[43 FR 60013, Dec. 22, 1978, as amended at 52 FR 33781, Sept. 4, 1987]

§ 58.190 Storage and retrieval of records and data.

(a) All raw data, documentation, protocols, final reports, and specimens (except those specimens obtained from mutagenicity tests and wet specimens of blood, urine, feces, and biological fluids) generated as a result of a nonclinical laboratory study shall be retained.

(b) There shall be archives for orderly storage and expedient retrieval of all raw data, documentation, protocols, specimens, and interim and final reports. Conditions of storage shall minimize deterioration of the documents or specimens in accordance with the requirements for the time period of their retention and the nature of the documents or specimens. A testing facility may contract with commercial archives to provide a repository for all material to be retained. Raw data and specimens may be retained elsewhere provided that the archives have specific reference to those other locations.

(c) An individual shall be identified as responsible for the archives.

(d) Only authorized personnel shall enter the archives.

(e) Material retained or referred to in the archives shall be indexed to permit expedient retrieval.

(Information collection requirements approved by the Office of Management and Budget under control number 0910-0203) [43 FR 60013, Dec. 22, 1978, as amended at 52 FR 33781, Sept. 4, 1987]

(a) Record retention requirements set forth in this section do not supersede the record retention requirements of any other regulations in this chapter.

(b) Except as provided in paragraph (c) of this section, documentation records, raw data and specimens pertaining to a nonclinical laboratory study and required to be made by this part shall be retained in the archive(s) for whichever of the following periods is shortest:

(1) A period of at least 2 years following the date on which an application for a research or marketing

permit, in support of which the results of the nonclinical laboratory study were submitted, is approved by the Food and Drug Administration. This requirement does not apply to studies supporting investigational new drug applications (IND's) or applications for investigational device exemptions (IDE's), records of which shall be governed by the provisions of paragraph (b)(2) of this section.

(2) A period of at least 5 years following the date on which the results of the nonclinical laboratory study are submitted to the Food and Drug Administration in support of an application for a research or marketing permit.

(3) In other situations (e.g., where the nonclinical laboratory study does not result in the submission of the study in support of an application for a research or marketing permit), a period of at least 2 years following the date on which the study is completed, terminated, or discontinued.

(c) Wet specimens (except those specimens obtained from mutagenicity tests and wet specimens of blood, urine, feces, and biological fluids), samples of test or control articles, and specially prepared material, which are relatively fragile and differ markedly in stability and quality during storage, shall be retained only as long as the quality of the preparation affords evaluation. In no case shall retention be required for longer periods than those set forth in paragraphs (a) and (b) of this section.

(d) The master schedule sheet, copies of protocols, and records of quality assurance inspections, as required by § 58.35(c) shall be maintained by the quality assurance unit as an easily accessible system of records for the period of time specified in paragraphs (a) and (b) of this section.

(e) Summaries of training and experience and job descriptions required to be maintained by § 58.29(b) may be retained along with all other testing facility employment records for the length of time specified in paragraphs (a) and (b) of this section.

(f) Records and reports of the maintenance and calibration and inspection of equipment, as required by § 58.63(b) and (c), shall be retained for the

length of time specified in paragraph (b) of this section.

(g) Records required by this part may be retained either as original records or as true copies such as photocopies, microfilm, microfiche, or other accurate reproductions of the original records.

(h) If a facility conducting nonclinical testing goes out of business, all raw data, documentation, and other material specified in this section shall be transferred to the archives of the sponsor of the study. The Food and Drug Administration shall be notified in writing of such a transfer.

[43 FR 60013, Dec. 22, 1978, as amended at 52 FR 33781, Sept. 4, 1987; 54 FR 9039, Mar. 3, 1989]

(a) The purposes of disqualification are: (1) To permit the exclusion from consideration of completed studies that were conducted by a testing facility which has failed to comply with the requirements of the good laboratory practice regulations until it can be adequately demonstrated that such noncompliance did not occur during, or did not affect the validity or acceptability of data generated by, a particular study; and (2) to exclude from consideration all studies completed after the date of disqualification until the facility can satisfy the Commissioner that it will conduct studies in compliance with such regulations.

(b) The determination that a nonclinical laboratory study may not be considered in support of an application for a research or marketing permit does not, however, relieve the applicant for such a permit of any obligation under any other applicable regulation to submit the results of the study to the Food and Drug Administration.

§ 58.202 Grounds for disqualification.

