21 CFR 12 - Investigational New Drug Application

Collectively, the case report forms and supporting data, including signed consent forms and medical records, that are required to be retained by investigators

Case histories

T/F: The investigator is required to divulge subject names to authorized FDA officials

False; the FDA may only ask this if more detailed study of individual subject records is required, or they have reason to believe the records are inaccurate or do not represent actual case studies or results obtained

T/F: Unexpected adverse drug reactions that are already known from a previous occurrence must still be subject to expedited reporting until the reaction is listed in the investigator's brochure or applicable source document.

True

Contract Research Organization (CRO)

a person that assumes, as an independent contractor with the sponsor, one or more of the obligations of a sponsor

For emergency research under 50.24, the IRB will prove the sponsor with information concerning the public disclosures required and the sponsor should promptly submit to_________________ copies of the information that was disclosed.

the IND file and to Docket Number 95S-0158 The sponsor is responsible for monitoring these studies

Subject

a human who participation in an investigation, either as a recipient of the investigational new drug or as a control. A subject may be a healthy human or a patient with a disease.

Investigational New Drug (IND)

a new drug or biological drug that is used in a clinical investigation or a biological product that is used in vitro for diagnostic purposes

Per 21 CFR 312.6, the labeling of an investigational new drug should:

-include the label "Caution: New Drug--Limited by Federal (or United States) law to investigational use" on the immediate package -not bear any statement that is false or misleading, or represent that it is safe or effective *FDA center director may grant exceptions for lots/batches that will be included in the Strategic National Stockpile*

Each submission relating to an IND is required to be numbered chronologically in sequence, starting with:

000

If investigations covered by an IND remain on clinical hold for ______ year(s) or more, the IND may be placed on inactive status by the FDA

1

A sponsor should submit background information on the sponsor's plan for phase 3, summaries of Phase 1/2 investigations, and specific protocols for Phase 3 clinical studies, plans for pediatric studies, and a timeline for protocol finalization through data analysis at least _____ month(s) in advance of an "end of Phase 2 meeting"

1 month

An investigator must promptly update any financial disclosures during the course of the investigation and for ___________.

1 year following completion of the study

To charge for expanded access to investigational drug treatment use under Subpart I, a sponsor must provide reasonable assurance that charging will not interfere with developing the drug for marketing approval. For expanded access under 312.320 Subpart I (treatment IND or treatment protocol/widespread use), such assurance must include:

1) Evidence of sufficient enrollment in ongoing clinical trials 2) Evidence of adequate progress in drug development for marketing approval 3) The drug development milestones the sponsor intends to meet in the next year (from the investigational plan) 4) Supporting documentation to show that the calculation for cost recovery is consistent with requirements of 312.8(d) (direct costs) and approved by an independent certified public accountant

The IND Cover sheet / FDA Form 1571 should include the following information:

1) Name and contact info of sponsor, date of application, and name of the drug 2) Phase of study 3) Commitment to not begin until IND is in effect 4) Commitment that an IRB complying with Part 56 will provide initial and continuing review, and investigator will report all proposed changes to IRB 5) Commit to adhered to all regulatory requirements 6) Monitor name and title 7) Name and title of those reviewing drug safety 8) CRO name/address, identification of clinical study, listing of obligations transferred / general statement of full transfer 9) Signature of sponsor or representative (if person signing does not reside or have a place of business in the US, must be signed by attorney, agent, authorized official, person who resides or maintains a place of business in US and include name/address in IND)

The introductory statement and general investigational plan of an IND should include:

1) Name of drug, active ingredients, pharmacological class, structural formula, doses to be used, route of administration, and broad objectives and planned duration of study 2) Previous human experience, if marketed or withdrawn in other countries 3) Overall investigational plan for the next year (rationale, indications to be studied, general approach to evaluating drug, kinds/phases of clinical trials to be conducted in first year, number of patients estimated to receive drug, any risks of particular severity anticipated from animal/human trials)

The investigational brochure provided to investigators and included in an IND, if applicable, should include:

