Agency Information Collection Activities; Proposed Collection; Comment Request; General Licensing Provisions: Biologics License Application, Changes to an Approved Application, Labeling, Revocation and Suspension, and Forms FDA 356h and 2567, 12693-12697 [05-5026]

Download as PDF Federal Register / Vol. 70, No. 49 / Tuesday, March 15, 2005 / Notices IV. Registration Instructions The Center for Medicare Management is coordinating meeting registration. While there is no registration fee, individuals must register to attend. As specified in the DATES section of this notice, individuals who wish to attend or make a presentation at the meeting or both must register by March 22, 2005. You may register by sending an e-mail to EMTALATAG@cms.hhs.gov, sending a fax to the attention of Ronda Allen at fax number (410) 786–0681 or (410) 786–0169, or calling (410) 786–4548. All registration requests must include your name, name of the organization (if applicable), address, telephone and fax numbers, e-mail address (if available), and topic to be addressed (if you want to do a presentation). You will receive a registration confirmation with instructions for your arrival at the Hubert H. Humphrey Building. If seating capacity has been reached, you will be notified that the meeting has reached capacity. All registered presenters must submit a hard copy of their presentation to the EMTALA TAG at the first meeting. V. Security Information Since this meeting will be held in a Federal government building, Federal security measures are applicable. In planning your arrival time, we recommend allowing additional time to clear security. In order to gain access to the building, participants must bring a government-issued photo identification (driver’s license, passport, etc.) and a copy of your confirmation of registration for the meeting. Access may be denied to persons without proper identification. All persons entering the building must pass through a metal detector. In addition, all items brought to HHS, whether personal or for the purpose of demonstration or to support a presentation, are subject to inspection. We cannot assume responsibility for coordinating the receipt, transfer, transport, storage, set-up, safety, or timely arrival of any personal belongings or items used for demonstration or to support a presentation. Authority: Section 945 of the Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (MMA). (Catalog of Federal Domestic Assistance Program No. 93.773, Medicare—Hospital Insurance; and Program No. 93.774, Medicare—Supplementary Medical Insurance Program) VerDate jul<14>2003 15:31 Mar 14, 2005 Jkt 205001 Dated: March 10, 2005. Mark B. McClellan, Administrator, Centers for Medicare & Medicaid Services. [FR Doc. 05–5028 Filed 3–14–05; 8:45 am] BILLING CODE 4120–01–P DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. 2005N–0083] Agency Information Collection Activities; Proposed Collection; Comment Request; General Licensing Provisions: Biologics License Application, Changes to an Approved Application, Labeling, Revocation and Suspension, and Forms FDA 356h and 2567 AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing an opportunity for public comment on the proposed collection of certain information by the agency. Under the Paperwork Reduction Act of 1995 (the PRA), Federal agencies are required to publish notice in the Federal Register concerning each proposed collection of information, including each proposed extension of an existing collection of information, and to allow 60 days for public comment in response to the notice. This notice solicits comments on the information collection requirements relating to the general licensing provisions regarding biologics license application, changes to an approved application, labeling, and revocation and suspension, and the use of Forms FDA 356h and 2567. DATES: Submit written or electronic comments on the collection of information by May 16, 2005. ADDRESSES: Submit electronic comments on the collection of information to: https://www.fda.gov/ dockets/ecomments. Submit written comments on the collection of information to the Division of Dockets Management (HFA–305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. All comments should be identified with the docket number found in brackets in the heading of this document. FOR FURTHER INFORMATION CONTACT: Jonna Capezzuto, Office of Management Programs (HFA–250), Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857, 301–827–4659. PO 00000 Frm 00049 Fmt 4703 Sfmt 4703 12693 Under the PRA (44 U.S.C. 3501–3520), Federal agencies must obtain approval from the Office of Management and Budget (OMB) for each collection of information they conduct or sponsor. ‘‘Collection of information’’ is defined in 44 U.S.C. 3502(3) and 5 CFR 1320.3(c) and includes agency requests or requirements that members of the public submit reports, keep records, or provide information to a third party. Section 3506(c)(2)(A) of the PRA (44 U.S.C. 3506(c)(2)(A)) requires Federal agencies to provide a 60-day notice in the Federal Register concerning each proposed collection of information, including each proposed extension of an existing collection of information, before submitting the collection to OMB for approval. To comply with this requirement, FDA is publishing notice of the proposed collection of information set forth in this document. With respect to the following collection of information, FDA invites comments on these topics: (1) Whether the proposed collection of information is necessary for the proper performance of FDA’s functions, including whether the information will have practical utility; (2) the accuracy of FDA’s estimate of the burden of the proposed collection of information, including the validity of the methodology and assumptions used; (3) ways to enhance the quality, utility, and clarity of the information to be collected; and (4) ways to minimize the burden of the collection of information on respondents, including through the use of automated collection techniques, when appropriate, and other forms of information technology. SUPPLEMENTARY INFORMATION: General Licensing Provisions: Biologics License Application, Changes to an Approved Application, Labeling, Revocation and Suspension, and Forms FDA 356h and 2567 (OMB Control Number 0910–0338)—Extension Under Section 351 of the Public Health Services Act (the PHS Act) (42 U.S.C. 262), manufacturers of biological products must submit a license application for FDA review and approval before marketing a biological product in interstate commerce. Licenses may be issued only upon showing that the establishment and the products for which a license is desired meets standards prescribed in regulations designed to insure the continued safety, purity, and potency of such products. All such licenses are issued, suspended, and revoked as prescribed by regulations in part 601 (21 CFR part 601). E:\FR\FM\15MRN1.SGM 15MRN1 12694 Federal Register / Vol. 70, No. 49 / Tuesday, March 15, 2005 / Notices Section 601.2(a) requires a manufacturer of a biological product to submit an application with accompanying information, including labeling information, to FDA for approval to market a product in interstate commerce. The container and package labeling requirements are provided under part 610 (21 CFR part 610) §§ 610.60, 610.61, and 610.62. The estimate for these regulations is included in the estimate under § 601.2(a) in table 1 of this document. Section 601.5(a) requires a licensee to submit to FDA notice of its intention to discontinue manufacture of a product or all products. Section 601.6(a) requires the licensee to notify selling agents and distributors upon suspension of its license, and provide FDA of such notification. Section 601.12 (a)(2) requires, generally, that the holder of an approved biologics license