Regulatory Class - Nov 14 Flashcards

Question

Sponsor Inspections

Answer 1

Inspection of sponsor and/or CRO:  Generally unannounced but not always  Assess how sponsor assures the validity of data submitted to them by clinical investigators  Verify compliance with applicable regulations 2 types of inspections:  Routine/Surveillance  For cause

Answer 2

```  Protocol (original & revisions)  Investigator agreements & financial disclosures  Organizational charts  Correspondence  CRO or vendor agreements  Product accountability records  Monitoring plan & reports  Qualification records for Monitors and Clinical Investigators  Training records  Study subject records (CRFs, diaries, etc.)  Adverse event reports  Clinical Databases/Data line listings  SOPs for conduct of study ```

Answer 3

 Inadequate monitoring  Failure to secure investigator compliance  Failure to submit Progress Reports  Inadequate adverse event analysis and reporting  Failure to notify FDA, investigators or IRBs  Inadequate product accountability  Failure to obtain signed Investigator Agreement/1572  Failure to obtain FDA or IRB approval

Answer 4

No Action Indicated (NAI)  No substantive noncompliances Voluntary Action Indicated (VAI)  Substantive noncompliances but no further regulatory action required  May or may not require response Official Action Indicated (OAI)  Serious deviations from regulations requiring prompt correction  Administrative and/or judicial regulatory actions required

Answer 5

Adulteration – quality-related deficiencies  Produced under unsanitary conditions or containing filthy, putrid or decomposed substance  Not manufactured in compliance with GMPs  Strength, quality or purity differs from how it is represented  Class III medical device without approved PMA (or not exempt)  Banned device

Answer 6

Misbranding – false or misleading labeling or other information  Label fails to include the manufacturer name/address  Label includes an inaccurate statement regarding quantity  Label does not include established name of the drug  Label does not contain adequate directions for use and warnings necessary to protect users  Dangerous to health when used in dosage or manner recommended by labeling

Answer 7

 Untitled letter  Warning letter  Reinspection to verify corrective actions  Regulatory meeting  Clinical hold on study  Withdrawal of approval  Rejection of data  FDA-initiated product recall  Initiation of Disqualification Proceedings  Deferral of substantive review of submissions

Answer 8

 Usually issued following Form 483  Repeated noncompliances  Company does not correct/resolve issues  Serious noncompliances  Issues are basic to quality control and require immediate correction  Respond within 15 days

Answer 9

Actions taken by manufacturer to remove from the market products that are in violation of FDA regulations May be:  Voluntary  In response to FDA request  By FDA order

Answer 10

 Class I recall – reasonable probability that use of or exposure to suspected product will cause serious adverse health consequences or death  Class II recall – use of or exposure to suspected product may cause temporary or medically reversible adverse health consequences; or probability of serious adverse health consequences is remote (most are Class II)  Class III recall – use of or exposure to suspected product is not likely to cause adverse health consequences

Answer 11

Notice of Initiation of Disqualification Proceedings and Opportunity to Explain (NIDPOE)  Process to disqualify clinical investigator from receiving investigational products  Investigator has repeatedly or deliberately failed to comply with regulatory requirements  Investigator has deliberately or repeatedly submitted false information to sponsor or FDA

Answer 12

 Injunction  Seizure  Civil money penalties  Referral to FDA’s Office of Criminal Investigations and Prosecution

Answer 13

Used where there is a likelihood that violations will continue or recur FDA seeks injunctions when:  Chronic violations and efforts by FDA to obtain voluntary compliance have been unsuccessful  Immediate court intervention is needed to address an imminent public health hazard Forcing an action or prohibition of an action - this is an action against the products

Answer 14

Civil action providing for government “arrest” of the goods  Initiated by FDA through the Department of Justice (DOJ)  US Attorney files Complaint for Forfeiture, judge signs order for arrest of good, US Marshalls Service executes the warrant  Indicated when company refuses to undertake recall requested by FDA or FDA has reason to believe a recall would not be effective or discovers a violation is continuing Response to FDA:  Propose that goods be reconditioned to bring into compliance  Deny FDA’s allegation of adulteration or misbranding (go to trial) *if not claimed, they are destroyed

Answer 15

Based on size  Lot - One or more lots of product in one location that is adulterated or misbranded  Multiple - More than one action to arrest goods located in different jurisdictions where goods are adulterated or lack required approval  Mass - Warehouse full of products deemed adulterated or misbranded

Answer 16

FDA Office of Criminal Investigations  Obtains and executes search warrants and arrest warrants  Conducts physical surveillance  Obtains and serves grand jury subpoenas  Obtains and reviews materials and documents to support case against an individual or company Department of Justice (not FDA) must bring criminal case to court FDA recommends criminal prosecution in cases where:  There are gross violations that are evidence of management’s disregard for compliance with FD&C Act  Obvious and continuing violations where management has not exercised appropriate care  Life-threatening violations or where injuries have already occurred  Deliberate attempts to circumvent the law