The Commissioner may disqualify a testing facility upon finding all of the following:

(a) The testing facility failed to comply with one or more of the regu

lations set forth in this part (or any other regulations regarding such facilities in this chapter);

(b) The noncompliance adversely affected the validity of the nonclinical laboratory studies; and

(c) Other lesser regulatory actions (e.g., warnings or rejection of individual studies) have not been or will probably not be adequate to achieve compliance with the good laboratory practice regulations.

§ 58.204 Notice of and opportunity for hearing on proposed disqualification.

(a) Whenever the Commissioner has information indicating that grounds exist under § 58.202 which in his opinion justify disqualification of a testing facility, he may issue to the testing facility a written notice proposing that the facility be disqualified.

(b) A hearing on the disqualification shall be conducted in accordance with the requirements for a regulatory hearing set forth in Part 16 of this chapter.

§ 58.206 Final order on disqualification.

(a) If the Commissioner, after the regulatory hearing, or after the time for requesting a hearing expires without a request being made, upon an evaulation of the administrative record of the disqualification proceeding, makes the findings required in § 58.202, he shall issue a final order disqualifying the facility. Such order shall include a statement of the basis for that determination. Upon issuing a final order, the Commissioner shall notify (with a copy of the order) the testing facility of the action.

(b) If the Commissioner, after a regulatory hearing or after the time for requesting a hearing expires without a request being made, upon an evaluation of the administrative record of the disqualification proceeding, does not make the findings required in § 58.202, he shall issue a final order terminating the disqualification proceeding. Such order shall include a statement of the basis for that determination. Upon issuing a final order the Commissioner shall notify the testing facility and provide a copy of the order.

§ 58.210 Actions upon disqualification.

(a) Once a testing facility has been disqualified, each application for a research or marketing permit, whether approved or not, containing or relying upon any nonclinical laboratory study conducted by the disqualified testing facility may be examined to determine whether such study was or would be essential to a decision. If it is determined that a study was or would be essential, the Food and Drug Administration shall also determine whether the study is acceptable, notwithstanding the disqualification of the facility. Any study done by a testing facility before or after disqualification may be presumed to be unacceptable, and the person relying on the study may be required to establish that the study was not affected by the circumstances that led to the disqualification, e.g., by submitting validating information. If the study is then determined to be unacceptable, such data such be eliminated from consideration in support of the application; and such elimination may serve as new information justifying the termination or withdrawal of approval of the application.

(b) No nonclinical laboratory study begun by a testing facility after the date of the facility's disqualification shall be considered in support of any application for a research or marketing permit, unless the facility has been reinstated under § 58.219. The determination that a study may not be considered in support of an application for a research or marketing permit does not, however, relieve the applicant for such a permit of any obligation under any other applicable regulation to submit the results of the study to the Food and Drug Administration.

§ 58.213 Public disclosure of information regarding disqualification.

(a) Upon issuance of a final order disqualifying a testing facility under § 58.206(a), the Commissioner may notify all or any interested persons. Such notice may be given at the discretion of the Commissioner whenever he believes that such disclosure would further the public interest or would promote compliance with the good laboratory practice regulations set forth

in this part. Such notice, if given, shall include a copy of the final order issued under § 58.206(a) and shall state that the disqualification constitutes a determination by the Food and Drug Administration that nonclinical laboratory studies performed by the facility will not be considered by the Food and Drug Administration in support of any application for a research or marketing permit. If such notice is sent to another Federal Government agency, the Food and Drug Administration will recommend that the agency also consider whether or not it should accept nonclinical laboratory studies performed by the testing facility. If such notice is sent to any other person, it shall state that it is given because of the relationship between the testing facility and the person being notified and that the Food and Drug Administration is not advising or recommending that any action be taken by the person notified.

(b) A determination that a testing facility has been disqualified and the administrative record regarding such determination are disclosable to the public under Part 20 of this chapter.

§ 58.215 Alternative or additional actions to disqualification.

(a) Disqualification of a testing facility under this subpart is independent of, and neither in lieu of nor a precondition to, other proceedings or actions authorized by the act. The Food and Drug Administration may, at any time, institute against a testing facility and/ or against the sponsor of a nonclinical laboratory study that has been submitted to the Food and Drug Administration any appropriate judicial proceedings (civil or criminal) and any other appropriate regulatory action, in addition to or in lieu of, and prior to, simultaneously with, or subsequent to, disqualification. The Food and Drug Administration may also refer the matter to another Federal, State, or local government law enforcement or regulatory agency for such action as that agency deems appropriate.