application must assess the effects of a manufacturing change before distributing a biological product made with the change. Section 601.12(a)(4) requires, generally, that the applicant must promptly review all promotional labeling and advertising to make it consistent with any labeling changes implemented. Section 601.12(a)(5) requires the applicant to include a list of all changes contained in the supplement or annual report; for supplements, this list must be provided in the cover letter. The burden estimates for § 601.12(a)(2) are included in the estimates for supplements (§ 601.12(b) and (c)) and annual reports (§ 601.12(d)). The burden estimates for § 601.12(a)(4) are included in the estimates under § 601.12(f)(4) in table 1 of this document or OMB control number 0910–0001 (expires March 31, 2005) because the required information is submitted with Forms FDA 2567 or 2253. Section 601.12(b)(1) and (b)(3), (c)(1) and (c)(3), and (c)(5), and (d)(1) and (d)(3) require applicants to follow specific procedures to inform FDA of each change, in the product, production process, quality controls, equipment, facilities, responsible personnel or labeling established in an approved license application. The appropriate procedure depends on the potential for the change to have a substantial, moderate, or minimal adverse effect on the identity, strength, quality, purity, or potency of the products as they may relate to the safety or effectiveness of the product. Under § 601.12(b)(4), an applicant may ask FDA to expedite its review of a supplement for public health reasons or if a delay in making the change described in it would impose VerDate jul<14>2003 15:31 Mar 14, 2005 Jkt 205001 an extraordinary hardship of the applicant. The burden estimate for § 601.12(b)(4) is minimal and included in the estimate under § 601.12(b)(1) and (b)(3) in table 1 of this document. Section 601.12(e) requires applicants to submit a protocol, or change to a protocol, as a supplement requiring FDA approval before distributing the product. Section 601.12(f)(1), (f)(2), and (f)(3) requires applicants to follow specific procedures to report labeling changes to FDA. Section 601.12(f)(4) requires applicants to report to FDA advertising and promotional labeling and any changes. Section 601.45 requires applicants of biological products for serious or life-threatening illnesses to submit to the agency for consideration, during the preapproval review period, copies of all promotional materials, including promotional labeling as well as advertisements. In addition to §§ 601.2 and 601.12, there are other regulations in parts 640, 660, and 680 (21 CFR parts 640, 660, and 680) that relate to information to be submitted in a license application or supplement for certain blood or allergenic products: §§ 640.6, 640.17, 640.21(c), 640.22(c), 640.25(c), 640.56(c), 640.64(c), 640.74(a), and (b)(2); 660.51(a)(4), 680.1(b)(2)(iii), and 680.1(d). In the table 1 of this document, the burden associated with the information collection requirements in these regulations is included in the burden estimate for § 601.2 and/or § 601.12. A regulation may be listed under more than one paragraph of § 601.12 due to the type of category under which a change to an approved application may be submitted. There are also additional container and/or package labeling requirements for certain licensed biological products: § 640.70(a) for Source Plasma; § 640.74(b)(3) and (b)(4) for Source Plasma Liquid; § 640.84(a) and (c) for Albumin; § 640.94(a) for Plasma Protein Fraction; § 660.2(c) for Antibody to Hepatitis B Surface Antigen; § 660.28(a) and (b) for Blood Grouping Reagent; § 660.35(a), (c) through (g), and (i) through (m) for Reagent Red Blood Cells; § 660.45 for Hepatitis B Surface Antigen; and § 660.55(a) and (b) for Anti-Human Globulin. The burden associated with the additional labeling requirements for submission of a license application for these certain biological products is minimal because the majority of the burden is associated with the requirements under §§ 610.60 through 610.62 or § 809.10 (21 CFR 809.10). Therefore, the burden estimates for these regulations is included in the estimate under §§ 610.60 through 610.62 in table 1 of this document. The burden PO 00000 Frm 00050 Fmt 4703 Sfmt 4703 estimates associated with § 809.10 are approved under OMB control number 0910–0485 (expires March 31, 2005). Section 601.25(b) requests interested persons to submit, for review and evaluation by an advisory review panel, published and unpublished data and information pertinent to a designated category of biological products that have been licensed prior to July 1, 1972. Section 601.26(f) requests that licensees submit to FDA a written statement intended to show that studies adequate and appropriate to resolve questions raised about a biological product have been undertaken for a product if designated as requiring further study under the reclassification procedures. Under § 601.25(b)(3), FDA estimates no burden for this regulation because all requested data and information had been submitted by 1974. Under § 601.26(f), FDA estimates no burden for this regulation because there are no products designated to require further study and none are predicted in the future. However, based on the possible reclassification of a product, the labeling for the product may need to be revised, or a manufacturer, on its own initiative, may deem it necessary for further study. As a result, any changes to product labeling would be reported under § 601.12. Section 601.27(a) requires that applications for new biological products contain data that are adequate to assess the safety and effectiveness of the biological product for the claimed indications in pediatric subpopulations, and to support dosing and administration information. Section 601.27(b) provides that an applicant may request a deferred submission of some or all assessments of safety and effectiveness required under § 601.27(a). Section 601.27(c) provides that an applicant may request a full or partial waiver of the requirements under § 601.27(a). The estimated for § 601.27(a) is included in the burden estimate under § 601.2(a) in table 1 of this document since these regulations deal with information to be provided in an application. Section 601.28 requires sponsors of licensed biological products to submit the information in § 601.28(a), (b), and (c) to the Center for Biologics Evaluation and Research (CBER) or Center for Drugs Evaluation and Research (CDER) each year, within 60 days of the anniversary date of approval of the license. Section 601.28(a) requires sponsors to submit to FDA a brief summary stating whether labeling supplements for pediatric use have been submitted and whether new studies in the pediatric population to support appropriate labeling for the E:\FR\FM\15MRN1.SGM 15MRN1 Federal Register / Vol. 70, No. 49 / Tuesday, March 15, 2005 / Notices pediatric population have been initiated. Section 601.28(b) requires sponsors to submit to FDA an analysis of available safety and efficacy data in the pediatric population and changes proposed in the labeling based on this information. Section 601.28(c) requires sponsors to submit to FDA a statement on the current status of any postmarketing studies in the pediatric population performed by, on or behalf of, the applicant. Sections 601.33 through 601.35 clarify the information to be submitted in an application to FDA to evaluate the safety and effectiveness of in vivo radiopharmaceuticals. The burden estimates for §§ 601.33 through 601.35 are included in the burden estimate under § 601.2(a) in table 1 of this document since these regulations deal with information to be provided in an application. Section 601.91(b)(3) requires applicants to prepare and provide labeling with relevant information to patient or