FDA Proposes Rules to Expand Availability of Investigational Drugs and Clarify Permissible Charges to Patients

In an effort to enable more patients who lack satisfactory alternatives to have access to unapproved medicines, while balancing the need to safeguard the individual patient and ensure the continued integrity of the scientific process that brings safe and effective drugs to the market, on December 11, 2006, FDA proposed significant regulatory changes to make investigational drugs more widely and easily available to seriously ill patients, including those with HIV/AIDS, who have no other treatment options. The proposed changes also seek to clarify the specific circumstances and the types of costs for which a manufacturer can charge for an investigational drug made available for the purpose of treatment.

FDA would like to increase awareness in the healthcare community of the range of options available for obtaining investigational drugs for seriously ill patients, encourage companies to make such drugs available, and reduce barriers to obtaining them.

The proposed rule defines three categories of patients to whom investigational drugs could be made available for the purpose treatment outside of a clinical trial through expanded access, when there is no satisfactory alternative therapy, and defines requirements and safeguards for each. They are

• individual patients,
• groups of patients smaller than that typical of a treatment IND or treatment protocol (FDA may ask a sponsor to consolidate expanded access under this section when the agency has received a significant number of requests for individual patient expanded access to an investigational drug for the same use),
• and larger populations where widespread treatment use is appropriate.

FDA has allowed many types of access to investigational therapies since the 1970's. Some of the larger programs, including those under the treatment IND (Investigational New Drug) regulations, enabled tens of thousands of patients with HIV/AIDS, cancer and cardiovascular diseases to receive promising therapies before the products were approved for marketing. However, the existing regulations do not adequately describe the full range of programs available, explicitly recognizing only emergency use for individual patients and widespread treatment use access for large groups of patients. The proposed changes are meant to clearly reflect the full range of treatment use programs available, and ensure broad and equitable access to investigational drugs for treatment use.

The current regulations describing when it is appropriate to charge for an investigational drug need revisions because they fail to account for the full range of circumstances in which charging should be permissible and because they have proven difficult to interpret in practice, resulting in confusion over what costs could be recovered by sponsors making drug products available through expanded access programs.

The proposed rules, which are open for comment for 90 days, are described in detail at www.fda.gov/cder/regulatory/applications/IND_PR.htm.

The most significant proposed changes would:

(1) Modernize applicable regulations to include all circumstances under which access to investigational drugs is permitted, including:

• single patients in non-emergency and emergency settings;
• small groups of patients; and
• larger groups of patients under a treatment IND. To authorize these expanded access treatment uses, FDA generally must be satisfied that the patient's serious or immediately life-threatening disease or condition has no satisfactory approved therapy; that the potential benefit for the patient justifies the potential risks; and that providing the therapy will not interfere with the drug's development.

(2) Make investigational drugs more widely available in appropriate situations by establishing criteria that link the level of evidence needed to support the use of an investigational drug to the seriousness of the disease and the number of patients likely to be treated with the drug in an expanded access program;

(3) Revise the current regulation regarding manufacturers' recovery of the costs of an investigational drug to:

• clarify that such charges are permissible in a clinical trial only to facilitate development of drugs that promise significant advantages over existing therapies, and might not otherwise be developed because of their high cost;
• clarify that allowing charging for treatment use of an investigational drug is intended to facilitate and encourage access to drugs that might not be made available for treatment use unless a manufacturer is able to recover its costs.

The proposal also would simplify the cost recovery calculation by making clear that charges for an investigational drug used in a clinical trial may include only direct costs associated with the drug's development, and that charges for investigational drugs for treatment use may also include administrative costs of making the drug available for intermediate patient populations and under large scale treatment INDs.

Written comments, identified by Docket No. 2006N-0062 and RIN 0910-AF14 (for expanded access proposals) and Docket No. 2006N-0061 and/or RIN 0910-AF13, (for cost recovery proposals), are encouraged, and may be submitted by any of the following methods:

• Federal eRulemaking Portal: www.regulations.gov. Follow the instructions for submitting comments.
• Agency Web site: www.fda.gov/dockets/ecomments. Follow the instructions for submitting comments on the agency Web site.
• FAX: 301-827-6870.
• Mail/Hand delivery/Courier [For paper, disk, or CD-ROM submissions]: Division of Dockets Management, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.