|ESTP Committee for Scientific Standards
Mission: Scientific standards for scientific value
The ESTP Committee for Scientific Standards (CSS) has reviewed the following guidance documents or position papers:
- FDA draft guidance on "Nonclinical safety evaluation of the immunotoxic potential of drugs and biologics" (February 2020) : a comparison with the withdrawn FDA guidance on Immunotoxicology evaluation of investigational new drugs (2002) was made and a tabulated summary of changes in the new guidance summary is presented here:
a FDA draft guidance for Nonclinical safety evaluation of the immunotoxic potential of drugs and biologics (February 2020) https://www.fda.gov/media/135312/download
|FDA Guidance - Version 2002b
||FDA Guidance - Draft Version 2020a
|Guidance applicable to small molecules only
||Guidance applicable to small molecules + some biologics (therapeutic proteins and recombinant/plasma-derived blood proteins)
|Focuses mainly on immunosupression
||Focuses also on immunostimulation (ex: TGN1412) with in vitro assays assessing immune activation, cytokine release and ligand-receptor interactions
|No corresponding ICH guidelines except ICH S6 (1st version)
||Refers to ICH S8c (2006), S11d (2020), S9e (2010), S5 R3f (2020) in addition to S6 R1g (2012)
|Developmental immunotoxicity limited to standard DART studies
||Juvenile Tox studies (all species) + NHP enhanced PPND study added in addition to standard DART studies
|For TDAR : SRBC Plaque Assay was recommended as 1st choice
||KLH is now the 1st choice for TDAR assay
T-DAR is also proposed for increased IgM/G production in addition de decreased IgM/G production.
|Dogs and monkeys were the only two NR species recommended
||Minipig added in non rodent species in addition to dogs and NHPs
||LLNA not recommended anymore (limits for this test) – In vitro tests recommended instead (OECD guidelines 2019 test No. 442C/D/E)
b FDA guidance for Industry Immunotoxicology Evaluation of Investigational New Drugs (October 2002) https://www.fda.gov/media/72228/download
c ICH S8 Immunotoxicity studies for human pharmaceuticals (April 2006)
d ICH S11 Nonclinical Safety Testing in Support of Development of Paediatric Medicines (January 2019)
e ICH S9 Nonclinical Evaluation for Anticancer Pharmaceuticals – Questions and Answers (June 2018)
f ICH S5(R3) Detection of Toxicity to Reproduction for Human Pharmaceuticals (November 2017)
g ICH S6(R1) Preclinical Safety Evaluation of Biotechnology-Derived Pharmaceuticals (May 2012)
- FDA guidance for industry, clinical laboratories, healthcare facilities, pathologists and FDA staff on "Enforcement Policy for Remote Digital Pathology Devices During the Coronavirus Disease 2019 (COVID-19) Public Health Emergency" (April 2020): this policy, which is effective during the public health emergency related to Covid-19 only, is provided by the FDA to expand the availability of devices for remote evaluation of digital pathology images. Although applying only to medical pathologists from clinical laboratories and hospitals, it is also a positive signal for the current shift toward a digital pathology approach in the preclinical safety and toxicologic pathology and its acceptance by the regulatory authorities.
- EMEA-related guidelines: there are 2 Final Guidelines that will be effective in July 2020
- Guideline on assessment and control of DNA reactive (mutagenic) impurities in veterinary medicinal products (1 July 2020)
- ICH S5 (R3) guideline on reproductive toxicology: Detection of toxicity to reproduction for human pharmaceuticals- step 5 (30 July 2020)
- EMEA: There is a lot of information concerning Covid-19 on the website of EMEA that may be of interest for the toxicologic pathologist (e.g the treatments and vaccines now under investigation and guidance for developers and companies)
- OECD GLP Position paper regarding possible influence of sponsors on conclusions of GLP Studies (7th May 2020)
Laetitia Elies, Eveline de Rijk, and Sibylle Gröters on behalf of the ESTP Committee for Scientific Standards
The Scope of the ESTP Committee for Scientific Standards (CSS, formerly the Guideline Committee) has a dual focus:
The internal focus is to update and inform the ESTP members about recent developments, changes and issues affecting guidelines and scientific standards which impact the daily work of toxicopathologists and correlated scientific fields. This should happen in an interactive fashion. Comments, proposals and criticism are welcome via email or in the Members Only area. The opinions and feed-back of the members will be a useful tool for the second focus:
The external focus of the CSS is the generation of comments or position papers related to guidelines and scientific standards which are then released by the ESTP Board and sent towards the regulatory bodies as input to these draft guidelines. The CSS may also review draft Points to Consider documents (eg from other Societies) which could have an impact on our work and thus ensure partnership with international STP Regulatory & Guideline committes. The process we follow is as follows:
- Individual members of the CSS are responsible for reviewing websites of specific regulatory bodies (namely EMA, FDA, ICH, OECD, EPA) and informing the Committee of any draft guidelines which fall within the scope of the CSS.
- The CSS will develop preliminary comments on behalf of the ESTP which are then submitted to the Society's Executive Board for endorsement; the Board will make efforts to respond within 10 days. The CSS comments will be made available in parallel in the Members Only area and any member of ESTP is invited to make further comments or suggestions.
- If the Executive Board feel that the draft guideline could have a particularly significant impact on our work then a more proactive engagement of the Society's membership may be proposed (including an extension of time available, if possible).
- The ESTP website will be updated with the final set of comments submitted to the regulatory body in question.
- Once the final guideline is published a statement to that effect (and a link) will be placed on the ESTP website.
The information available is placed under the categories shown below. Please note that most of the documents are available as PDF files.
If you would like to contact the members if the ESTP Committee for Scientific Standards, please click here.