INVESTIGATOR HELP:

The terms “investigational drug” or “investigational biologic” (also called “test articles”) mean a new drug (a substance taken by mouth, injection, or applied locally to prevent or treat a disorder) or new biologic (medical preparation made from living organisms and their products, as serums, vaccines, antioxidants) that are used in a clinical investigation. Clinical trials for investigational drugs or biologics are conducted for:

• A drug or biologic that has not been approved by the FDA;
• A commercially available drug to support a new indication or a change in advertising or labeling of a the product;
• A commercially available drug being administered via a new route or for use in a different part of the body;
• A commercially available drug being given at a dosage that may significantly increase the risk to the subject population; or
• A commercially available drug that is going to be used in a new patient population that may result in a significant increase in risk(s) to the patient population.

An Investigational New Drug Application (IND) is a request for authorization from the Food and Drug Administration (FDA) to administer an investigational drug or biological product to humans. Such authorization must be secured prior to interstate shipment and administration of any new drug or biological product that is not the subject of an approved New Drug Application or Biologics/Product License Application.

The following forms and informational material are provided for assistance in preparing and submitting an IND for a biological product. A copy of the 1572 form MUST be included with the IRB Application.

1. Investigational New Drug Application (Form FDA 1571) - Outlines the information required in an IND. All sections on form FDA 1571 must be addressed in the submission. Also, in signing the form, the sponsor agrees to certain important conditions that are summarized just above the section for the sponsor's signature.
2. Statement of Investigator (Form FDA 1572) - When this form is completed by each investigator, the original signed copy must be given to the IND sponsor.

Emergency Use of Investigational Drugs or Biologics without prior IRB approval may not be considered research:

Federal regulations do not permit research activities to be started, even in an emergency, without prior IRB review and approval. When emergency medical care is initiated without prior IRB review and approval, the patient may not be considered a research subject. Such emergency care may not be claimed as research, nor may any data regarding such care be included in any report of research activity. Nothing in this guidance is intended to limit the authority of a physician to provide emergency medical care for patients who need such care. Rather, the use of information collected about that treatment for research purposes is prohibited.

Emergency Use of Investigational Agents Requires Compliance with FDA Requirements:

A. The physician must provide a letter to the IRB justifying the need for emergency use. According to the FDA, each of the following conditions must be met to justify emergency use:

1. The patient is in a life-threatening condition that needs immediate treatment;
2. No generally acceptable alternative for treating the patient is available; and
3. Because of the immediate need to use the investigational agent, there is no time to use existing procedures to get FDA approval for the use.

B. The FDA expects the physician to follow as many subject protection procedures as possible. These include:

1. Obtaining an independent assessment by an uninvolved physician;
2. Obtaining informed consent from the patient or a legal representative;
3. Notifying the Assistant Director, Ethics and Human Research Protection Program, who will notify appropriate institutional officials, if any; and
4. Obtaining authorization from the IND or IDE holder, if an approved IND or IDE exists.

C. According to the FDA, after an unapproved investigational agent is used in an emergency, the physician should:

1. Report to the IRB within 5 days and otherwise comply with provisions of the IRB regulations;
2. Evaluate the likelihood of a similar need for the investigational agent occurring again, and if future use is likely, immediately initiate efforts to obtain IRB approval and an approved IND or IDE for the agent’s subsequent use; and
3. If an IND or IDE for the use does exist, notify the sponsor of the emergency use, or if an IND or IDE does not exist, notify FDA of the emergency use and provide the FDA with a written summary on the conditions constituting the emergency, subject protection measures, and results.

Advertising for Clinical Studies involving investigational agents:

Advertisements for recruitment into investigational drug, biologic or device studies should not use such terms as "new drug", "new medication" or "new device." The test article must be described as investigational. Phrases such as "receive a new drug, treatment or device" imply that all or some subjects will be given newly approved products of proven safety, efficacy and/or benefit. Describing the investigational agent as "new" is considered to be misleading. When the research involves investigational drugs, biologics and/or devices, no claims should be made, either explicitly or implicitly, that the test article is safe or effective for the purposes under investigation, or that the test article is in any way equivalent or superior to any other drug, biologic or device. Such representation would not only be misleading to the subjects but would also be a violation of the Food and Drug Administration regulations concerning the promotion of investigational drugs.

