(b) Exemptions. Exemptions or modifications shall be made only upon written approval, in the form of an amendment of the product license, issued by the Director, Center for Biologics Evaluation and Research.

[39 FR 39872, Nov. 12, 1974, as amended at 49 FR 23833, June 8, 1984; 50 FR 4133, Jan. 29, 1985; 50 FR 9000, Mar. 6, 1985; 55 FR 11013, Mar. 26, 1990]

Subpart C-Establishment Inspection § 600.20 Inspectors.

Inspections shall be made by an officer of the Food and Drug Administration having special knowledge of the methods used in the manufacture and control of products and designated for such purposes by the Commissioner of Food and Drugs, or by any officer, agent, or employee of the Department of Health and Human Services specifically designated for such purpose by the Secretary.

[38 FR 32048, Nov. 20, 1973]

§ 600.21 Time of inspection.

The inspection of an establishment for which a license is pending need not be made until the establishment is in operation and is manufacturing the complete product for which a product license is desired. In case the license is denied following inspection for the original license, no reinspection need be made until assurance has been received that the faulty conditions which were the basis of the denial have been corrected. An inspection of each licensed establishment and its additional location(s) shall be made at least once every 2 years. Inspections may be made with or without notice, and shall be made during regular business hours unless otherwise directed.

[38 FR 32048, Nov. 20, 1973, as amended at 48 FR 26314, June 7, 1983]

§ 600.22 Duties of inspector.

The inspector shall:

(c) Examine the details of location, construction, equipment and maintenance, including stables, barns, warehouses, manufacturing laboratories, bleeding clinics maintained for the collection of human blood, shipping rooms, record rooms, and any other structure or appliance used in any part of the manufacture of a product,

(d) Investigate as fully as he deems necessary the methods of propagation, processing, testing, storing, dispensing, recording, or other details of manufacture and distribution of each licensed product, or product for which a license has been requested, including observation of these procedures in actual operation,

(e) Obtain and cause to be sent to the Director, Center for Biologics Evaluation and Research, adequate samples for the examination of any product or ingredient used in its manufacture,

(f) Bring to the attention of the manufacturer any fault observed in the course of inspection in location, construction, manufacturing methods, or administration of a licensed establishment which might lead to impairment of a product,

(g) Inspect and copy, as circumstances may require, any records required to be kept pursuant to § 600.12,

(h) Certify as to the condition of the establishment and of the manufacturing methods followed and make recommendations as to action deemed appropriate with respect to any application for license or any license previously issued.

[38 FR 32048, Nov. 20, 1973, as amended at 49 FR 23833, June 8, 1984; 55 FR 11013, Mar. 26, 1990]

(a) Call upon the active head of the establishment, stating the object of his visit,

601.3

601.4

(b) Interrogate the proprietor or other personnel of the establishment as he may deem necessary,

Subpart F-Confidentiality of Information

601.50 Confidentiality of data and information in an investigational new drug notice for a biological product. 601.51 Confidentiality of data and information in applications for establishment and product licenses.

AUTHORITY: Secs. 201, 501, 502, 503, 505, 510, 513-516, 518-520, 701, 704, 706, 801 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321, 351, 352, 353, 355, 360, 360c360f, 360h-360j, 371, 374, 376, 381); secs. 215, 301, 351, 352 of the Public Health Service Act (42 U.S.C. 216, 241, 262, 263); secs. 2-12

of the Fair Packaging and Labeling Act (15 U.S.C. 1451-1461).

SOURCE: 38 FR 32052, Nov. 20, 1973, unless otherwise noted.

CROSS REFERENCES: For U.S. Customs Service regulations relating to viruses, serums, and toxins, see 19 CFR 12.21-12.23. For U.S. Postal Service regulations relating to the admissibility to the United States mails see parts 124 and 125 of the Domestic Mail Manual, that is incorporated by reference in 39 CFR part 111.

Subpart A-General Provisions

§ 601.1 Two forms of licenses. There shall be two forms of licenses: establishment and product.

§ 601.2 Applications for establishment and product licenses; procedures for filing. (a) General. To obtain a license for any establishment or product, the manufacturer shall make application to the Director, Center for Biologics Evaluation and Research, on forms prescribed for such purposes, and in the case of an application for a product license, shall submit data derived from nonclinical laboratory and clinical studies which demonstrate that the manufactured product meets prescribed standards of safety, purity, and potency; with respect to each nonclinical laboratory study, either a statement that the study was conducted in compliance with the requirements set forth in part 58 of this chapter, or, if the study was not conducted in compliance with such regulations, a brief statement of the reason for the noncompliance; statements regarding each clinical investigation involving human subjects contained in the application, that it either was conducted in compliance with the requirements for institutional review set forth in part 56 of this chapter or was not subject to such requirements in accordance with § 56.104 or § 56.105, and was conducted in compliance with requirements for informed consent set forth in part 50 of this chapter; a full description of manufacturing methods; data establishing stability of the product through the dating period;

sample(s) representative of the product to be sold, bartered, or exchanged or offered, sent, carried or brought for

sale, barter, or exchange; summaries of results of tests performed on the lot(s) represented by the submitted sample(s); and specimens of the labels, enclosures, and containers proposed to be used for the product. An application for license shall not be considered as filed until all pertinent information and data have been received from the manufacturer by the Center for Biologics Evaluation and Research. The applicant shall also include either a claim for categorical exclusion under § 25.24 of this chapter or an environmental assessment under § 25.31 of this chapter. In lieu of the procedures described in this paragraph, applications for radioactive biological products shall be handled as set forth in paragraph (b) of this section.

