Science and Judgment in Establishing a Safe Starting Dose for First-in-Human Trials of Biopharmaceuticals

Preclinical Safety Evaluation of Biopharmaceuticals: A Science-Based Approach to Facilitating Clinical Trials

Volumn , Issue , 2007, Pages 969-984

  Visich, Jennifer ^a   Ponce, Rafael ^b  

^a GENENTECH INC   (United States)

^b ZYMOGENETICS INC   (United States)

Author keywords

Biologics and starting dose calculation; Biopharmaceutical safe first in human doses; No adverse effect level (NOAEL) and maximal tolerated dose (MTD)

Indexed keywords

EID: 84891525317     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1002/9780470292549.ch40     Document Type: Chapter

References (24)

1. ICH , Topic S6. Note for Guidance on Preclinical Safety Evaluation of Biotechnology - Derived Pharmaceuticals, 1998 (CPMP/ICH/302/95).
2. ICH , Topic M3 (R1). Note for Guidance on Non - clinical Safety Studies for the Conduct of Human Clinical Trials for Pharmaceuticals, 2000 (CPMP/ICH/286/95).
3. FDA CBER , Points to Consider in the Manufacture and Testing of Monoclonal Antibody Products for Human Use, 1997
4. FDA CDER , Guidance for Industry: Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers, 2005
5. EMEA CPMP , Guideline on Strategies to Identify and Mitigate Risks for First - in -Human Clinical Trials with Investigational Medicinal Products (EMEA/CHMP/ SWP/28367), 2007
6. Ponce R , Armstrong K , A ndrews K , Hensler J , Waggie K , Heffernan J , Reynolds T , Rogge M . Safety of recombinant human factor XIII in a cynomolgus monkey model of extracorporeal blood circulation . Toxicol Pathol 2005 ; 33 ( 6 ): 702 - 10 .
7. Heffernan JK , Ponce RA , Zuckerman LA , Volpone JP , Visich J , Giste EE , Jenkins N , Boster D , Pederson S , Knitter G , Palmer T , Wills M , Early RJ , Rogge MC . Preclinical safety of recombinant human thrombin . Regul Toxicol Pharmacol 2007 ; 47 ( 1 ): 48 - 58 .
8. Ponce RA , Visich JE , Heffernan JK , Lewis KB , Pederson S , Lebel E , Andrews -Jones L , Elliott G , P almer TE , Rogge MC . Preclinical safety and pharmacokinetics of recombinant human factor XIII . Toxicol Pathol 2005 ; 33 ( 4 ): 495 - 506 .
9. Suntharalingam G , Perry MR , Ward S , Brett SJ , Castello - Cortes A , Brunner MD , Panoskaltsis N . Cytokine storm in a phase 1 trial of the anti - CD28 monoclonal antibody TGN1412 . N Engl J Med 2006 ; 355 ( 10 ): 1018 - 28 .
10. Duff GC . Expert scientifi c group on phase 1 clinical trials (Interim report). 2006 ; 356 pages. www.dh.gov.uk/en/consultations/closedconsultations/DH_4139038 .
11. Doi F , Kakizaki S , Takagi H , Murakami M , Sohara N , Otsuka T , Abe T , Mori M . Long - term outcome of interferon - alpha - induced autoimmune thyroid disorders in chronic hepatitis C . Liver Int 2005 ; 25 ( 2 ): 242 - 6 .
12. Nguyen DH , Hurtado - Ziola N , Gagneux P , Varki A . Loss of Siglec expression on T lymphocytes during human evolution . Proc Natl Acad Sci USA 2006 ; 103 ( 20 ): 7765 - 70 .
13. Wise MP , Gallimore A , Godkin A . T - cell costimulation . N Engl J Med 2006 ; 355 ( 24 ): 2594 - 2595 ; author reply 2595.
14. Colaco CA . T - cell costimulation . N Engl J Med 2006 ; 355 ( 24 ): 2595 ; author reply 2595.
15. Sharpe AH , Abbas AK . T - cell costimulation - biology, therapeutic potential, and challenges . N Engl J Med 2006 ; 355 ( 10 ): 973 - 5 .
16. Mehrishi JN , Szabo M , Bakacs T . Some aspects of the recombinantly expressed humanised superagonist anti - CD28 mAb, TGN1412 trial catastrophe lessons to safeguard mAbs and vaccine trials . Vaccine 2007 ; 25 ( 11 ): 3517 - 23 .
17. Liedert B , Bassus S , S chneider CK , Kalinke U , Lower J . Safety of phase I clinical trials with monoclonal antibodies in Germany - the regulatory requirements viewed in the aftermath of the TGN1412 disaster . Int J Clin Pharmacol Ther 2007 ; 45 ( 1 ): 1 - 9 .
18. Schneider CK , Kalinke U , Lower J . TGN1412 - a regulator ' s perspective . Nat Biotechnol 2006 ; 24 ( 5 ): 493 - 6 .
19. Kenter MJ , Cohen AF . Establishing risk of human experimentation with drugs: lessons from TGN1412 . Lancet 2006 ; 368 ( 9544 ): 1387 - 91 .
20. Hanke T . Lessons from TGN1412 . Lancet 2006 ; 368 ( 9547 ): 1569 - 70 ; author reply 1570.
21. Mordenti J . Dosage regimen design for pharmaceutical studies conducted in animals . J Pharm Sci 1986 ; 75 ( 9 ): 852 - 7 .
22. Mahmood I . Interspecies scaling of protein drugs: prediction of clearance from animals to humans . J Pharm Sci 2004 ; 93 ( 1 ): 177 - 85 .
23. Mahmood I . The correction factors do help in improving the prediction of human clearance from animal data . J Pharm Sci 2005 ; 94 ( 5 ): 940 - 5 ; author reply 946 - 7.
24. Mahmood I , Green MD , Fisher JE . Selection of the fi rst - time dose in humans: comparison of different approaches based on interspecies scaling of clearance . J Clin Pharmacol 2003 ; 43 ( 7 ): 692 - 7 .