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By Kenneth Norris

APQ1What progress has been made on establishing clinically relevant specification implementation, and what are the opportunities to align on the application of scientific approaches? Asking end product testing to adequately serve as a quality control and as a clinically relevant surrogate has always been a challenge. Because the dissolution test has been identified as a potential basis for granting biowaivers, it is a logical test to establish clinically relevant acceptance criteria.

For solid oral dosage forms and suspensions, dissolution is the first step in drug absorption; the importance of drug release on clinical performance of drug product has long been recognized. Dissolution testing is used throughout the drug development process to aid in formulation and process design and to assess product quality. An important property of solid oral dosage forms is its ability to provide the necessary rate and extent of active pharmaceutical ingredient (API) availability to the body. In some cases in vitro methods and in silico simulation modeling can provide fundamental information on the dissolution process of the API and correlate to in vivo performance.

Since clinically relevant specifications (CRS) may not always be applicable, it is suggested to consider a risk-based approach in determining the need of it and then focus on which attribute(s) will be correlated to the CRS for dissolution testing. There are multiple factors that need to be evaluated during the decision-making process. Some of those factors include potential biopharmaceutics risks such as absorption being limited by dissolution rate, practically achievable process robustness, potential post approval changes, costs, and gains. A decision tree may help the decision process for determining the usefulness of a CRS, assuming that a discriminatory dissolution method is indeed attainable.

As the pharmaceutical community builds the process of defining CRS for dissolution, this process may be easily applied to the various other attributes that may also be suitable as CRS.

Read the full article Moving Toward Clinically Relevant Dissolution Specifications, produced by the AAPS APQ section, in the AAPS Newsmagazine Online, and share your thoughts and opinions regarding dissolution testing in the comments below.

Kenneth Norris-finalKenneth Norris currently works for Pfizer as a principal scientist in Analytical Research & Development. He has been actively involved in AAPS and has been part of the APQ section leadership, currently serving as past chair.