Issue link: https://www.e-digitaleditions.com/i/1463386
24 April 2022 Inhalation ATTRIBUTE ADDITIONAL CONSIDERATIONS EXISTING QUALITY CONTROL METHODS AUGMENTED QUALITY CONTROL METHODS TO IMPROVE CLINICAL REALISM FURTHER ENHANCEMENTS TO OPTIMIZE CLINICAL RELEVANCE Method Capability Indicative data for respiratory tract deposition Improved realism of respiratory tract deposition, but may not provide perfect correlation with clinical outcomes Possibility of closest relationship with clinical outcomes Applicability Product QC Product development and potentially QC Early phase product development? Regulatory Considerations Recognition Recognition by regulatory agencies; methods in the pharmacopeias Limited recognition by regulatory agencies but being researched by these organizations Not recognized by regulatory agencies Compatibility Compatible with current product registration requirements May requires bridging studies Will almost certainly require bridging studies Ability to provide additional benefits, such as providing insights into patient use-misuse Methods adequate for product registration but of limited value in predicting effects of patient age/ disease/use-misuse Better IVIVCs/IVIVRs (important with second- entry products); potential for improved understanding of performance across intended patient profile May be able to enable influence of disease processes affecting aerosol transport/deposition to be quantified Management Considerations Compatibility with current regulatory practices No change Involves a break with methods for previous product registrations Involves a large break with methods for previous product registrations Cost Implications Perceived as acceptable One-time costs associated with new inlet options and breath simulation but costs to operate are low Higher costs associated with apparatus/model acquisition with likely higher operating costs Method Transferability Acceptable without additional effort from the norm More complex apparatus configurations may require additional effort to achieve transferability Methods are presently different from lab-to- lab with non-standard configurations making transferability difficult Familiarity Likely unfamiliar in many QC test environments Method improvements are well understood and easy to adopt Specialized training needed to implement and therefore likely impractical in QC environment Analytical Considerations Equipment Set-up Simplest option for new/existing labs More complex set- ups but off-the-shelf solutions are available commercially Still a research environment with little or no standardization of methods Method Robustness Offers the highest degree of robustness by well- understood methods Can be made analytically robust and capable of being validated with minimal development Lack of standardization for methods makes it difficult to achieve robustness Data Utility Provides data representative of ideal patient use and optimum inhaler performance Can provide realistic assessment of performance under patient use-misuse with minimal development Largely research tools—large learning curve, data may require specialist interpretation Table 1 The Three Streams for Inhaler Testing