Issue link: https://www.e-digitaleditions.com/i/1073928
8 February 2019 Inhalation some similarities and differences in the ways the US and European regions describe the label claim/labeling aspects of DPIs. For example, both the US and Euro- pean source documents describe the use of the active moiety, with the US preferring this as the metered dose and Europe, the delivered dose. However, there have also been various changes in the ways some regional source documents consider labeling. For example, in Europe, the Ph. Eur. 0671 proposed a more specific text for labeling in 2018, changing from "the delivered dose; alternatively, where the dose has been established as a metered dose or as a pre-dispensed dose, the label states either the metered dose or the pre-dispensed dose, as appropriate" to "the delivered dose or, if justified and authorised (e.g., where the dose has been established as a metered dose or as a pre-metered dose), the metered dose or pre-metered dose." is change in approach, however subtle, suggests that the delivered dose is becoming the preferred term for the label claim/labeling of inhaled products for the Ph. Eur. Interestingly, the corresponding European Medi- cines Agency (EMA) inhaled product quality guideline defines the label claim as "the amount of drug (usually on a per actuation basis) declared on the label of the product" and indicates that inhaled products should be labeled with the delivered dose. 1 Conversely, the 2018 FDA draft guidance, in alignment with the FDA defi- nition of strength, clearly states that the "labeling of oral DPIs should state the established name of the product (ChP), which has a somewhat arbitrary fine particle frac- tion limit of ≥ 10% for DPIs. 3 An additional, potential area of confusion for understanding the dose of DPIs is that phrases such as "metered," "pre-metered," "pre-dis- pensed" and "device-metered" are used in regulatory documents and product information literature. The dose conundrum for inhaled products and product labeling As with standard solid dosage forms, commercial DPIs are typically labeled with a label claim, which, in simple terms, is essentially the strength or dose of the product. For DPIs, however, the understanding of dose is more complex than for standard solid dosage forms because the entire labeled dose never reaches the target region of the patient's lung; and a medical device plays a pivotal role in the delivery of the API into the body. It is impor- tant to remember that label claim, labeling and label can also have subtly different definitions, and therefore interpretations. For example, USP<7> defines labeling as "all labels and other written, printed, or graphic mat- ter on an article's immediate container, or in, any pack- age or wrapper which it is enclosed," and label as "that part of the labeling on the immediate container." 4 The label claim/labeling of DPIs Some examples of the current source documents for definitions and requirements for the label claim and labeling of DPIs are presented in Table 1. There are Source Document Labeling and Label Claim for Dry Powder Inhalers (DPIs) Ph. Eur. Ph. Eur. 0671. Labeling: The delivered dose or, if justified and authorized (e.g., where the dose has been established as a metered dose or as a pre-metered dose), the metered dose or pre-metered dose. 6 EMA Guideline Label claim: The amount of drug (usually on a per actuation basis) declared on the label of the product. Labeling (SmPC): The content per actuation can be expressed either as ex-valve (metered dose) or ex-actuator (delivered dose). All products containing NCEs and products containing known drug substances used in inhalation for the first time should be labeled with the delivered dose or an appropriate alternative (e.g., fine particle mass) where agreed with the regulatory authorities. 1 EMA Standard Terms In Europe, standard terms for DPIs are: inhalation powder; inhalation powder, hard capsule; inhalation powder, pre-dispensed; inhalation powder, tablet. 12 USP<5> Inhalation and nasal drug products—general information and product quality tests. The established name for a DPI is inhalation powder. 13 USP<7> Labeling. Labels and labeling of drug products shall be expressed as active moiety in name and strength. 4 FDA Draft Guidance, 2018 DPIs: Labeling: (Drug) Inhalation powder and provide the strength as the amount per metered dose unit. Prescribing information: The metered amount of medication to be delivered to the patient. 5 Definitions: SmPC = Summary of product characteristics; NCE = New chemical entity Table 1 Labeling definitions and requirements for dry powder inhalers (DPIs), as described in source documents from the United States Pharmacopeia (USP), European Pharmacopeia (Ph. Eur.), European Medicines Agency (EMA) and the United States Food and Drug Administration (FDA)