EFFECTIVE VALIDATION

PLANNING IN

A PRODUCTION FACILITY

FONT COLOR, AHAS

By: Justin RooseHead Validation Engineer – Product Quality Assurance (Global Compliance)

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Session Agenda

• Open-forum training session

• What do you want to learn?

• Two-way / Your experiences

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1. Instruction

2. Questions

3. Do it! (Exercises)

3 Keys to Success

• Well-Developed Strategy

• Don’t miss anything

• Proper Resourcing & Support

• Validation is executed

• Communication

• Properly & Efficiently

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“Let’s not let our success

overshadow our how we did it.

We had a good plan, and

diligence against that plan. This

victory wasn’t coincidence…it

was the result of good planning,

hard work, and communication.”

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Skills & Qualities• Leadership

• Communication

• Written, Oral, Presentation

• Project Management

• Organized, Scheduling, Planning,

Coordination

• Subject Matter Expertise

• Collaboration & Teamwork

• Technical Writing

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Validation

Equipment

(incl. Facility & Utilities)

Process

Packaging

Control & Information

Systems Software

Test Methods

Laboratory Equipment

Sanitizing

Cleaning

Types of Validation

Verification(Med Device)

Assess & Identify Activities

• How is each one is impacted?

• What are the Product, Regulatory,

Company requirements?

• Leverage team expertise & peers

• Team buy-in & resources

• How will we prove capable equipment &

effective processes?

• Validation Requirements

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Activities (con’t)

• How to explore & develop

capability?

• Do your homework…understand it!

• Develop plan, schedule & expectations

• Things go wrong…include contingency.

• Master Validation Plan

• Organized summary of requirements

• Written rationale & justification

• Documents risk-based approach

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Timing of Validation Activities

Key Preparation Validation

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Equipment Qual(IQ/OQ/PQ)

Cleaning & Sanitizing Validation

Process & Packaging Validation

Specs, FAT, SAT

Coverage, Cleaning & Sanitizing Trials

Product Specs/Formulae, Instructions, Plant Trials

Full-scale Production

Facility & Utility Qual(IQ/OQ/PQ)

Standards, Specs, SAT

Classroom Discussion

• BEST Validation Projects

• Examples

• Why?

• CHALLENGING Validations

• Examples

• Why?

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Planning Best Practices

• Clear path & expectations

• Team developed & vetted plan

• History, relationships & expertise

• Good communication

• Thorough FAT, SAT, Plant Trials

• Contingency timing

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Pre-validation Activities

& Pre-requisites

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Development Phase

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• Over half of your validation work is

spent in the “Development” phase,

before you begin drafting a protocol

• The #1 Cause of Deviations is

insufficient development

• Equipment – Debug / FAT / SAT

• Process/Clean/Sanit – Plant Trials

Equipment Qualification

Pre-requisites

• Classroom Exercise

• Facility, Utility & Production Equipment

• (Critical, SISPPQ)

• What activities & documents are

required to perform a qualification?

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Qualification Development• Approved Specification

• URS, FRS, Scope, Functions, MOCs, Controls

• Timing, Plan & Resources Identified

• FAT Executed / Report

• Materials for SAT/OQ

• Vendor Documentation

• Manual(s), MOCs, Spare Parts, Drawing, Preventive

Maintenance info, I/Os, Calibration info, etc

• Align SAT, Routed & Approved (team)

• Facility Readiness

• Permits, install personnel, install equipment15

Qualification Pre-requisites

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• Quality Standards Approved

• Utilities are Installed (Water, Elec, Comp Air, etc)

• Equipment Delivery

• Equipment Installation

• Auxiliary Eqp, Calibration

• Safety Checklist

• Equipment Functional & “De-bugged”

• IOPQ Drafted, Approved

• Test Plan, Acceptance Crit

• Approved SOPs, Training

• Approved Drawings

Facility / Utility / Equipment

Qualification

Checklists

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Cleaning & Sanitizing

Validation Pre-requisites

• Teams – 3 minutes

• Discuss & Present top 3

• What activities & documents are

required to perform Cleaning &

Sanitizing Validation?

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Definitions

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• Cleaning Validation – Docu-

mented evidence that cleaning

process removes product and

cleanser to acceptable limits.

