validation strategies for multi-product facilities … 19_roose_pres.pdf · packaging line...

VALIDATION

STRATEGIES FOR

MULTI-PRODUCT

FACILITIES

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

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Session Agenda

• Open-forum training session

• Two-way dialog

• Your experiences

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1. Instruction

2. Questions

3. Do it!

Group Activities

• Determine multi-product

validation strategies (scenarios)

• Break into teams

• Scribe

• Presenter

3

Multiple products…or

Mixed-use?

• Session discusses both

• Concepts are the same

• Solved by understanding the product

…and other business lines

4

Multiple products…or

Mixed-use?

• Very similar product formulae

• Variety of sunscreen products

• Same type/business line

• Variety of oral OTC drugs

• Mixed-use (cross business-line)

• Drug/Cosmetic/Supplement/Foods/

Biologics/Device

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Considerations for various

business lines

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• Considerations based on regulations

inherent to necessary controls

• Drug

• Actives, Micro (sanitizing), CPPs, Critical

Characteristics

• Vaccine/Biologics

• Assay/Actives, Potency, Sterility, Micro

(sterilization), CPPs, Critical Characteristics,

Environmental conditions

Considerations for various

business lines (con’t)

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• Device

• Verification & Validation, Controls, Consumer

Feedback, Safety, Micro (sterilization), Bio

Burden, Black/White Box Testing

• Foods

• HACCP, Raw Material Controls & Variation,

Process Controls, Micro (sanitizing)

• Supplements

• Allergens, Therapeutic Ingredients

Micro (Sanitation)

Business Line & Regulations

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• Drive validation approach

• Regulations…what do you think?• (list)

• Many markets accept certifications from

comparable or more strict audits

• Example

How exactly do we approach

validating a mixed-use, or multiple-

product facility?

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First…how do we validate a

single product

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• What do you think?

• …

Validation

Equipment

Facilities & Utilities

Process & Packaging

Control & Information

Systems Software

Test Methods

Laboratory Equipment

Sanitizing

Cleaning

Types of Validation

Validating a mixed-use, or multiple-

product facility

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• Understand your business line

requirements (ie. Pharma)

• Understand the product characteristics

and production needs…

• …and consider them against other

products.

• Sometimes design for most critical product

need or regulation.

• Simple, but not easy?

Validation

Equipment

Facilities & Utilities

Process & Packaging

Control & Information

Systems Software

Test Methods

Laboratory Equipment

Sanitizing

Cleaning

Types of Validation

Questions?

• Multi-Product

• Mixed-Use

• Regulations

• Product needs

• Regulatory requirements

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Facility

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• What does the product

require?

• Facility

• GMP/Sanitary Design

• Washable surfaces

• Drainable floors, air gaps to drains

• Sloped piping

• Sealing doors

• Process / Material / People /

Waste Flow

Utilities

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• Clear utility specifications per

• product requirements

(product specifications?)

• business line requirements

• Drives the level of validation

• All critical utilities should be validated

Utilities – Water

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• Quality: RO, DI, WFI, other?

• Product requirements

• Validate to specification

• Tips for Success

• Design Capacity

• Consider manufacturing, cleaning and

sanitizing needs

Group Exercise –

Water System

• Drugs & cosmetics facility.

• Water used for cleaning, as a raw

material, sanitize rinse.

• What are the validation requirements

for this water system (IOPQ)?

• Break into teams – 3 minutes

• Scribe (laptop)

• Presenter18

Group Exercise –

Water System

• Share - 1 minutes

• Team 1 – Results?

• Do you agree?

• Were your results similar?

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Utilities – HVAC

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• Supports product quality

• Prevents cross-contamination

• Processing & Storage

• Air Quality

• Directional: room to room (ΔP), laminar

• Temp & Humidity

• Alarms

• Dedicated AHUs?

Class Exercise – HVAC

• Drug facility: Rx, OTCs.

• Mixing, kinetics, aseptic processing,

sterile fill, general filling

• What are the IOPQ requirements?

• (list)

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Utilities

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• Steam

• Capacity & Quality

• Intended use: Sterilize,

Process Heating, Facility?

• Cleaning & sanitizing

• Compressed Air (Product requirements)

• Capacity

• Quality required for the product

• Processing, drying

Other utilities

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• Product Contact Utilities

• Capacity & Quality (specification)

• Nitrogen/Hydrogen/Gases

• Other Support Utilities

• Dust Collection (Cross contamination)

• Vacuum

• Potable water (sanitation, cleaning?)

• Glycol/Refrigerant/Mineral Oil

• Cleanser/Sanitizer/Disinfectant

Warehousing / Storage

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• Raw, Bulk formula,

In-process/ Intermediates,

Components, Finished Goods, Rejected

• Material Control

• Storage limitations - What do you think?

