Oil-in-Water Nanosized Emulsions for Drug Delivery and Targeting. Tamilvanan Shunmugaperumal. Читать онлайн. Newlib. NEWLIB.NET

Автор: Tamilvanan Shunmugaperumal
Издательство: John Wiley & Sons Limited
Серия:
Жанр произведения: Химия
Год издания: 0
isbn: 9781119585251
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Each of these elements is essential for product development, manufacturing, and quality assurance. Through parallel evolution of QbD and PAT, it is now well established that developing a robust formulation and manufacturing process requires a thorough understanding of inter‐relationships between material attributes (MAs), processing parameters (PPs), and dependent product quality attributes at each stage of product development. In this regard, pharmaceutical, chemical, and engineering industries, research institutions, and regulatory agencies worldwide have significantly contributed through joint collaborations, workshops, conference presentations, and publications. More recently, a 5‐year pilot QbD program (March 2011–April 2016) was launched between the FDA and the EMEA (EMA 2017).

      In this pilot program, the subject matter experts from both agencies had thoroughly exchanged their viewpoints to allow a joint evaluation of QbD elements in an effort to harmonize agencies’ expectation for regulatory submissions worldwide. As a result of this pilot program, both the FDA and the EMEA have mutually agreed on several pertinent topics and level of details required in a regulatory submission (EMA 2014).

      The RPN values can be presented in a tabular format or as a Pareto plot for a quantitative display of relative risk rank order. It needs to be emphasized that all the MAs and PPs that can potentially affect CQAs are considered as part of the initial risk analysis; however, only a subset of these attributes and parameters are selected for development studies as warranted by the outcome of risk analysis (Badawy et al. 2016).

      This QbD element has originated from the Pareto principle. As a rule of thumb, about 80% of the problems originate from roughly 20% of the factors identified, that is why Pareto concept is sometimes referred to as 80/20 rule (Orloff 2011).

      Subsequently, the combinations and interactions of identified subset of MAs and PPs are studied as part of the product development through DOE, which is regarded as a “toolkit” component of a QbD approach. The collective outcome from formulation and process design DOEs is utilized in finalizing the list of critical material attributes (CMAs) and CPPs, thereby establishing a design space and an overall control strategy. Based on current ICH Q8(R2), a design space is defined as the “multidimensional combination and interaction of input variables (e.g., material attributes) and process parameters that have been demonstrated to provide assurance of quality” [ICH Q8(R2) guideline 2009].

      The case study initially starts with the risk assessment plan for o/w nanosized emulsions by utilizing Ishikawa fish‐bone diagram and RPN score.

       2.5.1.1. Initial Quality Risk Assessment Studies

Schematic illustration of the evolution of QbD and multidimensional combination and interactions of critical input variables on critical response variables for the preparation of o/w nanosized emulsions.

      [Adapted from Montgomery (2013) and Yu et al. (2014).]

      The parameter D is the ease that a failure mode can be detected because the more detectible a failure mode is, the less risk it presents to product quality. For D, the rank 1 is considered as easily detectable, 5 as moderately detectable, and 10 as hard to detect. The parameter O is the occurrence probability or the likelihood of an event occurring. For O, the rank 1 is considered as unlikely to occur, 5 as 50 : 50 chance of occurring, and 10 as likely to occur. The parameter S is a measure of how severe of an effect a given failure mode would cause. For S, the rank 1 is considered as no effect, 5 as moderate effect, and 10 as severe effect. Using this procedure, the REM carried out for qualitative analysis of risk associated with each MA and/or PP.