Particles and insoluble matter in API manufacturing: why is it a topic of great interest?
- Definition of particles
- Types of particles
- Possible reasons for the elevated presence of visible particles
- Hints in guidances on how to deal with visible particles
- Inspectional observations
- Expectations of API manufacturers, API users, API suppliers and supervisory authorities regarding visible particles in APIs
Foreign Matter in pharmaceutical Excipients – how to deal with “Technically Unavoidable Particles” (TUPs)
- Incident management – how to identify the source of insoluble matter
- Potential sources of insoluble matter
- Root cause analysis – examples of investigation techniques and aids
- Risk assessment: topics to be considered during the investigation/disposition decision
Acceptance criteria for particles in APIs
- Types of dosage forms and routes of administration
- Typical limits for particle size seen via a filter test
- Proposal for limits
Good practices to minimise the presence of particles in APIs – key preventive measures
- Typical construction materials in API manufacturing plants as source of particles
- Effective cleaning procedures
- Pretreatment of equipment/product contact utilities
- Inspection of equipment before and after production
- Cleaning after repairs
- Essential written procedures covering maintenance and cleaning procedures Environmental conditions during open handling in final stages of API manufacturing
- Effective training of operators
Analytical control methods for particle detection
- General conditions: design of an appropriate sampling process
- Application of different inspection techniques: filter test, visual inspection etc.
- Metal detectors, metal separators
- Weighing and/or visual inspection of pieces of equipment
- Periodic review of security sieves and/or filters
How can routine cleaning procedures detect or minimize the presence of particles in API production?
- Guides and Industry Standards regarding cleaning
- Equipment cleaning
- Production environment cleaning
- Equipment design considerations
- Detection/removal methods of particles
- Preventive measures
Foreign Particles in Excipients and Finished Product Quality and Safety
- Contamination Profile of Excipients meets Finished Product Quality Target Product Profile
- Excipient Process Risk Analysis and TUPP/ Particulate Contamination Profiling