potential patient for biological products approved under the subpart when human efficacy studies are not ethical or feasible (or based on evidence of effectiveness from studies in animals). Section 601.93 provides that biological products approved under this subpart are subject to the postmarketing recordkeeping and safety reporting applicable to all approved biological products. Section 601.94 requires applicants under this subpart to submit to the agency for consideration during preapproval review period copies of all promotional materials including promotional labeling as well as advertisements. Under § 601.93, any potential postmarketing reports and/or recordkeeping burdens would be included under the adverse experience reporting (AER) requirements under part 600 (21 CFR part 600) (OMB control number 0910–0308; expires May 31, 2005). Therefore, any burdens associated with these requirements would be reported under the AER information collection requirements (OMB control number 0910–0308). Section 610.11(g)(2) provides a manufacturer of certain biological products may request an exemption from the general safety test (GST) requirements contained in this subpart. Under § 610.11(g)(2), FDA requires only those manufacturers of biological products requesting an exemption from the GST to submit additional information as part of a license application or supplement to an approved license application. Therefore, the burden estimate for § 610.11(g)(2) is included in the estimate under VerDate jul<14>2003 15:31 Mar 14, 2005 Jkt 205001 §§ 601.2(a) and 601.12(b) in table 1 of this document. Section 610.67 requires certain biological products to comply with the bar code requirements at § 201.25 (21 CFR 201.25). Section 201.25 is approved under OMB control number 0910–0537 (expires February 28, 2007). Section 680.1(c) requires manufacturers to update annually their license file with the list of source materials and the suppliers of the materials. Sections 600.15(b) and 610.53(d) require the submission of a request for an exemption or modification regarding the temperature requirements during shipment and from dating periods, respectively, for certain biological products. Section 606.110(b) requires the submission of a request for approval to perform plasmapheresis of donors who do not meet certain donor requirements for the collection of plasma containing rare antibodies. Under §§ 600.15(b), 610.53(d), and 606.110(b), a request for an exemption or modification to the requirements would be submitted as a supplement. Therefore, the burden hours for any submissions under §§ 600.15(b), 610.53(d), and 606.110(b) are included in the estimates under § 601.12(b) in table 1 of this document. In July 1997, FDA revised Form FDA 356h ‘‘Application to Market a New Drug, Biologic, or an Antibiotic Drug for Human Use’’ to harmonize application procedures between CBER and the CDER. The application form serves primarily as a checklist for firms to gather and submit certain information to FDA. The checklist helps to ensure that the application is complete and contains all the necessary information, so that delays due to lack of information may be eliminated. The form provides key information to FDA for efficient handling and distribution to the appropriate staff for review. The estimated burden hours for submissions to CDER using FDA Form 356h are reported under OMB control number 0910–0001. Form FDA 2567 ‘‘Transmittal of Labels and Circulars’’ is used by manufacturers of licensed biological products to submit labeling (e.g., circulars, package labels, container labels, etc.) and labeling changes for FDA review and approval. The labeling information is submitted with the form for license applications, supplements, or as part of an annual report. Form FDA 2567 is also used for the transmission of advertisements and promotional labeling. Form FDA 2567 serves as an easy guide to assure that the manufacturer has provided the PO 00000 Frm 00051 Fmt 4703 Sfmt 4703 12695 information required for expeditious handling of their labeling by CBER. For advertisements and promotional labeling, manufacturers of licensed biological products may submit to CBER either Form FDA 2567 or 2253. Form FDA 2253 was previously used only by drug manufacturers regulated by CDER. In August of 1998, FDA revised and harmonized Form FDA 2253 so the form may be used to transmit specimens of promotional labeling and advertisements for biological products as well as for prescription drugs and antibiotics. The revised, harmonized form updates the information about the types of promotional materials and the codes that are used to clarify the type of advertisement or labeling submitted; clarifies the intended audience for the advertisements or promotional labeling (e.g., consumers, professionals, news services); and helps ensure the submission is complete. Under table 1 of this document, the number of respondents is based on the estimated annual number of manufacturers that submitted the required information to FDA or the number of submissions FDA received. Based on information obtained from CBER’s database system, there are 306 licensed biologics manufacturers. However, not all manufacturers will have any submissions in a given year and some may have multiple submissions. The total annual responses are based on the estimated number of submissions (i.e., license applications, labeling and other supplements, protocols, advertising and promotional labeling, notifications) for a particular product received annually by FDA. Based on previous estimates, the rate of submissions is not expected to change significantly in the next few years. The hours per response are based on information provided by industry and past FDA experience with the various submissions or notifications. The hours per response include the time estimated to prepare the various submissions or notifications to FDA, and, as applicable, the time required to fill out the appropriate form and collate the documentation. Additional information regarding these estimates is provided below as necessary. Under §§ 601.2 and 601.12, the estimated hours per response are based on the average number of hours to submit the various submissions. The estimated average number of hours is based on the range of hours to complete a very basic application or supplement and a complex application or supplement. Under § 601.6(a), the total annual responses are based on FDA estimates E:\FR\FM\15MRN1.SGM 15MRN1 12696 Federal Register / Vol. 70, No. 49 / Tuesday, March 15, 2005 / Notices that establishments may notify an average of 20 selling agents and distributors of such suspension, and provide FDA of such notification. The number of respondents is based on the estimated annual number of suspensions of a biologic license. Under §§ 601.12(f)(4) and 601.45, manufacturers of biological products may use either Form FDA 2567 or Form FDA 2253 to submit advertising and promotional labeling. Based on information obtained from CBER’s database system, there were an estimated 3,600 submissions of advertising and promotional labeling in fiscal year 2004. FDA estimates that approximately 15 percent of those submissions were received with Form FDA 2567 resulting in an estimated 540 submissions. The burden hours for the remaining submissions received using Form FDA 2253 are reported under OMB control number 0910–0376. Under §§ 601.91 through 601.94, FDA expects to receive very few applications of this nature; however, for calculation purposes, FDA is estimating the submission of one application annually. Under §§ 601.93(b)(3) and 601.94, FDA estimates 240 hours for a manufacturer of a new biological product to develop patient labeling, and to submit the appropriate information and promotional labeling to FDA. The majority of the burden for developing the patient labeling is included under the reporting requirements for § 601.94, therefore minimal burden is calculated for providing the guide to patients under § 601.91(b)(3). There were also 3,540 amendments to an unapproved application or supplement and 23 resubmissions (total of 3,563 submissions) submitted using Form FDA 356h. FDA estimates the burden of this collection of information as follows: TABLE 1.