IRB POLICIES AND PROCEDURES:

IRB Policy 7.1 - Storage, Handling, and Dispensing of Investigational Drugs, Agents, and/or Biologics

It is the policy of the DOH IRB that all investigational drugs, agents and/or biologics used in human subjects research be stored, handled, and dispensed in accordance with governing regulations and Institutional policy.

IRB Policy 7.2 - Investigational Devices

It is the policy of the DOH IRB that all investigational device use be reviewed and approved by the IRB in accordance with applicable laws and regulations.

IRB Policy 7.3 - Investigational Drugs, Agents, and Biologics

It is the policy of the DOH IRB that the use of investigational drugs, agents, and/or biologics be reviewed and approved for use in accordance with the Federal regulations.

IRB Policy 7.4 - Humanitarian Use Devices

It is the policy of the DOH IRB to review and approve the use of all Humanitarian Use Devices.

IRB Policy 7.5 - Emergency Use of FDA Regulated Products

It is the policy of the DOH IRB to recognize the provisions found in the Food and Drug Administration (FDA) regulations for the emergency use of investigational drugs, biologics, agents, or devices.

IRB Policy 4.9 - Reporting of Adverse Events, Serious Adverse Events and Unanticipated Problems

It is the policy of the DOH IRB to require reporting of adverse events, serious adverse events, and unanticipated problems that involve exposing research study participants to risk(s).

FEDERAL REGULATIONS/GUIDANCE:
OHRP IRB Guidebook
Chapter II: Regulations and Policies
Section B: EXPANDED AVAILABILITY OF INVESTIGATIONAL DRUGS

Treatment Investigational New Drug Exemption (Treatment INDs). The use of investigational drugs is usually limited to subjects enrolled in clinical studies covered by INDs. In 1987, the FDA established new procedures under which promising investigational new drugs may be made available to patients with life-threatening or other serious diseases for which no satisfactory alternative drug or other therapies exist. The purpose of the Treatment IND exemption is to facilitate the availability of promising new drugs to desperately ill patients as early in the drug development process as possible (before marketing begins) and to obtain additional data on the drug's safety and effectiveness. A Treatment IND is a treatment protocol that is added to an existing investigational new drug application (IND). It allows physicians to treat qualifying patients according to the protocol.

FDA permits Treatment INDs only for drugs that show some promise of therapeutic benefit. Two standards exist: For serious diseases, applications for Treatment INDs must show sufficient evidence of safety and effectiveness to support the use. Ordinarily, this standard means that a drug may be made available for treatment use either during Phase 3 investigations or after all clinical trials have been completed. For immediately life-threatening diseases, the evidence, taken as a whole, must show (i.e., there must be sufficient data reasonably to conclude) that the drug may be effective for its intended use in its intended patient population and would not expose the patients to whom the drug is to be administered to an unreasonable and significant additional risk of illness or injury. Under this standard, investigational drugs for treating immediately life-threatening diseases may be made available for treatment use earlier than Phase 3, but ordinarily not earlier than Phase 2 [21 CFR 312.34(a), 312.34(b)(2), and 312.34(b)(3)].

Treatment INDs must be reviewed by an IRB prior to their submission and must comply with the regulations governing informed consent (21 CFR Part 50) and IRBs (21 CFR Part 56) [21 CFR 312.34(c)]. The FDA will, however, consider waiving local IRB review for Treatment INDs, if waiver is in the best interests of the subjects and adequate alternative mechanisms for human subject protection are provided (e.g., to avoid duplication when a national review body has already reviewed the Treatment IND). The effect of the FDA waiver is to give permission to the local IRB to forego review; local IRBs may, as a matter of institutional policy, choose to review protocols for which an FDA waiver has been obtained by the sponsor or sponsor-investigator. Note also that if both the FDA and DHHS have jurisdiction over the Treatment IND activities, local IRB review will be required despite the FDA waiver. DHHS regulations apply if: (1) an MPA-holding institution that has agreed to review the research according to DHHS regulations is involved in the research; or (2) the research is supported by a DHHS department or agency [45 CFR 46.101, 45 CFR 46.103].

