Excipients functionality-related characteristics

European Pharmacopoeia. 2008. <5.15> Functionality-related characteristics of excipients, 6th ed. 

The Ph. Eur. monograph Pharmaceutical Preparations states When physico-chemical characteristics of active substances and functionality-related characteristics (FRCs) of excipients (e.g. particle-size distribution, viscosity, polymorphism) are critical in relation to their role in the manufacturing process and quality attributes of the pharmaceutical preparation, they must be identified and controlled. ... 

Subsequently, the BPI provides a Ust of all active substances and excipients, in a way that defines their identity and quality unambiguously. For example, it should be clear if the free active substance has to be used or the salt form, or, when multiple hydrates exist, which hydrated form is required (see Sect. 23.1).To define the quality of the raw materials it is advisable to use their pharmacopoeial names wherever possible. Preferably, additional specifications (Functional related characteristics, FRCs) which are not mentioned in the monograph that distinguish between different qualities, are added to the name of the raw material. Examples are the particle size of a solid material, the viscosity of a liquid or a cellulose derivative, or the concentration of a solution. Sometimes a brand name reflects the quality better (e.g. Witepsol H15 instead of Adeps solidus). If confusion may stiU be possible (crystal water, salt forms), addition of the chemical formula might be useful. 

The section includes the specifications for the raw materials and containers to be used. Preferably raw materials of a suitable pharmaceutical grade should be used (see Sect. 23.1.2), but this may not always be possible. All the considerations that played a role in the choice of the raw materials are recorded in this section, including the excipients, preservatives, colourants and flavours. Amounts and calculated doses are mentioned, and the need for specific properties (Functionally Related Characteristics) such as purity, fineness or viscosity where this is essential for the firtal quality. 

The choice of the excipients, their intended function, and their concentration will need to be considered in relation to those characteristics that may affect product performance. 

Examination of product control charts is most useful in trying to distinguish between process-related or non-process-related causes.Trend analysis of key production parameters and attributes could assist in localizing a possible cause of the OOS. For example, if the potency of the product has been trending higher than usual for the last few batches produced (and the OOS resulted from an upper limit failure), this could be indicative of such causations as inaccurate moisture analysis or operator compensation error, error in the batch record, weighing error due to balance or scale bias, change in excipient purity which could impact functional characteristics or failure to maintain and/or calibrate apiece of equipment. 

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