Production of radiopharmaceuticals for clinical and research uses

Transcription

1 Production of radiopharmaceuticals for clinical and research uses (A joint program with SNM, EANM, JSNM, and KSNM) Organizers: Sally Schwarz, Philip Elsinga, and Yasuhisa Fujibayashi Asia Perspective (Japan and Korea) FUJIBAYASHI, Yasuhisa, Ph.D., D.Med.Sci. Director, Molecular Imaging Center National Institute of Radiological Sciences Chiba, JAPAN

2 FIRST Delivery FDG for human study in the world Aug. 16, 1976 Aug Courtesy of Dr. Tatsuo IDO

3 18 F FDG (Mark IV 1976) Courtesy of Dr. Tatsuo IDO

4 JAPAN

5 PET Science in Japan (at NIRS) 1974 Installed Medical Cyclotron 1978 Synthesis of 18 F-FDG 1976 FDG in the US Mark IV PET 1979 Brain PET Scanner 1984 Imaging of Neuroreceptor 2000 GMP-oriented Hot Laboratory 2004 Medical Examination by PET

6 1979 at NIRS Positologica 18 F FDG (Mark IV 1976)

7 PET Drug!? Approvals in JAPAN 1996 O 15 Gas PET diagnosis approved Gas CBB, approved as medical device (by MHLW) O 15 gases, used as hospital preparation 2002 FDG PET diagnosis approved FDG Synthesizer, approved as medical device FDG, used as hospital preparation 2005 FDG approved FDG, approved as drug (Nihon Medi Physics Co. Ltd.) 2011 N 13 ammonia Synthesizer approved N 13 Ammonia Synthesizer, approved as medical device Myocardial blood flow diagnosis approved

8 PET Facilities in Japan (March, 2012) Total 299 With Cyclotron(s) 142 Without Cyclotron 157 FDG Delivery Sites 10

9 There are 3 types of RPs RPs, produced and delivered as an approved drug Produced under GMP (by Nihon Medi-Physics) Used for medical practice / private practice RPs, produced with an approved synthesizer as hospital preparation Produced under JSNM Guideline Used for medical practice / private practice RPs, produced with a non-approved synthesizer as hospital preparation Used for research / private practice (not covered by health insurance system)

10 RPs produced and delivered as an approved drug Under Pharmaceutical Affairs Act as pharmaceutical IND required for approval as pharmaceutical RPs production under full-gmp FDG, SPECT-RPs, etc. approved

11 RPs produced with an approved synthesizer as hospital preparation Under Pharmaceutical Affairs Act as a medical device, but not pharmaceutical Synthesizer manufactured as medical device under GMP IND required for approval as medical device RPs production under the Guideline of academic authority (= JSNM) Original guideline established in 2001 Revised in 2011 (JSNM-GMP with audit) FDG synthesizer, Ammonia Synthesizer approved. Amyloid RP synthesizers under IND

12 RPs produced with a non-approved synthesizer as hospital preparation Under Medical Care Act but not Pharmaceutical Affairs Act As part of medical care Approved by Institutional IRB No eind, IND, GMP regulation All other RPs for research are in this criteria.

13 RPs produced with a non-approved synthesizer as hospital preparation Recently, MHLW established a new system like eind. "Advanced Medical Care (AMC)" application for drugs, medical devices or medical procedure, being under research but already recognized its usefulness scientifically. C-11-Methionine and F-18-NaF will be applied soon. RPs production under JSNM-GMP!?

14 JSNM Strategic Committee for Promoting Molecular Imaging (JSNM MI Strategic Committee) established in 2010 Guidance for in house PET drug Preclinical testing Production, QA and QC Clinical evaluation Standardization of imaging/quantitative analysis Discussion with MHLW/PMDA MHLW : Ministry of Health, Labor and Welfare PMDA : Pharmaceuticals and Medical Devices Agency

15 Guidance for in house PET drug October, 2011 Proposed by JSNM MI Strategic Committee Approved by BoD Committee for JSNM Published in October, 2011 Minor revised in November, olecule_ pdf

