Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
59 Cards in this Set
- Front
- Back
|
IND Filing: 1. What does it look like? 2. How is it labeled? 3. When can study start? |
1. Pretty large binder 2. xx,xxx (as a number and date) 3. Study cannot start until 30 days after submission of IND to FDA |
|
|
Federal Register Act Date? Description? |
1935 - Daily published record of proposed rules, final rules, meetings |
|
|
Code of Federal Regulations: Date? 45 CFR 46 |
1937 45 CFR 46 - Public Welfare HHS |
|
|
Federal Food, Drug, & Cosmetics Act Date? Description? |
1938 - basic food and drug law of US - Assures consumers that food is safe, sanitary conditions - drugs/devices safe and effective - cosmetics safe and made from appropriate ingredients - labeling/package truthful |
|
|
Medical Device Amendments to FD&C Act Date? Description? |
1976 -1st major amendment specifically for devices |
|
|
Treatment Use of IND Date?
|
1987 |
|
|
ICH - International Conference on Harmonization Date?
|
1989 |
|
|
Food and Drug Modernization Act Date?
|
1997 |
|
|
45 CFR Part 46 "_______ Rule" Under which Dept.? Subpart A Subpart B Subpart C Subpart D
Who enforces this regulation?
|
Dept. of Health & Human Services (HHS) "Common Rule" - Federal policy for protection of human subjects
Subpart A - Basic HHS policy Subpart B - Pregnant women, fetuses, & neonates Subpart C - Prisoners Subpart D- Minors/Children OHRP - Office for Human Research Protections |
|
|
21 CFR Parts 50 and 56 (Under which Dept?)
21 CFR 312
21 CFR 812
Who enforces this regulation? |
Food and Drug Administration
21 CFR 312 - INDs (new drugs/biologics) 21 CFR 812 - IDEs (new devices)
Emergency use of test article
FDA does their own enforcement |
|
|
Do we have to abide by both OHRP & FDA requirements? If so, when? What is their span of authority? Can we be monitored/audited by both? |
Yes When under both Anything under OHRP or FDA Depends |
|
|
HHS & FDA Regulatory Differences - HHS allows for _____ of _____ consent in _____ risk research, not FDA - FDA clinical _____ = research, HHS's definition is _____ and _____ - scope of responsibility: FDA (_____, _____, _____, _____); HHS ) research funded by _____ or all research per _____
|
- HHS allows for waiver of written consent in minimal risk research, not FDA - FDA clinical investigation = research, HHS's definition is detailed and specific - scope of responsibility: FDA (food, drug, biologic, device); HHS ) research funded by Federal gov. or all research per FWA |
|
|
Offices of GCP in FDA Regulated Clinical Trials - Coordinates _____ polices - provides _____ and _____ through FDA's Human subject _____/_____ steering committee - coordinates FDA's bioreserach _____ program contributes to international _____ harmonization activities - plans/conducts _____/_____ programs -serves as _____ with HHS OHRP and others |
- Coordinates FDA polices - provides leadership and direction through FDA's Human subject protection/GCP steering committee - coordinates FDA's bioreserach monitoring program contributes to international good clinical practice harmonization activities - plans/conducts training/outreach programs -serves as liaison with HHS OHRP and others |
|
|
ICH stands for? When did they first meet? Joint efforts between? Primary purpose? Guidelines based on? |
- International Conference on Harmonisation - first met in 1991 - joint efforts of western Europe, US and Japan - coordinate drug regulatory process, prevent research redundancy - Declaration of Helsinki |
|
|
Definition of GCP _____ is an international _____ and _____ quality standard for _____, _____, _____, and _____ trials that involve the participation of human subjects. |
Good Clinical Practices is an international ethical and scientific quality standard for designing, conducting, recording, and reporting trials that involve the participation of human subjects. |
|
|
ICH Principles 1-5 Ethics: |
Ethics: |
|
|
ICH Principles 6-9 Responsibilities: |
Responsibilities:
|
|
|
ICH Principles 10-13 Data quality and integrity: |
Data quality and integrity: |
|
|
45 CFR 46 Subpart B- Allowable research if: - previous research has assessed _____ risks - risk to _____ minimal, or if greater than min. holds prospect of direct _____ for woman/fetuses -risk is the _____ possible for achieving objectives of the research - _____ obtained, _____ on impact on fetus - no _____ offered to terminate preg. - researchers have no involvement with _____ or _____ of fetus |
- previous research has assessed potential risks - risk to fetus minimal, or if greater than min. holds prospect of direct benefit for woman/fetuses -risk is the least possible for achieving objectives of the research - consent obtained, informed on impact on fetus - no inducements offered to terminate preg. - researchers have no involvement with termination or viability of fetus |
|
|
45 CFR 46 Subpart C- Allowable research if:
- majority of members have no _____ with prisoners - at least _____ member of review board is a _____/_____ - study of possible _____, _____, _____ of incarceration or _____ behavior, or prisons as _____ structures or prisoners as _____ persons - other than this need approval of _____, _____ |