1) description of the drug substance, formulation, and structural formula 2) pharmacological and toxicological effects known in animals/humans 3) pharmacokinetics and biological disparity of the drug in animals/humans 4) safety and effectiveness data from prior clinical trials 5) possible risks and side effects anticipated, special monitoring that may be required

In general, investigators are responsible for:

1) investigation is conducted according to signed investigator agreement, investigational plan, and FDA regulations 2) protecting the rights, safety, and welfare of subjects under his/her care 3) control of drugs under investigation 4) obtain the informed consent of each subject

The clinical investigation of a drug or biological product may be exempt from the requirements of Part 312 if:

1) investigation of a drug product lawfully marketed in U.S. (if compliant with parts 50, 56, 312.7; not intended to support a new use or labeling change; not intended to support change in advertising; does not involve dose/administration increasing the risk associated) 2) in vitro diagnostic biological product (used in a diagnostic procedure that confirms the diagnosis of another established procedure; is shipped in compliance with 312.160) OR is using blood grouping serum, reagent red blood cells, or anti-human globulin 3) intended solely for test in vitro or in lab animals 4) FDA will not otherwise accept an app because it is exempt under 312.2(b)(1) 5) involves use of placebo and investigation does not otherwise require submission of an IND 6) any studies involving an exemption from informed consent are NOT exempt

The protocol included with and IND app must contain the following:

1) objectives and purpose of study 2) name, address, and statement of qualifications of each investigator; the name of each sub investigator, name and address of research facilities to be used; name and address of each IRB 3) patient inclusion and exclusion criteria; number of patients to be studied 4) study design, controls, blinding, and methods used to minimize bias 5) method for determining doses, planned maximum dosage, duration of patient exposure to drug 6) observations and measurements to be made to complete objectives of study 7) clinical procedures, lab tests, other measures to monitor drug effects and minimize risk

Under 312.8, in order to charge for a drug in a clinical trial a sponsor must:

1) provide evidence of clinical benefit or significant advantage over other products 2) demonstrate trial is necessary to establish the drug is effective or safe/support a change in labeling or use 3) demonstrate the trial could not be conducted otherwise due to extraordinary costs (manufacturing complexity, quantity, etc)

The sponsor is responsible for keeping records for:

1) receipt, shipment, disposition of drug--incl. investigator name, date, purity, and batch of each shipment 2) financial interest records of investigators and payments maid to investigators by sponsor 3) reserve samples of test article and reference standards

In general, sponsors are responsible for:

1) selecting qualified investigators 2) providing all necessary information to investigators (investigator's brochure) 3) ensuring investigator compliance with IND/protocol 4) ensuring proper monitoring 5) maintaining an effective IND 6) ensuring FDA and investigators are promptly informed of significant new adverse effects and risks

Before permitting an investigator to begin participation in an investigation, the sponsor shall obtain the following:

1) signed investigator statement (Form FDA-1572) 2) investigator CV 3) clinical protocol 4) financial disclosure information (3454 / 3455) as required by part 54

The FDA may grant a waiver for any part of 21 CFR 312 if it would not post a significant and unreasonable risk to human subjects in the investigation and ONE of the following is met:

1) the sponsor's compliance is unnecessary for the agency to evaluate the application, or compliance cannot be achieved 2) the sponsor's proposed alternative satisfies the requirement 3) the applicant's submission otherwise justifies a waiver

A sponsor may request the FDA to waive applicable requirements under part 312 either in an IND or via information amendment (or telephone/rapid communication in an emergency), and the request must include at least ONE of the following:

1) why the sponsor's compliance with the requirement is unnecessary or cannot be achieved 2) alternative submission or course of action that satisfies the purpose of the requirement 3) other information justifying a waiver

Regarding IND safety reports, if the FDA responds with a request for additional information, the sponsor must submit the information ASAP but no later than _____ calendar days after receiving the request.