(b) The Food and Drug Administration may refuse to consider any particular nonclinical laboratory study in support of an application for a re

search or marketing permit, if it finds that the study was not conducted in accordance with the good laboratory practice regulations set forth in this part, without disqualifying the testing facility that conducted the study or undertaking other regulatory action.

§ 58.217 Suspension or termination of a testing facility by a sponsor.

Termination of a testing facility by a sponsor is independent of, and neither in lieu of nor a precondition to, proceedings or actions authorized by this subpart. If a sponsor terminates or suspends a testing facility from further participation in a nonclinical laboratory study that is being conducted as part of any application for a research or marketing permit that has been submitted to any Center of the Food and Drug Administration (whether approved or not), it shall notify that Center in writing within 15 working days of the action; the notice shall include a statement of the reasons for such action. Suspension or termination of a testing facility by a sponsor does not relieve it of any obligation under any other applicable regulation to submit the results of the study to the Food and Drug Administration.

[43 FR FR 60013, Dec. 22, 1978, as amended at 50 FR 8995, Mar. 6, 1985]

§ 58.219 Reinstatement of a disqualified testing facility.

A testing facility that has been disqualified may be reinstated as an acceptable source of nonclinical laboratory studies to be submitted to the Food and Drug Administration if the Commissioner determines, upon an evaluation of the submission of the testing facility, that the facility can adequately assure that it will conduct future nonclinical laboratory studies in compliance with the good laboratory practice regulations set forth in this part and, if any studies are currently being conducted, that the quality and integrity of such studies have not been seriously compromised. A disqualified testing facility that wishes to be so reinstated shall present in writing to the Commissioner reasons why it believes it should be reinstated and a detailed description of the corrective actions it

has taken or intends to take to assure that the acts or omissions which led to its disqualification will not recur. The Commissioner may condition reinstatement upon the testing facility being found in compliance with the good laboratory practice regulations upon an inspection. If a testing facility is reinstated, the Commissioner shall so notify the testing facility and all organizations and persons who were notified, under § 58.213 of the disqualification of the testing facility. A determination that a testing facility has been reinstated is disclosable to the public under Part 20 of this chapter.

360j, 371, 376); sec. 351 (42 U.S.C. 262); sec. 201 (35 U.S.C. 156).

SOURCE: 53 FR 7305, Mar. 7, 1988, unless otherwise noted.

Subpart A-General Provisions

§ 60.1 Scope.

(a) This part sets forth procedures and requirements for the Food and Drug Administration's review of applications for the extension of the term of certain patents under 35 U.S.C. 156. Patent term restoration is available for certain patents related to human drug products (as defined in 35 U.S.C. 156(f)(2)), and to medical devices, food additives, or color additives subject to regulation under the Federal Food, Drug, and Cosmetic Act. Food and Drug Administration actions in this area include:

(1) Assisting the United States Patent and Trademark Office in determining eligibility for patent term restoration;

(2) Determining the length of a product's regulatory review period;

(3) If petitioned, reviewing and ruling on due diligence challenges to the Food and Drug Administration's regulatory review period determinations; and

(4) Conducting hearings to review initial Food and Drug Administration findings on due diligence challenges.

(b) References in this part to the Code of Federal Regulations are to Chapter I of Title 21, unless otherwise noted.

(a) The definitions contained in 35 U.S.C. 156 apply to those terms when used in this part.

(b) The following definitions of terms apply to this part:

(1) The term "Act" means the Federal Food, Drug, and Cosmetic Act (secs. 201-901, 52 Stat. 1040 et seq. as amended (21 U.S.C. 301-392)).

(2) "Active ingredient" means any component that is intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the body of man. The term includes those components that may undergo chemical change in the manufacture of the drug product and be present in the drug product in a modified form intended to furnish the specified activity or effect.

(3) "Applicant" means any person who submits an application or an amendment or supplement to an application under 35 U.S.C. 156 seeking patent term restoration.

(4) "Application" means an application for patent term restoration submitted under 35 U.S.C. 156.

(5) "Clinical investigation or study" means any experiment that involves a test article and one or more human subjects and that is either subject to requirements for prior submission to the Food and Drug Administration under section 505(i), 507(d), or 520(g) of the Federal Food, Drug, and Cosmetic Act, or is not subject to the requirements for prior submission to FDA under those sections of the Federal Food, Drug, and Cosmetic Act, but the results of which are intended to be submitted later to, or held for inspection by, FDA as part of an application for a research or marketing permit. The term does not include experiments that are subject to the provisions of Part 58 regarding nonclinical laboratory studies.

(6) "Color additive" means any substance that meets the definition in sec