—ESTIMATED ANNUAL REPORTING BURDEN1 21 CFR Section Form FDA No. 601.2(a), 610.60, 610.61, and 610.62 No. of Respondents Annual Frequency per Response Total Annual Responses Hours per Response 2567/356h 14 2 28 601.5(a) NA 16 3.13 50 .33 17 601.6(a) NA 1 21 .33 7 601.12(a)(5) NA 190 601.12(b)(1) and (b)(3) 356h2 190 601.12(c)(1) and (c)(3) 356h2 601.12(c)(5) 21 24,080 2,983 1 2,983 4.75 903 80 72,240 98 2.60 255 50 12,750 356h2 34 1.38 47 50 2,350 601.12(d)(1) and (d)(3) 356h2 166 1.37 227 22.5 5,107.5 601.12(e) 356h2 14 1.43 20 120 2,400 601.12(f)(1) 2567 12 1 12 40 480 601.12(f)(2) 2567 10 1 10 20 200 601.12(f)(3) 2567 70 1.43 100 10 1,000 601.12(f)(4), 601.45 2567 15 36 540 10 5,400 601.25(b)(3) NA 0 0 0 0 0 601.26(f) NA 0 0 0 0 0 601.27(b) NA 3 1 3 24 72 601.27(c) NA 7 1 7 8 56 601.28(a) NA 44 3.27 144 8 1,152 601.28(b) NA 44 3.27 144 24 3,456 601.28(c) NA 44 3.27 144 601.91(b)(3), 601.94 NA 1 1 1 240 240 610.67 NA 174 31 5,400 24 129,600 680.1(c) NA 10 1 10 2 20 356h 306 11.6 3,563 20 71,260 Amendments/resubmissions 15.7 860 Total Hours 1.5 Total 1 There 216 335,086.5 are no capital costs or operating and maintenance costs associated with this collection of information. VerDate jul<14>2003 15:31 Mar 14, 2005 Jkt 205001 PO 00000 Frm 00052 Fmt 4703 Sfmt 4703 E:\FR\FM\15MRN1.SGM 15MRN1 12697 Federal Register / Vol. 70, No. 49 / Tuesday, March 15, 2005 / Notices 2 The reporting requirements under §§ 601.27(a), 601.33, 601.34, 601.35, 610.11(g)(2), 640.17, 640.25(c), 640.56(c), 640.74(b)(2), 660.51(a)(4), and 680.1(b)(2)(iii) are included in the estimate under § 601.2(a). The reporting requirements under § 600.15(b), 610.11(g)(2); 610.53(d), 606.110(b), 640.6, 640.17, 640.21(c), 640.22(c), 640.25(c), 640.56(c), 640.64(c), 640.74(a) and (b)(2), and 680.1(d) are included in the estimate under § 601.12(b). The reporting requirement under §§ 640.17, 640.25(c), 640.56(c), and 640.74(b)(2) is also included in the estimate under § 601.12(c). The reporting requirements under §§ 640.70(a), 640.74(b)(3) and (b)(4); 640.84(a) and (c); 640.94(a), 660.2(c), 660.28(a) and (b); 660.35(a), (c) through (g), and (i) through (m); 660.45, and 660.55(a) and (b) are included under §§ 610.60 through 610.62. Under Table 2, the estimated recordkeeping burden of 1 hour is based on previous estimates for the recordkeeping requirements associated with the AER system. TABLE 2.—ESTIMATED ANNUAL RECORDKEEPING BURDEN1 No. of Recordkeepers Annual Frequency per Record-keeping 1 21 CFR Section 1 601.91(b)(2)(iii) 1 There BILLING CODE 4160–01–S DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. 2003D–0386] Agency Information Collection Activities; Submission for Office of Management and Budget Review; Comment Request; Guidance for Industry on Formal Dispute Resolution: Scientific and Technical Issues Related to Pharmaceutical Current Good Manufacturing Practice Food and Drug Administration, HHS. ACTION: 1 Hours per Record Total Hours 1 1 are no capital costs or operating and maintenance costs associated with this collection of information. Dated: March 9, 2005. Jeffrey Shuren, Assistant Commissioner for Policy. [FR Doc. 05–5026 Filed 3–14–05; 8:45 am] AGENCY: Total Annual Records Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing that a proposed collection of information has been submitted to the Office of Management and Budget (OMB) for review and clearance under the Paperwork Reduction Act of 1995. DATES: Fax written comments on the collection of information by April 14, 2005. OMB is still experiencing significant delays in the regular mail, including first class and express mail, and messenger deliveries are not being accepted. To ensure that comments on the information collection are received, OMB recommends that written comments be faxed to the Office of Information and Regulatory Affairs, OMB, Attn: Fumie Yokota, Desk Officer for FDA, FAX: 202–395–6974. ADDRESSES: VerDate jul<14>2003 15:31 Mar 14, 2005 Jkt 205001 FOR FURTHER INFORMATION CONTACT: Karen L. Nelson, Office of Management Programs (HFA–250), Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857, 301–827–1482. SUPPLEMENTARY INFORMATION: In compliance with 44 U.S.C. 3507, FDA has submitted the following proposed collection of information to OMB for review and clearance. FDA previously issued this proposed collection of information in the Federal Register of January 26, 2005 (70 FR 3712). On February 24, 2005 (70 FR 9083), FDA withdrew the proposed collection of information to correct the title from ‘‘Draft Guidance for Industry on Formal Dispute Resolution: Scientific and Technical Issues Related to Pharmaceutical Current Good Manufacturing Practice’’ to ‘‘Guidance for Industry on Formal Dispute Resolution: Scientific and Technical Issues Related to Pharmaceutical Current Good Manufacturing Practice.’’ Title: Guidance for Industry on Formal Dispute Resolution: Scientific and Technical Issues Related to Pharmaceutical Current Good Manufacturing Practice Description: The guidance is intended to provide information to manufacturers of veterinary and human drugs, including human biological drug products, on how to resolve disputes of scientific and technical issues relating to current good manufacturing practices (CGMPs). Disputes related to scientific and technical issues may arise during FDA inspections of pharmaceutical manufacturers to determine compliance with CGMP requirements, or during FDA’s assessment of corrective actions undertaken as a result of such inspections. The guidance provides procedures that will encourage open and prompt discussion of disputes and lead to their resolution. The guidance PO 00000 Frm 00053 Fmt 4703 Sfmt 4703 describes procedures for raising such disputes to the Office of Regulatory Affairs (ORA) and center levels and for requesting review by the Dispute Resolution Panel for Scientific and Technical Issues Related to Pharmaceutical CGMP (DR Panel). When a scientific or technical issue arises during an FDA inspection, the manufacturer should initially attempt to reach agreement on the issue informally with the investigator. Certain scientific or technical issues may be too complex or time-consuming to resolve during the inspection. If resolution of a scientific or technical issue is not accomplished through informal mechanisms prior to the issuance of the FDA 483, the manufacturer can formally request dispute resolution and can use the formal two-tiered dispute resolution process described in the guidance. Tier-one of the formal dispute resolution process involves scientific or technical issues raised by a manufacturer to the ORA and center levels. If a manufacturer disagrees with the tier-one decision, tier-two of the formal dispute resolution process would then be available for appealing that decision to the DR Panel. If a manufacturer disagrees with the scientific or technical basis for an observation listed by an investigator on an FDA 483, the manufacturer can file a written request for formal dispute resolution with the appropriate ORA unit as described in the guidance. The request for formal dispute resolution should be made within 30 days of the completion of an inspection, and should include all supporting documentation and arguments for review, as described later in this document. If a manufacturer disagrees with the tier-one decision in the formal dispute resolution process, the manufacturer can file a written request for formal dispute resolution by E:\FR\FM\15MRN1.SGM 15MRN1