15

The sponsor must notify the FDA and all participating investigators of potential serious risks via an IND safety report ASAP - But no later than how many days after the sponsor makes the determination?

15

How long must sponsors and investigators retain their records related to a clinical investigation?

2 years after a marketing application is approved or until 2 years after shipment and delivery of the drug for investigational use is discontinued and the FDA has been notified

If no subjects are enrolled under an IND for ____ year(s) or more, or all investigations under an IND remain on clinical hold for ____ year(s) or more, the FDA may place all investigations covered under an IND on Inactive Status.

2; 1 sponsor may also request inactive status; reports to FDA are not required under this status; investigations may resume 30 days after a protocol amendment is received by FDA if placed on inactive status by sponsor choice

Information amendments should be submitted as necessary but, to the extent feasible, not more than every ______ days.

30

The sponsor should notify the FDA via protocol amendment within ______ days of adding a new investigator to a previously submitted protocol.

30

The Division Director responsible for review of the IND will notify the sponsor of a clinical hold by telephone or other rapid communication, and will provide the sponsor with a written explanation of the basis ASAP but no later than _____ days after imposition of the hold.

30 Investigation may only resume once notified by the division director (by telephone or otherwise) that the sponsor has corrected the deficiencies or otherwise satisfied the agency

Protocol amendments to add a new investigator or to provide additional information about investigators may be grouped and submitted at ______ day intervals.

30 if several submissions of new protocols or protocol changes are anticipated in a short period of time, those are also encouraged to be included in a single submission

When may a sponsor ship an investigational new drug to investigators named in an IND?

30 days after the FDA receives IND or on earlier notification

If the FDA intends to terminate an IND, they will notify the sponsor and invite a response within ____ days. If the sponsor responds and the FDA deems the response inadequate, the FDA will notify the sponsor and the sponsor may request a regulatory hearing under part 16 within _____ days of receipt of the FDA's notification of nonacceptance.

30; 10

An IND may be terminated by the FDA if it has remained in inactive status for ___ years or more.

5

Annual IND reports from the sponsor must be submitted within ______ days of the anniversary date that the IND went into effect and should serve as the focus for reporting the status of conducted studies and should update the investigational plan for the coming year

60

The sponsor must notify the FDA of any unexpected fatal or life-threatening suspected adverse reactions ASAP but no later than ____ calendar days after the sponsor's initial receipt of the information.

7

Unexpected Adverse Drug Reaction

An adverse reaction, the nature or severity of which is not consistent with the applicable product information / source document (typically investigator's brochure in pre-market) If an IB was not required, the general investigational plan or information elsewhere in the IND may serve as a reference

Suspected Adverse Reaction

Any adverse event for which there is a reasonable possibility that the drug caused the adverse event

Serious Adverse Event

Any event that: (1) results in death; (2) is life-threatening; (3) results in inpatient hospitalization or prolongation of existing hospitalization; (4) results in a persistent or significant disability/incapacity (5) results in a congenital anomaly/birth defect; or (6) based upon appropriate medical judgment, may jeopardize the subject's health and may require medical or surgical intervention to prevent one of the other outcomes listed above.

An order issued by FDA to the sponsor to delay a proposed clinical investigation or to suspend an ongoing investigation

Clinical hold (may be applied to one or more investigations under an IND, subject may not be given drug, no new subject recruited and placed on drug, patients on-study must be taken off therapy unless permitted by FDA for safety reasons)

If administrative or procedural issues arise with the FDA, the sponsor should first attempt to resolve the issue with the CDER/CBER ____________________ assigned to the IND. If unresolved, the issue is then raised to the designated _____________, whose function is to investigate what has happened and facilitate a timely and equitable resolution.

Consumer safety officer; ombudsman

For studied involving ________________, shipment, delivery, receipt and drug disposition records from the sponsor and/or investigator must be made available for inspecting/copying at the request of the DEA, and the sponsor should ensure the drugs are stored in a securely locked, substantially constructed cabinet to which access is limited.

