MSAT Steriles Flashcards
(39 cards)
What are the categories of controls for Sterile facilities?
Environmental controls
Personnel controls
Process controls
Equipment/facility controls
Monitoring and testing
Documentation and quality systems
Regulatory compliance
Describe some environmental controls for Sterile Facilities?
-Cleanroom classification: ISO standards. ISO 5 (grade A) is inside the isolator for filling. ISO 7 (old grade C) and ISO 8 (old grade D).
-Air-filtration: High efficient particulate air (HEPA) filters to remove particulate contaminants, and Air flow patterns (laminar flow) to minimise contamination.
-Pressure differentials: Airlocks, to prevent ingress of contaminants from less clean air.
-Temp/humidity control is monitored
Describe some Personnel controls for Sterile Facilities?
-Gowning procedures
-Training and qualification
-Behavioural controls: minimise movement and unnecessary talking
Describe some Process controls for Sterile Facilities?
-Aseptic Technique
-Sterilisation of equipment and materials: everything used must be sterile either from external companies (irradiated with indicator sticker and double/triple bagged (layering systems) e.g. single use technology or syringes into CF06 irradiated using ethylene oxide), internally autoclaved equipment, depyrogenation ovens, stoppers washed etc…
-Cleaning and disinfection: using validated cleaning procedures
Describe some Equipment and Facility controls for Sterile Facilities?
-Isolators and restricted access barrier systems: A physical barrier to protect product from contamination, and operator from exposure
-Validated equipment
-Routine maintenance and calibration
Describe some Monitoring and Testing controls for Sterile Facilities?
-Environmental monitoring: particulate counting, swabs, active airs, settles
-Surface and Personnel monitoring: finger dabs and garment monitoring
-Product testing: IPC and finished product testing e.g. sterility, endo, bioburden
Describe some Documentation and Quality controls for Sterile Facilities?
-SOPs
-Batch records: allow traceability and accountability
-Quality assurance / Quality Control: ensure products meet quality/regulatory standards
Describe some Regulatory controls for Sterile Facilities?
-Good manufacturing practice (GMP): adherence to facility design, process validation, documentation and quality control
-Audit and Inspection: Ensures compliance with standards and identifies areas for improvement
Give a summary of the Area Classification equivalences?
Grade A: ISO 5
Grade B: ISO 5 (when in operation)
Grade C: ISO 7
Grade D: ISO 8
How are the ISO’s achieved?
-Design and construction: smooth surfaces to prevent contamination (minimal ledges/crevices), airlocks
-Air flow: HEPA filters and laminar flow design
-Room materials: cleanroom-compatible (non-shedding and resistant to cleaning agents)
-Operational control: SOPs, personnel training and access control
-Cleaning schedule and equipment maintenance
-Monitoring and Testing: particulate counting, EM/microbial monitoring
-Validation: initial, ongoing and document all
What is an isolator?
An isolator is an enclosed, controlled environment that is used to conduct sterile or aseptic processes
What are the key features of an isolator?
- Physical Barrier: Prevents the ingress of contaminants from the surrounding area
- Glove Ports: Operators use glove ports to handle materials and perform procedures inside the isolator without compromising its sterility
- Air Filtration: Isolators are equipped with HEPA or ULPA filters to ensure that the air inside remains free of particulate contamination
- Transfer Systems: Materials and equipment are transferred into and out of the isolator through airlocks or rapid transfer ports (RTPs)
- Environmental Controls: The isolator maintains controlled temperature, humidity, and pressure conditions to support aseptic processes
What are some sterilisation methods?
Steam: autoclave, SIP
Dry heat: Depyrogenation ovens, SIP
Gamma Irradiation: Single use technology and Cabotegravir
Chemical sterilisation:
VHP: Decontaminate hatches, isolators, reinstatement (not a seeking agent)
Ethylene oxide: used externally to irradiate syringes
What are some sanitisation methods?
Actichlor
IPA
Quat
Dishwasher
Mechanical act of cleaning
UV: external suppliers have been irradiating with UV instead of gamma due to a supply shortage of cobalt
What are Critical Process Parameters?
Key variables within a manufacturing process that must be controlled within predefined limits.
This ensure that the process consistently produces products that meet quality standards.
e.g. temperature, pressure, mixing speed, flow rate
What are Critical Quality Attributes?
The physical, chemical, microbiological, or biological properties or characteristics of a product that must be maintained within predefined limits to ensure the desired product quality
e.g. sterility, particulate level, potency, endo levels
How are CPP’s linked to CQA’s?
Via Design of Experiments (DoE)
DoE is a systematic approach to investigating the relationships between multiple process variables (CPPs) and their impact on product quality attributes (CQAs).
By using DoE, MSAT teams can identify and optimize the key factors that influence product quality.
Often predetermined by R&D - sometimes in collaboration on a product to product basis
What is product lifecycle management?
The Methodology by which you design, implement, control and continuously improve your products and processes.
What are the stages of product lifecycle management?
Process Design
Process Qualification
Continued Process verification
What products undergo product lifecycle management?
New products at stage 1 (process design)
Established/legacy products (edited at stage 2 and 3)
It is a cyclical process
Describe process design in PLM?
Developing process knowledge/understanding by utilising development and manufacture history to produce a technical risk assessment.
The key output of a technical risk assessment is the Product Control Strategy. The PCS is a blob diagram that cross references CPP and CQA - with planned controls/additional assurances to assure process performance and product quality
Describe the process of Process Qualification in PLM?
Where you validate the product control strategy (PCS). This is only performed when the process is understood and therefore can be controlled. PQ is to confirm not develop
What are some inputs considered in process qualification?
Technical risk assessment
Product control strategy
Qualified facilities
validation master plan
Validated analytical methods
SOPs
Batch records
Cleaning validation assessment
What are some outputs of process qualification?
Validation summary report
Updated product control strategy
Data trending plan
Approval to proceed with commercial manufacture