• Sanitizing Validation – Documented

evidence that sanitizing process reduces

microbes to acceptable limits

Cleaning Validation Development

• Proposed Product Families & Cleanser(s)

• Cleanliness Standards

• MACO, cleanser carryover, visual standard

• Swab Qualification & Analyte Swab Lab Method

• Worst-case locations Identified

• Draft cleaning process & SOP

• Qualified Equipment

• CIP/Coverage Tests

• Cleaning Trial Protocol(s)

• Team collaborated, approved

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Cleaning Validation Pre-requisites

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• Product for testing

• Successful Cleaning Trial(s)

• Approved Product Families

• Qualified Cleansers (Released)

• Approved Cleaning SOPs

• Trained Staff

• Cleaning Validation Protocol

• Test Plan, Acceptance Crit

• Timing, Resources Identified

Sanitizing Validation Development

• Proposed Sanitizer(s)

• Microbial Standards

• Coliform/Obj.Org./Yeast&Mold

• Micro Swab Qualification

• Micro Recovery Lab Method

• Worst-case locations Identified

• Draft sanitizing process/SOP

• Clean Equipment (CV)

• Sanitizing Trial Protocol(s)

• Team collaborated, approved

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Sanitizing Validation Pre-requisites

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• Successful Sanitizing Trial(s)

• Qualified Sanitizer(s)

• Log-reduction, Obj. Organisms

• Released Chemicals

• Approved Sanitizing SOPs

• Trained Staff

• Sanitizing Val Protocol

• Test Plan, Acceptance Criteria

• Timing, Resources Identified

Cleaning & Sanitizing

Validation

Checklists

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Process & Packaging

Validation

Pre-requisites

• Teams – 3 minutes

• Discuss & Present top 3

• What activities & documents are

required to perform Process Validation

(& Packaging)?

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Definitions

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• Process Validation – Documented

evidence (scientific evidence) the

chemical characteristics of the

formula during the production

process consistently meets quality

requirements (strength, potency, purity, safety)

• Packaging Validation – Evidence…the physical

aspects of the product…meets quality

requirements (safety, identity, quality)

Validation Development

• Salable Goods!

• Qualified Equipment, Facility, Utilities

• Clean & Sanitized Equipment

• All Manufacturing SOPs – Approved & Trained

• Logs & In-process Tests – In Place & Effective

• Proposed Product Families

• Analyte Lab Method

• Draft documents

• Formula, Product Spec, Raw Spec, Instructions

• Component Specifications, Instructions

• Plant Trial Protocol(s)

• Team collaborated, approved

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Process Validation Pre-requisites

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• Successful Plant Trial(s)

• Approved Product Documentation

• Formula(e), Raw & Product Specs,

Manufacturing Instructions

• Standards (Product, Quality)

• Trained Staff

• Approved & Released Raw Materials

• Process Validation Protocol

• Test Plan, Acceptance Criteria

• Timing & Resources Identified

Packaging Validation Pre-requisites

• Successful Plant Trial(s)

• Approved Product Documentation

• Component Specifications, Packaging Instructions

• Standards (Product, Quality)

• Approved & Released Components & Bulk Product

• Packaging Validation Protocol

• Test Plan, Acceptance Criteria

• Timing & Resources Identified. And…trained staff.

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Process & Packaging

Validation

Checklists

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Questions?

• Strategy

• Development & Pre-requisites

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Planning & Executing

Validation Activities

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Considerations – Planning

• Make requirements clear early in a project

• Use of Project Management Tools

• Propose Schedule, Resource Plan,

Communication Plan, Critical Path

• Identify & notify departments needed for

support, for each validation phase:

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Develop Draft Execute Deviation Report

Planning Considerations (con’t)

• Support needed…all aspects of execution?

• Who – Draft, Train, sample, test

• Ensure Availability & transfer of knowledge

• What are the requirements?

• Criteria, Sampling, Testing, Results

• When – Our schedule…

• Where – Per the defined plan

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Scheduling Resources

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• Establish R&R

• RACI charts, procedures

• Identify departments needed for support

• Plant, Engr, R&D, QA, QC/Lab, Planning

• Work with departmental management to

ensure allocation of resources

Examples of Management Tools

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Appropriate for the volume of work…

• Project – 4 Levels

1. Individual Level – Checklists

2. Detail Level – Gantt Chart

3. Team Level – 2 Month Forecast

4. High Level – Monthly, by type (ie Eqp)

Management Tool Examples

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An Established Plant

Nashville Plant Validation Tracking

Type Description Date Status / Comments Owner PhaseIOPQ New Transfer Pump April Spec Issued B Marley 1 Plan

