Components Of Finished Pharmaceutical Product - Excipients

3.1.2 Excipients:

3.2.P.2.1.2 The choice of excipients listed in 3.2.P.1, their concentration and their characteristics that can influence the FPP performance should be discussed relative to their respective functions.”

When choosing excipients, those with a compendial monograph
are generally preferred and may be required in certain jurisdictions. Other resources are available for information on acceptable excipients and their concentrations such as the US-FDA IIG (13) list and the Handbook of pharmaceutical excipients (14). Use of excipients at concentrations outside the established ranges is discouraged and generally requires justification. In addition, available guidelines which address particular excipients to be avoided should usually be consulted, for example, azo colourants as listed in EMA guideline CPMP/463/00 (15). Other guidelines such as WHO’s Development of paediatric medicines: points to consider in pharmaceutical development (16) may provide useful general guidance in this regard.

The characteristics and amounts of excipients that can influence the performance of the pharmaceutical product or its manufacturing capability should usually be discussed relative to the respective function. The ability of functional excipients, e.g. pH-adjusting agents, buffers, stabilizers (such as antioxidants and chelating agents), preservatives and dissolution modifiers (such as surface active agents), to perform throughout the intended shelf-life of the FPP should usually be demonstrated.

Antimicrobial preservatives are discussed in 3.2.P.2.5.

Many excipients such as povidone, microcrystalline cellulose and lactose are by nature multifunctional. The chemically identical excipients may have different grades (physical properties) with different functional characteristics; therefore, conformance to pharmacopoeial specifications does not always provide sufficient confidence that an excipient will perform according to its intended purpose.

When an excipient is critical for manufacturing capability of the FPP, batch or batch variations should be minimized by including user requirements additional to those specified in the pharmacopoeia, e.g. particle size distribution.

Ranges or alternatives for excipients are normally not accepted unless supported by appropriate process validation data. Where relevant, compatibility study results (e.g. compatibility of a primary or secondary amine API with lactose) should be included to justify the choice of excipients. Specific details should usually be provided in the PD where necessary (e.g. on use of potato or corn starch). 

Pharmaceutical Development of multi source (generic) Finished Pharmaceutical Products - points to consider,  (Annex 3, WHO Technical Report Series 970, 2012)

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