- majority of members have no assoc. with prisoners - at least 1 member of review board is a prisoner/representative - study of possible causes, effects, processes of incarceration or criminal behavior, or prisons as institutional structures or prisoners as incarcerated persons - other than this need approval of Secretary, DHHS |
|
|
45 CFR 46 Subpart D
Risk Category I - no greater than ____ risk - ____ of child necessary - permission of parents/guardians ____ (only ____ adequate) |
- no greater than min. risk - assent of child necessary - permission of parents/guardians sought (only one adequate) |
|
|
45 CFR 46 Subpart D
Risk Category II |
- less than min. risk, prospect of direct benefit - anticipated benefit/risk comparable to alternatives - assent of child necessary - permission of parents/guardians sought (only one adequate) |
|
|
45 CFR 46 Subpart D
Risk Category III |
- min. risk, no prospect of direct benefit - intervention/procedure likely to yield generalizable knowledge of vital importance to understand disorder/condition - assent of child necessary - permission of parents/guardians sought (both needed except when one parent deceased/unknown, etc. or one has legal responsibility for child) |
|
|
45 CFR 46 Subpart D
Risk Category IV |
- research not otherwise approvable which presents opportunity to understand, etc. - can be approved by DHHS after: IRB review, DHHS consultation with expert panel, and opportunity for public review and comment, local IRB cannot approve this research |
|
|
21 CFR 312 Subpart A Subpart B Subpart C Subpart D Subpart E Subpart F
|
Drugs/Biologics Subpart A - general provisions Subpart B - IND application Subpart C - Administrative Actions Subpart D - Responsibilities of sponsors and investigators Subpart E - drugs intended to treat life-threatening and severely debilitating illnesses Subpart F - Misc. |
|
|
21 CFR 312 Applicability |
products that fall under Food, Drug and Cosmetic Act or licensing provisions of Public Health Service |
|
|
21 CFR 312 Exemptions |
studies exempt from IND - study involves lawfully marketed drug in US (all criteria must apply): -not intended to... be reported to FDA in support of new indication or to change label, support sig. change in advertising drug, involve route of administration/dosage level that increases risk - investigation conducted under IRB review with informed consent requirements - must adhere to section 312.7 -IRB applies these criteria to decide if investigator needs IND |
|
|
21 CFR 312.7 |
- all charging must be FDA approved - cant be promoted as safe and effective, no commercial distribution/test marketing - cant unnecessarily prolong investigation - charging must be justified by sponsor - must be pre-approved by FDA as part of IND |
|
|
IND Content and Format |
Cover sheet - form 1571 Table of Contents Intro statement & general investigational plan Investigator's brochure Protocols Chemistry, manufacturing, & control info Pharma and toxicology info Previous human experience with drug Additional info |
|
|
Investigator's Brochure |
- Descrip. of drug substance, formulation, structure - summary of pharma and toxi. data in animals and humans - summary of pharamcokinetics and bio. disposition in animals and humans - safety and effectiveness data in humans - possible risks and side effects - updated with new info - basic and clinical |
|
|
Protocols How many needed? Phase 1 Phase 2 and 3 |
- one for each planned study - 1: less detailed and more flexible, provide outline of investigation, # of subjects, safety exclusions, dosing and duration; details pertinent to safety - 2 and 3: detailed of all aspects of study; deviations, contingencies built in (cross over for non-responders, dose reduction for intolerance) |
|
|
Protocol Components |
Objectives and purpose Investigator qualifications (1572) Pt. selection criteria, numbers Design of study Dosing plan Observations and measurements to be made to fulfill study objectives Monitoring procedures |
|
|
What does it mean to sign the 1572? |
Investigator is saying he is responsible for everything - signing a "contract" with FDA to do everything right for the study (conduct study per protocol, reporting AEs in timely manner, qualified personnel, 21 CFR 50 and 21 CFR 56 are met, accurate records, IRB approval initial and continuing, and inform subjects drug investigational |
|
|
What special topics should be addressed? |
Drug dependency, abuse potential Radioactive Pediatric studes |
|
|
How many copies should be submitted with original? |
2 |
|
|
Submissions on same IND must have _______ numbering system |
consecutive 001 |
|
|
IND Amendments: Protocol Information |
Protocol: New, changes to existing that affects afety, addition of new investigator (new 1572), require IRB approval and FDA submission before implementation
Info: new toxi. chemistry data, new info for investigator's brochure |
|
|
IND Safety Reports
Written notification required for?