16 Guidance for in house PET drug : Production, QA and QC (JSNM GMP) Based on : PET drug production under CGMPs for IND In Japanese Guideline for Conducting Micro dose Clinical Trials (2008) Guidance: PET Drugs CGMP (2009, USA)

17 Japanese Guideline for Conducting Micro dose Clinical Trials (2008) マイクロドーズ治験 On June 3rd, 2008, The Ministry of Health, Labor and Welfare (MHLW) of Japan published a document Japanese Guideline for Conducting Microdose Clinical Trials As a guideline for exploratory investigational new drug (eind) studies using three sensitive measurements, namely positron emission tomography (PET), accelerator mass spectrometry (AMS) and liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS). N.Tamaki and Y.Kuge eds. in Molecular Imaging for Integrated Medical Therapy and Drug Development, Springer, 2010.

18 PET in Micro Dose Clinical Trial PET Exam, performed Under GCPs PET probe production, under CGMPs for IND

19 Guidance PET Drugs CGMP (2009, USA) to help positron emission tomography (PET) drug producers better understand FDA s thinking concerning compliance with the current good manufacturing practice (CGMP) regulations. addresses resources, procedures, and documentation for all PET drug production facilities, academic and commercial.

20 JSNM Strategic Committee for Promoting Molecular Imaging (JSNM MI Strategic Committee) Guidance : published by a scientific society (JSNM) no legal binding power, at present Needs from MHLW/PMDA Reasonable Guidance for In house PET drug production PET drug Standards General rules for preparations General tests Monographs Reasonable education / audit system

21 KOREA

22 PET Facilities in KOREA (December, 2011) Cyclotron 35 In House (Production) 14 Delivery (Production) 19 PET scanner 8 PET CT scanner 158

23 Guideline for Radiopharmaceutical Production Guideline for In house Compounding of Radiopharmaceuticals: published by the KSNM (Radiopharmaceutical Committee) The 1 st Edition (June, 2006): 33 radiopharmaceuticals listed The 2 nd Edition (January, 2009): 71 radiopharmaceuticals listed Guideline for Quality Assurance of FDG: proposed by the KSNM (July, 2012) Currently, radiopharmaceuticals are exempt from GMP regulations, however, the KFDA is planning to apply GMP regulations to radiopharmaceuticals within a few years.

24 Production of Radiopharmaceuticals for Clinical Use Manufacturing: Approved from the KFDA [ 18 F]FDG, [ 18 F]FLT, [ 18 F]FP CIT, [ 123 I]FP CIT, [ 123 I]NaI, [ 123 I]MIBG, [ 131 I]NaI, [ 131 I]MIBG, [ 67 Ga]Ga citrate, [ 201 Tl]TlCl 3 Hospital Compounding: Supervised by the Community Health Center [ 13 N]Ammonia, [ 15 O]H 2 O, [ 11 C]Flumazenil, [ 11 C]Raclopride, [ 11 C]Methionine, [ 11 C]Acetate, [ 11 C]Mespiperone, [ 18 F]FDOPA, [ 18 F]NaF, [ 82 Rb]RbCl KP (10 th Ed.) and KPC (Korea Pharmaceutical Codex, 4 th Ed.): [ 99m Tc]Sodium Pertechnetate, etc. (20 radiopharmaceuticals) Compounding: 99m Tc radiopharmaceuticals

25 Guideline: Production of PET Radiopharmaceuticals for Clinical Use Production, QA, and QC PET radiopharmaceuticals approved by the KFDA: licensed for Manufacturing [ 18 F]FDG, [ 18 F]FLT, and [ 18 F]FP CIT Production and QA: KPC, USP, EP PET radiopharmaceuticals listed in official Pharmacopoeia (USP, EP, etc): Hospital Compounding Guidance of PET Drugs CGMP (2009, USA) Guideline for In house Compounding of Radiopharmaceuticals (2009, KSNM)

26 Guideline: Production of Radiopharmaceuticals for Research Use Production, QA, and QC Production of radiopharmaceuticals for research use Requires approvals from KFDA and IRB Production and QA: similar level to hospital compounding or manufacturing Guidance of PET Drugs CGMP (2009, USA) Guideline for In house Compounding of Radiopharmaceuticals (2009, KSNM)

27 Thank you for your attention!