• Reject, Spatial Separation, Labeling,

Controls, Authorizations, Temperature,

Humidity, Routine Monitoring

• Software Systems

Questions?

• Product Utilities

• Support Utilities

• Warehousing & Storage

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Equipment Design

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• Design & Qualify

equipment for a broad

range of operations

• Contact surface

• Correct materials & finishes

• Understand equipment capabilities…and

limitations

• Types of products it cannot support?

Equipment Qualification

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• Define your overall IQ / OQ / PQ

requirements within the protocol

• Document intended products within the

equipment description section

• Challenge broad range of capability

• Provide justification for planned tests

• Consider equipment train PQs

Group Exercise –

Packaging Line

• Topical Pharma Facility

• Packaging Line 25 SKUs, different:

• Bottles & Cap Sizes

• Emulsions, Oral Suspensions

• What IQ/OQ tests to perform?

• Break into teams – 3 minutes

• Scribe (laptop)

• Presenter 28

Group Exercise –

Water System

• Share - 1 minutes

• Team 2 – Results?

• Do you agree?

• Were your results similar?

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Questions?

• Production Equipment Qualification

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Process & Packaging Validation

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• Understand each product’s needs/CPPs

• Leverage product understanding

• Access your developmental work

• Specify process flow & major unit ops

• Specifications (Acceptance Criteria)

• Actives, Physiochemical, Micro

• Batch Size, Order of Additions, Process

Steps & CPPs

• Temps, Speeds, Time, etc

Product Families

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• What do you think?

• Product grouping based

on similarities:

• Processing Steps or Addition Order

• Ingredients

• Product knowledge is key, leverage your

subject matter experts.

• Small differences can have a big

impact…be honest about

your processes.

Considerations

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• What similarities allow grouping?

• Document in protocol

• Grouping justification

• Similarities

• Development / Plant Trial supporting

data

• Demonstrate your product

understanding.

Class Exercise – PV

• Facility: Children's Acetaminophen

• 1 Strength: 160mg / 5 mL

• Flavors: Grape, Bubblegum, Cherry

• Batch Sizes: 500L, 1500L, 3000L

• What are the PV requirements?

• # Batches, # of Products?

• What to test?

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Class Exercise – Packaging

Facility: Sunscreen Bottle Filling

Bottle Sizes: 150mL, 400mL

• What are the test requirements?

• # of protocols, # of Products?

• # of runs? What to test?

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Name Viscosity Active #1 Active #2

Standard 20,000 – 28,000 cP 15% Avobenzone --

Kids 24,000 – 30,000 cP 30% Avobenzone 5% TiO2

Max 30,000 – 35,000 cP 30% Avovenzone 10% TiO2

Shimmer 22,000 – 30,000 cP 8% Avobenzone --

Questions?

• Process Validation

• Packaging Validation

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Cleaning Validation

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• Definition:• Definition: Documented evidence that

cleaning process removes product and

cleanser to acceptable limits.

• Cleaning Marker: Analyte(s) used to

represent surface cleanliness from the

target product.

• Typically Active Ingredient(s)

• Could be other ingredients (justification)

• Allergen

Cleaning Validation

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• Cleanliness Standards

• Markers for cleanliness

• Carryover Limits (this, and other products)

• Visual Cleanliness (Qualify staff)

• Dirty Hold Time (DHT

• Clean Hold Time

• Value of Process Development, results

support selection of cleaning families

• TACT

Cleaning Families

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• What do you think?• Based on similarities:

• Actives / Markers

• Similar ingredients

• Solubility

• Difficult to clean compounds

• Physical properties (drying, viscosity)

• Coupon studies and development work

to classify cleaning families

Campaigning & Cleaning Matrix

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• Reduce cleaning/sanitizing and

changeover (example)

• Full Clean: Different family

• Short Clean: Similar product

• Product flush: Similar product, higher

concentrationChange To:

Ch

an

ge

Fro

m BP-1 BP-2 BP-3 BP-4 BP-5

BP-1 X WC WC WC WC

BP-2 WC X DC DC DC

BP-3 WC DC X DC DC

BP-4 WC PF DC X DC

BP-5 WC DC DC DC X

Legend: Wet Clean - WCProduct Flush -

PF

Dry Clean

- DC

No Clean -

X

Group Exercise

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Name Actives Other ingredients Cleanser Family

Women’s Lotion Octocrylene 15% Fragrance, Color Base (pH 12) E1

Men’s Sun Octocrylene 14% Base (pH 12) E1

Moisturizing Ocrocrylene 5% Silicone Base (pH 12) E2

Germ-gone Ethyl Alcohol 70% Gel Water G1

Premium Gel Ethyl Alcohol 70% Gel, Fragrance Water G1

AB Moisturizing Ethyl Alcohol 70% Gel, Vitamin E Water G1

Facility: Sunscreen Filling

Bottle Sizes: 150mL, 400mL

• Validation requirements – 4 min

• # of validation protocols?