The sponsor and investigators must also comply with all applicable provisions of 21 CFR Part 312, including distribution of the drug through qualified experts, maintenance of adequate manufacturing facilities, and submission of IND safety reports.

A description of Treatment INDs and the requirements for receiving approval for treatment use is contained in the FDA's Clinical Investigator Information Sheet titled "Treatment Use of Investigational Drugs" (May 1989).

Charging for Treatment Use of Investigational Drugs. Ordinarily, sponsors or investigators may not charge for investigational drugs involved in clinical trials. FDA considers the cost of distributing drugs for investigational purposes to be part of the normal cost of doing business (unless the sponsor can show that charging subjects for the cost of the drug is necessary to enable the sponsor to undertake the clinical trial) [21 CFR 312.7(d)(1)]. Treatment use, however, is not part of a clinical trial and is therefore not considered to be a normal cost of doing business. Rather, the Treatment IND was created to encourage drug manufacturers to make potentially lifesaving drugs available before they receive FDA approval. Before charging for investigational drugs, the sponsor must notify FDA in writing in an information amendment submitted under §312.31. FDA may withdraw authorization to charge for treatment use drugs if it finds that the requirements of §312.7 are no longer being met [21 CFR 312.7(d)(4)].

Commencing Treatment Use. Treatment use may begin 30 days after FDA receives the application unless the request is denied by FDA [312.35(a)]. The required contents of a treatment protocol are provided in 21 CFR 312.35. Once approved for treatment use, the investigational drug may be prescribed by physicians who have been specially designated in the application. The physicians must agree to follow the treatment protocol, keep clinical records, and report adverse drug reactions to the FDA.

The Role of the IRB. The primary responsibility of the IRB in reviewing a Treatment IND is the same as in reviewing any proposed investigation involving human subjects: to determine whether the proposed use exposes the subjects to unreasonable or unnecessary risk, to review the informed consent forms and process, and to monitor the progress of the Treatment IND.

Informed consent is especially important in treatment use situations because the subjects are desperately ill and particularly vulnerable. They will be receiving medications, which have not been proven either safe or effective, in a clinical setting. Both the setting and their desperation may work against their ability to make an informed assessment of the risk involved. IRBs must ensure that potential subjects are fully aware of the risks involved in participation.

IRBs should also pay particular attention to Treatment INDs in which the subjects will be charged for the cost of the drugs. The question here is one of equitable selection and the involvement in research of vulnerable populations, particularly economically disadvantaged persons [21 CFR 56.111(a)(3)]. If subjects will be charged for use of the test article, economically disadvantaged persons will likely be excluded from participation. The stated purpose of the Treatment IND exemption is to facilitate the availability of promising new drugs to desperately ill patients while obtaining additional data on the drug's safety and effectiveness. Charging for participation may preclude economically disadvantaged persons as a class from receiving access to test articles. IRBs will need to balance this interest against the possibility that unless the sponsor can charge for the drug, it will not be available for treatment use until it receives full FDA approval [See also Guidebook Chapter 3, Section C, "Selection of Subjects," and Chapter 3, Section G, "Incentives for Participation."]

Both the research and ethics communities have expressed concern about the effect of the Treatment IND on the ability of investigators to attract subjects to clinical trials for Phase 3 testing. As one scientist put it, "Why would patients who are sophisticated, demanding, and willing to participate in experiments take a chance on receiving a placebo when they want the active compound?" IRBs should be concerned with the effect that the availability of an investigational drug product outside of a clinical trial would have on the ability of the investigator to recruit study subjects. As already mentioned, the cost of the drugs that sponsors can pass on to subjects under the Treatment IND, but not under a regular IND, will likely have an effect on subject recruitment, particularly since third-party payers usually will not reimburse the cost of investigational drugs. As mentioned above, this disparity raises ethical concerns about the equitable selection of subjects.

