manufacturing and Packaging)

Machine Validations - New Equipment (Sterilizers)

Equipment Qualification - Machine Adjustments / Modifications

Material Validation - Raw and Packaging (sterile barrier systems)

Quality Control Validation - Test methods

Click for Validation Protocol FORMAT

8.3 Process

CLICK refer flow diagram

Facilities, systems and equipment to be used should have been qualified and analytical testing methods should be validated.  Staff taking part in the validation work should have been appropriately trained.

Facilities, systems, equipment and processes should be periodically evaluated to verify that they are still operating in a valid manner.

8.3.1 Documentation

A written protocol is prepared and specifies how qualification and validation will be conducted.  (the format will follow the contents of the first document approved)

The Initiator is responsible for ensuring the protocol is followed.  However, all department representatives for departments involved are responsible for ensuring that relevant details and/or data required in the Protocol Procedure are documented, signed and completed.

The protocol is reviewed and approved and specifies critical steps and acceptance criteria.

A report that cross-references the qualification and/or validation protocol is  prepared, summarizing the results obtained, commenting on any deviations observed, and drawing the necessary conclusions, including recommending changes necessary to correct deficiencies.

Any changes to the plan as defined in the protocol are documented with appropriate justification.

After completion of a satisfactory qualification, a formal release for the next step in qualification and validation is made as a written authorisation.

8.3.2 Change Control 

Written procedures should be in place to describe the actions to be taken if a change is proposed to a starting material, product component, process equipment, process environment (or site), method of production or testing or any other change that may affect product quality or reproducibility of the process.  Change control procedures should ensure that sufficient supporting data are generated to demonstrate that the revised process will result in a product of the desired quality, consistent with the approved specifications.

All changes that may affect product quality or reproducibility of the process should be formally requested, documented and accepted.  The likely impact of the change of facilities, systems and equipment on the product should be evaluated, including risk analysis.  The need for, and the extent of, re-qualification and re-validation should be determined.

8.3.3 Re-validation

Facilities, systems, equipment and processes, including cleaning, should be periodically evaluated to confirm that they remain valid. Where no significant changes have been made to the validated status, a review with evidence that facilities, systems, equipment and processes meet the prescribed requirements fulfills the need for re-validation

8.3.4 Qualification.

8.3.5 Computerized Systems

Where a computerised system replaces a manual operation, there should be no resultant decrease in product quality or quality assurance.

Consideration should be given to the risk of losing aspects of the previous system by reducing the involvement of operators.

It is essential that there is the closest co-operation between key personnel and those involved with computer systems.  Persons in responsible positions should have the appropriate training for the management and use of systems within their field of responsibility which utilizes computers.  This should include ensuring that appropriate expertise is available and used to provide advice on aspects of design, validation, installation and operation of computerized system. 

The extent of validation necessary will depend on a number of factors including the use to which the system is to be put, whether it is prospective or retrospective and whether or not novel elements are incorporated.

Validation should be considered as part of the complete life cycle of a computer system.  This cycle includes the stages of planning, specification, programming, testing, commissioning, documentation, operation, monitoring and changing

9. Risk Based Approach

In the event of non compliance follow PROCEDURE FOR CONFORMANCE AND CORRECTIVE ACTION

Risk Based Approach Report

[Risk Assessment to is found in SOP PREVENTIVE ACTION RISK ASSESSMENT   refer Document]

9.1 Trend Analysis and Continual Improvement

The analytical reviews of internal audits, and any other quality related matters, are reported to management and as part of the input from Data Analysis to management review

The Trend Analysis may identify any potential and recurring incidents, where corrective action must be reported at the management review to facilitate continual improvement.

10. Revision History

Revision 16, 19.08.2021 - AA - 25.05.2022 SCR Medicine validation in VMP

Revision 15, 19.08.2021 - AA - Updated Information

Revision 14, 01.07.2021 - TNA - updating responsibilities

Revision 13, 03.05.2021 - AA Approved

Revision 12, 28.04.2021 - TNA - New format with Approval / Scope / Responsibilities, Risk based approach and Records and revision history added and new google site format.  Amending of Links and forms

Revision 11,  Digitally signed on 07.12.2020 by SCR

Revision 1-10, unknown due to google site change to new google site

11. Records

Name Retained by/ in Retention period Hard copies Destroyed by

Validation Protocol Management Representative 5 years Management Representative

Google Site


Associated reports as above

QMS Google Site

Validation reports refer TAB Documentation