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
