Fulfilling the Promise of Medicine Together New FDA Safety Reporting Requirements 2010 John McLane,...

Fulfilling the Promise of Medicine Together

New FDA Safety Reporting Requirements 2010

John McLane, Ph.D.COO & Vice President Clinical and Regulatory AffairsClinquest, Inc. [email protected]

Fulfilling the Promise of Medicine Together2

Safety Reporting Requirements Different requirements for

• Sponsors• Investigators• IRBs

Different requirements depending on type of study and funding• FDA

Drug IND vs Postmarketing

Device Food Supplements

• Federal• ICH


FDA: Sept 2010

Guidance for Industry And Investigators:• Safety Reporting Requirements for INDs and

BA/BE Studies New Regulations

• 21 CFR 312 IND Safety Reporting

• 21 CFR 320 BA/BE Studies Refers to Drugs and Biologicals Closer alignment to ICH/EMA

requirements


Why New Regs and Guidances?

Too many reports unfiltered SAE reports associated with

• Manifestations of the disease morbidity for stroke

• Common in study population Strokes in elderly population

• Study Endpoints Confusion with phrase: “associated with the use

of the drug” and “reasonable possibility” Refine definitions


Define: Adverse Event (AE)

Same as adverse experience Untoward medical occurrence

associated with the use of a drug• Whether or not considered drug related

Note separation from causality

Unfavorable or unintended sign or symptom

Temporally associated with any use of the drug


Define: Suspected Adverse Reaction (SAR)

Any AE reasonably possibility that drug caused AE

Decreased level of certainty then an adverse reaction

1st use of “reasonable possibility” The SAR & use of “reasonable

possibility” is consistent with concepts about causality defined in ICH E2A


Define “reasonable possibility”

Single occurrence of an uncommon event• AE know to be associated with drug

exposure

• Ex. Stevens-John syndrome 1 or more events not commonly

associated with drug exposure• Not common in the study population

Aggregate analysis of events that occur more frequently in tx arm


Define: Unexpected AE or SAR

Safety event:• Not described in IB or protocol

• Event is of greater severity/specificity than previously described

Hepato-necrosis is a Unexpected AE if IB has only hepatitus

• Event is described as seen in similar drugs (class effect) but not yet observed with this drug

First occurrence of this type of event is a UAE


Define: Serious (SAE)

Similar to prior use:• Death

• Life-threatening Excludes AE or SAR that had it occurred in

more serious form might have caused death

• In-patient hospitalization

• Prolongation of hospitalization

• Congenital anomaly/birth defect Refines the use of medical judgments

by either investigator or sponsor


Safety Monitoring

Sponsor Evaluate Safety of Drug for

subjects

Serious, Expectedness, Reasonable Possibility

Analysis with other events related to drug use


Review of Safety Information

Get safety information from all sources• Domestic/foreign trials

Foreign data to US: Safe Harbor Requirements

• Clinical epidemiology studies

• Annual literature review for safety

• Animal or in vitro expts.

Report in safety reports • ID all IND safety reports similar in nature

previously reported

• Notify FDA and all “participating investigators” 15 day reports


SUSARS

For the first time FDA recognizes SUSARs

Three criteria• Suspected adverse reaction

• Serious

• Unexpected Expedited IND safety report


Conclusion

Move towards harmonization• FDA will accept CIOMS I forms

• Use of SUSAR Clear definition

• Replace “associated with the use of the drug” with “reasonable possibility”


Relationship between AEs and UAPs

The diagram illustrates three key points: • The vast majority of adverse events occurring in human

subjects are not unanticipated problems (area A) and do not need to be reported to the IRB.

• A small proportion of adverse events are unanticipated problems (area B) and need to be reported to the IRB.

• Unanticipated problems include other incidents, experiences, and outcomes that are not adverse events (area C) and need to be reported to the IRB.

Fulfilling the Promise of Medicine Together New FDA Safety Reporting Requirements 2010 John McLane,...

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