IOPQA Motor drive upgrade 13-Apr Drafting, CC approved A Rose 2 DraftIOPQ Filler #4 Done Executed Protocol Review J Lennon 5 Report

CV New Transfer Piping June Getting quotes S Davis Jr 1 Plan

SV New Sanitizer - Pumps 15-Mar Protocol & comm issued G Brooks 3 ExecuteSV New Sanitizer - Fillers June Cleaning Trial May 15 R Starr 1 PlanPV New product X Late May Product ships NLT Apr 15 S Dogg 3 ExecutePV Upcoming Product August Feasibility D Parton 1 Plan

Communication Tips

• Clearly identify activities & responsibility

• Requirements, Action Items, or Expectations

• Status & Progress (management)

• Help people understand “why”

• Training, training…training!

• Communication ensures priority

• Be clear who does what, when.

• Engage affected groups earlier

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Training Tips

• “Here’s what matters to you”

• Make it simple

• Be clear who does what, when.

• Protocol/Test training within 24hr

• Include all those involved

• Assume they didn’t read the protocol

• Visually demonstrate: what, where, how

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Sample Communication Tools

Sampling EmailTo: QA, Manufacturing

Cc: Project Manager

Subject: Upcoming Cleaning Validation: *Title*

In case of a failure/issue/questions, stop immediately and call Who

Execution

When: Target to run late 1st/early 2nd shift

What to Sample: Active Ingredient Swabs (5), Rinse (3),

Sampler: Who?

The protocol & sample supplies are located where. Who delivers samples Where,

and communicate samples are delivered via email/phone to whom

Testing

When: Should be dropped off 2nd shift

What to Test: Active Ingredient X (5), pH Rinse (3),

Communicates results to Who

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Sample Communication Tools

Sampling Instructions (print & deliver with samples)Product Name: _________________ Protocol #: __________________

Validation Contact: ______________ Target Run Date: __________________

Location # of Samples Qty Required Testing (Lab)

Top 1 - N 3 sample jars 500mL Active #1, Active #2, Viscosity

Top 2 - S 3 sample jars 500mL Active #1, Active #2, Viscosity

Bottom 1 - N 3 sample jars 500mL Active #1, Active #2, Viscosity

Bottom 2 - S 3 sample jars 500mL Active #1, Active #2, Viscosity

Transfer - 1 2 sample jars 300mL Active #1, Active #2

Transfer - 2 2 sample jars 300mL Active #1, Active #2

Transfer - 3 2 sample jars 300mL Active #1, Active #2

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Execution Tips

• Try not to schedule too many concurrent

validation activities

• What’s the #1 cause of deviation?

• Ensure processes are well-developed

• Process/Cleaning/Sanitizing

• Be clear who is responsible for what

• Training & Communication

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3 Keys to Success

• Well-Developed Strategy

• Don’t miss anything

• Proper Resourcing & Support

• Validation is executed

• Communication

• Properly & Efficiently

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Next…Team Exercise

Questions?

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Group Exercise

• OTC manufacturing plant makes suspension

drug products. The company has decided to

build an expansion for its Blending operation.

• Team 1 - New Equipment:

• Three (3) 6,000L Mix Vessels

• Agitation – Turbine, 0-100rpm

• Team 2 - Daytime Cold & Flu (suspension)

• Acetaminophen 325mg

• Guaifenesin 300mg

• Dextromethorphan HBr 20mg

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Group Exercise

• Validation Requirements?

• What development work is needed?

• High-level schedule:

• Development, Trial, Protocol, Execution

• Resource Plan (who, and when)

• Training & Communication Plan

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Thank you!Justin B. Roose, Head Validation Engineer

Product Quality Assurance, Amway Corp.

7575 Fulton St. East, Ada MI, 49355. Bldg 52-2J

616-787-0031

jroose@amway.com

Biography

Justin is a Lead (Head) Validation Engineer at Nutrilite / Amway Corp in Ada, MI. He & his team

recently completed validation of a 3-phase supplement production facility. His team is

responsible for: equipment & utility qualifications, as well as process, packaging, cleaning,

sanitizing and software validation. He also supports a software validation team responsible for

37 corporate software systems used to govern GMP functions in North American Operations.

Justin received his BS in Chemical Engineering from Calvin College. He has enjoyed over 18

years of experience across the pharmaceutical, vaccine, biologics, foods and nutritional

supplements fields. Since joining Amway Corp in 2006 Justin has created and implemented an

effective change control program, led the Validation Department, and created both software &

process/packaging validation programs.

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