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An In-vitro in-vivo correlation (IVIVC) has been defined by the U.S. Food and Drug Administration (FDA) as "a predictive mathematical model describing the relationship between an in-vitro property of a dosage form and an in-vivo response". Generally, the in-vitro property is the rate or extent of drug dissolution or release while the in-vivo response is the plasma drug concentration or amount of drug absorbed. The United States Pharmacopoeia (USP) also defines IVIVC as "the establishment of a relationship between a biological property, or a parameter derived from a biological property produced from a dosage form, and a physicochemical property of the same dosage form". Typically, the parameter derived from the biological property is AUC or Cmax, while the physicochemical property is the in vitro dissolution profile. The main roles of IVIVC are: # To use dissolution test as a surrogate for human studies. # To supports and/or validate the use of dissolution methods and specifications. # To assist in quality control during manufacturing and selecting appropriate formulations == Levels == There are four levels of IVIVC that have been described in the FDA guidance, which include levels A, B, C, and multiple C. The concept of correlation level is based upon the ability of the correlation to reflect the complete plasma drug level-time profile which will result from administration of the given dosage form.〔Sakore S., Chakraborty B.S. (2011). In-Vitro-In-Vivo Correlation (IVIVC): A Strategic Tool in Drug Development. Journal of Bioequivalence & Bioavailability, S3, doi:10.4172/jbb.S3-001.〕 Level A correlation: An IVIVC that correlates the entire in vitro and in vivo profiles has regulatory relevance and is called a Level A Correlation .This level of correlation is the highest category of correlation and represents a point-to-point relationship between in vitro dissolution rate and in vivo input rate of the drug from the dosage form. Level A correlation is the most preferred to achieve; since it allows bio waiver for changes in manufacturing site, raw material suppliers, and minor changes in formulation. The purpose of Level A correlation is to define a direct relationship between in vivo data such that measurement of in vitro dissolution rate alone is sufficient to determine the biopharmaceutical rate of the dosage form.〔 Level B correlation: A level B IVIVC is based on the principles of statistical moment analysis. In this level of correlation, the mean in vitro dissolution time (MDT vitro) of the product is compared to either mean in vivo residence time (MRT) or the mean in vivo dissolution time (MDTvivo). A level B correlation does not uniquely reflect the actual in vivo plasma level curves, also in vitro data from such a correlation could not be used to justify the extremes of quality control standards hence it is least useful for regulatory purposes.〔 Level C correlation: Level C correlation relates one dissolution time point (t50%, t90%, etc.) to one mean pharmacokinetic parameter such as AUC, tmax or Cmax. This is the weakest level of correlation as partial relationship between absorption and dissolution is established since it does not reflect the complete shape of plasma drug concentration time curve, which is the critical factor that defines the performance of a drug product. Due to its obvious limitations, the usefulness of a Level C correlation is limited in predicting in vivo drug performance. In the early stages of formulation development Level C correlations can be useful when pilot formulations are being selected while waiver of an in vivo bioequivalance study (biowaiver) is generally not possible. Multiple Level C correlations: This level refers to the relationship between one or more pharmacokinetic parameters of interest (Cmax, AUC, or any other suitable parameters) and amount of drug dissolved at several time point of dissolution profile. Multiple point level C correlation may be used to justify a biowaivers provided that the correlation has been established over the entire dissolution profile with one or more pharmacokinetic parameters of interest. A multiple Level C correlation should be based on at least three dissolution time points covering the early, middle, and late stages of the dissolution profile. The development of a level A correlation is also likely, when multiple level C correlation is achieved at each time point at the same parameter such that the effect on the in vivo performance of any change in dissolution can be assessed.〔 Level D correlation: It is not a formal correlation but it is a semi quantitative (qualitative analysis ) and rank order correlation and is not considered useful for regulatory purpose but can be serves as an aid in the development of a formulation or processing procedure. 〔 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「IVIVC」の詳細全文を読む スポンサード リンク
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