Agencies

[Federal Register Volume 70, Number 49 (Tuesday, March 15, 2005)]
[Notices]
[Pages 12693-12697]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 05-5026]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 2005N-0083]


Agency Information Collection Activities; Proposed Collection; 
Comment Request; General Licensing Provisions: Biologics License 
Application, Changes to an Approved Application, Labeling, Revocation 
and Suspension, and Forms FDA 356h and 2567

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing an 
opportunity for public comment on the proposed collection of certain 
information by the agency. Under the Paperwork Reduction Act of 1995 
(the PRA), Federal agencies are required to publish notice in the 
Federal Register concerning each proposed collection of information, 
including each proposed extension of an existing collection of 
information, and to allow 60 days for public comment in response to the 
notice. This notice solicits comments on the information collection 
requirements relating to the general licensing provisions regarding 
biologics license application, changes to an approved application, 
labeling, and revocation and suspension, and the use of Forms FDA 356h 
and 2567.

DATES: Submit written or electronic comments on the collection of 
information by May 16, 2005.

ADDRESSES: Submit electronic comments on the collection of information 
to: https://www.fda.gov/dockets/ecomments. Submit written comments on 
the collection of information to the Division of Dockets Management 
(HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, 
Rockville, MD 20852. All comments should be identified with the docket 
number found in brackets in the heading of this document.

FOR FURTHER INFORMATION CONTACT: Jonna Capezzuto, Office of Management 
Programs (HFA-250), Food and Drug Administration, 5600 Fishers Lane, 
Rockville, MD 20857, 301-827-4659.

SUPPLEMENTARY INFORMATION: Under the PRA (44 U.S.C. 3501-3520), Federal 
agencies must obtain approval from the Office of Management and Budget 
(OMB) for each collection of information they conduct or sponsor. 
``Collection of information'' is defined in 44 U.S.C. 3502(3) and 5 CFR 
1320.3(c) and includes agency requests or requirements that members of 
the public submit reports, keep records, or provide information to a 
third party. Section 3506(c)(2)(A) of the PRA (44 U.S.C. 3506(c)(2)(A)) 
requires Federal agencies to provide a 60-day notice in the Federal 
Register concerning each proposed collection of information, including 
each proposed extension of an existing collection of information, 
before submitting the collection to OMB for approval. To comply with 
this requirement, FDA is publishing notice of the proposed collection 
of information set forth in this document.
    With respect to the following collection of information, FDA 
invites comments on these topics: (1) Whether the proposed collection 
of information is necessary for the proper performance of FDA's 
functions, including whether the information will have practical 
utility; (2) the accuracy of FDA's estimate of the burden of the 
proposed collection of information, including the validity of the 
methodology and assumptions used; (3) ways to enhance the quality, 
utility, and clarity of the information to be collected; and (4) ways 
to minimize the burden of the collection of information on respondents, 
including through the use of automated collection techniques, when 
appropriate, and other forms of information technology.

General Licensing Provisions: Biologics License Application, Changes to 
an Approved Application, Labeling, Revocation and Suspension, and Forms 
FDA 356h and 2567 (OMB Control Number 0910-0338)--Extension

    Under Section 351 of the Public Health Services Act (the PHS Act) 
(42 U.S.C. 262), manufacturers of biological products must submit a 
license application for FDA review and approval before marketing a 
biological product in interstate commerce. Licenses may be issued only 
upon showing that the establishment and the products for which a 
license is desired meets standards prescribed in regulations designed 
to insure the continued safety, purity, and potency of such products. 
All such licenses are issued, suspended, and revoked as prescribed by 
regulations in part 601 (21 CFR part 601).

[[Page 12694]]