Controlled substances (the investigator should also take adequate precautions to ensure the drugs are stored as described)

Life-threatening adverse event/suspected adverse reaction

Event occurrence places the subject at immediate risk of death

The sponsor must submit an IND safety report in a narrative format or on FDA form _______ to the Center for Drug Evaluation and Research or Center for Biologics Evaluation and Research, as appropriate. Reports of overall findings or pooled analyses may be submitted in narrative format only.

FDA Form 3500A

If a sponsor withdraws an IND due to a safety reason, the ___________, _____________and _______________ must be notified, all clinical investigations conducted under the IND ended, and all stocks of the drug returned to the sponsor or otherwise disposed of at the request of the sponsor.

FDA, all clinical investigators, all reviewing IRBs (for non-safety reasons, the sponsor must only notify the FDA and all investigators; investigators must notify their IRBs)

For end of phase 2 and pre-NDA meetings, the ________________is responsible for documenting meeting minutes and these along with other written material provided to the __________________ will serve as the permanent record of any agreements reached.

FDA; sponsor

T/F: A sponsor is not required to submit IND safety reports for suspected adverse reactions that are associated with the use of a marketed/approved drug that are observed in the clinical study at domestic or foreign study sites.

False

T/F: An IND will typically not be subject to a clinical hold by the FDA if the study is for an investigational drug intended to treat a life-threatening disease that affects both genders, and men or women of reproductive potential are excluded from the trial due to reproductive and developmental toxicity risks.

False This is a potential reason for a hold, provided the study is: not pertinent to only one gender (drug excretion in semen), another study including the other gender is ongoing/completed, or is conducted only in subjects who do not suffer from the disease or condition for which the drug is being studied)

T/F: For focused FDA regulatory research conducted under 312.86, the Commissioner and other agency officials will monitor the trial progress and ensure all safeguards within parts 50, 56, 312, 314, and 600 are incorporated, with the exception that animal studies are not required prior to initial human testing.

False animal testing is still required

21 CFR 312.23

IND Content and Format (for commercially sponsored new molecular entity) 1) Cover sheet (FDA Form 1571) 2) Table of contents 3) Introductory statement and general investigational plan 4) Investigator's brochure 5) Protocols for each planned study 6) Chemistry, manufacturing, and control information 7) Pharmacology and drug dispositions 8) Previous human experience with drug 9) Additional information (drug abuse potential, radiation dose, pediatric studies planned, etc) 10) Relevant information requested by FDA

21 CFR 312

Investigational New Drug Application 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- Miscellaneous Subpart G- Drugs for Investigational Use in Laboratory Research Animals or In Vitro Tests Subpart I- Expanded Access to Investigational Drugs for Treatment Use

IND

Investigational New Drug Application; synonymous with "Notice of Claimed Investigational Exemption for a New Drug"

Who is required to maintain adequate records of the disposition of the investigational drug, including date, quantity, and use by subjects?

Investigator

Who is responsible for ensuring that an IRB that meets the requirements of part 56 is responsible for initial and continuing review, and ensuring all changes in research activity and unanticipated problems involving risk to human subjects is reported to the IRB?

Investigator

Per 312.21, the initial introduction of an investigational new drug into humans that is closely monitored and is designed to determine the pharmacokinetics and pharmacologic actions of the drug in humans, side effects with increasing doses, and early evidence of efficacy; usually 20-80 subjects

Phase 1

Meetings with FDA officials are most common at the end of ________ studies and before submission of a marketing application. These meetings are often useful to help determine the safety of proceeding to later studies, and discuss plans to assess pediatric safety and effectiveness

Phase 2

Per 312.21, the well-controlled, closely monitored clinical studies primarilly conducted to evaluate the effectiveness of an investigational drug for a particular indication/condition; may determine short term side effects/risks associated with drug; typically several hundred subjects

Phase 2

Per 312.21, the expanded controlled and uncontrolled trials performed after preliminary evidence suggesting effectiveness of the drug has been obtained and are intended to gather additional info about safety and effectiveness to evaluate the overall benefit-risk relationship of the drug and provide an adequate basis for labeling; typically several hundred to several thousand subjects

Phase 3

Who is responsible for ensuring the investigator's brochure is up to date?

