Risk-Based Approaches in GMPs Project

Life Cycles

Jorge A. Cordero-Monroig; BSChE, MBA-GM

Sr. Equipment/Control System Validation Engineer
B+L Greenville Solutions Plant

CONFIDENTIAL [1]
Risk-Based Approaches in GMPs Project Life Cycles

Agenda:

How to identify a GMP Project

Why Risk-based Approach
GMP Project Life Cycle The Structure
GMP Project Life Cycle The Implementation
Interactive Exercise: GMP Project Life Cycle The Application
Q&A

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Risk-Based Approaches in GMPs Project Life Cycles

How to identify a GMP Project:

GMP (Good Manufacturing Practices) - GMP is a group of practices
used to ensure that a product is consistently manufactured within quality
standards. In other words, practices that guarantee the strength-potency,
purity, quality, identity and safety of the product.
What is a GMP Project Any project that affect any equipment, control
system, software, process or facility (ECS-SPF) that have direct impact in
the safety, identity, potency-strength, quality and/or purity of the product.
For example:
Equipments: Mix Tanks (Reactors)
Control Systems: DCS (Distribute Control System)
Software: Blue Mountain (Calibration/Metrology Software)
Process: Product Compounding // Cleaning // Chemistry final
product test.
Facility: Clean Rooms (Class A / 100 / ISO 5) renovations

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Risk-Based Approaches in GMPs Project Life Cycles

How to identify a GMP Project (Cont.):

The first step to identify a GMP project is listing all the
equipment, control system, software, process or facility
(ECS-SPF) affected by the project.
After break down all the equipment, control system,
software, process or facility (ECS-SPF) related with the
project, we need to perform an impact assessment for
each one.
Impact Assessment Classifications:
Direct Impact
Indirect Impact
No Impact

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Risk-Based Approaches in GMPs Project Life Cycles

How to identify a GMP Project (Cont.):

Direct Impact (ECS-SPF) shall answer YES to one of the
following questions:
Does the ECS-SPF come in direct physical contact with the
product?
Example: Filler, Tanks, Pumps, Agitators, etc

Does the ECS-SPF produce or distribute a material that has direct

contact with product?
Example: Bottles/Caps Molding machines, Form Fill & Seal
(FFS) Machines, etc

Is the ECS-SPF used for cleaning, sanitize or sterilize?

Example: SIP and CIP systems, Autoclaves, etc

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Risk-Based Approaches in GMPs Project Life Cycles

How to identify a GMP Project (Cont.):

Does the ECS-SPF create or maintain a specified environmental
condition required to preserve product quality?
Example: HVAC, Class A / ISO 5 rooms, etc

Does the ECS-SPF produce, monitor, evaluate, store or report

data used to accept or reject product or GMP materials or data
used to support Regulatory Compliance-Practices?
Example: DCS, E-Batch Records, EMS, etc

Does the ECS-SPF perform a critical process step or operation in

the manufacturing, processing, packaging, labeling testing or
holding of the product?
Example: Inspections Systems, Process Filters, scales, etc

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Risk-Based Approaches in GMPs Project Life Cycles

How to identify a GMP Project (Cont.):

Indirect Impacts ECS-SPF shall answer YES to the
following question:
Is the ECS-SPF linked or support a direct impact systems?
Example: DI Water Systems, Chillers, Compressed Air Units,
etc

No Impact ECS-SPF answer NO to all previous questions.

Example: Cooling Towers, Sand Filters, Office HVAC Units,
OEE Systems, etc
No impact ECS-SPF are not critical for the product quality
but could be critical for business purpose.

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Risk-Based Approaches in GMPs Project Life Cycles

How to identify a GMP Project (Cont.):

After classify the impact for the ECS-SPF projects, it is
important determine the risk level for the Direct Impact.
Indirect impact can be included in the risk analysis based on
the impact on business.
Risk Assessments Categories:
High
Medium
Low
The purpose of the risk assessment classification is to focus on
issues that impact the patient safety, product quality and data
integrity on the early stages of the process.

