Cell and Tissue Banking

, Volume 12, Issue 1, pp 3–5

Efficacy and safety of new medicines: a human focus

Original Paper

Abstract

The introduction of safe and effective new medicines is proving ever more difficult, a problem arguably due at least in part to over-reliance on experimental animal-based test systems. In light of the increasing awareness of the lack of predictiveness of such non-human approaches, the necessity to focus on human-based test methods is clear. There has been considerable progress in human in vivo (microdosing) and in silico approaches, primarily to identify ADMET issues, however, in vitro functional studies using human tissues are receiving inadequate attention. The potential scope of human tissue-based research is considerable, but much methodological development is required, which necessitates an increased willingness on the part of the Pharma industry to support it. This approach also requires considerably improved access to the cells and tissues themselves. While current acquisition is almost exclusively from surgery and post mortem, the range of tissue types, the quantity, quality and frequency of supply will remain inadequate to support human tissue as a key component of pre-clinical efficacy and safety testing. Additional routine access to non-transplantable tissues from organ donors for research purposes would be of inestimable value, but in order to realise this, true collaboration will be required between NHS, the Pharma and biotech industries, and the general public.

Keywords

Heart-beating donors Drug safety TGN1412 

References

  1. Animal Procedures Committee: The use of primates under the Animals (Scientific Procedures) Act (1986): Analysis of current trends with particular reference to regulatory toxicology, December 2002 (published by Home Office, March 2003)Google Scholar
  2. Findlay L, Eastwood D, Stebbings R, Sharp G, Mistry Y, Ball C, Hood J, Thorpe R, Poole S (2010) Improved in vitro methods to predict the in vivo toxicity in man of therapeutic monoclonal antibodies including TGN1412. J Immunol Methods 352:1–12PubMedCrossRefGoogle Scholar
  3. Grass GM, Sinko PJ (2002) Physiologically-based pharmacokinetic simulation modelling. Adv Drug Deliv Rev 54:433–451PubMedCrossRefGoogle Scholar
  4. Lappin G, Garner RC (2010) The utility of microdosing over the past 5 years. Expert Opin Drug Metab Toxicol 4:1499–1506CrossRefGoogle Scholar
  5. Matthews RA (2008) Medical progress depends on animal models—doesn’t it? J Roy Soc Med 101:95–98PubMedCrossRefGoogle Scholar
  6. Olson H, Betton G, Robinson D, Thomas K, Monro A, Kolaja G, Lilly P, Sanders J, Sipes G, Bracken W, Dorato M, Van Deun K, Smith P, Berger B, Heller A (2000) Concordance of the toxicity of pharmaceuticals in humans and in animals. Regul Toxicol Pharmacol 32:56–67PubMedCrossRefGoogle Scholar
  7. Stebbings R, Findlay L, Edwards C, Eastwood D, Bird C, North D, Mistry Y, Dilger P, Liefooghe E, Cludts I, Fox B, Tarrant G, Robinson J, Meager T, Dolman C, Thorpe SJ, Bristow A, Wadhwa M, Thorpe R, Poole S (2007) “Cytokine storm” in the phase I trial of monoclonal antibody TGN1412: better understanding the causes to improve preclinical testing of immunotherapeutics. J Immunol 179:3325–3331PubMedGoogle Scholar
  8. Suntharalingam G, Perry MR, Ward S, Brett SJ, Castello-Cortes A, Brunner MD, Panoskaltsis N (2006) Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412. N Engl J Med 355:1018–1028PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  1. 1.Safer Medicines TrustLondonUK

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