Certified Clinical Research Professional (CCRP) Exam Already Passed

Certified Clinical Research Professional (CCRP) Exam Already Passed When isn't an IND application needed? IND Application is not needed if investigation does not support change in labeling What information must the general IND include? (21 CFR Part 312.23) FDA Form 1571: -FDA Form 1571 cover sheet -Table of contents -Investigative plan -Investigator's brochure -Protocol -Chemistry/Manufacturing information -Pharmacology/toxicology -Previous human research/literature information -Additional information (drug dependence and abuse potential) How many days after FDA receives IND submission does the IND go into effect? (21 CFR 312.40) An IND goes into effect 30 days after the FDA receives the submission unless the FDA notifies the Sponsor of a clinical hold When must an IND amendment be submitted? (21 CFR Part 312.31) -If there are changes to the protocol that affects safety of subjects, scientific quality of the study, or scope of investigation -If a new investigator is added to the study -Information amendments must be submitted for chemistry/microbiology, pharm/toxicology, or clinical OTHER SUBMISSIONS: --IND safety reports --Response to clinical hold --Response to FDA request for information --IRB Annual report What are t he requirements for expanded access? (21 CFR Part 312.300 - Subpart 1) -Population must have serious or life-threatening disease or condition -No comparable/significant alternate therapy/treatment -Patient cannot obtain drug under another IND or protocol -Potential benefit outweighs risks of treatment -Expanded access won't interfere with completion of studies that could support marketing approval -Must apply to treatment protocols and should be for individual use (1 person) How many days does a Physician or Sponsor have to submit written summary of expanded access to the FDA after use? 15 days 21 CFR Part 312.34 Treatment use of an Investigational new drug During which phases is a treatment protocol usually made available? During Phase 3 but if data is compelling, may be available during Phase 2, OR, after all clinical trials have been completed and Sponsor of trials is awaiting/pursuing marketing approval How long is the waiting period before a treatment IND study can be initiated? 30 days When will the FDA permit use of an investigational drug in widespread use? -If the criteria for expanded access are met (benefits outweigh risk, illness is life threatening, or if no other alternative treatments are available) -If drug is being investigated in a controlled clinical trial under an IND designed to support a marketing application for the expanded use or all clinical trials are completed What are the steps for withdrawing an IND? (21 CFR Part 312.38) A sponsor may withdraw an IND at any time without prejudice by: -Notifying the FDA -Stopping all studies and notifying the investigators -Returning all drug to the Sponsor, or destroying all drug as directed by Sponsor -If the study is withdrawn for safety reasons, the Sponsor must notify investigators and the IRBs Which form is used to certify absence of financial interest? FDA Form 3454 What form is used for the mandatory reporting of serious adverse events? FDA Form 3500A What is 21 CFR Part 50 Subpart D? Additional Safeguards for Children in Clinical Investigations What is the FDA Form 482? Notice of Inspection What is 21 CFR Part 50.20 Subpart B? General requirements for informed consent What steps must be taken if IND is put on clinical hold? (CFR Part 312.42) -Proposed study: Subjects may not be given the investigational drug -Ongoing study: No recruiting of new subjects & subjects receiving investigational drug must discontinue therapy unless specifically permitted by FDA in the interest of patient safety What are the reasons for clinical hold? -Exposure of unreasonable/significant risk/injury to subjects -Unqualified investigators (lack of scientific training/experience) -Investigator brochure is misleading, erroneous, or incomplete -IND does not contain sufficient information to assess risk to subjects of proposed studies Phase 1 Clinical Trials -Usually 20-80 subjects -Meant to assess initial safety and efficacy -Usually single center sites Phase 2 Clinical Trials -Usually no more than several hundred subjects -Multi-centered sites Phase 3 Clinical Trials -Confirmation of short-term efficacy and establish long term efficacy -Establish benefit-risk relationship -Provide adequate basis for labeling -Several hundred to several thousand subjects Phase 4 Clinical Trials -Post-marketing -Continue assessing overall therapeutic value -Size depends on design When was the Food, Drug, and Cosmetic Act established and why? 1938; to establish the FDA's jurisdiction over cosmetic and medical devices in the US What year did they amend the Federal Food Drug and Cosmetic act specifically for medical devices? 