Sally Robinson

Publications (8)21.59 Total impact

• Article: A Global Pharmaceutical Company Initiative: An Evidence-Based Approach to Define the Upper Limit of Body Weight Loss in Short Term Toxicity Studies.

  Kathryn Chapman, Fiona Sewell, Linda Allais, Jean-Luc Delongeas, Elizabeth Donald, Matthias Festag, Sophie Kervyn, Deborah Ockert, Vicente Nogues, Helen Palmer, Marija Popovic, Wendy Roosen, Ankie Schoenmakers, Kevin Somers, Claudia Stark, Peter Stei, Sally Robinson
  [show abstract] [hide abstract]
  ABSTRACT: Short term toxicity studies are conducted in animals to provide information on major adverse effects typically at the maximum tolerated dose (MTD). Such studies are important from a scientific and ethical perspective as they are used to make decisions on progression of potential candidate drugs, and to set dose levels for subsequent regulatory studies. The MTD is usually determined by parameters such as clinical signs, reductions in body weight and food consumption. However, these assessments are often subjective and there are no published criteria to guide the selection of an appropriate MTD. Even where an objective measurement exists, such as body weight loss (BWL), there is no agreement on what level constitutes an MTD. A global initiative including 15 companies, led by the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), has shared data on BWL in toxicity studies to assess the impact on the animal and the study outcome. Information on 151 studies has been used to develop an alert/warning system for BWL in short term toxicity studies. The data analysis supports BWL limits for short term dosing (up to 7 days) of 10% for rat and dog and 6% for non-human primates (NHPs).
  Regulatory Toxicology and Pharmacology 04/2013; · 2.43 Impact Factor
• Article: Opportunities to minimise animal use in pharmaceutical regulatory general toxicology: a cross-company review.

  Susan S Sparrow, Sally Robinson, Sue Bolam, Christopher Bruce, Andy Danks, David Everett, Stephen Fulcher, Rose E Hill, Helen Palmer, Elspeth W Scott, Kathryn L Chapman
  [show abstract] [hide abstract]
  ABSTRACT: Toxicity studies in animals are carried out to identify the intrinsic hazard of a substance to support risk assessment for humans. In order to identify opportunities to minimise animal use in regulatory toxicology studies, a review of current study designs was carried out. Pharmaceutical companies and contract research organisations in the UK shared data and experience of standard toxicology studies (ranging from one to nine months duration) in rodents and non-rodents; and carcinogenicity studies in the rat and mouse. The data show that variation in study designs was primarily due to (i) the number of animals used in the main study groups, (ii) the use of animals in toxicokinetic (TK) satellite groups, and (iii) the use of animals in off-treatment recovery groups. The information has been used to propose a series of experimental designs where small adjustments could reduce animal use in practice, while maintaining the scientific objectives.
  Regulatory Toxicology and Pharmacology 08/2011; 61(2):222-9. · 2.43 Impact Factor
• Article: Evaluation of blood microsampling techniques and sampling sites for the analysis of drugs by HPLC-MS.

  Christopher Smith, Angela Skyes, Sally Robinson, Elizabeth Thomas
  [show abstract] [hide abstract]
  ABSTRACT: the potential for whole blood sampling (20 µl) in toxicokinetic studies to reduce the sample volume was investigated. Blood microsamples were collected in three ways, either as a dried blood spot (DBS), a blood sample collected in a micropipette placed in a plastic tube and mixed with water or as plasma in the normal manner. blood samples on the DBS and the whole blood microtube (WBMT) were compared along with DBS and plasma to determine the toxicokinetic data equivalency. The DBS and WBMT comparison was shown to be equivalent, as demonstrated on a correlation plot with an R(2) value of 0.97 for an x = y plot. The plasma comparison with DBS also gave a good correlation. A correction factor (x(2)) was applied to the blood data to allow for the distribution of the compound between plasma and bloods, and therefore, a direct comparison could be made. The correlation plot derived from the sample data gave an R(2) value 0.98 (x = y plot), indicating dataset equivalency. Sampling sites were evaluated in a dog study. Blood was collected from the peripheral region, in this case the ear, and a venous region of the dog; and spotted onto DBS cards. Comparison of the mean area under the curve data for the sampling sites showed equivalent data: 5095 and 5175 ng.h/ml for the 25 mg/kg dose and 16695 ng.h/ml and 16000 ng.h/ml for the 50 mg/kg dose for the ear and the venous samples, respectively. the DBS cards were shown to be an equivalent microsampling process when compared with WBMT and conventional plasma analysis. With the added benefits of sample storage, shipment and ease of use for DBS, this technology could change the way samples are taken and then analyzed in bioanalysis in the future.
  Bioanalysis 01/2011; 3(2):145-56. · 3.22 Impact Factor
• Article: The value of acute toxicity studies to support the clinical management of overdose and poisoning: a cross-discipline consensus.

