療 臨 1 療 療 FDA 1991 年 量 Point to Consider in Human Somatic Cell Therapy and Gene Therapy 療 陸 autologous cell 量 (1996) 異 xenotransplantation (1996, 1997) 量 (1997) 1998 年 Guidance for Human Somatic Cell Therapy and Gene Therapy 療 療 了 療 Somatic cell therapy is the administration to humans of autologous, allogeneic, or xenogeneic living cells which have been manipulated or processed ex vivo. 療 Gene therapy is a medical intervention based on modification of the genetic material of living cells. 1998 年 Guidance 2008 年 Guidance for FDA Reviewers and Sponsors: Content and Review of Chemistry, Manufacturing, and Control (CMC) Information for Human Somatic Cell Therapy Investigational New Drug Applications (INDs) 療 CMC 諸 donor selection criteria cell culture procedure (quality control procedures, culture media, adventitious agents in cell culture etc.) cell banking system procedures cell identity potency 率 viability sterility 1 行 RegMed 2010 Vol. 2 14
度 purity 了 2008 年 臨 pre clinical 臨 FDA 2008 年 2009 年 領 論 例 Safety of Cell Therapies Derived from Human Embryonic Stem Cells (OCTGT Advisory Committee meeting, April 2008) Next Generation Beta Cell Transplantation (workshop, Nov., 2009) Current Good Tissue Practice (CGTP) and Additional Requirements for Manufacturers of Human Cells, Tissues, and Cellular and Tissue Based Products (HCT/Ps) (draft guidance, Jan. 2009) Clinical Considerations for Therapeutic Cancer Vaccines (draft guidance, Sep. 2009) Consideration for Allogeneic Pancreatic Islet Cell Products (draft guidance, Sep. 2009) 療 product specific guidance FDA 2010 年 10 了 Guidance for Industry Cellular Therapy for Cardiac Disease 療 臨 量 了 療 療 CMC 度 CMC 來 行 / 離 不 來 adventitious agents / 離 RegMed 2010 Vol. 2 15
臨 1. 臨 臨 safety profile 了 delivery system (1). (2). (3). 不良 逸 不良 不 (4). 量 數 復 / 來 度 度 狀 microenvironmental milieu 狀 臨 device specific endpoints (1). 例 / 理 理 (2). (3). simulated use 狀 2. 臨 來臨 例 塞 RegMed 2010 Vol. 2 16
例 猪 臨 量 行 律不 臨 料 理 量 臨 delivery system patient biocompatibility delivery system product biocompatibility 臨 shelf life 療 臨 臨 量 臨 療 紐 臨 行 1. 療 理 臨 不 (1). / refractory angina/ischemia (2). / 塞 acute ischemia/infarction (3). heart failure 療 RegMed 2010 Vol. 2 17
率 度 錄 療 American College of Cardiology/American Heart Association (ACC/AHA) guidelines single photon emission computed tomography, SPECT 錄 來 錄 例 / 塞 例 ACC/AHA 狀 錄 臨 行 stenting, angioplasty, coronary bypass grafting 行 臨 狀 度 療 錄 參 New York Heart Association classification 類 療 參 ACC/AHA 錄 說 ST Elevation Myocardial Infarction (STEMI, non STEMI) 罹 度 量 drug eluting coronary stent 2. 數 度 流 3. RegMed 2010 Vol. 2 18
療 不良 adverse experiences 立 不良 錄 律不 神 狀 不良 (1). cardiac markers (2). 律不 異 arrhythmias and conduction abnormalities (3). / myocardial perforation/pericardial effusion (4). unique monitoring requirements (5). stopping rules (6). duration of follow up 療 療 量 量 量 療 EKG 錄 律 Holter monitoring 識 律不 myoblasts 律 了 療 療 行 療 立 行 療 4 6 行 異 allogeneic cells 異 數 療 量 量 療 了 不良 度 4. 臨 療 RegMed 2010 Vol. 2 19
量 臨 數 療 了 不 異 臨 療 / 若 量 療 / 塞 臨 mortality number of subsequent cardiovascular hospitalizations 臨 mortality the number of subsequent cardiovascular hospitalizations cardiopulmonary exercise testing six minute walk change in ejection fraction the need for various interventions 療 臨 量 異 療 益 數 來 臨 臨 療 5. 臨 說來 行 療 add on design 行 療 臨 control for surgical administration controls for percutaneous administration 兩 倫理 度 量 不 了 療 來 行 surgical procedure percutaneous procedure sham cardiac catheterization sham surgical procedure 利益 / 倫理 量 RegMed 2010 Vol. 2 20
6. 了 7. 量 參 不論 行 療 intent to treat 行 療 療 索 都 參 料 1. Guidance for Industry: Guidance for Human Somatic Cell Thearpy and Gene Therapy (March 1998). 2. Guidance for FDA Reviewers and Sponsors: Content and Review of Chemistry, Manufacturing, and Control (CMC) Information for Human Somatic Cell Therapy Investigational New Drug Applications (INDs) (April 2008) 3. Guidance for Industry and FDA Staff: Early Development Considerations for Innovative Combination Products (September 2006) 4. Guidance for Insudtry: Cellular Therapy for Cardiac Disease (October 2010) RegMed 2010 Vol. 2 21