• Testing requirements?

Group Exercise –

Water System

• Share - 1 minutes

• Team 3 – Results?

• Do you agree?

• Were your results similar?

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Sanitizing/Sterilizing Validation

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• Definition:• Definition: Documented evidence that

sanitizing process reduces microbes to

acceptable limits.

• Standards

• Sanitizers

• Microbial Limits

• Bioburden / Log-reduction

• Sanitized Hold Time (storage conditions)

• Single (1) method possible

Class Exercise –

Sanitizing

• Facility: Mixed-Use Bulk Mixing.

• Medicated Ointment – 1000 cfu/100cm2

• Topical Pharmaceutical – 1000 cfu/100cm2

• Fish Oil Products (3) – 300 cfu/100cm2

• Sanitizing Validation?

• How many Sanitizing Validations?

• How many Sanit Processes?44

Questions?

• Cleaning Validation

• Sanitizing Validation

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Multi-Product and Mixed-Use

Scenarios

Classroom Exercises &

Tips for Success

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Same Product Family

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• Scenario: Multiple products with the

same active ingredient.

• Hydrocortisone 0.5% – 150mL tubes

• Hydrocortisone 1.5% – 150mL tubes

• Hydrocortisone 0.5% – 30mL tubes

• Hydrocortisone 1.5% – 30mL tubes

• Process Validation Requirements?

• Packaging Validation Requirements?

• # of Sanitizing Validations?

Considerations

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• Same Product Families

• How similar is the manufacturing

process?

• CPPs / Product specifications

• Fewer Process & Packaging Validations

• Likely same equipment utilized (IOPQs)

• Possibility for bracketing approach

• 1 worst case cleaning

Mixed Families

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• Scenario: Multiple families, same

business line.

• Different oral analgesic suspensions

• Acetaminophen 160mg/5mL

• Acetaminophen 350mg/5mL

• Ibuprofen 100mg/5mL

• Ibuprofen 250mg/5mL

• PV, Cleaning?

• Equipment Qualification?

Considerations

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• Potentially similar equipment

• Different cleaning requirements, but

potentially similar cleaning methods.

May be possible to establish one

cleaning family

• Worst case product

• Likely similar or “representative”

sanitizing

True mixed-use

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• Scenario: Drugs, Cosmetics &

Supplements

• Different raw material purity requirements

• Varying cleaning/micro requirements

• Documentation requirements (such as

2nd person verification, in-process

release requirement)

• What different storage, handling &

control requirements?

Considerations

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• Food/Supplement

• HACCP requirements needed for food

• Raw material control and storage is more

critical for Supplements

• Allergen storage limitations

• Cross contamination

• Robust sanitizing & environmental

monitoring programs

Ingestible Drug / Non-

drug products

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• Many policy & procedures default to

drug production for mixed-use.

• Qualification and Validation only required

for drug products.

• But, consider cleaning for non-drug,

carryover risk!

• Enforce GMPs for all production, or

only drug? Pros & Cons?

Dedicated equipment?

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• Risks:

• Cleaning / micro, cross-contamination

• Complicated, time consuming to manage

• Extreme controls needed

• Examples:

• Heart medication (low dosage)

• Controlled substances

• Penicillin

• Kosher / Halal certification

Questions?

• Multi-product scenarios

• Mixed-use scenarios

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Policy & Procedures

to support Multi-Product and

Mixed-Use Facilities

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Validation Policy

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• Specify the scope of which

business lines / products require validation

• Outline requirements by validation type

• Facility & Utilities

• Equipment Qualification

• Process & Packaging Validation

• Cleaning & Sanitizing Validation

• Lab Equipment & Methods

• Software Validation

Procedures for Supporting

Quality Systems

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• Validation Procedures

• Quality Manual

• Master Validation Plan

• Change Control

• GMPs & GDPs,

• Gowning & Access

• Cleaning, Sanitizing/Sterilization

• Training

Session Summary

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• Demonstrate Product / Process knowledge

• Understand regulation requirements

• Provide Justification

• Summarize your validation program for

audit compliance and alignment

• Consider product interactions

Questions?

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Thank you!• Justin B. Roose, Head Validation Engineer – Global Compliance, Amway

Corp.

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

• 616-787-0031

• jroose@amway.com

•

• Biography – Justin Roose

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

currently leading validation activities in a new 4-phase production facility. His team is

responsible for: process, packaging, cleaning, sanitizing and software validation, as well as

equipment and utility qualification. His software validation team is also responsible over 25

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

• Justin received his BS in Chemical Engineering from Calvin College. He has obtained over

15 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 software &

process/packaging validation programs.

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