§310.547 21 CFR Ch. I (4–1–99 Edition)

1 21 cfr ch . I (4 1 99 Edition). for marketing. In the absence of an ap- tion or abbreviated new drug applica- proved new drug application or abbre- tion, such product is also misbranded viated new drug application, such prod- under section 502 of the act. uct is also misbranded under section (c) Clinical investigations designed 502 of the act. to obtain evidence that any drug prod- (c) Clinical investigations designed uct labeled, represented, or promoted to obtain evidence that any drug prod- for OTC use for the treatment and/or uct labeled, represented, or promoted prevention of malaria is safe and effec- for OTC use for the treatment and/or tive for the purpose intended must prevention of nocturnal leg muscle comply with the requirements and pro- cramps is safe and effective for the pur- cedures governing the use of investiga- pose intended must comply with the re- tional new drugs set forth in part 312 of quirements and procedures governing this chapter.

2 The use of investigational new drugs (d) After April 20, 1998, any such OTC. set forth in part 312 of this chapter. drug product initially introduced or (d) After February 22, 1995, any such initially delivered for introduction into OTC drug product initially introduced interstate commerce that is not in or initially delivered for introduction compliance with this section is subject into interstate commerce that is not in to regulatory action. compliance with this section is subject [63 FR 13528, Mar. 20, 1998]. to regulatory action. [59 FR 43252, Aug. 22, 1994] PART 312 INVESTIGATIONAL NEW. Drug products containing DRUG APPLICATION. quinine offered over-the-counter (OTC) for the treatment and/or pre- Subpart A General Provisions vention of malaria. Sec. (a) Quinine and quinine salts have Scope. been used OTC for the treatment and/or Applicability. prevention of malaria, a serious and Definitions and interpretations.

3 Potentially life-threatening disease. Labeling of an investigational new Quinine is no longer the drug of choice drug. for the treatment and/or prevention of Promotion and charging for investiga- tional drugs. most types of malaria. In addition, Waivers. there are serious and complicating as- pects of the disease itself and some po- Subpart B Investigational New Drug tentially serious and life-threatening Application (IND). risks associated with the use of quinine at doses employed for the treatment of Requirement for an IND. malaria. There is a lack of adequate Phases of an investigation. General principles of the IND submis- data to establish general recognition of sion. the safety of quinine drug products for IND content and format. OTC use in the treatment and/or pre- Protocol amendments. vention of malaria. Therefore, quinine Information amendments. or quinine salts cannot be safely and IND safety reports.

4 Effectively used for the treatment and/ Annual reports. or prevention of malaria except under Treatment use of an investigational the care and supervision of a doctor. new drug. Submissions for treatment use. (b) Any OTC drug product containing Emergency use of an investigational quinine or quinine salts that is labeled, new drug. represented, or promoted for the treat- Withdrawal of an IND. ment and/or prevention of malaria is regarded as a new drug within the Subpart C Administrative Actions meaning of section 201(p) of the act, for General requirements for use of an in- which an approved application or ab- vestigational new drug in a clinical in- breviated application under section 505 vestigation. of the act and part 314 of this chapter Comment and advice on an IND. is required for marketing. In the ab- Clinical holds and requests for modi- sence of an approved new drug applica- fication.

5 58. Food and Drug Administration, HHS Termination. Subpart G Drugs for Investigational Use in Inactive status. Laboratory Research Animals or in Meetings. Vitro Tests Dispute resolution. Drugs for investigational use in lab- Subpart D Responsibilities of Sponsors oratory research animals or in vitro and Investigators tests. AUTHORITY: 21 321, 331, 351, 352, 353, General responsibilities of sponsors. 355, 371; 42 262. Transfer of obligations to a contract research organization. SOURCE: 52 FR 8831, Mar. 19, 1987, unless Selecting investigators and monitors. otherwise noted. Emergency research under of this chapter. Subpart A General Provisions Informing investigators. Review of ongoing investigations. Scope. Recordkeeping and record retention. (a) This part contains procedures and Inspection of sponsor's records and requirements governing the use of in- reports.

