9:30 -10:30 am Session 1 - Verification and Validation ...€¦ · Part 1: Process Validation - Back to Basics: Gina Guido-Redden, Owner; COO and Managing Partner, Coda Corp USA Part

WWW.CODACORPUSA.COM 1

9:30 -10:30 am – Session 1 - Verification and Validation

Part 1: Process Validation - Back to Basics: Gina Guido-Redden,

Owner; COO and Managing Partner, Coda Corp USA

Part 2: Why Group Think Kills Effective Critical Design Transfer:

Walt Murray, CSSMB, RAB/QSA/IATCA/IRCA, CTS Facilitator,

SPC/SQC; Principal Consultant of PinPoint Consulting

Summary: Jessie Verna, Director, Regulatory Affairs, ConMed

Corporation; and Julie Miller, Complaint Handling Supervisor,

ConMed Corporation

Verification and Validation

D E V E L O P E D A N D P R E S E N T E D B Y:

GINA GUIDO -REDDEN

COO, CODA CORP USA

WWW.CODACORPUSA.COM

BACK TO BASICS

Outline

1. Quality Assurance and Validation

2. The Fundamentals of Process Validation

3. Risk Management – TO BE DISCUSSED IN SECTION 2 OF THIS PRESENATION

4. Precision in Language

5. Technology Specific Examples by Stage

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The Systemized Approach to Quality Begins with Validation

ESTABLISHING AND PRESERVING CONTROL AND QUALITY

www.CodaCorpUSA.com

© Coda Corp USA 2010

On Going Control is the Objective

The intent of Title 21, the structure of the FDA, and the nature of the cGMPsall are components of a program designed to help manufacturers;

• Establish Control

• Maintain Control

• Prove it!

The fundamentals tools utilized by industry, and expected by FDA are;

• The establishment of Control = Validation

• The maintenance of Control = Quality Systems

• Proof = Accurate and complete documentation


Validation and Quality Assurance

While the function that you perform may be within an engineering group – it is critical to note that ….

FDA sees Validation as the initial step in the assurance of quality.

For this reason, the goals of Validation and Quality Assurance can not be met unless they are considered together.


Assuring Quality =

STEP 1

The Fundamentals of

PROCESS VALIDATION

What is a Process?

Any proceduralized sequence of activities, when executed properly, assures a reproducible outcome

Facility+ Utilities

+ Equipment+ Manufacturing Methods

+ Control Procedures+ Materials

+ Components

+ Trained Personnel= PROCESS


The Product Lifecycle(Guidance for Industry; Process Validation, General Principles and Practices, FDA January 2011)

Stage 1: Design Control and Process Design: The commercial

process is defined based on knowledge gained throughout

development and scale-up.

Stage 2: Process Qualification: Design confirmed as being capable

of reproducible commercial manufacturing.

Stage 3: Continued Process Verification: Assurance gained by

demonstrating that the process controls and Quality Systems are

capable of maintaining control during routine production.


Stage 3: Monitor

Stage 2: Confirm

Stage 3: Assess

Stage 1:Design

Validation Lifecycle: Simple Diagram – The Circle is Unbroken


Stages 1 and 2, must be

completed successfully prior to the

release of any process for

commercial use.

Stage 1: Process Design

Process design is the activity of gaining knowledge and

understanding of the process. These activities should

determine;

• The CQAs and the process parameters that can effect those

attributes

• The limitations of the process and/or equipment

• The components of the process that contribute variability to the

outcome (e.g., components, people, measurement systems)

• The impact of that variability

• Methods that can deployed to control and detect that variation


Stage 1: Process Design and Development Studies

Development and Design Studies engineered to:

• Identify operating ranges and critical processing parameters

• Discover variability (including multivariate interactions)

• Identify and establish mechanisms to limit and control variability based on experimental data

• Aim for a definition of a robust process (i.e., one that can tolerate input variability and still produce consistent acceptable output).