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Risk-Based Approaches in GMPs Project Life Cycles

Why Risk-based Approach

What are the benefits of Risk-Based Approach?
Identify and evaluate every single component, system, or
unit of the project.
Classify each component, system, or unit of the project as
Direct, Indirect or No Impact.
Justify decisions made based on risk criticality.
Identify areas that will require more evaluation, adjustments,
or re-design prior to the implementation.
Provide a solid rational of the project plan, schedule, and
project due date.
Put more effort in the design stage of the process but
minimize the qualification effort which means less down
time.
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Risk-Based Approaches in GMPs Project Life Cycles

Why Risk-based Approach

What are the requirements of Risk-Based Approach?
Determine the overall impact of the project in the patient
safety, product quality, and data integrity
Analyze the risk to the business
Identify risk to specific process
Identify risk to specific functions
Design to eliminate risk
Define controls to mitigate risk that cannot be eliminated
Define validation strategy
Revise the risk assessments as require during the project
life.

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Risk-Based Approaches in GMPs Project Life Cycles

Why Risk-based Approach

Most Common Risk Assessments Models:
FMEA (Failure Modes & Effects Analysis)
FTA (Fault Tree Analysis)
HAZOP (Hazard Operability Analysis)
Risk Priority
Etc

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Why Risk-based Approach
Risk Priority:

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Risk-Based Approaches in GMPs Project Life Cycles

GMP Project Life Cycle The Structure

Project Phase Life Cycle :
Project Origination
Project Initiation
Project Planning and Design
Project Execution and Control
Project Close-out

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Risk-Based Approaches in GMPs Project Life Cycles
GMP Project Life Cycle The Structure
Task and Responsibilities
Project Origination
Project identification: Process Owner (PO), Quality Assurance
(QA), or Process Excellence (PEx) based on business, and/or
regulation needs
Project evaluation: By process excellence team
Project selection: By upper management
Project Initiation
Project team development: Project Manager (PM)
Project definition: Project Manager, Project Engineer (PE), PO, QA,
Procurement
Initial risk identification: PEx, PO and QA
Project plan: PM
Project Plan Approval: Project team members
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Risk-Based Approaches in GMPs Project Life Cycles

GMP Project Life Cycle The Structure

Task and Responsibilities
Project Planning and Design
Project meeting and expectations: Team Members
Refine project Definition:
Scope: PE and PO
Schedule: PM and PE
Quality Standards: QA
Budget: PM, PE, and Procurement
Approve Project Plan
Vendor Selection and PO approval: PE and
Procurement
Design Verification and approval: PE, PO, and QA
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ASC

GMP Project Life Cycle The Structure

Task and Responsibilities
Project Execution and Control
Equipment, control system, software, process or facility
(ECS-SPF) development verification: PE, PO, and QA
Installation and Operational verification: PE and QA
Calibration, procedures, and preventive maintenance
implementation: PM and PO
Project Close-out
Implementation verification: PM and PE
Risk Assessment Review: PEx, PO and QA
Close-out Letter: PM

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Risk-Based Approaches in GMPs Project Life Cycles

GMP Project Life Cycle The Structure

Tools:
Project Origination:
Project Proposal,
Evaluation Rating Matrix
Project Initiation:
Project Charter
Proposed Schedule
Impact Assessment (GMP or Not GMP)
User Requirement Specification
Project Plan (Project Strategy)
Budget Estimate
Initial Risk Assessment (High/Medium/Low Risk)

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Risk-Based Approaches in GMPs Project Life Cycles
GMP Project Life Cycle The Structure
Tools:
Project Planning and Design:
Functional Requirement Specifications
Functional Risk Assessment
Traceability Matrix
Revised Schedule
Revised Budget
Validation Strategy
Design Specification/Qualification (DS/DQ)
Project Execution and Control
Factory Acceptance Test (FAT)
Commissioning / Site Acceptance Test (SAT) / Engineering Studies
Risk Assessment Review
Qualification / Validation Protocols
SOPs, PMs, and Calibration Program
Project Close-out
Traceability Matrix Review
Closing Letter

