How characterization of excipient physical and chemical properties helps build quality into drug product

1. How characterization of excipient physical and chemical properties helps build quality into drug product Dr Brian A Carlin FMC BioPolymer

2. Excipient \Ex*cip"i*ent\, n. 1. An exceptor. [R.] 2. (Med.) An inert or slightly active substance used in preparing remedies as a vehicle or medium of administration for the medicinal agents Excipient \Ex*cip"i*ent\, a. [L. excipients, -entis, p. pr. of exipere. See Except, v. t.] Taking an exception. Exceptor \Ex*cept"or\, n. [L., a scribe.] One who takes exceptions. Excipient Does characterization of excipient physical and chemical properties help build quality into drug product?

3. Compliance with specifications Drug product, raw materials Consistency Processability, yield Functionality, utility PATability >70% perform additional functionality or processability testing 76% to determine excipient suitability 66% always for the excipient >50% for oral solutions. 87% for solid oral dosage forms. Definition of Quality?

4. “About 25% of the time drug product manufacturers test excipient suitability for processing, using experimental (laboratory) scale batches, or pilot scale manufacturing batches. This was higher than expected.” Quality NOT by Design? “An excipient's functionality can only be assessed in the context of a particular formulation and manufacturing process” RC MoretonPharmaceutical Technology, May 2004

5. Application dependent (why do you add it?) Formulation dependent (effect of other ingredients) Process dependent (application may be process-specific) Trade-off (competing formulation objectives) Multi-functional excipients Functionality transcends the excipient

6. Chemical Synthesis* Mining of Minerals Harvesting of Vegetation Formulated Products Biotechnology Genetic Modification Animal By-Products *Often less defined than single low mol wt entities Diverse Materials Base

7. Primarily safety and purity focused Mainly chemical with some limited physical characterisation Functionality Related Characteristics (FRCs) in European Pharmacopoeia IPEC opposed to inclusion of functionality in monographs but supportive of USP proposal for general chapters on Compactability, Lubrication & Disintegration Physical testing a necessary but insufficient guarantee of functionalities Grade specification Pharmacopoeial compliance of limited relevance

8. Variable Raw Material + Fixed Process = Variable Product Raw Materials Product Process Control

9. Variable Raw Material + (Anti)variable Process = Constant Product Raw Materials Product Process PAT Control (Anti-phase)

10. Holistic definition of Quality User/Supplier collaboration FDA 21st century cGMP initiative (PAT) Functionality testing and specification Sourcing higher specification materials Tailored excipients Questions/Issues