Sponsor

Whenever a sponsor intends to conduct a study that is not covered by a protocol in the original IND, the sponsor should submit a protocol amendment to the FDA. The study is permitted to begin once:

The protocol has been submitted to the FDA AND the protocol has been approved by an IRB

T/F: A sponsor does not need to satisfy the requirements of 312.8 in order to charge for an approved drug obtained from another entity not affiliated with the sponsor for use as part of its clinical trial evaluation (either new use of approved drug, or as an active control)

True

T/F: A sponsor may transfer some or all responsibilities to a CRO provided which responsibilities, or all, are transferred specified in writing

True

T/F: A sponsor-investigator who, as a research tool, uses an investigational drug in their protocol that is already subject to a manufacturer's IND or marketing application may, if authorized by the manufacturer, refer to the manufacturer's IND in providing the technical information supporting the proposed clinical investigation.

True

T/F: An investigational new drug for which an IND is in effect in accordance with Part 312 is exempt from the pre marketing approval requirements that are otherwise applicable and may be shipped lawfully for the purpose of conducting clinical investigations of that drug.

True

T/F: Modifications of the experimental design of Phase 1 studies that do not affect critical safety assessments are required to be reported to the FDA only in the annual report.

True

T/F: Phase 2 and 3 study protocols should describe all aspects of the study in detail and should be designed to include alternatives or contingencies for any anticipated deviations

True

T/F: Study endpoints such as all-cause mortality are typically not subject to IND reporting to FDA, but if there is a serious and unexpected adverse event that occurs for which there is evidence of a causal relationship between the drug and event, it must be reported even if it is a component of the study endpoint.

True

T/F: Unexpected suspected adverse drug reactions are still said to have occurred if the reaction was listed in the investigator's brochure as occurring with a class of drugs or as anticipated from the pharmacological properties of the drug, but are not mentioned as occurring specifically with the drug being investigated

True

T/F: Regarding investigational drug exports to another country for stockpile purposes in anticipation of a national emergency, exportation may not proceed until the FDA has authorized exportation

True Exportation MAY proceed without authorization for sudden and immediate national emergencies

T/F: An investigator must report any serious adverse event, whether or not considered drug related and including those listed in the protocol or IB, to the sponsor and must include an assessment of whether there is a reasonable probability that the drug caused the event

True Study endpoints that are serious adverse events must be reported to the sponsor per protocol, unless there is evidence suggesting a causal relationship between the drug and event in which case it must immediately be reported to the sponsor. Non-serious adverse events are reported to sponsor per protocol.

T/F: A protocol change intended to eliminate an apparent immediate hazard to subjects may be implemented immediately provided FDA is subsequently notified and the IRB is notified in accordance with 56.104(c).

True The IRB should be notified within 5 working days

T/F: The FDA may immediately terminate an IND if it concludes an investigation presents an immediate and substantial danger to the health of individuals and will immediately notify the sponsor in writing.

True subject to reinstatement via additional submissions that eliminate such danger or regulatory hearing under part 16

T/F: A sponsor must submit a separate IND for any study involving an exception from informed consent, and may not begin that part of the investigation until a written determination from the FDA is received

True; FDA should provide a written determination 30 days after receiving or earlier, but must be received before proceeding

T/F: For investigational drugs, a sponsor or investigator may not promote that a drug is safe or effective, otherwise promote the drug, or commercially distribute or test market

True; the intent is to restrict promotional claims of safety/effectiveness and preclude commercialization of the drug

An investigational new drug is allowed for import into the United States if the drug is subject to an IND and any of the following are true, except: a) the the foreign authority exporting the device provides a certification of safety and signed copies of an investigational plan b) the consignee in the United States is a sponsor of the IND c) the consignee is a qualified investigator names in the IND d) the consignee is the domestic agent of a foreign sponsor, is responsible for control and distribution of the drug, and the IND identifies the consignee and the actions they will take with respect to the drug

a) the the foreign authority exporting the device provides a certification of safety and signed copies of an investigational plan

