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PREPARATION AND MANAGEMENT OF TREATMENT INDS

This summary information is provided to assist with the step-wise decision-making, preparation and management of Treatment INDs.

Refer to 21 CFR 312.34 for details (excerpt in Attachment 1).

• Establish the appropriate time during investigational new drug development to allow compassionate use under a Treatment IND.
• Determine whether the investigational drug meets FDA criteria for “treatment use”.

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. [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.]

(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.

1. Determine the appropriate type of IND
1. Commercial
1. Submitted by company planning to obtain marketing approval for drug.
2. Research
1. Investigator-initiated. Physician initiates and conducts the investigation. Physician directly responsible for administering and dispensing drug.
2. May be appropriate for company sponsored IND for product not under review and/or development for marketing approval.

1. Develop plan for complying with FDA “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.

1. Modify/simplify protocol and CRFs
1. Entrance criteria
1. FDA may allow case-by-case decisions
2. Eliminate some exclusions in clinical development studies
2. Efficacy
1. Minimize or eliminate collection of efficacy data
3. Safety
1. Define expected, non-serious AEs
2. Describe collection of SAEs
3. Describe safety parameters
2. Collect study documents
1. Protocol
2. Investigator CV, 1572
3. Informed Consent Form
4. IRB approval

1. Develop plan for drug supply
1. Manufacturing, shipping labeling
2. Plan for drug re-supply
3. Drug accountability, retrieval and destruction

1. Develop follow-up plan
1. Obtaining periodic updates from site(s)
2. Submitting SAEs
3. Summarizing ad submitting o-serious SAEs with Annual Report and/or NDA
4. Recovery and destruction of unused drug

1. Prepare FDA submission
1. Justification for Treatment ND
2. Protocol
3. Informed Consent Form
4. RB approval status
5. Investigator documents (1572, signed CV)
6. Plans for drug supply and follow-up
7. Consider need to cross-reference drug development IND for CMC

ATTACHMENT 1
Reproduced for reference.

[Code of Federal Regulations]

[Title 21, Volume 5, Parts 300 to 499]

[Revised as of April 1, 1999]

From the U.S. Government Printing Office via GPO Access

TITLE 21--FOOD AND DRUGS DEPARTMENT OF HEALTH AND HUMAN SERVICES

--Continued PART 312--

INVESTIGATIONAL NEW DRUG APPLICATION--

Table of Contents

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.

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Dr. Carlson has utilized innovative approaches to update and enhance pharmaceutical product labeling resulting in product growth and increased revenue. She has an excellent track record in Regulatory Affairs including preparing for and participating in meetings with regulatory authorities in the U.S., Canada and Europe, organizing and preparing successful submissions, working with sales and marketing to achieve creative scientifically and medically valid promotional and sales training materials.