In response to these concerns, the FDA has recently revised the "clinical hold" provisions of the Treatment IND regulations to allow FDA to place such investigations on clinical hold if it finds that there is reasonable evidence that the investigation is "impeding enrollment in, or otherwise interfering with the conduct or completion of a study that is designed to be an adequate and well-controlled investigation of the same or another investigational drug" [Federal Register 57 (April 15, 1992): 13249, adding paragraph b(4)(i)-(vii) to 21 CFR 312.42]. Also addressing these concerns, the revised regulations allow the FDA to place a Treatment IND on clinical hold if insufficient quantities of the investigational drug exist adequately to conduct both the controlled trial and the Treatment IND, if one or more "adequate and well-controlled investigations" strongly suggest lack of effectiveness, and if another drug (either under investigation or approved) for the same indication and available to the same patient population has demonstrated a better potential risk/benefit balance [21 CFR 312.42(b(4)(iii-v)].

For Additional Information. The FDA's Clinical Investigator Information Sheets provide further useful information, and also describe the differences between a "single patient use" situation (see description, below) and a Treatment IND, and between an "emergency use" situation and a Treatment IND. [See pp. 29-35.]

United States Federal Drug Administration
PART 312--INVESTIGATIONAL NEW DRUG APPLICATION
Subpart A--General Provisions
Sec. 312.2 Applicability:

(a) Applicability. Except as provided in this section, this part applies to all clinical investigations of products that are subject to section 505 of the Federal Food, Drug, and Cosmetic Act or to the licensing provisions of the Public Health Service Act (58 Stat. 632, as amended (42 U.S.C. 201 et seq.)).

(b) Exemptions. (1) The clinical investigation of a drug product that is lawfully marketed in the United States is exempt from the requirements of this part if all the following apply:

(i) The investigation is not intended to be reported to FDA as a well-controlled study in support of a new indication for use nor intended to be used to support any other significant change in the labeling for the drug;

(ii) If the drug that is undergoing investigation is lawfully marketed as a prescription drug product, the investigation is not intended to support a significant change in the advertising for the product;

(iii) The investigation does not involve a route of administration or dosage level or use in a patient population or other factor that significantly increases the risks (or decreases the acceptability of the risks) associated with the use of the drug product;

(iv) The investigation is conducted in compliance with the requirements for institutional review set forth in part 56 and with the requirements for informed consent set forth in part 50; and

(v) The investigation is conducted in compliance with the requirements of Sec. 312.7.

(2)(i) A clinical investigation involving an in vitro diagnostic biological product listed in paragraph (b)(2)(ii) of this section is exempt from the requirements of this part if (a) it is intended to be used in a diagnostic procedure that confirms the diagnosis made by another, medically established, diagnostic product or procedure and (b) it is shipped in compliance with Sec. 312.160.
(ii) In accordance with paragraph (b)(2)(i) of this section, the following products are exempt from the requirements of this part: (a) blood grouping serum; (b) reagent red blood cells; and (c) anti-human globulin.
(3) A drug intended solely for tests in vitro or in laboratory research animals is exempt from the requirements of this part if shipped in accordance with Sec. 312.160.
(4) FDA will not accept an application for an investigation that is exempt under the provisions of paragraph (b)(1) of this section.
(5) A clinical investigation involving use of a placebo is exempt from the requirements of this part if the investigation does not otherwise require submission of an IND.
(6) A clinical investigation involving an exception from informed consent under Sec. 50.24 of this chapter is not exempt from the requirements of this part.

(c) Bioavailability studies. The applicability of this part to in vivo bioavailability studies in humans is subject to the provisions of Sec. 320.31.

(d) Unlabeled indication. This part does not apply to the use in the practice of medicine for an unlabeled indication of a new drug product approved under part 314 or of a licensed biological product.

