Critical stability attribute

Critical stability attribute (CSA)-. An attribute (e.g., particle size) which will primarily determine API shelf life (via SLLA) when stored at fixed conditions and will be part of API release requirements. CSAs are a subset of critical quality attributes (CQAs). 

Sterility, freedom from pyrogens, and acceptably low level of extraneous particulate matter are critical quality attributes of all injectable products. Additional critical quality attributes depend on the clinical use of the product. For example, for IV, IM, and SC routes, isotonicity and physiological pH (7.4) are always desirable in order to minimize potential irritation upon injection. Other factors may preclude this, however. If the required dose of drug must be administered in a small volume, it may not be feasible to formulate an isotonic solution. Likewise, solubility or stability considerations may preclude formulation at physiological pH. This explains why formulation pH for injectable drugs varies from about pH 2 to about pH 11. 

The basic concepts of stability data evaluation are the same for single- vs. multifactor studies and for full- vs. reduced-design studies. Data evaluation from the formal stability studies and, as appropriate, supporting data should be used to determine the critical quality attributes likely to influence the quality and performance of the drug substance or product. Each attribute should be assessed separately and an overall assessment made of the findings for the purpose of proposing a retest period or shelf life. The retest period or shelf life proposed should not exceed that predicted for any single attribute. 

A solid understanding of a product s critical quality attributes and what aspects of the manufacturing process control them is necessary to fully gain the benefits of PAT [94]. Furthermore, the inherent complexity of protein-based biopharma-ceutical products makes it difficult to use PAT to assess product characteristics critical to safety, efficacy, and stability. In addition, it is difficult, compared with... 

Stability is a critical quality attribute therefore, the stability program plays an important role when developing new pharmaceutical products. This applies in particular to pharmaceutical products that are to be marketed in several strengths and package types. Multiple strengths and package types combined with multiple... 

As introduced in Sect. 8.2.1, the roadmap of any QbD approach starts with the Target Product Proflle (TPP) definition this summary of drug characteristics (e.g., pharmacokinetic properties and stability) will serve as the basis for a set of performance parameters (e.g., immediate release drug 80 % in < 30 min, 36-month shelf life at room temperature, respectively) that, in turn, will be linked to a set of Critical Quality Attributes (CQAs e.g., shelf life will depend on the amount of residual solvents due to its impact on chemical stability release profile will depend on particle size for some drugs due to its impact on dissolution). 

Prior to developing a drug product, a number of experiments need to be conducted that will fully characterize the API. This information will then be used to help guide formulation development efforts. Each of the critical pieces of information that are needed for formulation development will be discussed below. These include a screening process where an ideal soHd-state salt form is selected and the generation of a suite of analytical methods necessary to probe the critical quality attributes of the new chemical entity, to support synthetic optimization scale-up, stability studies, and the release of material for GLP and experimental use. 

Relevant critical-to-quahty product attributes should be considered by the design space model (e.g., content uniformity, bioavailability, stability). 

Despite these advantages, native enzymes almost universally exhibit very low activities in organic solvents-often 4-5 orders of magnitude lower than in aqueous solutions. This loss in catalytic activity may be attributed to several factors, including a decrease in the polarity of the enzyme s microenvironment, the loss of critical water residues from the enzyme s surface, the decreased conformational mobility of the enzyme s structure, ground-state stabilization of hydrophobic substrates, and deactivation during the preparation of the biocatalyst for use in nonaqueous media,... 

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