HW 11
dkf.j
Lecture12-10.25.2017-Validation1.pptValidation
What is Validation?
- Definition
- Documented evidence that provides a high degree of assurance that a specific process, facility, or support system will consistently produce a product meeting its predetermined specifications and quality attributes.
Part of cGMP’s?
- Biologics and Pharmaceuticals – NO
- CFR 210/211
- Medical Devices – YES
- CFR 820
- BUT, FDA expects and requires validation in all cases
- Validation helps assure that products are pure, safe and effective
Where did it come from?
- Originally from need to consistently control sterilization cycles for injectable solutions
- Expanded over years to include utilities and equipment
- Further expansion to processes, methods and computers
- Latest expansion has been cleaning of equipment
The Parts of Validation
- Design qualification
- Installation qualification
- Operating qualification
- Process qualification
- Re-qualification
The Parts of a Qualification
- Protocol
- Written pre-defined acceptance criteria
- A description of procedures (and tests) to be conducted, data to be collected, and methods to be utilized.
- Criteria by which a successful validation will be judged
The Parts of a Qualification
- Results and Report
- Written compilation of results
- Actual, traceable data
- Evaluation against pre-defined criteria
- Explanation and justification of deviations
- Conclusion supporting or refuting a successful validation
Validation Review Board
- Reviews and approves all validation documents
- Typically 3-6 members for appropriate disciplines
- Manufacturing
- Engineering
- Validation
- Quality Assurance
- Validation Coordinator
Example – pH Meter
Design Qualification
- Defines the requirements for the system based on its intended function
- Possible sources
- vendor information sheets
- Internal user requirements documents
Installation Qualification
- Assures that systems/equipment are installed as desired
- Assures that you got what you wanted
- Possible sources
- Purchase order
- Design drawings
Installation Qualification
pH Meter
- Is the model number correct?
- Does it have the desired pH probe?
- Is anything broken?
- Does it have the requested inputs and outputs
- Temperature compensating probe
- Recorder output
Operating Qualification
- Assures that the system/equipment operates as desired
- Possible sources
- Instruction manual
- User requirements document
Operating Qualification
pH Meter
- Does the on/off switch work?
- Do the modes work (with temp compensation and without)?
- Does the printer output work?
- Does the keyboard work?
Process Qualification
- Assures that the system/equipment performs its intended function as desired
- Possible sources
- Design qualification
Process Qualification
pH Meter
- Does it standardize appropriately?
- Will it read standards and unknowns correctly?
- Does it provide a printout as directed?
- Does it provide the expected result in all modes?
Re-qualification
- Periodic assurance that system remains in a validated state
- Frequency determined by procedure, or as specified in original validation
- Test regimen typically a sub-set of original validation
- Covering those things that might drift over time
Real Life Example – Validation of API
- One chemical processing step
- 15 sub-steps
- 10 critical parameters
- 7 days of processing time
API Process
Pre-validation Development
- Experiments conducted, typically at lab scale, to determine critical parameters and worst case conditions
- Critical parameters – those parameters which directly affect qualify of product
- Outcomes of development work define parameters for process validation protocol
Before You Validate the Process
- Everything else must be validated!
- Facilities
- Utilities
- Equipment
- Computer Control Systems
- Methods
- Operators?
Facility Validation
- Assures that building and processing room are designed, built and operated in an acceptable manner for the operations being performed
Utility Validation
- Assures that utilities such as compressed air, nitrogen, water, vacuum and sewers/drains are designed, built and operated in an acceptable manner for the operations being performed
Equipment Validation
- Assures that equipment used to process the API is sufficient for the operations being performed
Computer Validation
- Assures that the computer control systems are designed, built and operated in a manner sufficient to control the process
- Checks inputs, outputs, expected responses, program logic, emergency failures, etc
Method Validation
- Assures that the analytical methods used to measure the product attributes are themselves accurate, precise and robust sufficiently to deliver acceptable data
Operator Validation
- People cannot be validated
- They do not provide consistent outputs!
- People are trained and qualified to do the job
- Based on experience, education, and training
Process Validation Document
Validation Master Plans
- Project based
- Time based
- Pre-approved by review board
- Used as project tracking device
- Post-approval indicates successful completion of job
Validation Master Plans
- Project based
- Major activities
- New building
- New production line
- Describe plan for validation
- Systems to be validated
- Specific protocols to be executed
- Completion of project
Validation Master Plans
- Time Based
- Identifies major projects for validation
- Identifies re-validation activities to take place
- Identifies significant validation issues to address
- Cleaning
- Methods
- New guidance documents
- Tracked by Validation Review Board
