[ 1 ]CONFIDENTIAL

Risk-Based Approaches in GMP’s Project

Life Cycles

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

Sr. Equipment/Control System Validation Engineer

B+L Greenville Solutions Plant

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Risk-Based Approaches in GMP’s 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 GMP’s 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, controlsystem, software, process or facility (ECS-SPF) that have direct impact inthe 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 finalproduct test.

Facility: Clean Rooms (Class A / 100 / ISO 5) renovations

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Risk-Based Approaches in GMP’s 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 GMP’s 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 GMP’s 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 GMP’s 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 GMP’s 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 GMP’s 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 GMP’s 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 GMP’s 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 GMP’s 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 GMP’s 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 GMP’s 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 GMP’s 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 GMP’s 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

SOP’s, PM’s, and Calibration Program

Project Close-out

Traceability Matrix Review

Closing Letter

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Risk-Based Approaches in GMP’s 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 GMP’s 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 GMP’s 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 GMP’s 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 GMP’s Project Life Cycles

GMP Project Life Cycle – The Implementation

Who, How, and When:

– SOP’s 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 GMP’s 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 GMP’s 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 GMP’s 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 GMP’s Project Life Cycles

Questions and Answers

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