# Presentation: 537889

## Field Investigators:ADE Detectives

## Section One

**Introduction to the Team**
**and Their Roles**

## FDA’s Postmarketing Adverse

**Drug Experience Inspectional Program**

## ...”promote and protect public health

**by assuring that safe and effective drugs**
**are available to Americans.”**

## ...”provide pharmacovigilance resources

**to the Center for Drug Evaluation and**
**Research to ensure the safety of**
**marketed drugs.”**

##  Field Investigations

** ****Office of Drug Safety**
** ****Office of Compliance**
** ****Regulatory Policy Staff**
** ****Office of Chief Counsel**

## ...”serve as industry watchdog, performing

**inspections or investigations that help**
**protect the safety of all our citizens.”**

##  After approval, drugs are used in manytypes of patients -- including older, sickeror those taking medications --- that were not studied during the pre-approvalperiod.

** ****Rare, serious adverse reactions are often****not discovered until many thousands****of patients have taken the drug.**

##  Labeling changes related to prescribinginformation are complete and up-to-date.

** ****Drug risks are quickly and appropriately****managed.**

##  Regulations

** ****Guidance**
** ****Information on how to conduct an****  inspection**
** ****Helpful tips and information**

## Section Two

**The Regulations**

## Safety reporting requirementscover all persons who marketover-the-counter drugs withapproved applications andprescriptions drugs

** ****Applicants**
** ****Manufacturers**
** ****Packers**
** ****Distributors**
** **

## Title 21 of the Code of Federal Regulations

## Section 314.80 - Postmarketing SafetyReporting Regulations for Human Drugswith Approved New Drug Applications

## Section 314.98 - Postmarketing SafetyReporting Regulations for Human Drugswith Approved Abbreviated New DrugApplications

## Section 211.198 - Requires Industryto Establish Written Procedures forHandling Complaints, Including ADEs

##  An adverse event occurring in the course ofthe use of a drug product inprofessional practice;

** ****An adverse event ****occurring in the course of****the use of a drug product in****professional practice;**
** ****from a drug overdose, whether****accidental or intentional;**
** ****from drug abuse;**
** ****from drug withdrawal;**
** ****and from any failure of expected****pharmacological action**
** **

##  Death

** ****Death**
** ****A life-threatening ADE**
** ****Inpatient hospitalization or****  prolongation of existing ****  hospitalization**
** ****A persistent or significant disability****  or incapacity**
** ****A congenital anomaly or birth defect**
** ****Other important medical events**
** **

## What must be reported?

** ****Any spontaneous adverse event****  occurring within the U. S.**
** ****Any foreign reports, literature and****  study reports that involve serious****  and unexpected events.**

## 3 Types of Required Reports?

** ****Expedited or 15-day alert reports**
** ****Periodic reports**
** ****Follow-up reports**

## Four Basic Elements :

** ****identifiable patient**
** ****Identifiable reporter**
** ****Suspect drug**
** ****An adverse experience or fatal ****  outcome **

## Form 3500A or CIOMS 1 Form - Fromthe council for International Organizationsof Medical Sciences

##  Surveillance

** ****Surveillance**
** ****Receipt**
** ****Evaluation**
** ****Reporting**
** **

##  Firms should collect  quality information

** ****Firms should collect****  quality information**
** ****Identify and confirm drug****  safety issues as soon as possible**
** ****Communicate drug safety****  information to FDA and to the****  public efficiently and effectively**
** ****Maintain all ADE records, including****  all raw data, for 10 years**
** **

## http://www.fda.gov/medwatch/how.htm

##  By Mail: Use the postage-paid  MedWatch form

** ****By Mail: Use the postage-paid****  MedWatch form**
** ****By Phone: 1-800-FDA-1088**
** ****By FAX: 1-800-FDA-0178**
** ****And by Internet**

