Scrutiny Made to SUPAC-IR Dealing with Postapproval Changes in Immediate Release Sold Oral Dosage Forms

경구용 속방성 성형제품의 허가 후 변경사항을 다루는 SUPAC-IR에 대한 검토

  • 사홍기 (대구가톨릭대학교 약학대학) ;
  • 박상애 (식품의약품안전청 의약품평가부) ;
  • 윤미옥 (식품의약품안전청 의약품평가부) ;
  • 강신정 (식품의약품안전청 의약품평가부)
  • Published : 2004.02.20


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.


  1. FDA, Department of Health and Human Services, Supplements and other changes to an approved application, Federal Register, 64, 34608-34625 (1999)
  2. FDA, Center of Drug Evaluation and Research, Guidance for Industry-Changes to an approved NDA or ANDA, November 1999
  3. FDA, Center for Drug Evaluation and Research, Guidance for Industry-Immediate release solid oral dosage forms: Scale-up and postapproval changes: Chemistry, manufacturing, and controls, in vitro dissolution testing, and in vivo bioequivalence documentation, November 1995
  4. FDA, Center for Drug Evaluation and Research, Guidance for Industry: Waiver of in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms based on a biopharmaceutics classification system, August 2000
  5. 식품의약품안전청고시 제 2002-60호 '생물학적동등성시험 기준' 제 3조 제 5항
  6. M. Cho, J Kim, H. Lee and H. Sah, Understanding of f$f_2$ mettics used to evaluate similarity of dissolution profiles, J. Kor. Pharm. Sci., 33, 245-253 (2003)
  7. J.P. Skelly, G.A. Van Buskirk, DR Savello, G.L. Amidon and et ai., Scale-up and immediate release oral solid dosage forms,.Phann. Res., 10, 313-16 (1993)
  8. FDA, Federal Register, 59, 48754-48759 (1994)
  9. FDA, Center for Drug Evaluation and Research, SUPAC-IR questions and answers to SUPAC-IR guidance, February 1997
  10. FDA, Center for Drug Evaluation and Research, Guidance for Industry: SUPAC-IRIMR: Immediate release and modified release solid oral dosage forms; Manufacturing equipment addendum, January 1999
  11. 일본국립의약식품위생연구소(National Institute of Health Sciences), Division of Drugs, Guideline for bioequivalence studies for formulation changes of oral solid forms, February 2000
  12. 식품의약품안전청고시 제 2002-60호 '생물학적동등성시험 기준' 제 3조 제 4항
  13. J.A. Cook, Industrial experience with the BCS guidance in NDA: Value and limitations, AAPS Workshop on Biopharmaceutics Classification System: Implementation Challenges and Extension Opprotunities, Arlington, VA, September 2002
  14. FDA, Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research & Center for Veterinary Medicine, Guidance for Industry: Comparability protocolschemisty, manufacturing, and controls information, February 2003