IM P A C T A S S E S S M EN T
EQUIPMENT
SCOPE – TO PERFORM IMPACT ASSESSMENT
AGENDA
• BRIEF OVERVIEW OF EQUIPMENT QUALIFICATION
• LIST OF PRODUCTION EQUIPMENT
• PERFORM IMPACT ASSESSMENT
VALIDATION PRINCIPLE
• MULTIDISCIPLINARY APPROACH: A SPECIFIC CHARACTERISTIC OF
VALIDATION WORK IS THAT IT REQUIRES THE COLLABORATION OF
EXPERTS OF VARIOUS DISCIPLINES.
• TIME CONSTRAINTS: GENERALLY VALIDATION WORK IS SUBMITTED
TO RIGOROUS TIME SCHEDULES.
• COSTS: VALIDATION STUDIES ARE COSTLY AS THEY REQUIRE TIME
OF HIGHLY SPECIALIZED PERSONNEL AND EXPENSIVE TECHNOLOGY.
VALIDATION LIFECYCLE
Qualificatio
VMP Validation
n
VMP – FORMAT AND CONTENT
• THE CORE OF THE VMP BEING THE LIST/INVENTORY OF THE ITEMS TO BE VALIDATED AND
THE PLANNING SCHEDULE
• THE VMP SHOULD BE A SUMMARY DOCUMENT AND SHOULD THEREFORE BE BRIEF,
CONCISE AND CLEAR
Annex Production Engineering QA/QC Technical
Services
Facility ✔ ✔ ✔ ✔
Utilities ✔ ✔ ✔ ✔
Production ✔ ✔ ✔ ✔
Equipment
SAMPLE Laboratory ❌ ✔ ✔ ❌
VALIDATION Equipment
Analytical ❌ ❌ ✔ ❌
TEAM Methods
MEMBERSHIP Process
Cleaning
✔
✔
✔
✔
✔
✔
✔
✔
Methods
Computerized ✔ ✔ ✔ ✔
Systems
QUALIFICATION FRAMEWORK: V-MODEL
change monitor
• FACTORY ACCEPTANCE TESTING (FAT)
EQUIPMENT, ESPECIALLY IF INCORPORATION NOVEL OR
COMPLEX TECHNOLOGY, MAY BE EVALUATED, IF APPLICABLE, AT
FAT AND SAT THE VENDOR PRIOR TO DELIVERY.
• FAT MAY BE SUPPLEMENTED BY THE EXECUTION OF A SITE
ACCEPTANCE TESTING (SAT) FOLLOWING THE RECEIPT OF
EQUIPMENT AT THE MANUFACTURING SITE.
COMMISSIONING
• PLANNED AND DOCUMENTED SERIES OF INSPECTIONS, ADJUSTMENTS, AND TESTS
CARRIED OUT SYSTEMATICALLY TO SET THE INSTALLATION INTO CORRECT TECHNICAL
OPERATION AS SPECIFIED.
REFERENCE: ISO/TC209 WORKING GROUPS AT 2001-03-31 -COMMITTEE
DRAFT ISO/CD 14644-6 “CLEANROOMS AND ASSOCIATED CONTROLLED ENVIRONMENTS”
–PART 6: TERMS AND DEFINITIONS
INSTALLATION
QUALIFICATION
• THE DOCUMENTED VERIFICATION THAT THE FACILITIES, SYSTEMS AND
EQUIPMENT, AS INSTALLED OR MODIFIED, COMPLY WITH THE APPROVED
DESIGN AND THE MANUFACTURER’S RECOMMENDATIONS.
Responsibility
• Commissioning is the responsibility of the Supplier
• IQ/OQ the responsibility of the user
Purpose
WHAT IS THE • The purpose of commissioning is to identify and fix
problems, if any.
DIFFERENCE • IQ/OQ should start when everything works and is
installed as it should be.
BETWEEN
COMMISSIONI Documentation
NG AND IQ/OQ? • Commissioning uses supplies document
• IQ/OQ requires a pre-approved protocol
Change Control
• Changes resulting from IQ must be documented in the
Validation Report
• Commissioning changes are not (supplier
responsibility)
IQ/OQ/PQ can be applied for
DO WE USE both new and legacy
THE SAME equipment.