## Slide 27

## Section Three

**Compliance Program Guidance**

## Your job as an investigator will depend moreon computers and telecommunications.

## Types of Inspections :

** ****For-cause or directed inspections**
** ****Routine surveillance inspections**

## Selection Criteria:

** ****A review of the Adverse Event Reporting****  System database**
** ****Firms that have a history of violations, are ****  on the Application Integrity Policy List, or ****  that have a history of recalls**
** ****Routine surveillance**
** ****The drug is a new molecular entity or Is on****  the TOP 200 List**** **

## Selection Criteria:

** ****Safety issues**
** ****Bioequivalence issues and**
** ****Special situations**

##  Timeliness reports

** ****Timeliness reports**
** ****Direct reports vs. Mandatory reports**
** ****Completeness reports**

## 	Getting Ready for an Inspection

**Review previous establishment inspection reports**
**Review information provided with the assignment,****which may include 3500A forms, current****approved labeling and AERS-generated ADE lists**
**Review applicable CFR sections, Compliance****Program Information, and FDA guidelines**
**Contact the staff member who initiated your****assignment**

##  All of the firm’s written procedures that describe  receipt, evaluation, and submissions of ADEs  during the time period under investigation.

** ****Organizational charts showing which persons were ****  or are responsible for all compliant handling during ****  the time period under investigation.**
** ****All written procedures describing who is responsible****  for changing complaint handling procedures during****  the time period under investigation.**

##  All correspondence, meeting minutes, and documents  relating to all ADEs.

** ****List of all the company’s drug products and approval****  dates.**
** ****Package inserts for products covered under the****  inspection.**

##  A listing of all ADE complaints received over a specific  timeframe, such as 2 years, including foreign and  domestic events.

** ****Periodic reports, specific 3500A forms, and associated****  raw data.**
** ****Lists of collection sites, processing centers, and****  reporting units.**
** ****Copies of all contractual agreements related to collection,****  evaluation and reporting ADEs.**

## Section Four

**How to Conduct an Inspection**

## Is there a difference between a GMP inspectionand a post-marketing ADE inspection?

## What is the main objective of these ADEinspections?

## What are some the questions you typically askwhile interviewing representatives of thecompany?

##  How do they do their job when each type of  ADE comes into the company?

** ****Are there meetings on ADEs?  Who presides;****  how often; what topics are discussed?**
** ****Which persons in the company are responsible****  for labeling and making sure the labeling reflects****  the ADEs coming into the company?**

##  How does the process work for assuring  labeling reflects ADEs?

** ****Who first receives the incoming mail or calls****  relating to ADEs?**
** ****Where are and how are ADEs logged in?**
** ****Who performs the medical evaluations?**
** ****Who performs follow-up?**

##  Who assesses seriousness?

** ****Who determines if the ADE is a labeled or an****  unlabeled event?**
** ****Who determines if the ADE is a 15-day or a****  periodic report?**
** ****Who transmits or sends the 3500A Form to FDA?**

##  How is information shared among  departments?  Be aware that the legal  department might be receiving and maintaining  ADEs too.

** ****Who determines if the ADE is a labeled or an****  unlabeled event?**
** ****How are ADEs tracked?**
** ****How are control numbers assigned?**

##  Does the firm use a computerized database for  tracking

** ****Is this database national or global?  What****  information is kept in the database?**
** ****Is there an audit trail?  How does the firm track****  ADE receipt and submission?**

## What about a firm’s written procedures?

## What kind of procedures do you mean?

## What are some common deficiencies foundin these inspections?

## Inspectional deficiencies :

** ****A firm’s failure to submit or the untimely****  submission of the 15-day report.**
** ****Failure to submit or the untimely submission****  of periodic reports.**
** ****Submission of inaccurate or incomplete ADEs.**

## Inspectional deficiencies :

** ****Failure to conduct follow-up investigations into****  the outcome of serious and unexpected ADEs.**
** ****No written SOPs; inadequate SOPs; or failure to****  follow SOPs.**
** ****Failure to validate computer systems used to****  generate ADE report.**

## 301-827-9057

## Section Five

**Tips**

## www.fda.gov/cder/aers/index.htm

**www.fda.gov/medwatch/report/mfg.htm**