6 Vestigational new drugs, including pro- Disposition of unused supply of inves- cedures and requirements for the sub- tigational drug. General responsibilities of investiga- mission to, and review by, the Food tors. and Drug Administration of investiga- Control of the investigational drug. tional new drug applications (IND's). Investigator recordkeeping and An investigational new drug for which record retention. an IND is in effect in accordance with Investigator reports. this part is exempt from the premar- Assurance of IRB review. keting approval requirements that are Inspection of investigator's records otherwise applicable and may be and reports. shipped lawfully for the purpose of con- Handling of controlled substances. ducting clinical investigations of that Disqualification of a clinical investi- drug. gator. (b) References in this part to regula- tions in the Code of Federal Regula- Subpart E Drugs Intended to Treat Life- tions are to chapter I of title 21, unless threatening and Severely-debilitating otherwise noted.

7 Illnesses Applicability. Purpose. Scope. (a) Applicability. Except as provided Early consultation. in this section, this part applies to all Treatment protocols. clinical investigations of products that Risk-benefit analysis in review of are subject to section 505 of the Federal marketing applications for drugs to treat Food, Drug, and Cosmetic Act or to the life-threatening and severely-debilitating licensing provisions of the Public illnesses. Health Service Act (58 Stat. 632, as Phase 4 studies. amended (42 201 et seq.)). Focused FDA regulatory research. (b) Exemptions. (1) The clinical inves- Active monitoring of conduct and tigation of a drug product that is law- evaluation of clinical trials. fully marketed in the United States is Safeguards for patient safety. exempt from the requirements of this part if all the following apply: Subpart F Miscellaneous (i) The investigation is not intended Import and export requirements.

8 To be reported to FDA as a well-con- Foreign clinical studies not con- trolled study in support of a new indi- ducted under an IND. cation for use nor intended to be used Availability for public disclosure of to support any other significant change data and information in an IND. in the labeling for the drug;. Address for correspondence. (ii) If the drug that is undergoing in- Guidelines. vestigation is lawfully marketed as a 59. 21 cfr ch . I (4 1 99 Edition). prescription drug product, the inves- (d) Unlabeled indication. This part tigation is not intended to support a does not apply to the use in the prac- significant change in the advertising tice of medicine for an unlabeled indi- for the product; cation of a new drug product approved (iii) The investigation does not in- under part 314 or of a licensed biologi- volve a route of administration or dos- cal product.

9 Age level or use in a patient population (e) Guidance. FDA may, on its own or other factor that significantly in- initiative, issue guidance on the appli- creases the risks (or decreases the ac- cability of this part to particular in- ceptability of the risks) associated vestigational uses of drugs. On request, with the use of the drug product; FDA will advise on the applicability of (iv) The investigation is conducted in this part to a planned clinical inves- compliance with the requirements for tigation. institutional review set forth in part 56. [52 FR 8831, Mar. 19, 1987, as amended at 61. and with the requirements for informed FR 51529, Oct. 2, 1996; 64 FR 401, Jan. 5, 1999]. consent set forth in part 50; and (v) The investigation is conducted in EFFECTIVE DATE NOTE: At 64 FR 401, Jan. compliance with the requirements of 5, 1999, was amended by removing or 507'' from paragraph (a) and by removing or antibiotic drug'' from paragraph (d), effec- (2)(i) A clinical investigation involv- tive May 20, 1999.

10 Ing an in vitro diagnostic biological product listed in paragraph (b)(2)(ii) of Definitions and interpretations. this section is exempt from the re- quirements of this part if (a) it is in- (a) The definitions and interpreta- tended to be used in a diagnostic proce- tions of terms contained in section 201. dure that confirms the diagnosis made of the Act apply to those terms when by another, medically established, di- used in this part: agnostic product or procedure and (b) it (b) The following definitions of terms is shipped in compliance with also apply to this part: (ii) In accordance with paragraph Act means the Federal Food, Drug, (b)(2)(i) of this section, the following and Cosmetic Act (secs. 201 902, 52. products are exempt from the require- Stat. 1040 et seq., as amended (21 ments of this part: (a) blood grouping 301 392)). serum; (b) reagent red blood cells; and Clinical investigation means any ex- (c) anti-human globulin.