(e) Guidance. FDA may, on its own initiative, issue guidance on the applicability of this part to particular investigational uses of drugs. On request, FDA will advise on the applicability of this part to a planned clinical investigation.

United States Federal Drug Administration
PART 312--INVESTIGATIONAL NEW DRUG APPLICATION
Subpart B--Investigational New Drug Application (IND)
Sec. 312.22 General principles of the IND submission.

(a) FDA`s primary objectives in reviewing an IND are, in all phases of the investigation, to assure the safety and rights of subjects, and, in Phase 2 and 3, to help assure that the quality of the scientific evaluation of drugs is adequate to permit an evaluation of the drug`s effectiveness and safety. Therefore, although FDA`s review of Phase 1 submissions will focus on assessing the safety of Phase 1 investigations, FDA`s review of Phases 2 and 3 submissions will also include an assessment of the scientific quality of the clinical investigations and the likelihood that the investigations will yield data capable of meeting statutory standards for marketing approval.

(b) The amount of information on a particular drug that must be submitted in an IND to assure the accomplishment of the objectives described in paragraph (a) of this section depends upon such factors as
the novelty of the drug, the extent to which it has been studied previously, the known or suspected risks, and the developmental phase of the drug.

(c) The central focus of the initial IND submission should be on the general investigational plan and the protocols for specific human studies. Subsequent amendments to the IND that contain new or revised protocols should build logically on previous submissions and should be supported by additional information, including the results of animal toxicology studies or other human studies as appropriate. Annual reports to the IND should serve as the focus for reporting the status of studies being conducted under the IND and should update the general investigational plan for the coming year.

(d) The IND format set forth in Sec. 312.23 should be followed routinely by sponsors in the interest of fostering an efficient review of applications. Sponsors are expected to exercise considerable discretion, however, regarding the content of information submitted in each section, depending upon the kind of drug being studied and the nature of the available information. Section 312.23 outlines the information needed for a commercially sponsored IND for a new molecular entity. A sponsor-investigator who uses, as a research tool, an investigational new drug that is already subject to a manufacturer’s IND or marketing application should follow the same general format, but ordinarily may, if authorized by the manufacturer, refer to the manufacturer’s IND or marketing application in providing the technical information supporting the proposed clinical investigation. A sponsor-investigator who uses an investigational drug not subject to a manufacturer’s IND or marketing application is ordinarily required to submit all technical information supporting the IND, unless such information may be referenced from the scientific literature.

United States Federal Drug Administration
PART 312--INVESTIGATIONAL NEW DRUG APPLICATION
Subpart B--Investigational New Drug Application (IND)
Sec. 312.34 Treatment use of an investigational new drug.

(a) General. A drug that is not approved for marketing may be under clinical investigation for a serious or immediately life-threatening disease condition in patients for whom no comparable or satisfactory alternative drug or other therapy is available. During the clinical investigation of the drug, it may be appropriate to use the drug in the treatment of patients not in the clinical trials, in accordance with a treatment protocol or treatment IND. The purpose of this section is to facilitate the availability of promising new drugs to desperately ill patients as early in the drug development process as possible, before general marketing begins, and to obtain additional data on the drug's safety and effectiveness. In the case of a serious disease, a drug ordinarily may be made available for treatment use under this section during Phase 3 investigations or after all clinical trials have been completed; however, in appropriate circumstances, a drug may be made available for treatment use during Phase 2. In the case of an immediately life-threatening disease, a drug may be made available for treatment use under this section earlier than Phase 3, but ordinarily not earlier than Phase 2. For purposes of this section, the “treatment use'' of a drug includes the use of a drug for diagnostic purposes. If a protocol for an investigational drug meets the criteria of this section, the protocol is to be submitted as a treatment protocol under the provisions of this section.

