Qualification and validation (Annex 15)
All equipment used in the manufacture of medicinal products must be appropriately qualified. Follow the principles outlined in Annex 15 section 3. Acceptability of the approach taken will be assessed during inspections on a case-by-case basis.
Determine the nature and extent of qualification based on risk management principles. It is generally expected that all stages outlined in Annex 15 section 3 would be addressed in the qualification of new and/or complex equipment. Some of the stages may be omitted, where appropriately justified based on risk, depending on:
- stage in the equipment life cycle
- nature of the equipment
On this page: Application of concurrent process validation | Number of batches used in process validation | Performance qualification and process validation | Critical Quality Attributes (CQA) and Critical Process Parameters (CPP) | Ongoing Process Verification (OPV) | Transport verification
Application of concurrent process validation
For medicinal gas manufacture, concurrent process validation is permitted.
Concurrent process validations should:
- be approved under the sites PQS
- make results and conclusion of any supporting data available to the authorised person performing release for supply
Number of batches used in process validation
Manufacturers are to determine and justify the number of batches used for process validation based on risk management principles. TGA’s general expectations are that:
- for a new process or product, a minimum of 3 batches are to be conducted for validation purposes
- for a process subject to technology transfer from one site to another, an extensive evaluation and risk assessment (with supporting data) should be in place to justify performing less than three batches. The assessment should cover the similarities and differences:
- in manufacturing processes
- methods and materials
Performance qualification and process validation
For medicinal gas manufacture, performance qualification may be performed in conjunction with operational qualification and process validation.
Installation qualification and operational qualification can be combined as an installation/operation qualification.
Critical Quality Attributes (CQA) and Critical Process Parameters (CPP)
Importance and use of CQAs and CPPs
CQAs and CPPs:
- are important elements of product and process knowledge
- should be used in the design, validation and control of manufacturing processes
- can be used in periodic critical revalidation
Descriptions of CQA and CPP
- are physical, chemical, biological, or microbiological properties or characteristics that should be within an appropriate limit, range, or distribution to ensure the desired product quality
- are used to guide process development and control strategies
- can be modified as product knowledge and process understanding increase
- should have appropriate acceptance criteria to demonstrate product quality, including identity, assay, water content and any other relevant attributes
- are process parameters whose variability has an impact on CQAs
- should be monitored or controlled to ensure the process produces the desired quality
- should consider verification for process controls, such as evacuation of cylinders, fill pressure and weight
Ongoing Process Verification (OPV)
Periodically use ongoing process verification (OPV) to:
- evaluate process parameters and trends
- ensure that processes are consistent and remain in a validated state (Annex 15 clauses 5.28-5.32)
Use the outcomes from the OPV to look at any correlation between process capability and trends identified in the PQR. Base the frequency of OPV on risk management principles.
Investigate any adverse trends concerning product quality attributes to determine if processes are consistent and remain in a validated state.
OPV should be:
- used to support the validated status of the product
- documented in the Product Quality Review
The basic expectation is that manufacturers:
- will transport all products (including bulk products and finished products) in full accordance with appropriate storage conditions
- will not store or transport medicines outside their labelled and approved storage conditions
For medicinal products, clearly specify in quality or technical agreements responsibilities for:
Further information about the transport of packaged medicinal gases is included in the Annex 6 clause 45.