title: GMP production of [18F]FDOPA and issues concerning its quality analyses as in USP "Fluorodopa F 18 Injection".
abstract: BACKGROUND
  Lately, 6-[(18)F]fluoro-L: -DOPA (FDOPA) has found increase in its clinical demand for whole-body positron emission tomography (PET) scans, and two key issues in fulfilling this demand are the difficulties in producing FDOPA under the recently imposed PET drug good manufacturing practice (GMP) regulations and in providing it in the quality meeting the terms of major compendia. This paper describes the approaches for the GMP production of FDOPA and for the product testing to meet the standard of United States Pharmacopeia (USP) "Fluorodopa F 18 Injection."
  
  
  METHODS
  FDOPA was produced by the carrier-added electrophilic aromatic substitution reaction in the facility complying Pharmaceutical Inspection Cooperation Scheme clean room standard. The special aseptic handling technique was applied to minimize the bioburden. The product quality control followed all testing items and procedures, including three different settings of HPLC.
  
  
  RESULTS
  The process yielded FDOPA average 2.60 ± 0.26 GBq (N = 22) in every batch. All qualities of the product were within the specifications described in the USP "Fluorodopa F 18 Injection." The entire production was audited by the government authority and certified to comply with the latest PET drug GMP regulation.
  
  
  CONCLUSIONS
  Our efforts in producing FDOPA following all aspects of GMP requirements have resulted in a product with the USP quality and certified as GMP complied. The routine production yields enough doses for three to four whole-body scans in each batch. The issues discussed in the report provide good reference for producers planning in routine production for PET drugs that are not commonly produced or with complicated compendial quality control tests.
authors.affiliation: Department of Nuclear Medicine, Buddhist Tzu Chi General Hospital, Hualien, 97002, Taiwan. kevin_kao@tzuchi.com.tw
authors.forename: Chih-Hao K
authors.initials: CH
authors.lastname: Kao
authors.forename: Wen-Lin
authors.initials: WL
authors.lastname: Hsu
authors.forename: Heng-Li
authors.initials: HL
authors.lastname: Xie
authors.forename: Ming-Chi
authors.initials: MC
authors.lastname: Lin
authors.forename: Wen-Chun
authors.initials: WC
authors.lastname: Lan
authors.forename: Hao-Yu
authors.initials: HY
authors.lastname: Chao
mesh_terms: D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000191:economics / Q000592:standards; D004866:Equipment Contamination / Q000517:prevention & control; D007267:Injections; D008420:Manufactured Materials / Q000191:economics* / Q000592:standards*; D008829:Microbiology; D009939:Organizations, Nonprofit; D049268:Positron-Emission Tomography; D011786:Quality Control; D014481:United States
chemical_list: C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine