Target Animal Safety. Target Animal Safety. Pharmacologic/Toxicologic Characterization as Part of Target Animal Safety Technical Section

Transcription

1 Pharmacologic/Toxicologic Characterization as Part of Target Animal Safety Technical Section Laura L. Hungerford, DVM, MPH, PhD Senior Advisor, Science and Policy, ONADE Professor, University of Maryland School of Medicine Target Animal Safety A sponsor must submit adequate tests by all methods reasonably applicable to show whether or not a drug is safe for its proposed uses. CFR Sections 512(d)(1); 514.1(b)(8)(i). Target Animal Safety A sponsor must submit adequate tests by all methods reasonably applicable to show whether or not a drug is safe for its proposed uses. CFR Sections 512(d)(1); 514.1(b)(8)(i). 1

2 The design of the TAS evaluation and the assisted by reference to data i.e. The design of the TAS evaluation and the assisted by reference to data including published literature and preliminary studies including pharmacokinetics, pharmacodynamics and toxicology from target and non-target laboratory animal studies The design of the TAS evaluation and the assisted by reference to data including published literature and preliminary studies including pharmacokinetics, pharmacodynamics and toxicology from target and non-target laboratory animal studies 2

3 Tailor plan to each drug Encourage alternate approaches Efficiently build on existing knowledge Identify and eliminate submission of unneeded studies and measurements Find efficient path to safety decision Describe the toxic syndrome and/or potential adverse effects Identify crucial gaps that still remain Support study design (dose, frequency, duration, type and timing of measurements) Identify questions that are already answered When and as what submission type? As soon in discovery/development as possible Prior to pre-submission conference Prior to submission of a protocol Generally, an H submission; possibly as a Z, P or other type; succint and to the point 3

4 Overall summary Relevant published literature Preliminary study summaries/reports Foreign ADE and epidemiologic reports Additional relevant information Overall summary What is known and what are the gaps How the provided information addresses known and gaps What else should be done to fill the gaps Specific questions or issues or proposals Anything goes but tell how it is relevant Relevant published literature Not just a stack of papers (or pdfs) Should be referenced in and support summary Should be considered critically and scientifically Include and discuss pro s and con s Weight of evidence is important 4

5 Preliminary study summaries/reports Preliminary can include almost anything Should be tied to overall summary How does it relate to target animal safety?! Not all other information Usually not raw data Should fill information gaps Preliminary study summaries/reports Possibly pharmacokinetics (individual animal data may be useful) to support dose, study duration, bioavailability, etc. Possibly other pharmacology metabolites, protein binding, mechanism of action, nanoparticle size, vector for DNA product, etc. Preliminary study summaries/reports Possibly preliminary toxicology in laboratory or other animals (including humans if data exist for this species) Possibly preliminary toxicology in target species 5

6 Foreign ADE and epidemiologic reports Information on safety under actual conditions of use Summary information rather than raw data May be observational data Additional relevant information Linked to the information gaps, summary and proposed Can be outside-the-box Novel information types Identify questions that are already answered: Benefit more efficient path to decision Waive margin of safety study Show why other types of studies are not needed Waive post-mortem examinations Scientific basis of answer is critical 6

7 Responses to submission: Depends on submission type Could include: Acknowledgement letter with or without a Memorandum of conference Specific response to sponsor questions or proposals SUMMARY Describe the toxic syndrome and/or potential adverse effects Identify crucial gaps that still remain Support study design (dose, frequency, duration, type and timing of measurements) Identify questions that are already answered SUMMARY A sponsor must submit adequate tests by all methods reasonably applicable to show whether or not a drug is safe for its proposed uses. CFR Section 512(d)(1); 514.1(b)(8)(i). The design of the TAS evaluation and the assisted by reference to data 7

8 SUMMARY A sponsor must submit adequate tests by all methods reasonably applicable Is to show the drug whether safe or for not the a drug target is safe animals? for its proposed uses. CFR Section 512(d)(1); 514.1(b)(8)(i). The design of the TAS evaluation and the assisted by reference to data 8