1976 21 CFR Part 812 Investigational Device Exemption 21 CFR Part 814 Premarket approval of medical devices Medical device Device is NOT dependent on chemical action or being metabolized and; -also must be recognized in official national formulary or US pharmacopoeia -intended for use in the diagnosis, treatment, mitigation or prevention of disease in man or other animals What are the clinical development stages for devices? 1.) Pilot study 2.) Pivotal study 3.) Post-market studies Compared to drugs and biologics, which typically have 1000s of subjects, device studies usually have 100s of subjects Class I (device) Lowest risk --General controls are sufficient to provider reasonable assurance of the safety and effectiveness Ex. powered wheelchairs, infusion pumps, and surgical drapes Class II (device) Moderate risk, usually requires a 510k (pre-market submission made to FDA) --General controls are insufficient to assure safety and effectiveness --Special controls include: special labeling requirements, mandatory performance standards, post-market surveillance Ex. powered wheelchairs, infusion pumps, and surgical drapes Class III (device) Highest risk, usually requires a 510k (pre-market submission made to FDA) -Usually those that support or sustain human life -Important for preventing impairment of human health -Present a potential risk of illness or injury Ex. implant, used in supporting or sustaining human life Pre-Market Approval (PMA) Required process of scientific review (usually Class III) to ensure reasonable safety and effectiveness of device *Must be FDA "approved" or NOT cleared before marketing per 21 CFR Part 814 Pilot studies (device) -Exploratory -Includes small numbers of subjects Pivotal studies (device) -Determine safety and effectiveness -Include most of overall subject numbers Post-market studies -Design improvement -Expansion of safety and effectiveness data -Development of new uses What are the abbreviated requirements for device studies? (21 CFR Part 812.2[b]) Abbreviated requirements: -Label device -Ensure investigators maintain records and make reports -Obtain IRB approval: significant risk (SR) vs non-significant risk (NSR) -Informed consent -Monitoring of studies -Refrain from promotion Exemption for investigation of a device: Abbreviated Requirements (21 CFR Part 812.2[c]) Categories of investigations considered to have approved IDE applications, unless FDA has notified sponsor otherwise -Those in use in accordance with its labeling & in commercial distribution before 5/28/1976 -A diagnostic device if the testing is: --noninvasive --does not require invasive sampling of significant risk --does not introduce energy into subjects, and, --is not used as a diagnostic procedure without confirmation by another medically established diagnostic product/procedure -Device undergoing consumer preference testing modification testing, or combo of 2/more devices in commercial distribution -Device solely for veterinary use or lab animal research Who designates a device study as significant risk (SR) or non-significant risk (NSR)? The Sponsor makes the initial determination of SR or NSR and then the IRB evaluates the study. Sometimes the IRB may defer to the FDA to make the initial determination Minimal risk The likelihood of harm is no greater than that encountered in daily life or during routine PE IDE (Investigational Device Exemption) An approved IDE permits device to be shipped lawfully 21 CFR Part 312 vs 21 CFR Part 812 21 CFR Part 312 = FDA Form 1572, Serious Adverse Event 21 CFR Part 812 = Investigational agreement, Unanticipated Adverse Device Effects How many days do you have to report a deviation from an investigational device plan to Sponsor and IRB, and why? Five days. Deviations are to protect human life or physical well-being How many days do you have to report an unanticipated adverse device effect? As soon as possible, but no later than 10 days after Investigator first learns of the event What must a Sponsor do if they determine that the invesetigational product presents significant and unreasonable risk to Subjects? 1.) Immediately discontinue all studies that present risk 2.) Report FDA and IRB 3.) Assure return and accounting for all investigational products/devices Sponsor responsiblities 1.) Maintain an effective IND or IDE 2.) Ensure studies are conducted according to the general investigative plan and protocols in IND/IDE 3.) Promptly report adverse events 4.) Select qualified Investigators 5.) Provide information such as: investigative brochures 6.) Ensure proper monitoring (medical monitor, DSMB, on-site monitoring) 7.) Manufacture and label drug/device What must the Sponsor obtain from the Investigator prior to start of study? Signed Investigator Statement (Form FDA 1572) CVs Phase 1: Clinical protocol Phase 2/3: Protocol outline with approximate number of subjects to get treatment & number to be used as controls (sex, age, and condition) Financial Disclosure Equity interest in publicly traded company greater than $____ should be reported? $50,000 How long is the reporting period for equity interest and significant payments? Study period plus one year