    Section 601.2(a) requires a manufacturer of a biological product to 
submit an application with accompanying information, including labeling 
information, to FDA for approval to market a product in interstate 
commerce. The container and package labeling requirements are provided 
under part 610 (21 CFR part 610) Sec. Sec.  610.60, 610.61, and 610.62. 
The estimate for these regulations is included in the estimate under 
Sec.  601.2(a) in table 1 of this document.
    Section 601.5(a) requires a licensee to submit to FDA notice of its 
intention to discontinue manufacture of a product or all products. 
Section 601.6(a) requires the licensee to notify selling agents and 
distributors upon suspension of its license, and provide FDA of such 
notification.
    Section 601.12 (a)(2) requires, generally, that the holder of an 
approved biologics license application must assess the effects of a 
manufacturing change before distributing a biological product made with 
the change. Section 601.12(a)(4) requires, generally, that the 
applicant must promptly review all promotional labeling and advertising 
to make it consistent with any labeling changes implemented. Section 
601.12(a)(5) requires the applicant to include a list of all changes 
contained in the supplement or annual report; for supplements, this 
list must be provided in the cover letter. The burden estimates for 
Sec.  601.12(a)(2) are included in the estimates for supplements (Sec.  
601.12(b) and (c)) and annual reports (Sec.  601.12(d)). The burden 
estimates for Sec.  601.12(a)(4) are included in the estimates under 
Sec.  601.12(f)(4) in table 1 of this document or OMB control number 
0910-0001 (expires March 31, 2005) because the required information is 
submitted with Forms FDA 2567 or 2253.
    Section 601.12(b)(1) and (b)(3), (c)(1) and (c)(3), and (c)(5), and 
(d)(1) and (d)(3) require applicants to follow specific procedures to 
inform FDA of each change, in the product, production process, quality 
controls, equipment, facilities, responsible personnel or labeling 
established in an approved license application. The appropriate 
procedure depends on the potential for the change to have a 
substantial, moderate, or minimal adverse effect on the identity, 
strength, quality, purity, or potency of the products as they may 
relate to the safety or effectiveness of the product. Under Sec.  
601.12(b)(4), an applicant may ask FDA to expedite its review of a 
supplement for public health reasons or if a delay in making the change 
described in it would impose an extraordinary hardship of the 
applicant. The burden estimate for Sec.  601.12(b)(4) is minimal and 
included in the estimate under Sec.  601.12(b)(1) and (b)(3) in table 1 
of this document.
    Section 601.12(e) requires applicants to submit a protocol, or 
change to a protocol, as a supplement requiring FDA approval before 
distributing the product. Section 601.12(f)(1), (f)(2), and (f)(3) 
requires applicants to follow specific procedures to report labeling 
changes to FDA. Section 601.12(f)(4) requires applicants to report to 
FDA advertising and promotional labeling and any changes. Section 
601.45 requires applicants of biological products for serious or life-
threatening illnesses to submit to the agency for consideration, during 
the preapproval review period, copies of all promotional materials, 
including promotional labeling as well as advertisements.
    In addition to Sec. Sec.  601.2 and 601.12, there are other 
regulations in parts 640, 660, and 680 (21 CFR parts 640, 660, and 680) 
that relate to information to be submitted in a license application or 
supplement for certain blood or allergenic products: Sec. Sec.  640.6, 
640.17, 640.21(c), 640.22(c), 640.25(c), 640.56(c), 640.64(c), 
640.74(a), and (b)(2); 660.51(a)(4), 680.1(b)(2)(iii), and 680.1(d). In 
the table 1 of this document, the burden associated with the 
information collection requirements in these regulations is included in 
the burden estimate for Sec.  601.2 and/or Sec.  601.12. A regulation 
may be listed under more than one paragraph of Sec.  601.12 due to the 
type of category under which a change to an approved application may be 
submitted.
    There are also additional container and/or package labeling 
requirements for certain licensed biological products: Sec.  640.70(a) 
for Source Plasma; Sec.  640.74(b)(3) and (b)(4) for Source Plasma 
Liquid; Sec.  640.84(a) and (c) for Albumin; Sec.  640.94(a) for Plasma 
Protein Fraction; Sec.  660.2(c) for Antibody to Hepatitis B Surface 
Antigen; Sec.  660.28(a) and (b) for Blood Grouping Reagent; Sec.  
660.35(a), (c) through (g), and (i) through (m) for Reagent Red Blood 
Cells; Sec.  660.45 for Hepatitis B Surface Antigen; and Sec.  
660.55(a) and (b) for Anti-Human Globulin. The burden associated with 
the additional labeling requirements for submission of a license 
application for these certain biological products is minimal because 
the majority of the burden is associated with the requirements under 
Sec. Sec.  610.60 through 610.62 or Sec.  809.10 (21 CFR 809.10). 
Therefore, the burden estimates for these regulations is included in 
the estimate under Sec. Sec.  610.60 through 610.62 in table 1 of this 
document. The burden estimates associated with Sec.  809.10 are 
approved under OMB control number 0910-0485 (expires March 31, 2005).
    Section 601.25(b) requests interested persons to submit, for review 
and evaluation by an advisory review panel, published and unpublished 
data and information pertinent to a designated category of biological 
products that have been licensed prior to July 1, 1972. Section 
601.26(f) requests that licensees submit to FDA a written statement 
intended to show that studies adequate and appropriate to resolve 
questions raised about a biological product have been undertaken for a 
product if designated as requiring further study under the 
reclassification procedures. Under Sec.  601.25(b)(3), FDA estimates no 
burden for this regulation because all requested data and information 
had been submitted by 1974. Under Sec.  601.26(f), FDA estimates no 
burden for this regulation because there are no products designated to 
require further study and none are predicted in the future. However, 
based on the possible reclassification of a product, the labeling for 
the product may need to be revised, or a manufacturer, on its own 
initiative, may deem it necessary for further study. As a result, any 
changes to product labeling would be reported under Sec.  601.12.
    Section 601.27(a) requires that applications for new biological 
products contain data that are adequate to assess the safety and 
effectiveness of the biological product for the claimed indications in 
pediatric subpopulations, and to support dosing and administration 
information. Section 601.27(b) provides that an applicant may request a 
deferred submission of some or all assessments of safety and 
effectiveness required under Sec.  601.27(a). Section 601.27(c) 
provides that an applicant may request a full or partial waiver of the 
requirements under Sec.  601.27(a). The estimated for Sec.  601.27(a) 
is included in the burden estimate under Sec.  601.2(a) in table 1 of 
this document since these regulations deal with information to be 
provided in an application.
    Section 601.28 requires sponsors of licensed biological products to 
submit the information in Sec.  601.28(a), (b), and (c) to the Center 
for Biologics Evaluation and Research (CBER) or Center for Drugs 
Evaluation and Research (CDER) each year, within 60 days of the 
anniversary date of approval of the license. Section 601.28(a) requires 
sponsors to submit to FDA a brief summary stating whether labeling 
supplements for pediatric use have been submitted and whether new 
studies in the pediatric population to support appropriate labeling for 
the

