validation strategies for multi-product facilities … 19_roose_pres.pdf · packaging line...
TRANSCRIPT
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
2
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
6
• 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
33
• 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
49
• 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
50
• 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
52
• 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?
54
• 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
•
• 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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