Guidelines to

Audit

Validation

Qualification

Document

Rosnelma García

Purpose & Scope– The purpose of this presentation is provide a clear

guideline to follow during the audit and evaluation

process of the validation packages.

– The scope of this presentation is the qualification and

validation documentation located in the Facility.

– As part of the Remediation Project the contents of this

presentation can be used during the evaluation process of

any validation or qualification document.

Key activities & items

Validation

Worst case scenario of the

current manufacturing

process

Qualification

Critical parameters and limits

Calibration

Critical parameters and limits

Remediation Project List Use the excel file during the evaluation process of

each binder.

Enter all the information requested by the excel spreadsheet as possible.

If during the evaluation process easy or “low hanging fruit” items are identified use the comment column to document.

Process Validation List Summary Example

Product # Product Name PV Scope Facility Lot # Equipment Use Calibrated Equipment

Equip # Description Protocol #Functional Requirements

Design Specifications

Design Qualification Parameters Executed Report Approval

Equipment Qualification List Summary Example

List Summary Example

Check List Form

(optional) Use the excel file during the

evaluation process of each binder.

General Guidelines to follows when planning validation process

• History

• Description

• Qualification/Validation Status

• Risk Assessment

• References

• Impact of the changes

• How to handled thru the entire process

• Critical Parameters and Attributes

• Acceptance Criteria

• Changes versus challenges (test cases)

• Evidence of the

• SOP

• Policy

• Protocol to execute

Training Records

Validation Strategy

SummaryQuality Risk

Management

Documentation Stages

Changes

• Changes in the acceptance criteria or parameters

• Discrepancies with scientifically justification

Results

• Fail pre-define and approved acceptance criteria

• Deviation and follow local investigation process

Final Report

• Review of the results vs. acceptance criteria

• Conclusion and recommendation

Release

• Formal release needs to be approved

• Conditional release needs to be documented thru deviation

Qualification Stages for the Equipment,

Facilities and Utilities

– URS needs to be created minimizing GMP risks

– Design Qualification can be the first document as draft version

– Design review needs to be execute and compare with the standards, requirements, specifications, and changes

– SAT & FAT activities are recommended for equipment novel or with complex technology

– IOPQ can be created either of the possible combination. For example IQ, OQ, IOQ, IOPQ and etc

– Also, Performance and Process Validation can be created, executed and documented in one qualification document as PPQ

Installation QualificationIQ should be performed on equipment, facilities, utilities, or systems.

Major Components

• Collect information of the suppliers

• Verification of the installation

Drawing

• Verification of material of construction

• Correct Installation of the equipment and instruments

• Correct installation of the pipe work and services (Utilities)

PM & Calibrations

• Collect information to enter in the systems

• Verify the calibration certificates

Operational Qualification

Confirm upper and lower operating limits and/or “worst case”

conditions

Develop from knowledge of the process ensuring the systems operate as

designed

Operational System Cleaning Procedures Operators training

Preventive Maintenance

Performance QualificationPreparation

Use production materials, qualified substitutes or simulated product proven to have equivalent behavior under normal operating conditions.

Worst case batch sizes

Cover the operating range of the intended process, unless documented evidence form during the develop phase confirm the operational ranges available.

Sampling

Frequency of sampling used to confirm process control should be justified

Process Validation– Types of process validation

– Traditional

– Batch size needs to be 10% of the maximum production scale or 100,000 units whatever is the greater.

– In the protocol body needs to include the following aspects:

– product dossier

– manufacturing process

– Tests

– acceptance criteria

– description of any additional control

– justification

Process Validation

– Continuous (science and risk based real time approach)

– Relevant data of the Quality attributes of incoming material or components, In-process

material and finished product

– Verification of attributes, parameters, end points, assessment of CQA and CPP trends

– In the protocol body needs to include the following aspects:

– product dossier (support with laboratory data)

– description of a CPV strategy

– process parameters

– material attributes

– analytical methods

– stage that the process is considered under control

– Justification: number of batches and the variability

Process Validation– Hybrid

– Clear dossier

– Design space verification

– Scale up

Referenceshttp://www.fda.gov/downloads/Drugs/.../Guidances/UCM070336.pdfhttps://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?CFRPart=820http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2014/02/WC500162136.pdfhttp://ec.europa.eu/health/files/eudralex/vol-4/2015-10_annex15.pdfhttp://www.imdrf.org/documents/doc-ghtf-sg3.asp