The Summary of Product Characteristics (SmPC) is legally required by regulatory agencies. In the USA, the SmPC is referred to as the ‘Prescribing Information’ in either case, it is a dynamic document updated throughout the life-cycle of a drug, as new data emerges from the reporting of adverse effects and clinical practice. It forms the basis of information for healthcare professionals to use in order to administer and prescribe the drug in the correct way and with appropriate information required to guide a treatment decision. The risks associated with any particular drug can be managed by following the SmPC guidance. A summary of the typical contents of an SmPC is shown in Figure 1. The EMA define the SmPC functions as “Describing the properties and the officially approved conditions of use of a medicine” (EMA, 2017).
Absolute bioavailability is sometimes referred to as absolute oral bioavailability (Fp.o.). These studies are carried out to determine how much of an investigational product is absorbed in the gastrointestinal system and metabolised in the body (Toutain and Bousquet-Melou, 2004). A determination of the quantity of the drug successfully enters the systemic circulation, and is therefore available to the target, can be made. This information is used to inform important assessments over investigational drug activity during the analysis of further pharmacokinetic (PK) data (FDA.gov, 2014).
In traditional studies, both intravenous (IV) and oral routes of administration are observed Toutain and Bousquet-Melou, 2004). These studies are often structured as ‘crossover studies’. Participants receive clinically relevant doses of both an oral and IV administration form (FDA.gov 2014), so that a characterisation of the PK profile of the product and any active metabolites can be made. These PKs are compared to determine the absolute oral bioavailability. If the drug formulation has been primarily prepared for oral use there may be an extensive re-formulation task required to produce an IV administrable drug that is both stable and sterile, This can be particularly difficult for investigational products that are not freely soluble and may be extremely challenging to re-formulate into an IV appropriate dosage form (ICH, 2009). Further complications surround the administration of a new drug through a route not previously studied as the only data available will be from animal toxicology studies (ICH, 2009). Figure 2 shows the equations used to determine absolute oral bioavailability.
Radio-label studies are a more modern approach, approved by licencing authorities. A radio-labelled 14C micro-dose is administered by IV alongside an oral dose form. Results are measured by liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) or accelerator mass spectrometry (AMS). LC–MS/MS allows simultaneous detection of both drug administrations so, has cost and time benefits. However, for investigational products that have a particularly high volume of distribution AMS can provide a more specific lower limit of quantitation (Xu et al., 2014). The full science paper can be found here.
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