If the sponsor determines its investigational drug presents an unreasonable or significant risk to subjects, the sponsor must notify ________________ and discontinue the investigation ASAP, but no later than ______ working days after making the determination

all investigators, all reviewing IRBs, FDA; 5 also must ensure disposition of all outstanding stocks of drugs and furnish FDA with full report of its actions

Marketing application

application for a new drug submitted under section 505(b) of the act or a biologics license application for a biological product submitted under the Public Health Service Act

Which of the following is not an in vitro diagnostic biological product that may be exempt from the requirements of part 312? a) blood grouping serum b) prothrombin clotting factor c) reagent red blood cells d) anti-human globulin

b) prothrombin clotting factor

A drug product that is lawfully marketed in the U.S. is exempt from the requirements of part 312 if all of the following are true, except: a) the investigation is not intended to be reported to the FDA in support of a new indication for use nor a labeling change b) the investigation is intended only to support a significant change in the advertising of the drug c) the investigation does not involve a route of administration or dosage level or use in a patient population or other fact that significantly increases the risks associated with use d) the investigation is conducted in compliance with the requirements of part 56 and part 50 e) the investigation is conducted in compliance with 312.7

b) the investigation is intended only to support a significant change in the advertising of the drug must not be intended to support a change in advertising

Examples of changes requiring a protocol amendment from the sponsor to the FDA include all of the following except: a) increase in drug dosage or duration of exposure b) change in study design, such as adding a control group c) minor increase in the number of subjects d) addition/removal of test or procedure intended to monitor safety or reduce the risk of adverse events

c) minor increase in the number of subjects

A sponsor may only charge for the direct costs exclusively attributed to providing the drug for the investigational use for which FDA has authorized cost recovery. Which of the following is not a direct cost? a) costs per unit to manufacture the quantity of drug needed (labor, materials, etc.) b) drug storage, shipping, and handling c) research and development, administrative, and costs incurred to produce the drug for commercial sale d) costs to acquire the drug from another manufacturing source

c) research and development, administrative, and costs incurred to produce the drug for commercial sale *For expanded access use under 312.315 (intermediate size) and 312.320 (widespread), the sponsor may also recover the costs of monitor the expanded access IND, complying with reporting requirements, and other administrative costs directly associated

Which of the following is common to ALL conditions in which an investigational new drug is allowed for export from the United States? a) an IND must be in effect for the drug b) then drug may only be exported to countries in the European Union c) the drug must comply with the laws of the country to which it is being exported d) the person exporting must send a written certification to the Office of International Programs

c) the drug must comply with the laws of the country to which it is being exported

Which of the following is NOT a reason why the FDA may impose a clinical hold on a clinical investigation that is not designed to be adequate and well-controlled? a) the drug has been studied in one or more adequate and well-controlled studies that strongly suggest lack of effectiveness b) the drug has already received marketing approval for the same indication in the same patient population c) the sponsor of the study that is adequate and well-controlled is actively pursuing marketing approval of the investigational drug with due diligence d) the investigation is impeding enrollment in, or otherwise interfering with the conduct or completion of a study that is designed to be adequate and well-controlled

c) the sponsor of the study that is adequate and well-controlled is actively pursuing marketing approval of the investigational drug with due dilligence This goes back to the concept of a poorly designed study impeding the success of a well-designed study, which will ultimately affect the credibility of the data and reduce the likelihood of a treatment getting to market

A clinical investigation involving an in-vitro diagnostic biological product listed in 312.2(b) is exempt from the requirements of part 312 if: a) it is intended to be used in a diagnostic procedure that confirms the diagnosis made by another medically-established diagnostic product b) is shipped in compliance with 312.160 c) involves an exception from informed consent under part 50.24 d) both A and B e) all of the above

d) both A and B

Typical phase 4 studies may investigate:

different doses or schedules of administration, use in different patient populations or other stages of disease, or longer study duration