[[Page 12695]]

pediatric population have been initiated. Section 601.28(b) requires 
sponsors to submit to FDA an analysis of available safety and efficacy 
data in the pediatric population and changes proposed in the labeling 
based on this information. Section 601.28(c) requires sponsors to 
submit to FDA a statement on the current status of any postmarketing 
studies in the pediatric population performed by, on or behalf of, the 
applicant.
    Sections 601.33 through 601.35 clarify the information to be 
submitted in an application to FDA to evaluate the safety and 
effectiveness of in vivo radiopharmaceuticals. The burden estimates for 
Sec. Sec.  601.33 through 601.35 are included in the burden estimate 
under Sec.  601.2(a) in table 1 of this document since these 
regulations deal with information to be provided in an application.
    Section 601.91(b)(3) requires applicants to prepare and provide 
labeling with relevant information to patient or potential patient for 
biological products approved under the subpart when human efficacy 
studies are not ethical or feasible (or based on evidence of 
effectiveness from studies in animals). Section 601.93 provides that 
biological products approved under this subpart are subject to the 
postmarketing recordkeeping and safety reporting applicable to all 
approved biological products. Section 601.94 requires applicants under 
this subpart to submit to the agency for consideration during 
preapproval review period copies of all promotional materials including 
promotional labeling as well as advertisements. Under Sec.  601.93, any 
potential postmarketing reports and/or recordkeeping burdens would be 
included under the adverse experience reporting (AER) requirements 
under part 600 (21 CFR part 600) (OMB control number 0910-0308; expires 
May 31, 2005). Therefore, any burdens associated with these 
requirements would be reported under the AER information collection 
requirements (OMB control number 0910-0308).
    Section 610.11(g)(2) provides a manufacturer of certain biological 
products may request an exemption from the general safety test (GST) 
requirements contained in this subpart. Under Sec.  610.11(g)(2), FDA 
requires only those manufacturers of biological products requesting an 
exemption from the GST to submit additional information as part of a 
license application or supplement to an approved license application. 
Therefore, the burden estimate for Sec.  610.11(g)(2) is included in 
the estimate under Sec. Sec.  601.2(a) and 601.12(b) in table 1 of this 
document.
    Section 610.67 requires certain biological products to comply with 
the bar code requirements at Sec.  201.25 (21 CFR 201.25). Section 
201.25 is approved under OMB control number 0910-0537 (expires February 
28, 2007).
    Section 680.1(c) requires manufacturers to update annually their 
license file with the list of source materials and the suppliers of the 
materials.
    Sections 600.15(b) and 610.53(d) require the submission of a 
request for an exemption or modification regarding the temperature 
requirements during shipment and from dating periods, respectively, for 
certain biological products. Section 606.110(b) requires the submission 
of a request for approval to perform plasmapheresis of donors who do 
not meet certain donor requirements for the collection of plasma 
containing rare antibodies. Under Sec. Sec.  600.15(b), 610.53(d), and 
606.110(b), a request for an exemption or modification to the 
requirements would be submitted as a supplement. Therefore, the burden 
hours for any submissions under Sec. Sec.  600.15(b), 610.53(d), and 
606.110(b) are included in the estimates under Sec.  601.12(b) in table 
1 of this document.
    In July 1997, FDA revised Form FDA 356h ``Application to Market a 
New Drug, Biologic, or an Antibiotic Drug for Human Use'' to harmonize 
application procedures between CBER and the CDER. The application form 
serves primarily as a checklist for firms to gather and submit certain 
information to FDA. The checklist helps to ensure that the application 
is complete and contains all the necessary information, so that delays 
due to lack of information may be eliminated. The form provides key 
information to FDA for efficient handling and distribution to the 
appropriate staff for review. The estimated burden hours for 
submissions to CDER using FDA Form 356h are reported under OMB control 
number 0910-0001.
    Form FDA 2567 ``Transmittal of Labels and Circulars'' is used by 
manufacturers of licensed biological products to submit labeling (e.g., 
circulars, package labels, container labels, etc.) and labeling changes 
for FDA review and approval. The labeling information is submitted with 
the form for license applications, supplements, or as part of an annual 
report. Form FDA 2567 is also used for the transmission of 
advertisements and promotional labeling. Form FDA 2567 serves as an 
easy guide to assure that the manufacturer has provided the information 
required for expeditious handling of their labeling by CBER. For 
advertisements and promotional labeling, manufacturers of licensed 
biological products may submit to CBER either Form FDA 2567 or 2253. 
Form FDA 2253 was previously used only by drug manufacturers regulated 
by CDER. In August of 1998, FDA revised and harmonized Form FDA 2253 so 
the form may be used to transmit specimens of promotional labeling and 
advertisements for biological products as well as for prescription 
drugs and antibiotics. The revised, harmonized form updates the 
information about the types of promotional materials and the codes that 
are used to clarify the type of advertisement or labeling submitted; 
clarifies the intended audience for the advertisements or promotional 
labeling (e.g., consumers, professionals, news services); and helps 
ensure the submission is complete.
    Under table 1 of this document, the number of respondents is based 
on the estimated annual number of manufacturers that submitted the 
required information to FDA or the number of submissions FDA received. 
Based on information obtained from CBER's database system, there are 
306 licensed biologics manufacturers. However, not all manufacturers 
will have any submissions in a given year and some may have multiple 
submissions. The total annual responses are based on the estimated 
number of submissions (i.e., license applications, labeling and other 
supplements, protocols, advertising and promotional labeling, 
notifications) for a particular product received annually by FDA. Based 
on previous estimates, the rate of submissions is not expected to 
change significantly in the next few years. The hours per response are 
based on information provided by industry and past FDA experience with 
the various submissions or notifications. The hours per response 
include the time estimated to prepare the various submissions or 
notifications to FDA, and, as applicable, the time required to fill out 
the appropriate form and collate the documentation. Additional 
information regarding these estimates is provided below as necessary.
    Under Sec. Sec.  601.2 and 601.12, the estimated hours per response 
are based on the average number of hours to submit the various 
submissions. The estimated average number of hours is based on the 
range of hours to complete a very basic application or supplement and a 
complex application or supplement.
    Under Sec.  601.6(a), the total annual responses are based on FDA 
estimates