  Kathryn Chapman, Stuart Creton, Hugo Kupferschmidt, G Randall Bond, Martin F Wilks, Sally Robinson
  [show abstract] [hide abstract]
  ABSTRACT: Acute toxicity studies are no longer required to support first clinical trials of pharmaceuticals in man. However, it is unclear in the wording of the revised ICH M3 whether acute toxicity studies are required later in drug development (e.g., phase 3) in order to support the management of overdose. The NC3Rs held a workshop in January 2010 with representatives from international poison centres, the pharmaceutical and chemical industries, and regulatory and government bodies to explore further whether acute toxicity studies are used to support the clinical management of overdose of pharmaceuticals and whether this work can be translated to other sectors such as the chemical industry. The consensus formed at the workshop was that acute toxicity studies are not used for managing overdose of pharmaceuticals and are of little value in treating human poisoning from chemicals. In this paper, the authors describe the key considerations in treating human overdose and poisoning, challenge the value of the classification and labelling process of chemicals for this purpose and discuss how acute toxicity studies can be improved to better inform risk assessment.
  Regulatory Toxicology and Pharmacology 12/2010; 58(3):354-9. · 2.43 Impact Factor
• Source

  Available from: PubMed Central

  Article: Cross-sector review of drivers and available 3Rs approaches for acute systemic toxicity testing.

  Troy Seidle, Sally Robinson, Tom Holmes, Stuart Creton, Pilar Prieto, Julia Scheel, Magda Chlebus
  [show abstract] [hide abstract]
  ABSTRACT: Acute systemic toxicity studies are carried out in many sectors in which synthetic chemicals are manufactured or used and are among the most criticized of all toxicology tests on both scientific and ethical grounds. A review of the drivers for acute toxicity testing within the pharmaceutical industry led to a paradigm shift whereby in vivo acute toxicity data are no longer routinely required in advance of human clinical trials. Based on this experience, the following review was undertaken to identify (1) regulatory and scientific drivers for acute toxicity testing in other industrial sectors, (2) activities aimed at replacing, reducing, or refining the use of animals, and (3) recommendations for future work in this area.
  Toxicological Sciences 08/2010; 116(2):382-96. · 4.65 Impact Factor
• Article: Are acute toxicity studies required to support overdose for new medicines?

  Sally Robinson, Kathryn Chapman
  Regulatory Toxicology and Pharmacology 07/2009; 55(1):110. · 2.43 Impact Factor
• Article: Dissemination strategies: how do they influence the uptake of the new Three Rs methods across laboratories and other boundaries? A report of a workshop held by the European Partnership for Alternative Approaches to Animal Testing (EPAA) Working Group 3.

  Sally Robinson, David Basketter, Rita Bussi, Joachim Coenen, Philip Connolly, Signe G Elvig-Jørgensen, Helma Hermans, Alan Hoffmeister, Antonio Lacerda, Jens P Linge, Horst Spielmann, Michael Török, Jan van der Valk, Tim Watson
  Alternatives to laboratory animals: ATLA 10/2008; 36(4):453-8. · 1.58 Impact Factor
• Article: A European pharmaceutical company initiative challenging the regulatory requirement for acute toxicity studies in pharmaceutical drug development.

  Sally Robinson, Jean-Luc Delongeas, Elizabeth Donald, David Dreher, Matthias Festag, Sophie Kervyn, Ann Lampo, Kamil Nahas, Vicente Nogues, Deborah Ockert, Kirsty Quinn, Sally Old, Nigel Pickersgill, Kev Somers, Claudia Stark, Peter Stei, Lynne Waterson, Kathryn Chapman
  [show abstract] [hide abstract]
  ABSTRACT: Regulatory guidelines indicate acute toxicity studies in animals are considered necessary for pharmaceuticals intended for human use. This is the only study type where lethality is mentioned as an endpoint. The studies are carried out, usually in rodents, to support marketing of new drugs and to identify the minimum lethal dose. A European initiative including 18 companies has undertaken an evidence-based review of acute toxicity studies and assessed the value of the data generated. Preclinical and clinical information was shared on 74 compounds. The analysis indicated acute toxicity data was not used to (i) terminate drugs from development (ii) support dose selection for repeat dose studies in animals or (iii) to set doses in the first clinical trials in humans. The conclusion of the working group is that acute toxicity studies are not needed prior to first clinical trials in humans. Instead, information can be obtained from other studies, which are performed at more relevant doses for humans and are already an integral part of drug development. The conclusions have been discussed and agreed with representatives of regulatory bodies from the US, Japan and Europe.
  Regulatory Toxicology and Pharmacology 05/2008; 50(3):345-52. · 2.43 Impact Factor