• Journal of Pharmaceutical Investigation
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• 제35권3호
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• pp.207-224
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• 2005

The objective of this study was to explore the principles of SUPAC-SS and its regulatory application in handling postapproval changes to nonsterile semisolid dosage forms. The types of postapproval changes that SUPAC-SS described were modifications in formulation (components and composition), batch size, manufacturing equipment & process, and the site of manufacturing. SUPAC-SS defined the levels of postapproval changes and what chemistry, manufacturing, and control tests should be conducted for each change level. The guidance also specified several occasions the manufacturers should perform in vitro release test (Franz cell diffusion test) and/or in vivo bioequivalence test. Finally, SUPAC-SS classified appropriate filing forms to be used in supporting postapproval changes. It was crystal clear that SUPAC-SS helped maintain the safety and quality of approved semisolid dosage forms when they were subject to certain postapproval changes. The availability of SUPAC-SS made contributions to reducing regulatory burdens of the industry, as well as expediting the postapproval process of regulatory agencies. This study also shed light on the background of relevant pharmaceutical sciences that the SUPAC-SS guidance adopted. Finally, the KFDA and the industry were strongly urged to implant a similar guidance in handling postapproval changes to semisolid dosage forms available in the Korean marketplace.

• Journal of Pharmaceutical Investigation
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• 제34권1호
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• pp.57-71
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• 2004

The objective of this study was to provide a better understanding of SUPAC-IR and its application in handling postapproval changes to immediate release solid oral dosage forms. Originally, SUPAC-IR was aimed at reducing the regulator burdern of the industry when they were making postapproval changes, but still at maintaining the formulation quality and performance of a drug product. The postapproval changes that were covered under SUPAC-IR included variations in the components ad composition of formulation, the site of manufacturing, batch size, manufacturing equipment, and manufacturing process. The guidance defined levels of changes, based on the likelihood of risk ocurrence and potential impact of postapproval changes upon the safety and efficacy of a drug product I suggested what a type of fing report should be submitted to the FDA for each level of change. Chemist, manufacturing, and control tests to be executed were also recommended for each change level The important tests specified in the guidance included batch release, stability, in vitro dissolution, and in vivo bioequivalence tests. However, there have been strong demands on revising the current SUPAC-IR in order to resolve some issues and to improve its usefulness in evaluating postapproval changes to immediate release solid oral dosage forms. In particular, the rigorous requirement of case C dissolution test and the definition of batch size were challenged by both academia and the industry. A revision work was in progress to reflect these inputs and to expand the utility of SUPAC-IR. As a result of these concerted efforts, an updated 2nd version of SPAC-IR would be likely to be issued ver soon to the public.

• Journal of Pharmaceutical Investigation
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• 제34권3호
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• pp.229-254
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• 2004

The objective of this study was to scrutinize the rationale of SUPAC-MR and its application in processing postapproval changes to modified release solid oral dosage forms. The types of postapproval changes that were primarily covered with SUPAC-MR included variations in the components and composition, the site of manufacturing, batch size, manufacturing equipment, and manufacturing process. SUPAC-MR defined levels of postapproval changes that the industry might make. Classification of such categories was based on the likelihood of risk occurrence and potential impact of changes upon the safety and efficacy of approved drug products. In most cases, the changes could be classified into 3 levels. It described what chemistry, manufacturing, and control tests should be conducted for each change level. The important tests specified in SUPAC-MR were batch release, stability, in vitro dissolution, and in vivo bioequivalence tests. It then suggested what type of a filing report should be submitted to the FDA for each change level. In general, level 1 changes could be reported in an annual report, whereas level 2 and/or 3 changes could be submitted in changes-being-effected or prior approval supplements. It could be understood that the purpose of SUPAC-MR was to maintain the safety and quality of approved modified release solid oral dosage forms undergoing certain changes. At the same time, it contributed to providing a less burdensome regulatory process with the manufacturers when they wanted to make postapproval changes. European regulatory agencies also implemented SUPAC-like regulations in handling such changes to drug products. Therefore, in this study a recommendation was made for KFDA and the Korean industry to evaluate thoroughly the usefulness of these guidances and regulations in dealing with postapproval changes to modified release solid oral dosage forms.