[[Page 12696]]

that establishments may notify an average of 20 selling agents and 
distributors of such suspension, and provide FDA of such notification. 
The number of respondents is based on the estimated annual number of 
suspensions of a biologic license.
    Under Sec. Sec.  601.12(f)(4) and 601.45, manufacturers of 
biological products may use either Form FDA 2567 or Form FDA 2253 to 
submit advertising and promotional labeling. Based on information 
obtained from CBER's database system, there were an estimated 3,600 
submissions of advertising and promotional labeling in fiscal year 
2004. FDA estimates that approximately 15 percent of those submissions 
were received with Form FDA 2567 resulting in an estimated 540 
submissions. The burden hours for the remaining submissions received 
using Form FDA 2253 are reported under OMB control number 0910-0376.
    Under Sec. Sec.  601.91 through 601.94, FDA expects to receive very 
few applications of this nature; however, for calculation purposes, FDA 
is estimating the submission of one application annually. Under 
Sec. Sec.  601.93(b)(3) and 601.94, FDA estimates 240 hours for a 
manufacturer of a new biological product to develop patient labeling, 
and to submit the appropriate information and promotional labeling to 
FDA. The majority of the burden for developing the patient labeling is 
included under the reporting requirements for Sec.  601.94, therefore 
minimal burden is calculated for providing the guide to patients under 
Sec.  601.91(b)(3).
    There were also 3,540 amendments to an unapproved application or 
supplement and 23 resubmissions (total of 3,563 submissions) submitted 
using Form FDA 356h.
    FDA estimates the burden of this collection of information as 
follows:

                                 Table 1.--Estimated Annual Reporting Burden\1\
----------------------------------------------------------------------------------------------------------------
                    Form FDA      No. of     Annual Frequency   Total Annual       Hours per
 21 CFR Section       No.      Respondents     per Response       Responses         Response        Total Hours
----------------------------------------------------------------------------------------------------------------
601.2(a),           2567/356h           14               2              28                860          24,080
 610.60, 610.61,
 and 610.62
----------------------------------------------------------------------------------------------------------------
601.5(a)                   NA           16               3.13           50                   .33           17
----------------------------------------------------------------------------------------------------------------
601.6(a)                   NA            1              21              21                   .33            7
----------------------------------------------------------------------------------------------------------------
601.12(a)(5)               NA          190              15.7         2,983                  1           2,983
----------------------------------------------------------------------------------------------------------------
601.12(b)(1) and      356h\2\          190               4.75          903                 80          72,240
 (b)(3)
----------------------------------------------------------------------------------------------------------------
601.12(c)(1) and      356h\2\           98               2.60          255                 50          12,750
 (c)(3)
----------------------------------------------------------------------------------------------------------------
601.12(c)(5)          356h\2\           34               1.38           47                 50           2,350
----------------------------------------------------------------------------------------------------------------
601.12(d)(1) and      356h\2\          166               1.37          227                 22.5         5,107.5
 (d)(3)
----------------------------------------------------------------------------------------------------------------
601.12(e)             356h\2\           14               1.43           20                120           2,400
----------------------------------------------------------------------------------------------------------------
601.12(f)(1)             2567           12               1              12                 40             480
----------------------------------------------------------------------------------------------------------------
601.12(f)(2)             2567           10               1              10                 20             200
----------------------------------------------------------------------------------------------------------------
601.12(f)(3)             2567           70               1.43          100                 10           1,000
----------------------------------------------------------------------------------------------------------------
601.12(f)(4),            2567           15              36             540                 10           5,400
 601.45
----------------------------------------------------------------------------------------------------------------
601.25(b)(3)               NA            0               0               0                  0               0
----------------------------------------------------------------------------------------------------------------
601.26(f)                  NA            0               0               0                  0               0
----------------------------------------------------------------------------------------------------------------
601.27(b)                  NA            3               1               3                 24              72
----------------------------------------------------------------------------------------------------------------
601.27(c)                  NA            7               1               7                  8              56
----------------------------------------------------------------------------------------------------------------
601.28(a)                  NA           44               3.27          144                  8           1,152
----------------------------------------------------------------------------------------------------------------
601.28(b)                  NA           44               3.27          144                 24           3,456
----------------------------------------------------------------------------------------------------------------
601.28(c)                  NA           44               3.27          144                  1.5           216
----------------------------------------------------------------------------------------------------------------
601.91(b)(3),              NA            1               1               1                240             240
 601.94
----------------------------------------------------------------------------------------------------------------
610.67                     NA          174              31           5,400                 24         129,600
----------------------------------------------------------------------------------------------------------------
680.1(c)                   NA           10               1              10                  2              20
----------------------------------------------------------------------------------------------------------------
Amendments/              356h          306              11.6         3,563                 20          71,260
 resubmissions
----------------------------------------------------------------------------------------------------------------
Total             ...........  ...........  .................  ..............  .................      335,086.5
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.

[[Page 12697]]

 
\2\ The reporting requirements under Sec.  Sec.   601.27(a), 601.33, 601.34, 601.35, 610.11(g)(2), 640.17,
  640.25(c), 640.56(c), 640.74(b)(2), 660.51(a)(4), and 680.1(b)(2)(iii) are included in the estimate under Sec.
    601.2(a). The reporting requirements under Sec.   600.15(b), 610.11(g)(2); 610.53(d), 606.110(b), 640.6,
  640.17, 640.21(c), 640.22(c), 640.25(c), 640.56(c), 640.64(c), 640.74(a) and (b)(2), and 680.1(d) are included
  in the estimate under Sec.   601.12(b). The reporting requirement under Sec.  Sec.   640.17, 640.25(c),
  640.56(c), and 640.74(b)(2) is also included in the estimate under Sec.   601.12(c). The reporting
  requirements under Sec.  Sec.   640.70(a), 640.74(b)(3) and (b)(4); 640.84(a) and (c); 640.94(a), 660.2(c),
  660.28(a) and (b); 660.35(a), (c) through (g), and (i) through (m); 660.45, and 660.55(a) and (b) are included
  under Sec.  Sec.   610.60 through 610.62.

    Under Table 2, the estimated recordkeeping burden of 1 hour is 
based on previous estimates for the recordkeeping requirements 
associated with the AER system.

                               Table 2.--Estimated Annual Recordkeeping Burden\1\
----------------------------------------------------------------------------------------------------------------
                                                      Annual
         21 CFR Section           No. of Record-   Frequency per   Total Annual      Hours per      Total Hours
                                      keepers     Record-keeping      Records         Record
----------------------------------------------------------------------------------------------------------------
601.91(b)(2)(iii)                              1               1               1               1               1
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.


    Dated: March 9, 2005.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 05-5026 Filed 3-14-05; 8:45 am]
BILLING CODE 4160-01-S

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