Validation - Qualification Training
Validation - Qualification Training
ISO
➔ ISO 13485: Medical devices
◆ quality management systems
◆ requirements for regulatory purposes
◆ for organizations involved in the design, production, installation and servicing
of medical devices and related services
➔ ISO 14644-1: Classification of air cleanliness and associated controlled environments
◆ for HVAC systems
Intended use: when performing a validation, its focus should be on the intended use of the
system or process
Software categories:
➔ GAMP Category 1: Layered software, software used to manage the operating
environment
◆ It supports or runs diverse applications
◆ Operating systems in general (Windows, iOS, Linux)
➔ GAMP Category 2: Custom built hardware components
◆ USUALLY NOT PERFORMED
◆ For camera, computer, mouse, etc.
➔ GAMP Category 3: Non Configured, software cannot be configured to suit the
business process
◆ Commercial software; people buy it, install it and use it
◆ Not adaptable to the needs of the user
◆ Office (Word, Powerpoint)
➔ GAMP Category 4: Software, often very complex, that can be configured by the user
to meet the specific needs of the user’s business process
◆ Base software
◆ ERP, ORACLE, SAP, Excel spreadsheets
➔ GAMP Category 5: Custom, software custom designed and coded to suit the
business process
◆ Usually made and designed from scratch, according to the needs of the user;
nobody else can use it
◆ Code
V-Model strategy:
Category 3:
User requirements → Non configured product → PQ/Validation plan testing
Category 4/5:
User requirements → Functional specification → Configuration specification → Code review
→ IQ/Validation plan testing → OQ/Verification plan testing → PQ/Validation plan testing
Documentation:
Category 3:
➔ Software Validation Master Plan (SMVP)
➔ Software Validation Applicability (SVA)
➔ User Requirements Specification (URS)
➔ Software Installation Qualification plan in production environment (SIQ Production)
➔ Software Installation Qualification report in production environment (SIQ Production)
➔ Performance Qualification / Validation plan (PQ)
➔ Performance Qualification / Validation report
➔ Software Validation Master Report (SVMR)
Category 4/5:
➔ Software Validation Master Plan (SMVP)
➔ Software Validation Applicability (SVA)
➔ User Requirements Specification (URS)
➔ Functional Requirement Specification (FRS)
➔ Functional Risk Assessment (FRA)
➔ Design Specification (DS)
➔ Code review (CR)
➔ Software Installation Qualification plan in test environment (SIQ Test)
➔ Software Installation Qualification report in test environment
➔ Operation Qualification / Verification plan (OQ)
➔ Operation Qualification / Verification report
➔ Software Installation Qualification plan in production environment (SIQ Production)
➔ Software Installation Qualification report in production environment (SIQ Production)
➔ Performance Qualification / Validation plan (PQ)
➔ Performance Qualification / Validation report
➔ Software Validation Master Report (SVMR)
Master plan:
➔ Document that structures and describes the software, the intention of use, the roles
and responsibilities, how to perform the validation, the strategy to follow according to
the GAMP5 category of the software and the deliverable documents
➔ It can also explain how many softwares are used in the company/project
User requirement:
➔ Requirements to be satisfied based on the intended use of the system
➔ Clear, not vague and testeable
➔ Elaborated by the subject matter expert of the area or process that requires the
software, but user gives us the expectations
➔ References - regulations (820, GAMP5), SMVP and SVA
Functional specification:
➔ How the system functions satisfy the user requirements
➔ Each user requirements can have one or more functionalities that help the system
execute the user requirements
➔ Each functionality must be linked to a user requirement; an identifier is assigned to
the user requirement that its linked
➔ Clear, not vague and testable
➔ Elaborated by subject matter expert/developer that develops the solution
➔ References - user requirements
Functional risk assessment:
➔ Functionalities are evaluated for risk analysis
➔ The risk, possible failure scenarios and focus validation efforts on high impact
functionalities are defined