Stage 1: Process Design Key Outputs

• Thorough knowledge and understanding of the process and all sources (and impact) of process variation

• A strategy for process control (addressing variability)

• The manufacturing sequence, including parameters that require monitoring

• The cGMP documents to be used for commercial manufacturing;

• Master Batch Records

• Production Control Records (21 CFR 211.186)

• Product and Process Specifications

• all associated SOPs



Stage 1: Process Design Activities

Stage 2: Process Qualification

Process Qualification is the stage that confirms the process as defined as being capable of reliably reproducing quality results when executed on a commercial scale.

The confirmation stage has 2 qualification elements;

• Design and build of the facility and qualification of the equipment and utilities (IQ,OQ, PQ)

• Performance of the process (PPQ)


GMPs APPLY HERE!

Stage 2 Element 1: Facility, Utility and Equipment Qualification

16

Before starting process validation activities, appropriate qualification of critical equipment and ancillary systems should be completed. Qualification is usually carried out by conducting the following activities:

Verifying that the utility system and equipment are built and installed in compliance with design specifications.

Verifying that the utility system and equipment as installed, operate and perform as intended throughout all the anticipated operating ranges.

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Stage 2 Element 2: Process Performance Qualification (Process Validation)

The objective of Process Performance Qualification (PPQ) is to demonstrate with evidence that the qualified equipment and ancillary systems, as connected together (i.e. the PROCESS), can perform effectively and reproducibly when executed by trained resources execute the fully developed processes.

Objectives:

• The demonstration of the reliability of the combination of the facilities, utilities, equipment, operators, raw materials, components and procedures.

• The demonstration of consistency (i.e. PPQ/PV testing requires the evaluation of commercial scale process runs.)


Milestone!

Stage 2 Element 2: Process Performance Qualification (Process Validation)

The knowledge gained during stage 1 is critical to developing the approach to testing the performance of the process.

The greatest sources of potential variation, pose the greatest risk of process failure, and the risk can be increased significantly when combinations of those sources are present.

Performance testing utilizes the “worst case scenario” approach, attempting to realize the greatest number of combinations of those sources as possible.

Collecting and evaluating data generated under those circumstances provides the highest degree of assurance that the process is reliable and reproducible as designed and controlled.


Stage 2: Confirmation: Element 2: Performance Qualification/Process Validation

The equipment, procedures and CPPs utilized during PPQ/PV runs become the definition of the Validated Process.

This definition becomes the baseline for change control.

Use of any other equipment, procedural steps or parameters from that point in time forward will require control via approved change management procedures.

The scope and scale of the changes once evaluated through change management will require confirmation of effectiveness and impact.

Based on those procedures and the results of the evaluation, effectiveness and impact of proposed changes will need to be confirmed through either verification or validation studies.


Design Space, Validated Process

Boundariesand

Management of Change



Stage 2: Confirmation: Element 2: Performance Qualification/Process ValidationSetting Limits (whether you mean to or not)

Stage 3: Continuing Process Verification

The objective of this stage is the continued assurance that any process remains in the state of control demonstrated by the qualification /validation stage.

A formal and proceduralized system (s) designed to detect unplanned departures from the designed process is essential and required by law (21 CFR 211.180(e)).

Components of these systems collect and evaluate data during routine process execution that is comparable to that collected during the initial validation, enabling detection of process drift.


Stage 3: Continuing Process Verification

Routine monitoring of processing is designed to confirm that the Critical Processing Parameters continued to be in control and Critical Quality Attributes continue to be met.

Process Monitoring and Assessment activities may result in the need to effect changes or improvements.

It is critical not to confuse change control with routine monitoring or assessment.

Stage 3 activities are routine in nature and must be conducted whether or not change has occurred.



Validation Lifecycle: Detailed Diagram

Risk Management And its Role in the Assurance of Quality

TO BE DISCUSSED IN SECTION 2 OF THIS PRESENTATION

Precision in Language

WORDS THAT SOUND ALIKE… BUT ARE NOT!


Confirmation by examination and provision of objective evidence that specified requirements have been fulfilled.

Speaks only to a specific point in time.

Does not provide any confidence going forward.