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Risk-Based Approaches in GMPs Project Life Cycles

GMP Project Life Cycle The Structure

Phases Approach:
After completion of each phase a formal Phase Review Report
should be evaluated and approved by the Project Team Members.
Phase criteria should be completed before move to the next
phase.
Incomplete criteria shall be justified on the Phase Review Report.
Benefits of Phases Approach:
Ensure that there is no missing elements during each phase.
Force the team members to evaluate the project goals and
expectations constantly.
Keep control of the project

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Risk-Based Approaches in GMPs Project Life Cycles

GMP Project Life Cycle The Structure

How to measure Success
Align schedule with Phase Review Reports deliverables
Project design mitigate, control, and measure the identified
risks
User requirements, functional requirements, and design
specs were addressed and tested satisfactorily on FAT,
SAT, IQ, OQ, PQ, or PV.
IOPQ and PV have been executed satisfactorily and
approved.
Project has been implemented and closed as scheduled.
Project cost are within the budget requested.

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Risk-Based Approaches in GMPs Project Life Cycles

GMP Project Life Cycle The Implementation

Who, How, and When:
Change Control:
Who: PM, PE, or PO
How: Any project that affect a GMP equipment, control system,
software, process or facility shall be managed under local change
control process.
When: Before start with the project execution and control phase.
Schedule and Timing:
Who: PM and PE
How: Progress report and meeting should be implemented to
manage the schedule and keep visibility of the project progress.
Milestone shall be identified and addressed.
When: Across the entire project, typically weekly.

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Risk-Based Approaches in GMPs Project Life Cycles

GMP Project Life Cycle The Implementation

Who, How, and When:
Protocols and Verifications:
Who: Vendor, Consultant, Operation personnel, PE, or QA-Validation
How:
FAT and SAT shall be reviewed an approved by quality in order
to be leverage on the IQ, OQ, and PQ. As specified on
Validation Strategy.
FAT and SAT shall cover all details, configurations,
functionalities, and safety requirements.
Limited IQ, OQ, and PQ can be performed based on FAT and
SAT successful test. PV, as applicable, to demonstrate that the
process is suitable for intended use (process is validated).
When:
FAT is performed at vendor facility. SAT performed at the site.
Qualifications / Validation: After success FAT and SAT.
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Risk-Based Approaches in GMPs Project Life Cycles

GMP Project Life Cycle The Implementation

Who, How, and When:
SOPs and Preventive Maintenance:
Who: PO, PE, and/ or Plant Engineer
How:
Update and/or create standard operational procedure and
preventive maintenance task, and include any critical
instrumentation to the calibration process.
Include the changes in the Change control plan
When:
Update and development (draft) before the operational
qualification.
Approved for the Performance qualification
Effectives after qualification/validation completion but before start
the normal operation.

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Risk-Based Approaches in GMPs Project Life Cycles

GMP Project Life Cycle The Implementation

Who, How, and When:
Traceability Matrix, Risk Assessment Review and Closing Letter:
Who: PM, or PE
How:
Using a matrix verify that all critical requirement in URS, FRS,
and DS, as applicable, were tested in one of the deliverables.
Reviewing the Risk Assessment to confirm that the risk were
mitigated or controlled.
Write a memo or project plan final report summarizing the
activities performance and completion.
When:
After approval of all qualification protocols final reports.

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Risk-Based Approaches in GMPs Project Life Cycles

Interactive Exercise: GMP Project Life Cycle The

Application
Determine if the project is GMP or not GMP (Direct/Indirect/No
Impact)
Outline a Project Life cycle
Perform a Risk Assessment
Manage Constraints

Projects:
Sampling Booth in a Warehouse
Metrology Software
Mix Tank (Reactor)
Compressed Air

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Risk-Based Approaches in GMPs Project Life Cycles

Bonus Material
Risk Based Approach Project Life Cycle Phase Matrix
Phase Review Report Template

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Risk-Based Approaches in GMPs Project Life Cycles

Questions and Answers

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