When should notifications be made?
|
Reuired for AEs associated with use of drug that is serious and unexpected; new finding in animal data that shows change in risk for humans (cancer, tetratogenicity, mutagenicity)
ASAP, within 15 days of awareness (FDA can change this at will) |
|
|
Clinical holds Timeframe? Grounds? |
FDA can impose at or prior 30 days after IND receipt
Grounds: risk unreasonable, investigator not qualified, IB misleading, insufficient data to assess risk potential, not enough time to review IND, design inadequate, not enough investigation drug exists, lack of efficacy, another drug has better potential, lack of due diligence of sponsor to pursue marketing approval of drug |
|
|
Meetings with FDA |
Pre-IND meeting
End of Phase 2 Meeting - encouraged by FDA, purpose to determine safety of processing to 3 and to evaluate proposed plan for 3
Pre-NDA meeting - uncover major unresolved issues that might delay approval for marketing |
|
|
Criteria for Medical Device Determination |
A medical device is "an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including a component part, or accessory which is: * recognized in the official National Formulary, or the United States Pharmacopoeia, or any supplement to them,* intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals, or * intended to affect the structure or any function of the body of man or other animals, and which does not achieve any of its primary intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of any of its primary intended purposes."
|
|
|
Which CFRs must clinical investigations of medical devices comply with? |
21 CFR 50 and 21 CFR 56 respectively |
|
|
Federal requirements governing investigations involving medical devices were enacted as part of: |
Medical Device Amendments of 1976 Safe Medical Devices Act of 1990 |
|
|
Premarket Notification Is the device substantially equivalent to "pre-amendments" device? If yes... If no... |
Yes, device can be marketed immediately No, device must undergo clinical testing and premarket approval |
|
|
IDE Must be conducted according to CFR? |
Investigational Device Exemption 21 CFR part 812 is the effectiveness/safety of device being studied |
|
|
Non-exempt studies for Medical Devices Must be categorized as? Who makes this determination? Where is the proposed study submitted to? |
Significant risk (SR) or Non-sig. risk (NSR) Initially made by sponsor Submitted to FDA for SR or IRB for NSR |
|
|
SR Device Studies Conducted in full accordance with? Cannot commence until? Is IRB approval needed? |
21 CFR 812
Until 30 days after filing of IDE application
Yes |
|
|
NSR Device Studies Is IRB approval needed? |
Does not meet def. of SR study Not to be confused with min. risk Yes |
|
|
All SR studies must be reviewed by? Study may not commence until what is approved? Assumed that what type of risk is involved? |
full IRB committee FDA approved IDE app. and IRB has approved study greater than min. risk |
|
|
NSR Device Studies Does not require... Sponsor is require to... When may it commence? |
IDE app conduct study with abbreviated requirements of 21 CFR 812.2(b) Following IRB approval |
|
|
Once NSR determination has been made by IRB, study is reviewed by IRB using? |
Same criteria as other studies of FDA regulated product (21 CFR 56.111) |
|
|
Class I Device |
General controls (crutches, bandaids) |
|
|
Class II Device |
Special Controls (wheelchairs, tampons) |
|
|
Class III Device |
Pre-market approval (heart valve) Known to present hazards |
|
|
510K vs PMA |
New device substantially equivalent to another device legally on market without PMA If FDA agrees, can be marketed
Pre Market Approval New device not substantially equivalent to existing device Clinical data required |
|
|
Who decides if SR or NSR? |
Initially sponsor
If NSR, submit IRB If IRB oks, then reviews and approves study If no, then notifies FDA then need IDE app Study begins after IDE and IRB approvals obtained |
|
|
Emergency Use of Unapproved Medical Device Requirements: |
-life-threatening situation exists - no alternative - no time to seek FDA approval - physician must justify criteria after the fact - physician needs to follow subject protection procedures (uninvolved MD, consent, notify institutional officials/IRB, auth from IDE holder |
|
|
After emerg. use of unapproved medical device: How soon does physician report? Physician evaluates... If IDE exists... If no IDE |
within 5 days likelihood that another instance of emerg. need may occur (initiate IDE and IRB for future use) notify sponsor immediately notify FDA of emerg. use and provide summary |
|
|
FDA Form 483 When is it issued? What is the response? |
Issued to institution when FDA finds conditions that may violate FD&C, issued upon arrival Institute responds in writing with corrective action plan
|