➔ Run test scenarios - positive (correct) and negative (wrong); these detect failures in
the system and possible mitigation actions
➔ Low risk - only perform positive test
➔ Medium/High risk - perform positive and negative test
➔ Probability (given by expert/developer) vs Severity (given by user)
➔ Elaborated by all experts (manufacturing, quality, etc.), development/support team
and validation
➔ Fail mode - given by developer on how the system can fail
Design specification:
➔ How the system design satisfies the functionalities of the system; how the developed
solution will look like
➔ Each design specification must be linked to a functional specification; an identifier is
assigned to the functional requirement that its linked
➔ Clear, not vague and testable
➔ Elaborated by subject matter expert/developer that develops the solution
➔ References - user requirements, functional requirements
Configuration review:
➔ Checklist of the solution code developed
➔ Comply with good practices of software development, clear, without dead code and
without sections of code in comments
➔ Once performed and approved, no modifications are allowed without prior
authorization
➔ Run in OQ and PQ
Traceability matrix:
➔ Requirements are addressed and traced to the appropriate functional and design
elements in the specifications, so requirements can be traced to the appropriate
verification
➔ Can assist the assessment and management of change
➔ Should be focused on aspects critical to patient safety, product quality and data
integrity
PQ / Validation plan:
➔ User requirements of the system are tested in production environment to
demonstrate that it is secure for production use
➔ Negative scenarios are not tested, they were already tested in OQ
SISTEMAS DEJADOS DE TAREA
➔ LIMS ➔ SOX
➔ ERP ➔ ALM
➔ EAM ➔ EDHR
➔ MES ➔ Shop floor
Shop floor
➔ Easy-to-read front-end to show manufacturing performance, efficiency, quality details
and current activities developed
➔ Real-time production status, inventory and warehouse management and
adjustments, documentation, quality
➔ GAMP category 4
Documents:
➔ Validation master plan
➔ Qualification plan
➔ URS (User Requirement Specification)
➔ FS (Functional Specification)
➔ Functional Risk Assessment (FRA)
➔ DS (Design Specification)
➔ FAT (Factory Acceptance Test)
➔ SAT (Site Acceptance Test)
➔ Commissioning
➔ IQ (Installation Qualification)
➔ IQ-R (Installation Qualification Report)
➔ OQ (Operation Qualification)
➔ OQ-R (Operation Qualification Report)
➔ PQ (Performance Qualification)
➔ PQ-R (Performance Qualification Report)
Qualification plan:
➔ Equipment and its intention of use is described
➔ Validation strategy according to GAMP5
➔ Similar to CSV, due to presence of control systems like embedded software/PLC
Functional specification:
➔ How the system functions satisfy the user requirements
➔ User requirements can have one or more functionalities
➔ Functionalities are linked to a user requirement by identifier
➔ Elaborated by subject matter expert (manufacturer); you have to check with them if
the functionalities satisfy the user requirements
➔ Which component satisfy the user requirement
Design specification:
➔ Material and how components work
➔ How the system design satisfies the functionalities
➔ Each must be linked to a function specification
➔ Clear, not vague and testable
➔ Elaborated by subject matter expert/manufacturer
Commissioning:
➔ Assuring all systems and components of a building/plant are designed installed,
tested, operated and maintained according to the operational requirements
➔ Also for existing units and systems subject to expansion, renovation or revamping
Equipment IQ OQ PQ
Weight Verify that the weighing Repeatability test (repeatedly Weight Variation test (Verify
checker balance is securely anchored weighting to check that the weight variation
and shock proof consistency) complies with the user
Verify that all electrical Corner Load test (a load is requirements, using 3 samples
connections are done properly weighed on all 4 sides of the at different machine speeds
and that they’re safe weighing area) (rpm))
Equipment is vibration free Accuracy test (different
That is no observable damage masses ranging from minimum
load to max load are weighed
for accuracy)
Blister Testing of programmable Verification of rejection of
packaging logic controller’s processor blister without product (All
PLC (Verify by observation the empty blisters shall be rejected
normal operation of the by the system)
processor module’s LED Verification of rejection for
status indicator after turning broken units
on) Verification of rejection of one
Verification of Man-Machine empty pocket
Interface Screens (verify that
all of the functions on each
screen is according to the
manual)
Power & Emergency Failure
Recovery Verification (verify
that in the event of a power
loss or communications failure,
the equipment will stop in safe
conditions)
Emergency Operation
Verification (verify that the
equipment will be inoperative
in case of an emergency stop)
Alarms Verification (verify
the alarms function and
respond according to the
system design)
Sleever
Biosafety Utilities verification Initial certifications (Prior to Airflow smoke pattern test
cabinet (electrical services, gas use a qualified certifier tested (ensure that the system in an
services specifically to Valves) the cabinet) aseptic area provides an
Verification of the technical Alarm conditions and their unidirectional airflow using a
specifications for in-house & expected results dry ice/Titanium chloride torch,
subcomponents (Damage and watching the smoke flow
claims occurred while in transit being unidirectional up to the
or within the building) working height)
Connecting to an Exhaust HEPA Filters Leak test (using
System (verify if a qualified the PAO/ DOP liquid
installer has completed the penetration through the filter
connections to the BSC) media and obtaining a result of
Hygienic Hermetic Finish less than 0.01% to test
efficiency)
UV radiation intensity test
(determines the energy output
of the UV lamp’s sufficiency in
killing the microorganisms
within the cabinet’s work)
Vibration Test (determines
the amount of vibration in an
operating cabinet using a
vibrating testing meter)
Freeze Leak test (using a placebo run Sensor calibration (to ensure
drying verify that the sealing and the equipment is reaching the
capping phase is done specified temperatures)
correctly and the finished Vacuum system (to verify that
product has no leaks) the pressure can be achieved
Temperature and relative from ambient conditions)
humidity test (demonstrate
the ability of the system to
provide a Temp and RH within
a specified range/to help verify
that the moisture of the sample
is removed by the correct
process of sublimation w/Data
Logger equipment)
OQ
medición de corrientes de aire
medir el aire y verificar que este aire realmente esté balanceado en toda el cuarto/cámara
cómo se mueve y qué tanto cambia la corriente de aire; si bien no tienes puerta, solo entras
normal
se realiza con el cuarto cerrado
realizado por anemómetro; mide el cambio/reemplazo de aire por hora
integridad de filtro HEPA
calidad del filtro; el filtro debe retener todas las partículas
pongo aerosol frente al filtro, hago que opere (le pasas aire), usas un aerosol fotómetro y
con eso conoces si tuviste penetración del producto por el filtro
si no pasa, el filtro sí funciona bien (1 partícula de 1M), dependiendo de la necesidad del
lugar donde estás trabajando
poner una capa de aceite y hago que pase el aire, el aire que regresa/pasa tiene que pasar
limpio (0.01%)
DOP/PAO; contador/medidor de partículas
diferencia de presión
medir la capacidad que tiene tu sistema que tiene la capacidad de crear una gradiente de
presiones
la gradiente se genera entre dos lugares con diferente presión y permite que se mueva a un
cuarto de mayor a menor presión
con manómetro
tipos de esclusa:
pozo
burbuja
cascada
partículas no viables
contador de partículas
para contar qué tantas partículas hay y que esté permitido por la ISO
puedo tener según la clasificación ISO
clasificación ISO - te da el nivel de esterilidad del cuarto para poder realizar sus actividades;
indicado por tamaño de partícula
1: aséptico (vacunas)
3-4: para trabajos farmacéuticos
7: preparaciones farmacéuticas
partículas viables
vas, dejas una placa con dos diferentes agares (soya tricaseína y papa dextrosa para
hongos); uso de medio y condiciones más comunes para las bacterias/hongos más
comunes
se realiza a dos condiciones porque las bacterias y los hongos crecen a diferentes
condiciones
PQ
se puede repetir
temperatura humedad
partículas viables
partículas no viables