In the event of investigator noncompliance with the signed agreement, the general investigational plan, or FDA regulations, the sponsor shall either secure compliance or:

discontinue drug shipments to the investigator, end investigator's participation, request return or disposition of investigational drug, and notify the FDA

Per 21 CFR 312.8, which of the following regarding general requirements for charging for investigational drugs under an IND by a sponsor is true? a) sponsor must justify amount to be charged b) sponsor must obtain prior written authorization from FDA to charge c) a sponsor my charge for the length of the trial, unless a shorter period is specified by the FDA d) FDA may withdraw authorization to charge if it is interfering with drug development for marketing approval or specific criteria of 312.8(b) are no longer met e) all of the above

e) all of the above

As it pertains to IND safety reports, a sponsor must review safety information from and report which of the following if it suggests a significant risk in humans exposed?: a) pertinent findings from other clinical or epidemiological studies of the drug not conducted under an IND b) findings from new animal or in vitro studies of the drug not conducted by the sponsor c) safety reports from foreign regulatory authorities d) reports in the scientific literature as well as unpublished scientific papers e) all of the above

e) all of the above typically such findings will result in safety-related changes to the protocol, informed consent, and investigator's brochure

The central focus of the IND app should be the ____________________________

general investigational plan and protocols for specific human studies amendments should include new or revised protocols that build logically on submissions and supported by additional info (animal tox results/other clinical studies)

If a regulatory hearing is conducted and the Commissioner determines that an investigator has repeatedly or deliberately failed to comply with parts 50, 56, and 312, or has repeatedly or deliberately submitted false information to the sponsor or FDA, who is notified of the investigator's ineligibility to receive test article in all studies?

investigator, sponsors of any investigations in which the investigator has been named as a participant, and the reviewing IRBs the investigator also becomes ineligible to conduct any investigation used to support an application for a research or marketing application for FDA regulated products

Information amendments report essential information for the IND that is not within the scope of a protocol amendment, IND safety report, or annual report. Examples include:

new toxicology, chemistry or technical information; report on the discontinuation of a clinical investigation

The amount of information required by the FDA on a particular drug in an IND application will vary with:

novelty of drug, extent of previous studies, known or suspected risks, and developmental phase of the drug

Charging for an investigational drug under expanded access/treatment use is limited to:

number of patients authorized to receive the drug under the treatment use (if limited) and may continue for 1 year from the time of FDA authorization

Protocols for Phase 1 studies may be less detailed and more flexible than Phase 2/3 studies, and should be directed primarily at providing:

outline of investigation, estimate of number of subjects, description of safety exclusions, dosing plan; should specify in detail only those elements in study critical to SAFETY

For drugs intended to treat life-threatening or severely debilitating illnesses, _________ meetings and end of _____________ meetings may be held with FDA-reviewing officials to decide animal studies needed to initiate human testing and to ensure adequate study design to provide sufficient data on the drug's safety and effectiveness for later trials.

pre-IND and end of phase 1

Protocol amendments should be submitted for Phase 1 studies if the change affects ______________ and to Phase 2/3 studies if it affects _______________, _________________, or ______________.

safety of the subjects safety of the subjects; scope of the investigation; scientific quality of the study

T/F: In evaluating an IND, the FDA's primary focus is assessing __________ in Phase 1 investigations and the ____________________ in Phase 2/3 investigations and the likelihood that the investigations will yield data capable of meeting statutory standards for marketing approval.

safety; scientific quality

Sponsor must report any suspected adverse reaction that is both...

serious and unexpected (only if there is evidence to suggest a causal relationship between the drug and adverse event such as: 1) single occurrence of an uncomment event known to be strongly associated with drug exposure 2) one or more occurrences not commonly associated with drug exposure, but is otherwise uncommon in the population exposed 3) known consequences of the studied underlying conditions that occur more frequently in the drug treatment group than the control)