To provide the strongest possible control over the distribution and use of methadone, the Commissioner has concluded that both the IND and NDA control mechanisms should be utilized together with the authority granted under the Comprehensive Drug Abuse Control Act of 1970. Like an NDA, the drug will be available for treatment in all cases where there is medical justification. Like an IND controlled drug, there will be a permanent record showing the pattern of distribution of the drug because the institutions using the drug and the physicians and pharmacists operating in cooperation with the institution will be required to register all use of the drug. It will permit the Food and Drug Administration to withdraw methadone from its present unqualified approval status in pharmacies for detoxification, analgesic, and antitussive purposes. Thus, a new closed system of distribution will be established, under which any diversion or misuse can imnediately be stopped at the source of supply. At the same time the drug will be available for use without all the IND restrictions for all addicts for whom it is medically justified.

The Commissioner recognizes that this is a novel form of control designed to reflect the unique problems posed by this drug. It has not previously been necessary to utilize IND and the NDA procedures concurrently in order to assure the safe and effective use of a new drug. Because of the seriousness of the medical and social problems associated with heroin addiction and because methadone is the only drug available for the treatment of heroin addiction, the Commissioner has concluded that it is no longer feasible to retain methadone solely

for investigational use. It is therefore appropriate to add the special requirements set forth in this proposal in order to permit the drug to be available wherever medical opinion concludes that it should be used in the treatment of heroin addiction.

The Commissioner feels that the mandate in section 4 of the

Comprehensive Drug Abuse Prevention and Control Act of 1970 can be appropriately applied to determining the conditions under which methadone may be safely used in treating, narcotic addicts. This requires the Secretary of Health, Education and Welfare ... after consultation with the Attorney General

section

and with national organizations representative of persons with knowledge and experience in the treatment of narcotic addicts, to determine the appropriate methods of professional practice in the medical treatment of narcotic addiction

The Starretary has delegated the authority

to make this determination to the Commissioner of Food and Drugs. In carrying out the requirements of the Comprehensive Drug Abuse Prevention and Control Act, the Commissioner has widely consulted and maintained close communications with the medical profession regarding use of methadone. Among those associations or groups consulted are the American Medical Association's Council on Mental Health, the National Research Council's Committee on Problems: of Drug Dependence, the American Psychiatric Association's Commission on Drug Abuse, a task force of the American Society of Pharmacology and Experimental Therapeutics, the Joint Food and Drug Administration/National Institutes of Mental Health Psychotomimetic Advisory Committee, the FDA Drug Abuse Advisory Committee, the Special Action Office of the White House, and

the National Institute of Mental Health.

The consensus is strong

among medical experts and the Food and Drug Administration that currently available evidence on the safety and effectiveness of methadone is sufficient to permit its use for the maintenance treatment of narcotic addiction as proposed in this notice.

On the basis of the above considerations, the Commissioner of Food and Drugs, after consultation with the associations and groups listed above and the Bureau of Narcotics and Dangerous Drugs, and with the endorsement of the Special Action Office of the White House, proposes that the special requirements set out in this notice be imposed upon the use of methadone. These mew controls should not interfere with the availability of methadone in the treatment of severe pain or for detoxificatiom of hospitalized addicts. Methadone for the treatment of severe pain either an inpatient or outpatient basis will be available from hospital pharmacies.

It is proposed that patients under 18 not be admitted to a treatment program using methadone until additional study is completed to determine whether methadone may be safely and effectively used in their treatment. Such additional study masit be conducted pursuant to all the requirements of the usual investigational new drug plan. This will mean that juveniles will be excluded from virtually all ongoing treatment programs using methadone except investigational programs with an IND approval. Comment is solicited as to whether the benefits of completing additional studies outweigh the risks of excluding these patients from treatment programs at this time with the likely result that they will continue to use injected heroin.

Under this proposal, the distribution of the drug is limited to

treatment programs using methadone and to hospital pharmacies approved by the Food and Drug Administration. Requests for approval of programs received by FDA will be sent to BNDD for any comment it may have prior to FDA approval. BNDD may inspect any such program or may furnish FDA any relevant information from its files. FDA will give great weight to any information, comments, or recommendation received from BNDD in determining whether approval should be granted or, once granted, should Methadone will no longer be permitted for antitussive use as the benefits of methadone for this use do not outweigh the risk involved from unsafe and ineffective use.

be revoked.

The Food and Drug Administration believes that State health or mental health authorities are essential to adequately controlling methadone, to assuring that the need for a methadone program exists, and to establishing criteria and guidance for rehabilitation efforts. Approval of a program by the State health or mental health authority designated under the provisions of section 314 (d) of the Public Health Service Act or by his designee will be a part of approval of the treatment programs using methadone by FDA. The Food and Drug Administration will contact each State to establish the necessary channels of communication and to establish procedure for the implementation of the program, and will provide information upon request.

Section 130.44 conditions for investigational use of methadone for maintenance programs for narcotic addicts (21 CFR 130.44) will continue in effect until a final order is issued after consideration

of the comments submitted on this proposal. To increase control over methadone and to improve patient care prior to the finalization of this proposal, however, the guidelines in § 130.44 will be enforced as a requirement for a methadone maintenance investigational program. Any IND that varies in any material respect from the protocol in § 130.44 will require justification.

The following additional provisions will be required of all methadone maintenance investigational programs during the time between the publication of this proposal and its final promulgation:

1. Only oral dosage forms of methadone formulated in such a way as to reduce its potential for parenteral abuse and accidental ingestion will be provided patients for unsupervised use under approved programs.

2. The selection of patients is to be carried out in accordance with the requirements of item V, B, of the foam "Application for Approval of Treatment Program Using Methadone” which appears in proposed section 130.48 (b)(2)(1).

3. Dosage for detoxification and maintenance is to be in accordance with the requirements of item VIII, A, of the form "Application for Approval of Treatment Program Using Methadone" which appears in proposed section 130.48 (b)(2)(i).

4. The recordkeeping requirements are to be in accordance with the information requested in the form "Annual Report for Treatment

Program Using Methadone" which appears in proposed section 130.48

(b)(2)(iii).