(b) Criteria. (1) FDA shall permit an investigational drug to be used for a treatment use under a treatment protocol or treatment IND if:

(i) The drug is intended to treat a serious or immediately life-threatening disease;
(ii) There is no comparable or satisfactory alternative drug or other therapy available to treat that stage of the disease in the intended patient population;
(iii) The drug is under investigation in a controlled clinical trial under an IND in effect for the trial, or all clinical trials have been completed; and
(iv) The sponsor of the controlled clinical trial is actively pursuing marketing approval of the investigational drug with due diligence.

(2) Serious disease. For a drug intended to treat a serious disease, the Commissioner may deny a request for treatment use under a treatment protocol or treatment IND if there is insufficient evidence of safety and effectiveness to support such use.

(3) Immediately life-threatening disease.
(i) For a drug intended to treat an immediately life-threatening disease, the Commissioner may deny a request for treatment use of an investigational drug under a treatment protocol or treatment IND if the available scientific evidence, taken as a whole, fails to provide a reasonable basis for concluding that the drug:
(A) May be effective for its intended use in its intended patient population; or
(B) Would not expose the patients to whom the drug is to be administered to an unreasonable and significant additional risk of illness or injury.
(ii) For the purpose of this section, an ``immediately life-threatening'' disease means a stage of a disease in which there is a reasonable likelihood that death will occur within a matter of months or in which premature death is likely without early treatment.

(c) Safeguards. Treatment use of an investigational drug is conditioned on the sponsor and investigators complying with the safeguards of the IND process, including the regulations governing informed consent (21 CFR part 50) and institutional review boards (21 CFR part 56) and the applicable provisions of part 312, including distribution of the drug through qualified experts, maintenance of adequate manufacturing facilities, and submission of IND safety reports.

(d) Clinical hold. FDA may place on clinical hold a proposed or ongoing treatment protocol or treatment IND in accordance with Sec. 312.42.

United States Federal Drug Administration
PART 312--INVESTIGATIONAL NEW DRUG APPLICATION
Subpart B--Investigational New Drug Application (IND)
Sec. 312.35 Submissions for treatment use.

(a) Treatment protocol submitted by IND sponsor. Any sponsor of a clinical investigation of a drug who intends to sponsor a treatment use for the drug shall submit to FDA a treatment protocol under Sec. 312.34 if the sponsor believes the criteria of Sec. 312.34 are satisfied. If a protocol is not submitted under Sec. 312.34, but FDA believes that the protocol should have been submitted under this section, FDA may deem the protocol to be submitted under Sec. 312.34. A treatment use under a treatment protocol may begin 30 days after FDA receives the protocol or on earlier notification by FDA that the treatment use described in the protocol may begin.

(1) A treatment protocol is required to contain the following:
(i) The intended use of the drug.
(ii) An explanation of the rationale for use of the drug, including, as appropriate, either a list of what available regimens ordinarily should be tried before using the investigational drug or an explanation of why the use of the investigational drug is preferable to the use of available marketed treatments.
(iii) A brief description of the criteria for patient selection.
(iv) The method of administration of the drug and the dosages.
(v) A description of clinical procedures, laboratory tests, or other measures to monitor the effects of the drug and to minimize risk.

(2) A treatment protocol is to be supported by the following:
(i) Informational brochure for supplying to each treating physician.
(ii) The technical information that is relevant to safety and effectiveness of the drug for the intended treatment purpose. Information contained in the sponsor's IND may be incorporated by reference.
(iii) A commitment by the sponsor to assure compliance of all participating investigators with the informed consent requirements of 21 CFR part 50.

(3) A licensed practitioner who receives an investigational drug for treatment use under a treatment protocol is an ``investigator'' under the protocol and is responsible for meeting all applicable investigator responsibilities under this part and 21 CFR parts 50 and 56.

(b) Treatment IND submitted by licensed practitioner.