Verification = NOW

Establishes documented evidence that a product or process conforms to its specifications prior to final release of the product or process.

Action of proving, in accordance with the principles of GMP, that any procedure, process, equipment, material, activity or system will lead to the expected results.

Validation = FUTURE


Validation = PROCESS Qualification = COMPONENT

Establishes documented evidence that a product or process conforms to its specifications prior to final release of the product or process.

Action of proving, in accordance with the principles of GMP, that any procedure, process, equipment, material, activity or system will lead to the expected results.

Action of proving that any premise, system and/or piece of equipment operates and performs reliably, leading to expected results.

(Validation usually incorporates the concept of qualification)


Action of proving that any premise, system and/or piece of equipment operates and performs reliably, leading to expected results.

Covers ranges of operating and performance abilities (full and target).

Speaks to reliability of operation and performance within that range.

Speaks to operable condition of equipment.

Speaks to accuracy and precision within a specified period of time, when used within established parameters.

Recognizes that adjustments within qualified ranges can be made.

Speaks to readiness for use.

Qualification = ABILITY Calibration = ACCURACY

Technology Specific Validation

EXAMPLES BY VALIDATION LIFECYCLE BY STAGE


New Facilities and Products; Validation Planning for new facility and/or product

Process and Method Development

Technology Transfer

Facility/Utility Qualification and Environmental Control

Container/Closure Validation

Sterile Filtration Validation

Filter Validation

Product Specific; Process Validation and Equipment PQs

Analytical Method Validation

Sterile and Clean Supply; OOP Cleaning and Sterilization

Sterilization and Cleaning; SIP and CIP

Environmental Monitoring (Continuing Verification of Facility/Utility Control)

Media Challenges (Continuing Verification of Manufacturing Process Validation + Sterile hold)

Periodic Assessments of SIP and CIP systems

STAGE 3

STAGE 2

STAGE 1


Facility/Utility Qualification; • Material Flow/Personnel Flow• HVAC, WFI/PW, Process Gasses,

Steam

Analytical Method Qualification; • Method development• Critical quality characterization• Sensitivity, limitations

Equipment Qualification; • Component qualification• Installation/design qualification• Operational qualification

Technology: Stage 2; Element 1 (Qualification)


Process Validation, Cleaning Processes;

• In Place (CIP)

• Out of Place (Washers, Sonicators)

Process Validation, Sterilization Processes;

• Wet Heat; Autoclaves (out of Place); SIP (Steam In Place)

• Dry Heat; Dry Heat Ovens

• Sterile Filtration

Component PQs; Container/Closure Performance;

• Any well defined components designed to act as a boundary to prevent microbiological ingress during storage, transport, handling or production

Process Related Equipment PQs;

• Thermally Controlled Storage Units (e.g., Freezers, Incubators)

• Process Equipment (e.g., Sonicators, Thaw Baths, Inactivation Tanks)

Technology:Stage 2; Element 2 (Process Performance Qualification)


Sterile Hold: (definition of the upper limit of performance of a sterilization process)

• The length of time that equipment or a component can remain available for use post execution of a validated sterilization process

Clean Hold and Dirty Hold: (definition of the upper limits of the performance of a cleaning process)

• Clean: The length of time equipment can remain available for use post execution of a validated cleaning process

• Dirty: The upper limit of the age of the soil that the cleaning method was shown to be effective on throughout validation

Technology:Stage 2; Element 2 (Process Performance Qualification)

Supplemental Studies


Continuing Validation:• A subset of the initial validation functional tests that provide

confidence that the process performance has not drifted, and continues to be capable of generating the expected outcome.

Periodic Assessment:• A documentation review which evaluates critical documentation

generated over the previous 12 months, (Documentation generated by other Stage 3 systems is reviewed, including deviations, change management, calibration and maintenance documentation.)

Examples by Technology: Stage 3 (Continuing Verification)

Documents

9:30 -10:30 am Session 1 - Verification and Validation ...€¦ · Part 1: Process Validation - Back to Basics: Gina Guido-Redden, Owner; COO and Managing Partner, Coda Corp USA Part