Fundamental Toxicological Sciences

Paper Details

Fundamental Toxicological Sciences
Vol. 10 No. 7 December 27, 2023 p.307-313
Letter
Derivation of permitted daily exposure value for trifluoroacetic acid as an impurity in pharmaceutical products
  • Hisakazu Sanada (Translational Research Division, Chugai Pharmaceutical Co., Ltd. / sanada.hisakazu52@chugai-pharm.co.jp)
Hisakazu Sanada 1) , Tsukasa Kikuno 2) , Kimiyoshi Kitamura 2) , Kiyohiro Hashimoto 3) , Masayuki Mishima 1)
1) Translational Research Division, Chugai Pharmaceutical Co., Ltd. , 2) Pharmaceutical Impurities Safety Assessment Research Institute (PhiAS), Co., Ltd. , 3) Drug Safety Research Laboratory, Takeda Pharmaceutical Co., Ltd.
Keywords: Trifluoroacetic acid, PDE, Impurity, Pharmaceutical
Abstracts

Trifluoroacetic acid (TFA) has been used for production of pharmaceuticals including recently emerging middle size peptides. TFA has severe local toxicity like skin and respiratory tract irritation due to the strong acidity. Because almost all pharmaceutical products are prepared at neutral pH, derivation of permitted daily exposure (PDE) of TFA from the information with neutralized form could provide useful information on the risk management for protection of patients and production of pharmaceuticals. Sodium TFA caused hepatotoxicity in a rat 90-day. Based on the results of the 90-day study, we respectively proposed PDE for oral, parenteral and inhalation routes as 1.7, 0.005 and 0.84 mg/person/day. The derivation of PDE was done according to the concept described in ICH Q3C(R8) and Q3D(R2).