Validation Flashcards
Annex 15
User Requirements Specification (URS): The set of user & engineering requirements to create a feasible design meeting the intended purpose of the system.
Factory Acceptance Test (FAT): Performed at factory to ensure equipment manufactured against Design Specification
Site Acceptance Test (SAT): Performed at delivery to ensure equipment received against Design Specification
Design qualification (DQ): Documented verification that proposed design of the facilities, systems and equipment is suitable for the intended purpose. Verify requirements of design spec.
Installation Qualification (IQ): Documented verification that facilities, systems and equipment, as installed/modified, comply with the approved design & manufacturer’s recommendations.
Operational Qualification (OQ): Documented verification that facilities, systems and equipment, as installed/modified, perform as intended throughout the anticipated operating ranges.
Performance Qualification (PQ): Documented verification that systems/equipment can perform effectively and reproducibly based on approved process method & product specification.
QUALIFICATION: Suitability of equipment/utilities/facilities/systems confirmed & documented against a set of predefined requirements. Pre-requisite to validation.
VALIDATION: Documented evidence that a process, method or piece of equipment consistently achieves desired result
Validation basics
Based on QRM & regularly reviewed & revised
Knowledge management key
Activities planned and covers the lifecycle (eqp, process or product)
QA oversight of validation lifecycle
Defined & documented in VMP
Q & V policy – inc. analytical methods/cleaning/computer systems
Roles & Responsibilities for Q & V
Summary facilities/eqp/systems/process on-site & the Q & V status
CC process for Q & V
Q & V strategy, including where re-validation is required
Validation protocols and reports:
Outlines scope and purpose of activity
Approved before protocol execution
Inc. materials/equipment/testing/sampling/acceptance criteria
Critical attributes & parameters
Deviations recorded & scientifically justified
Outcome documented in validation report
Process validation
Initial PV, re-PV of modified processes, site transfers & on-going process ver
Use Annex 15 in conjunction with EMA guideline on Process Validation
Can be 1) Traditional 2) Continuous Process Verification 3) Hybrid Approach.
Concurrent validation accepted in exceptional circumstances
Hybrid approach typically used where have a large amount of process/product knowledge and also for PV activities after changes
No. of batches for PV based on QRM, to provide enough data to ensure process is consistently capable of delivering quality product (Min 3)
PV for new products should cover all strengths, but bracketing may be justified if extensive knowledge from Dev & with on-going verification program
Site transfer no. of validation batches may use bracketing
Confirm all CQAs/CPPs consistently met. Document why critical/non-critical.
Batch size normally same as commercial (other sizes may be justified)
Cleaning/Eqp/Processes/Facilities/Utilities/Systems - qualified & validated
Manufacture by trained personnel to GMP
Starting/in-going/packaging mats qualified for use
If batches to be released to market – must be pre-defined
Continuous Process Verification (Type of PV – QbD):
For products developed using QbD, where established control strategy provides high assurance of product quality, can be used as alternative to traditional PV.
Method by which process is verified must be defined.
Scientific based control strategy for incoming materials, CQAs and CPPs, with regular re-evaluation.
PAT (Process Analytical Technology) and Multivariate Statistical Process Control may be used as tools.
Must determine & define number of batches required.
On-Going Process Verification during Lifecycle:
Assurance of product quality & to ensure a state of control is maintained throughout product lifecycle, with relevant trends evaluated.
Extent & frequency reviewed periodically and updated if required
Conduct under protocol & final report with results. Stats support capability.
Cleaning Validation:
Performed to confirm effectiveness of cleaning for product contact eqp. Non-product contact eqp dependant on risk (must be documented rationale).
May take some time to complete CV validation with verification after each batch acceptable approach until sufficient data to consider cleaning method validated
Visual check importance, but cannot be only criteria used demonstrate API removal
Factors which impact the effectiveness of cleaning should be assessed, e.g. rinse times. Use worst case situations for basis of validation studies.
Limits for carryover should be tox based, with limits used justified in risk assessment.
CHMP Guidance on setting HBEL in manufacture of products in shared facilities
Is compound toxic: PDEs calculated using NOAEL and safety factors
Non EU: 1/1000 therapeutic dose still an expectation therefore many companies calculate both and apply tightest limit
Limits to include removal of cleaning agents.
Worst case product approach used Justify
Micro & Endotoxin risk considered
Clean & dirty hold times and maximum campaign length times
Cleaning procedures to detail location & rationale for swab points & define acceptance criteria
Swab recovery from all cleaning methods validated demonstrate recovery from all PC materials
Manual cleaning must be check for effectiveness.
If can’t clean, product dedicate with other controls.
Initial new product assessment: Potency, toxicity, solubility, allergenic ingredients, cleanability
PDE
NOAEL x Weight adjustment divided by 5Fs
Verification of Transport:
Transportation routes clearly defined
Seasonal variations considered
Ensure product (bulk & samples) is transported in accordance with MA
Risk assess the transport variables, e.g. delays, failure of monitoring devices, topping up of cooling materials etc.
Continuous monitoring expected, unless justifiedTransportation routes clearly defined
Seasonal variations considered
Ensure product (bulk & samples) is transported in accordance with MA
Risk assess the transport variables, e.g. delays, failure of monitoring devices, topping up of cooling materials etc.
Continuous monitoring expected, unless justified
Packaging Validation:
Primary & secondary equip qualified
For primary equipment qualify at:
Min & Max operating ranges defined for CPPs inc. forming & sealing temp/machine speed/sealing pressure
Utilities Qualification:
Quality of steam, water, air, gases should be confirmed during qual
Reflect intended use of facility
Reflect seasonal changes
QRA where direct contact with product, e.g. HVAC
GAMP5 Categories (4):
1: Infrastructure software, e.g. operating systems
3: Non configurable software, e.g. COTs
4: Configured software, e.g. LIMS
5: Bespoke software
Annex 11 Computerised Systems
