lecture 3: GMP validation Flashcards
What is validation?
documented program that provides a high degree of assurance that a specific process, method or system will consistently produce a product meeting its pre-determined acceptance criteria
Why do we validate?
ensures quality is built in from the start (from product development through production, quality testing, to product release)
ensures premises, equipment and processes are capable of routinely producing products of the specified quality
reduces production faults, rejects and reworking
reduces reliance on finished product testing (which requires destroying of the product)
essential for regulatory approval
What kinds of things should be validated?
new manufacturing formula or revised formulation (e.g. change in materials)
new manufacturing process or change in production process
new or change in equipment
new raw material specification
testing methods
construction of new facility and installation (e.g. water system, quality testing of water for extra filtration, building ventilation system)
computerised systems (as computers are used widely to control many aspects of GMP activity)
What is the validation policy?
that critical parameters are identified during the product development stage (stability of colouring agents, low strength active ingredient)
process parameters that could affect the quality of the active pharmaceutical ingredient are identified.
The range for each process parameter expected to be used during routine manufacturing process is determined
What are the types of validation?
process validation
equipment validation
cleaning validation
analytical methods validation
What is process validation?
the documented evidence that the process can perform effectively and reproducibly to produce a product meeting its pre-determined specs and quality attributes
What does process valiation ensure?
products are of acceptable quality and consistent from batch to batch
process used to manufacture the product is controlled
process produces a product comparable in quality and performance with biobatch
What sort of products need to be validated?
all newly devloped pharmaceutical products
products undergoing technology transfer (e.g. scale-up, change of facility)
What products are not validated?
currently marketed products are not validated
what are the benefits of process validation?
it is required by the regulatory associations
ensures thorough and detailed knowledge of the process
results in fewer reject batches
minimises risk of recalls
can reduce intensive in process and finished product testing to ensure quality
What are the requirements of process validation
- written validation protocol which specifies procedures and tests to be done and data to be collected
- sufficient replicate runs to demonstrate reproducibility and accurate measure of variability among successive runs
- test conditions to encompass upper and lower processing limits, which pose the greatest chance of product failure compared to ideal conditions
What are the process validation parameters for granulation?
- equipment used
- batch size
- blender/mixer speed
- amount of granulation fluid
- feed rate of granulating fluid
- granulation time
What type of things are tested in in process validation parameters for granulation?
assay of dry-mixed powders or granules
the loss of substance on drying
What are the process validation parameters for fluid bed drying?
batch size inlet air volume and temperature drying time humidity of incoming/exhaust air porosity of filter bags
What type of things are tested in process validation parameters for fluid bed drying?
particle size/ size distribution bulk and tapped density loss on drying assay powder flow if appropriate
What is the purpose of equipment validation?
ensures that equipment
meet their specs
does what they are expected to do
limits of operation are known
What makes up equipment validation?
qualification of equipment including
design qualification
installation qualification
operational qualification
performance qualification
what is qualification?
a documented verification that the system performs and produces as intended
what is design qualification?
documented verification that the equipment design is suitable for the intended purpose
what is installation qualification?
documented verification that the installed or modified equipment complies with the approved design/specifications
what is operational qualification?
documented verification that the installed or modified equipment performs as intended throughout the anticipated operating ranges (commissioning of equipment to ensure it works)
WHat is performance qualification?
documented verification that the equipment can perform effectively and reproducibly based on the appoved process method and specs
What is the purpose of cleaning validation?
provide documented evidence that the cleaning undertaken for equipment and the environment is effectively in consistently reducing the contamination levels to acceptable/insignificant levels.
When is cleaning validation used?
where contamination or carryover of materials poses the greatest risk to product quality
what should cleaning procedures describe?
the equipment to be cleaned
acceptable cleaning levels
the type of samples to be obtained
how they are collected
What should sampling detect?
quantitatively both soluble and insoluble residues remaining on equipment surfaces after cleaning
What should the residue or contaminant limits be?
practical and achieveable
What is the purpose of analytical methods validation
these are not required if the method is obtained in pharmacopoeias or other recognised standard references
They determine the suitability of an analytical test for a given product/material
Allows us to be confident that the method will perform as expected in various conditions
e.g. when using different analytical equipment, different testing sites etc.
What are the parameters for analytical method validation?
accuracy specificity precision limit of detection limit of quantification linearity
what is accuracy?
the closeness of agreement between the measured value and the true value of analytical standards
what is specificity?
the ability to unequivocally assess the analyte in the presence of components which may be expceted to be present
what is precision?
the degree of reproducibility of individual assays.
intra-assay precision is within days while inter assay precision is between-days testing
What is detetion limit?
the lowest amount of analyte that can be detected by a procedure
what is quantification limit?
the lowest amount of analyte that can be quantitatively determined with suitable precision and accuracy
what is linearity?
the ability to obtain test results which are directly proportional to the concentration or amount of analyte in a sample
What is the purpose of computer system validation?
This establishes documented evidence which provides a high degree of assurance that a specific computer related system will operate consistently in accordance with pre-determined specs
Which computer systems require validation?
those that control manufacturing
or those that provide documentation e.g. inventory control
validation often depends on the competence of the hardware and software suppliers
These systems must work as planned to achieve operational qualification
What are the two main types of documentation?
SOP - which are appropriate and provides definitions, specs and instructions to be followed
Reports - which records facts and results to prove the efficacy of each stage of the validation exercise
