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Quality by Design, In-Process Testing and End Product Testing

Peart J, Byron PR.

RDD Asia 2014. Volume , 2014: 109-122.

Abstract:

A large number of interacting variables influence the quality of the final aerosol delivered to the patient from an inhalation product even though delivered dose content uniformity (DDCU) and aerodynamic particle size distribution (APSD) are generally considered to be the most relevant critical quality attributes (CQAs). However, based upon recently reported in vitro-in vivo correlations (IVIVCs) for lung deposition, the total lung dose estimated in vitro may be a more clinically relevant CQA than DDCU and APSD. Product quality is discussed in light of publications that relate lung delivery efficiency to the variability seen in lung dose in the clinic. The topic is also linked to the industry adoption of quality by design (QbD) and improved in-process testing during manufacture, and illustrated using examples from the literature shown to have resulted in improved product quality assessed by end product testing. However, while it remains possible to tightly control the design of inhaler components and manufacturing processes, variability in end product metrics is still observed following final assembly of these complex inhalation drug delivery systems. Devices with defined CQAs, which deliver low variability, high lung doses, are unfortunately subjected to the same required “end product metrics” as their low efficiency, and less well understood, counterparts. This one size fits all approach may, ironically, slow the industry’s adoption of QbD because pharmaceutical companies see little regulatory relief despite substantial research investment.