(1) If a licensed medical practitioner wants to obtain an investigational drug subject to a controlled clinical trial for a treatment use, the practitioner should first attempt to obtain the drug from the sponsor of the controlled trial under a treatment protocol. If the sponsor of the controlled clinical investigation of the drug will not establish a treatment protocol for the drug under paragraph
(a) of this section, the licensed medical practitioner may seek to obtain the drug from the sponsor and submit a treatment IND to FDA requesting authorization to use the investigational drug for treatment use. A treatment use under a treatment IND may begin 30 days after FDA receives the IND or on earlier notification by FDA that the treatment use under the IND may begin. A treatment IND is required to contain the following:
(i) A cover sheet (Form FDA 1571) meeting Sec. 312.23(g)(1).
(ii) Information (when not provided by the sponsor) on the drug's chemistry, manufacturing, and controls, and prior clinical and non-clinical experience with the drug submitted in accordance with Sec. 312.23. A sponsor of a clinical investigation subject to an IND who supplies an investigational drug to a licensed medical practitioner for purposes of a separate treatment clinical investigation shall be deemed to authorize the incorporation-by-reference of the technical information contained in the sponsor's IND into the medical practitioner's treatment IND.
(iii) A statement of the steps taken by the practitioner to obtain the drug under a treatment protocol from the drug sponsor.
(iv) A treatment protocol containing the same information listed in paragraph (a)(1) of this section.
(v) A statement of the practitioner's qualifications to use the investigational drug for the intended treatment use.
(vi) The practitioner's statement of familiarity with information on the drug's safety and effectiveness derived from previous clinical and non-clinical experience with the drug.
(vii) Agreement to report to FDA safety information in accordance with Sec. 312.32.
(2) A licensed practitioner who submits a treatment IND under this section is the sponsor-investigator for such IND and is responsible for meeting all applicable sponsor and investigator responsibilities under this part and 21 CFR parts 50 and 56.

United States Federal Drug Administration
PART 312--INVESTIGATIONAL NEW DRUG APPLICATION
Subpart B--Investigational New Drug Application (IND)
Sec. 312.36 Emergency use of an investigational new drug.

Need for an investigational drug may arise in an emergency situation that does not allow time for submission of an IND in accordance with Sec. 312.23 or Sec. 312.34. In such a case, FDA may authorize shipment of the drug for a specified use in advance of submission of an IND. A request for such authorization may be transmitted to FDA by telephone or other rapid communication means. For investigational biological drugs, the request should be directed to the Division of Biological Investigational New Drugs (HFB-230), Center for Biologics Evaluation and Research, 8800 Rockville Pike, Bethesda, MD 20892, 301-443-4864. For all other investigational drugs, the request for authorization should be directed to the Document Management and Reporting Branch (HFD-53), Center for Drug Evaluation and Research, 5600 Fishers Lane, Rockville, MD 20857, 301-443-4320. After normal working hours, eastern standard time, the request should be directed to the FDA Division of Emergency and Epidemiological Operations, 202-857-8400. Except in extraordinary circumstances, such authorization will be conditioned on the sponsor making an appropriate IND submission as soon as practicable after receiving the authorization.

United States Federal Drug Administration
PART 312--INVESTIGATIONAL NEW DRUG APPLICATION
Subpart C--Administrative Actions

Sec. 312.40 General requirements for use of an investigational new drug in a clinical investigation.

(a) An investigational new drug may be used in a clinical investigation if the following conditions are met:

(1) The sponsor of the investigation submits an IND for the drug to FDA; the IND is in effect under paragraph (b) of this section; and the sponsor complies with all applicable requirements in this part and parts 50 and 56 with respect to the conduct of the clinical investigations; and
(2) Each participating investigator conducts his or her investigation in compliance with the requirements of this part and parts 50 and 56.

(b) An IND goes into effect:

(1) Thirty days after FDA receives the IND, unless FDA notifies the sponsor that the investigations described in the IND are subject to a clinical hold under Sec. 312.42; or
(2) On earlier notification by FDA that the clinical investigations in the IND may begin. FDA will notify the sponsor in writing of the date it receives the IND.

(c) A sponsor may ship an investigational new drug to investigators named in the IND:

(1) Thirty days after FDA receives the IND; or
(2) On earlier FDA authorization to ship the drug.
(d) An investigator may not administer an investigational new drug to human subjects until the IND goes into effect under paragraph (b) of this section.