Dear members

I would like to hear your thoughts on what safety margins you believe we need when evaluating results from ex vivo action potential recordings (e.g. GP papillary muscle APD90).

Any references would also be greatly appreciated.

Also, how big an effect do you consider to be relevant?

Best regards, Morten - H. Lundbeck A/S

Does anybody know a method to study the effects of compounds on gap junctions?

Webinar

I found the Webinar on ICH S9 very interesting and informative. The Panel discussion was particularly interesting to me. There seems to be a preference for rolling large molecule work into the Toxicology studies. Here are my questions.

1) If we perform Cardiovascular, CNS and Respiratory studies in toxicology studies, should the model all be tested with positive controls to indicate that the study design would detect an effect if it was present?

2) Are the standards for sensitivity the same for these add-ons to Toxicology studies the same as for safety pharmacology?

3) What would be a reasonable positive control study to show the sensitivity and specificity?

I look forward to your insights.

I’m looking for input regarding the outsourcing of abuse liability testing.  I’m curious as to which models are being used and which contract organizations have offerings and experience in this area.

In models where in-vivo tests are monitored over days and not hours, a tremendous amount of data is generated. How are other researchers handling these large databases and what tools are used to select the subsets of the total data set for analysis?

Does anyone have any suggestions for in vitro or in vivo models to evaluate the potential for a drug to cause pericarditis?

How do others handle the issue of loosing a telemetry animal in a 4×4 Latin square design. For example if you loose one animal after two doses and still have two additional dosing periods.

What is the current practice in the industry when this occurs? One suggestion was to substitute in an animal and simply finish out the study in the normal 4 doses. Another was to substitute in an animal and give 4 more doses. Yet another is to continue on with missing cells. What is your opinion or experience?

I would also like to get the perspective on how you feel these options might impact the statistics.

The SPS will be in its tenth year of existence in 2009 and safety pharmacology as a defined scientific enterprise is also about a decade old. Have we made an impact on the safety of drug development? How is safety pharmacology data viewed by our management in the pharmaceutical industry; are we giving good value for their investments? How are our data being received by regulators? Do we contribute effectively to the safety of early clinical trials? Is our data being taken seriously and is it thought to be predictive by the authorities?

The program committee for the 2009 annual meeting to be held in September in Strasbourg, France is contemplating organizing some programming that will examine this type of question. It should however not only give Safety Pharmacology a ten year “report card” but also look into the future for areas of improvement or expansion.

We’d love to get your input and ideas to give some content to these important questions to help guide us in identifying critical themes and finding appropriate speakers to address them. We may attempt either a panel discussion format or perhaps a debate setting, but regardless of how it turns out, we would appreciate your contribution!

Dear members

Are any of you aware of a realiable supplier of a testing kit for the kidney injury molecule-1 (KIM-1)

Bonventre JV. Kidney Injury Molecule-1 (KIM-1): a specific and sensitive biomarker of kidney
injury. Scand J Clin Lab Invest Suppl. 2008;241:78-83.

Regards
Tomas Mow, Head of Safety Pharmacology, H. Lundbeck.

USDA Policy #3 (Nov 7, 2007) requires the use of pharmaceutical compounds in animals, specifically covered species.  Interested in how other pharmaceutical companies and CROs are handling this new guideline with respect to any and all compounds other than NCEs or NBEs that are administered.  Materials used for analgesia, anesthesia, euthanasia and any animal health medications would most certainly be pharmaceutical grade, but what about reference compounds, competitor compounds and various pharmacological tool compounds used in the performance of many assays?