• For legacy equipment, DQ can be
APPROACH – replaced by a design
DQ, IQ, OQ, PQ review/installation review (depending
– FOR NEW on availability of relevant
documentation, e.g. equipment
AND LEGACY instruction and operational manuals,
EQUIPMENT? purchase orders and supplier
quotations).
Direct Impact
• Equipment which is product contact, or which
controls or maintains a critical process parameter, or
both.
Indirect Impact
IMPACT • Equipment which is not product contact, but which
ASSESSMENT has an impact on the performance or operation of
direct impact equipment.
No Impact
• Equipment which is not product contact, does not
impact on the performance or operation of direct or
indirect impact equipment.
SAMPLE QUALIFICATION MATRIX
IMPACT HIGH MEDIUM LOW
BASED ON DIRECT IMPACT IQ OQ PQ IQ OQ PQ IQ OQ
PROBABILITY AND INDIRECT IMPACT IQ OQ PQ IQ OQ IQ
CONSEQUENCE
NO IMPACT NOT POSSIBE NOT POSSIBLE COMMISSION ONLY
IMPACT SIMPLE COMPLEX
BASED ON SYSTEM DIRECT MINIMUM PQ IQ OQ PQ
COMPLEXITY INDIRECT COMMISSIONING IQ OQ
ONLY
NO IMPACT COMMISSIONING COMMISSIONING
ONLY ONLY
IMPACT ASSESSMENT EXAMPLE
Direct Impact Indirect Impact No Impact
Mixing Tanks Production balances Trolleys/ pallet trucks
Filling equipment Cartoning machine
Process water generators
Capping machine
• A process parameter whose
Critical variability has an impact on a critical
Process quality attribute and therefore should
Parameter be monitored or controlled to ensure
the process produces the desired
(CPP) quality.
ICH Q8 – Critical
• A physical, chemical, biological, or
microbiological property or
PHARMACEUTICAL Quality characteristic that should be within
Attribute an appropriate limit, range, or
DEVELOPMENT (CQA) distribution to ensure the desired
product quality.
• A physical, chemical or
Critical microbiological property or
characteristic of an input material
Material that should be within an appropriate
Attribute limit, range, or distribution to ensure
(CMA)* the desired quality of output material.
• *CMA is not defined in ICH Guidance
WHEN IS A PROCESS PARAMETER A
CPP?
CPP
A PROCESS PARAMETER IS CRITICAL WHEN IT HAS A HIGH IMPACT ON A
Impact on CQA
CQA.
PP
• CPP’S ARE RESPONSIBLE FOR ENSURING THE RIGHT CQA
• CPP’S ARE IDENTIFIED FROM A LIST OF POTENTIALS CPP’S USING RISK
ASSESSMENT AND EXPERIMENTAL WORK
Operation Process Parameters Product Attributes
Wet granulation Loading capacity Granulation size
Quantity of granulation solution distribution
Addition rate of granulation solution
SAMPLE
Impeller and chopper speed
Wet massing time
PROCESS Fluid bed drying Loading capacity Moisture content
PARAMET
Temperature and RH of drying air Solvent residue
Volume/flow rate of drying air
Drying time
ER (SOLID Encapsulation Fill volume
Tamper setting
Appearance
Capsule weight
DOSE) Encapsulation Speed Content uniformity
dissolution
Strip Packaging Sealing temperature Seal integrity
Machine speed
Operation Process Parameters Product Attributes
Dispersion of API’s Homogenization Homogeneity
and preservatives settings/speed Potency
Mixing time and speed
SAMPLE
Temperature
Dissolution of non- Mixing time and speed Appearance of solution
PROCESS
active compounds Temperature Viscosity
Specific gravity
pH
PARAMETE Final mixing Mixing time and speed Appearance of solution
Potency
RS (LIQUID Viscosity
Specific gravity
pH
DOSE) Filling process Equipment settings Fill volume weight
Filling speed Content homogeneity
Filling time Torque/seal integrity
Microbial content
