Reporting Scenario # 4Reporting Scenario # 4

September 18, 2005September 18, 2005

Scenario # 4Scenario # 4 Mr Brando is entered on single-Mr Brando is entered on single-

arm phase I/II tiral of allogeneic arm phase I/II tiral of allogeneic unrelated donor MSCs for the unrelated donor MSCs for the treatment of GvHD.treatment of GvHD.

MSCs are manufactured & MSCs are manufactured & released by study sponsor using released by study sponsor using proprietary methods.proprietary methods.

The hospital Cell Therapy Lab The hospital Cell Therapy Lab stores, thaws and issues the stores, thaws and issues the cells.cells.

Scenario # 4Scenario # 4 Four hrs after infusion of the 3Four hrs after infusion of the 3rdrd MSC MSC

product, the patient has product, the patient has Temp 39C, hypotension, chills, Temp 39C, hypotension, chills,

arthralgias, sever headache.arthralgias, sever headache. This reaction has been observed in This reaction has been observed in

patients who receive cells cultured in patients who receive cells cultured in FBS.FBS.

You are aware the FBS is part of the You are aware the FBS is part of the proprietary manufacturing process.proprietary manufacturing process.

Informed consent (sponsor-Informed consent (sponsor-prepared) doesn’t mention this side prepared) doesn’t mention this side effect.effect.

Scenario # 4Scenario # 4

Is this an adverse event?Is this an adverse event?

Yes.Yes.

Scenario # 4Scenario # 4

If an adverse event, is the event If an adverse event, is the event serious? Life-threatening? serious? Life-threatening? Unexpected?Unexpected?

This meets the definition of This meets the definition of serious and unexpected AE.serious and unexpected AE.

It was not life-threatening.It was not life-threatening.

Scenario # 4Scenario # 4

Is this reportable to the FDA? If Is this reportable to the FDA? If so, how should it be reported?so, how should it be reported?

Yes, the laboratory should Yes, the laboratory should report the event immediately to report the event immediately to the Sponsor.the Sponsor.

The IND sponsor should report The IND sponsor should report this to the FDA within 15 this to the FDA within 15 calendar days.calendar days.

Scenario # 4Scenario # 4

What else should you do?What else should you do?

Notify your IRB.Notify your IRB. The sponsor will notify other study The sponsor will notify other study

participants.participants. With the sponsor you should:With the sponsor you should:

Evaluate this patient for anti-bovine Evaluate this patient for anti-bovine protein antibodies.protein antibodies.

Consider monitoring other patients.Consider monitoring other patients. Amend study informed consent to Amend study informed consent to

discuss this risk.discuss this risk.