(b) Radioactive biological products. In lieu of submitting an establishment and product license for the manufacture of a radioactive biological product, as defined in § 600.3(ee) of this chapter, the manufacturer of such a product shall submit a new drug application to the Director, Division of Medical Imaging, Surgical, and Dental Products (HFD-160), Center for Drug Evaluation and Research, Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857, consistent with the procedures set forth in § 314.50 of this chapter. For such products, the approval of the new drug application will be in lieu of issuing a product and an establishment license. Compliance with the provisions of part 314 of this chapter shall be deemed to constitute compliance with the provisions of Subchapter F of this chapter unless the Commissioner makes a determination that a particular regulation from Subchapter F shall be applicable to radioactive drugs containing a biological product, e.g., § 610.2 of this chapter.

[40 FR 31313, July 25, 1975, as amended at 46 FR 8955, Jan. 27, 1981; 47 FR 6618, Feb. 16, 1982; 49 FR 23833, June 8, 1984; 50 FR 7518, Feb. 22, 1985; 50 FR 16669, Apr. 26, 1985; 55 FR 11013 and 11014, Mar. 26, 1990]

§ 601.3 License forms.

(a) Establishment license. The establishment license form shall be prescribed by the Director, Center for

(1) The name and address of the manufacturer.

(2) The name and address of the establishment.

(3) The names and addresses of all locations of the establishment.

(4) The license number.

(5) The date of issuance.

(b) Product license. The product license form shall be prescribed by the Director, Center for Biologics Evaluation and Research and shall include:

(1) The name and address of the manufacturer.

(2) The name and address of the establishment.

(3) The name and address of each location at which the product is manufactured.

(4) The license number of the establishment.

(5) The proper name of the product, with additional specifications, if any, which may be approved or required for additional labeling purposes.

[38 FR 32052, Nov. 20, 1973, as amended at 49 FR 23833, June 8, 1984; 55 FR 11013, Mar. 26, 1990]

§ 601.4

Issuance and denial of license.

(a) An establishment or product license shall be issued upon a determination by the Director, Center for Biologics Evaluation and Research that the establishment or the product, as the case may be, meets the applicable standards established in this chapter. Licenses shall be valid until suspended or revoked.

(b) If the Commissioner determines that the establishment or product does not meet the standards established in this chapter, he shall deny the application and inform the applicant of the grounds for, and of an opportunity for a hearing on, his decision. If the applicant so requests, the Commissioner shall issue a notice of opportunity for hearing on the matter pursuant to § 12.21(b) of this chapter. [42 FR 4718, Jan. 25, 1977, as amended at 42 FR 15676, Mar. 22, 1977; 42 FR 19142, Apr. 12, 1977; 49 FR 23833, June 8, 1984; 55 FR 11013, Mar. 26, 1990]

(a) An establishment or product license shall be revoked upon application of the manufacturer giving notice of intention to discontinue the manufacture of all products or to discontinue the manufacture of a particular product for which a license is held, and waiving an opportunity for a hearing on the matter.

(b) If the Commissioner finds that (1) authorized Food and Drug Administration employees after reasonable efforts have been unable to gain access to an establishment or a location for the purpose of carrying out the inspection required under § 600.21 of this chapter, (2) manufacturing of products or of a product has been discontinued to an extent that a meaningful inspection or evaluation cannot be made, (3) the manufacturer has failed to report a change as required by § 601.12, (4) the establishment or any location thereof, or the product for which the license has been issued, fails to conform to the applicable standards established in the license and in this chapter designed to ensure the continued safety, purity, and potency of the manufactured product, (5) the establishment or the manufacturing methods have been so changed as to require a new showing that the establishment or product meets the standards established in this chapter in order to protect the public health, or (6) the licensed product is not safe and effective for all of its intended uses or is misbranded with respect to any such use, he shall notify the licensee of his intention to revoke the license, setting forth the grounds for, and offering an opportunity for a hearing on, the proposed revocation. Except as provided in § 601.6 or in cases involving willfulness, the notification required in this paragraph shall provide a reasonable period for the licensee to demonstrate or achieve compliance with the requirements of this chapter, before proceedings will be instituted for the revocation of the license. If compliance is not demonstrated or achieved and the licensee does not waive the opportunity for a hearing, the Commissioner shall issue a notice of opportunity for hearing on the matter pursuant to § 12.21(b) of this chapter.

