The purpose of this page is to let you know more options on how to obtain prescription drugs that may not be approved in the United States yet, or that may be approved for indications other than the disease that is being treated. First, let's look at some common abbreviations that are used in the pharmaceutical development field:
Clinical Trial: Research studies on human subjects that seek to
answer specific questions of safety and efficacy of a particular drug, device,
or treatment regimen.
FDA: Food and Drug Administration, the agency which regulates drugs in the United States.
IND: Investigational New Drug Application. What a drug maker needs to file with the FDA to begin the drug approval process and start clinical studies.
CFR: Code of Federal Regulations, the regulations that FDA uses to govern the manufacture and distribution of drugs.
FR: Federal Register, the periodical that the government publishes updated regulations in. Published daily.
Protocol: A set of criteria rules established under which a Clinical Trial (drug study) is accomplished.
IRB: Institutional Review Board, a group of independent doctors and professionals that reviews and approves/disapproves IND protocols. Most hospitals and universities have their own IRB's.
SOP: Standard Operating Procedure, a set of written instructions on how to perform tasks involved in drug development and clinical trials.
In order to be able to obtain and use a drug in the United States that is not yet approved by the FDA, an IND must be filed with the FDA and approved by the FDA and the local IRB. IND's may be filed by a drug company or by an individual doctor, and they may be for individual patients, multiple patients, or for a large number of patients. Below, I describe the numerous types of IND processes.
For many drug and biologic products, the pharmaceutical companies that are developing the product, or the Universities, National Cancer Institute, Phone: 800-422-6237, or Children's Oncology Group, Phone 800-458-6223 or 626-447-1674 have already filed an IND and have received IRB and IND approval for their clinical trials. Contact information for those clinical trials may be obtained by utilizing the clinical trials search resources on our foundation home page at http://www.cureourchildren.org . For products that you wish have your doctor obtain that are not currently the subject of an approved clinical trial, please read on for more information and procedures to follow.
It should be noted that drugs that are approved for any indication in the United States may be prescribed by a physician for any use, even if that use is not approved specifically by the FDA. This is called off-label use, and it is legal and very common. For instances, if your physician decides that he wants to use oxaliplatin for Ewing's Sarcoma, in combination with other drugs, he or she may do so even though oxaliplatin is only approved by FDA for treatment of other types of cancers. There is even a specific FDA regulation which exempts off-label use of approved drugs. It is 21 CFR 312.2(d). FDA has also issued a guidance document to clarify its policy that broadens the exemptions from an IND. That guidance document is here: IND Exemptions for Studies of Lawfully Marketed Drug or Biological Products for the Treatment of Cancer You may click on this link to print out and provide your healthcare provider these FDA regulations and guidances.
Many doctors are familiar with the IND process, but
some are not. For drugs that are not yet approved, it will be essential to
have the cooperation of the manufacturer both to provide the supply of the drug
manufactured according to pharmaceutical standards, and to support the IND
filing with FDA with the data on the drug. Below, I describe the
procedures and policies of how to file IND's to get drugs, and I provide
numerous resources to assist doctors, patients, and pharmaceutical development
companies to make it easier for cancer patients to obtain new therapies.
All IRB's have procedures for applying for and obtaining approval to use an investigation product; however, if you are being treated by a private doctor, he or she can contact a local university and apply to their IRB for approval, or I have listed an IRB that accepts applications from private doctors below. Also, most IRB's have a procedure in place already to apply for and receive approval for emergency use of a drug; however, for those IRB's and facilities that do not have such a procedure, I have provided links and information in after the Emergency IND paragraph below to assist.
There is also a foundation that is active in trying to expand investigational drugs for cancer patients. It is the Abagail Alliance, Phone: 703-525-9266 , Fax: 703-243-2892. The website is http://abigail-alliance.org .
Warm Regards.....Barry Sugarman
The Main FDA Investigational New Drug Application (IND) Page is here.
The Treatment Referral Center (TRC) is a means for the National Cancer Institute (NCI) to provide information to community oncologists and other health care professionals about therapeutic options for cancer patients. Phone (301)496-5725, Fax (301)402-4870.
Group C Treatment IND--The "Group C" treatment IND was established by agreement between FDA and the National Cancer
Institute (NCI). The Group C program is a means for the compassionate distribution of investigational
agents to oncologists for the treatment of cancer under protocols outside the controlled clinical trial.
Group C drugs are generally Phase 3 study drugs that have shown evidence of relative and reproducible efficacy in a specific tumor type. They can generally be administered by properly trained physicians without the need for specialized supportive care facilities. Group C drugs are distributed only by the NIH under NCI protocols.
