ADE inspections drop from fiscal '06, but 150+ ADE inspections expected in fiscal '08: Krueger.

WASHINGTON -- There were 27 voluntary action indicated (VAI) results in post-marketing adverse drug experience (ADE) reporting inspections in fiscal 2007, a drop from 38 for the prior fiscal year, according to a supervisor in the surveillance programs team at the Center for Drugs, who spoke here Jan. 16.

Addressing a Drug Information Assn. (DIA) conference on pharmacovigilance and risk management strategies, Carol Krueger noted there also was a drop in NAI inspection results, with 43 in fiscal '07 compared to 57 in fiscal '06. There also was a significant drop in the total number of ADE inspections--100 in fiscal '06 and 70 in fiscal '07.

The data generally matches the decline in inspections and other enforcement actions the last few years--a fact that has alarmed Congress and consumer-advocacy groups.

Krueger said the trend in citations is late reporting, which netted 42 observations in fiscal '06 (the most recent numbers available). Also common were written procedures citations (19), non-reporting (16), no follow-up (4) and incomplete/inaccurate reports (3).

She noted that overall, post-marketing ADE field inspections have increased from 35 in fiscal '97 to an estimated 150+ in fiscal '08. Field inspection staff has increased from one in fiscal '97 to 10 in fiscal '08.

Kreuger stressed that it is an FDA requirement to "submit within 15 business days any report of a serious adverse event associated with the use in the U.S. of a nonprescription drug or dietary supplement."

Companies also should "submit within 15 business days any related medical information received within one year of the initial report." The report is to be accompanied by a copy of the label on or within the retail package of the product."

Records should be maintained related to each report for six years. Labels of OTC drugs marketed in the U.S. must have a domestic address or phone number to receive AE reports, she said.

Krueger noted that a typical ADE inspection determines if the firm:

* Has adequate procedures;

* Is following procedures;

* Submits all individual and summary ADE reports to the agency; and

* Submits complete, accurate and timely reports.

Pharmacovigilance reports, she said, should have comprehensive SOPs, reflect actual performance, contain all sources of data, all data transfers, evaluation and coding, follow up and data management.

Anne Champsaur, M.D., VP of drug safety at Exelixis, South San Francisco, CA, noted that in the European Union (EU), targeted (non-routine) inspections are conducted usually for:

* Failure to carry out specific obligations/follow-up measures;

Delays in reporting individual cases and ADE reports;

* Incomplete/poor quality reporting;

* Inconsistencies between reports and source;

* Change in benefit-risk balance; and

* Failure to communicate these changes.

Some of the documents always requested in an EU pharmacoviglance inspection include:

* CVs, job descriptions, training records;

* Organization charts;

* Procedural documents;

* Individual ADE case files and CIOMS reports;

* Contracts and agreements with third parties;

* Risk management systems;

* Meeting minutes; and

* Line listings of ADR reports.

Also required, she said, is all information pertaining to databases, such as, software system description, name of the vendor or developer, relationships between multiple systems, statement of compliance with the internationally agreed standards for electronic submission, registration with the EudraVigilance system, validation status of each system and of connections between multiple systems, and a list of legacy systems used.

By Joseph Pickett, Associate Editor