[42 FR 4718, Jan. 25, 1977, as amended at 42 FR 15676, Mar. 22, 1977; 42 FR 19143, Apr. 12, 1977; 49 FR 23833, June 8, 1984]

§ 601.6 Suspension of license.

(a) Whenever the Commissioner has reasonable grounds to believe that any of the grounds for revocation of a license exist and that by reason thereof there is a danger to health, he may notify the licensee that his license for the establishment or the product is suspended and require that the licensee (1) notify the selling agents and distributors to whom such product or products have been delivered of such suspension, and (2) furnish to the Director, Center for Biologics Evaluation and Research, complete records of such deliveries and notice of suspension.

(b) Upon suspension of a license, the Commissioner shall either (1) proceed pursuant to the provisions of § 601.5(b) to revoke the license, or (2) if the licensee agrees, hold revocation in abeyance pending resolution of the matters involved.

[42 FR 4718, Jan. 25, 1977 as amended at 49 FR 23833, June 8, 1984; 55 FR 11013, Mar. 26, 1990]

§ 601.7 Procedure for hearings.

(a) A notice of opportunity for hearing, notice of appearance and request for hearing, and grant or denial of hearing for a biological drug pursuant to this part, for which the exemption from the Federal Food, Drug, and Cosmetic Act in § 310.4 of this chapter has been revoked, shall be subject to the provisions of § 314.200 of this chapter except to the extent that the notice of opportunity for hearing on the matter issued pursuant to § 12.21(b) of this chapter specifically provides otherwise.

(b) Hearings pursuant to §§ 601.4 through 601.6 shall be governed by part 12 of this chapter.

(c) When a license has been suspended pursuant to § 601.6 and a hearing request has been granted, the hearing shall proceed on an expedited basis.

[42 FR 4718, Jan. 25, 1977, as amended at 42 FR 15676, Mar. 22, 1977; 42 FR 19143, Apr. 12, 1977]

§ 601.8 Publication of revocation.

Notice of revocation of a license, with statement of the cause therefor, shall be issued by the Commissioner and published in the FEDERAL REGISTER.

[42 FR 4718, Jan. 25, 1977]

§ 601.9 Licenses; reissuance.

(a) Compliance with standards. An establishment or product license, previously suspended or revoked, may be reissued or reinstated upon a showing of compliance with required standards and upon such inspection and examination as may be considered necessary by the Director, Center for Biologics Evaluation and Research.

(b) Exclusion of noncomplying location. An establishment or product license, excluding a location or locations that fail to comply with required standards, may be issued without further application and concurrently with the suspension or revocation of the license for noncompliance at the excluded location or locations.

[42 FR 4718, Jan. 25, 1977, as amemded at 49 FR 23833, June 8, 1984; 55 FR 11013, Mar. 26, 1990]

Subpart B-Establishment Licensing

§ 601.10 Establishment licenses; issuance and conditions. (a) Inspection-compliance with standards. An establishment license shall be issued only after inspection of the establishment and upon a determination that the establishment complies with the applicable standards prescribed in the regulations in this subchapter.

(b) Availability of product; simultaneous request for and issuance of product license. No establishment license shall be issued unless (1) a product intended for sale, barter or exchange or intended to be offered, sent, carried or brought for sale, barter or exchange is available for examination, (2) such product is available for inspection during all phases of manufacture and (3) a product license is requested and issued simultaneously with the establishment license.

(c) One establishment license to cover all locations. One establishment

license shall be issued to cover all locations meeting the establishment standards.

§ 601.12 Changes to be reported.

(a) General. Important proposed changes in location, equipment, management and responsible personnel, or in manufacturing methods and labeling, of any product for which a license is in effect or for which an application for license is pending, shall be reported to the Director, Center for Biologics Evaluation and Research, by the manufacturer, and unless in case of an emergency, not less than 30 days in advance of the time such changes are intended to be made.

(b) Manufacturing methods and labeling. Proposed changes in manufacturing methods and labeling may not become effective until notification of acceptance is received from the Director, Center for Biologics Evaluation and Research.

[38 FR 32052, Nov. 20, 1973. Redesignated and amended at 42 FR 4718, Jan. 25, 1977; 49 FR 23833, June 8, 1984; 55 FR 11013, Mar. 26, 1990]

Subpart C-Product Licensing

§ 601.20 Product licenses; issuance and conditions.

(a) Examination—compliance with standards. A product license shall be issued only upon examination of the product and upon a determination that the product complies with the standards prescribed in the regulations in this subchapter: Provided, That no product license shall be issued except upon a determination that the establishment complies with the establishment standards prescribed in the regulations contained in this subchapter, applicable to the manufacture of such product.

(b) Manufacturing process—impairment of assurances. No product shall be licensed if any part of the process of or relating to the manufacture of such product, in the judgment of the Commissioner of Food and Drugs, would impair the assurances of continued safety, purity and potency as provided by the regulations contained in this subchapter.