Although treatment is the primary objective and patients treated under Group C guidelines are not part of a clinical trial, safety and effectiveness data are collected. Because administration of Group C drugs is not done with research intent, the FDA has generally granted a waiver from the IRB review requirements. Even though the FDA has granted a waiver for these drugs, an IRB may still choose to conduct a review under its policies and procedures. The usage of a Group C drug is described in its accompanying Guideline Protocol document. The Guideline Protocol contains an FDA-approved informed consent document which must be used if there has been no local IRB review.
Here--The Special Exception mechanism is the functional equivalent of an emergency IND but differs from it
in that any registered investigator may obtain an agent directly from CTEP instead of having to obtain
an IND from the FDA. The following information is required to consider a Special Exception request: patient identifier (name or ID #), age, sex, diagnosis, previous cancer therapy, current clinical status, intended dose and schedule of the requested agent (this should be based on the current literature), potential concomitant therapy, pertinent laboratory data.
Each request is reviewed and approved on a case by case basis.
Open Label Protocol or Open Protocol IND--Example
Open Label Protocol IND, Phone 510-540-2646, Fax 510-540-3205
These are usually uncontrolled studies, carried out to obtain additional safety data (Phase 3 studies). They are typically used when the controlled trial has ended and treatment is continued so that the subjects and the controls may continue to receive the benefits of the investigational drug until marketing approval is obtained. These studies require prospective IRB review and informed consent.
Treatment IND--The treatment IND (21 CFR 312.34, 312.35) is a mechanism for providing eligible
subjects with investigational drugs for the treatment of serious and life-threatening
illnesses for which there are no satisfactory alliterative treatments. A treatment
IND may be granted after sufficient data have been collected to show that the drug
may be effective and does not have unreasonable risks. Because data related to
safety and side effects are collected, treatment INDs also serve to expand the
body of knowledge about the drug.
There are four requirements that must be met before a treatment IND can be issued:
1) The drug is intended to treat a serious or immediately life-threatening disease;
2) There is no satisfactory alternative treatment available;
3) The drug is already under investigation, or trials have been completed; and
4) The trial sponsor is actively pursuing marketing approval.
Treatment IND studies require prospective IRB review and informed consent. A sponsor may apply for a waiver of local IRB review under a treatment IND if it can be shown to be in the best interest of the subjects, and if a satisfactory alternate mechanism for assuring the protection of human subjects is available (e.g., review by a central IRB). Such a waiver does not apply to the informed consent requirement. An IRB may still opt to review a study even if FDA has granted a waiver.
Parallel Track--The FDA’s Parallel Track policy
(57 FR 13250) permits wider access to promising new drugs for AIDS and HIV-related diseases under a separate "treatment"
protocol that parallels the controlled clinical trials that are essential to establish the
safety and effectiveness of new drugs. It provides an administrative system that
expands the availability of drugs for treating acquired immunodeficiency syndrome
(AIDS) and other HIV-related diseases. These studies require prospective IRB
review and informed consent.
Emergency Use IND--FDA
may grant approval for use of an investigational new drug in an emergency
situation where time does not allow for submission of an IND in the usual
manner. The authority for this is specified in the regulations (21 CFR
312.36). IRB review may be waived under the conditions specified in
the regulations (21 CFR 56.104(c) and 21 CFR 56.102(d) ). Informed
consent may be waived under the conditions listed in the regulations (21 CFR
50.23). See the bottom of this page for links to these FDA regulations.
The FDA offices for filing an Emergency IND are:
Drug Products: Division of Drug Information, HFD-240, Center for Drug Evaluation and Research, Phone: 301-827-4570, Fax: 301-827-4577.
Biological Drug Products: Office of Communication, Training and Manufacturer's Assistance, HFM-40, Center for Biologics Evaluation and Research, Phone: 301-827-2000, Fax 301-827-3843..
For Submissions after Normal Working Hours, Eastern Standard Time: FDA Office of Emergency Operations, HFA-615, Phone 301-443-1240, Fax: 301-443-3757.
Emergency IND and IND Resources:
Investigational New Drug Applications (IND's):
IND Regulations Table of Contents (21 CFR 312)
Text File PDF File 21 CFR 312.34 Treatment use of an investigational new drug.
Text File PDF File 21 CFR 312.35 Submission for treatment use.
Text File PDF File 21 CFR 312.36 Emergency use of an investigational new drug.
Institutional Review Board Regulations (IRB's):
IRB Regulations Table of Contents (21 CFR 56)
Text File PDF File 21 CFR 56.102 Definitions
Text File PDF File 21 CFR 56.104 Exemptions from IRB requirement.
Protection of Human Subjects Regulations (21 CFR 50):
Protection of Humans Subjects Regulations Table of Contents
Text File PDF File 21 CFR 50.23 Exception from general requirements.
Text File PDF File 21 CFR 50.24 Exception from informed consent requirements for emergency research.