Agency Information Collection Activities; Proposed Collection; Comment Request; General Licensing Provisions: Biologics License Application, Changes to an Approved Application, Labeling, Revocation and Suspension, Postmarketing Studies Status Reports, and Form FDA 356h, 44868-44872 [2016-16352]

Download as PDF 44868 Federal Register / Vol. 81, No. 132 / Monday, July 11, 2016 / Notices DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA–2013–N–0578] Agency Information Collection Activities; Proposed Collection; Comment Request; General Licensing Provisions: Biologics License Application, Changes to an Approved Application, Labeling, Revocation and Suspension, Postmarketing Studies Status Reports, and Form FDA 356h AGENCY: Food and Drug Administration, HHS. ACTION: Notice. 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 collection of information relating to general licensing provisions for biologics license applications (BLAs), changes to an approved application, labeling, revocation and suspension, postmarketing studies status reports, and Form FDA 356h. DATES: Submit electronic or written comments on the collection of information by September 9, 2016. ADDRESSES: You may submit comments as follows: SUMMARY: sradovich on DSK3GDR082PROD with NOTICES Electronic Submissions Submit electronic comments in the following way: • Federal eRulemaking Portal: http:// www.regulations.gov. Follow the instructions for submitting comments. Comments submitted electronically, including attachments, to http:// www.regulations.gov will be posted to the docket unchanged. Because your comment will be made public, you are solely responsible for ensuring that your comment does not include any confidential information that you or a third party may not wish to be posted, such as medical information, your or anyone else’s Social Security number, or confidential business information, such as a manufacturing process. Please note that if you include your name, contact information, or other information that identifies you in the body of your VerDate Sep<11>2014 16:55 Jul 08, 2016 Jkt 238001 comments, that information will be posted on http://www.regulations.gov. • If you want to submit a comment with confidential information that you do not wish to be made available to the public, submit the comment as a written/paper submission and in the manner detailed (see ‘‘Written/Paper Submissions’’ and ‘‘Instructions’’). Written/Paper Submissions Submit written/paper submissions as follows: Mail/Hand delivery/Courier (for written/paper submissions): Division of Dockets Management (HFA–305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. • For written/paper comments submitted to the Division of Dockets Management, FDA will post your comment, as well as any attachments, except for information submitted, marked and identified, as confidential, if submitted as detailed in ‘‘Instructions.’’ Instructions: All submissions received must include the Docket No. FDA– 2013–N–0578 for ‘‘General Licensing Provisions: Biologics License Application, Changes to an Approved Application, Labeling, Revocation and Suspension, Postmarketing Studies Status Reports and Form FDA 356h.’’ Received comments will be placed in the docket and, except for those submitted as ‘‘Confidential Submissions,’’ publicly viewable at http://www.regulations.gov or at the Division of Dockets Management between 9 a.m. and 4 p.m., Monday through Friday. • Confidential Submissions—To submit a comment with confidential information that you do not wish to be made publicly available, submit your comments only as a written/paper submission. You should submit two copies total. One copy will include the information you claim to be confidential with a heading or cover note that states ‘‘THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.’’ The Agency will review this copy, including the claimed confidential information, in its consideration of comments. The second copy, which will have the claimed confidential information redacted/blacked out, will be available for public viewing and posted on http:// www.regulations.gov. Submit both copies to the Division of Dockets Management. If you do not wish your name and contact information to be made publicly available, you can provide this information on the cover sheet and not in the body of your comments and you must identify this information as ‘‘confidential.’’ Any PO 00000 Frm 00031 Fmt 4703 Sfmt 4703 information marked as ‘‘confidential’’ will not be disclosed except in accordance with 21 CFR 10.20 and other applicable disclosure law. For more information about FDA’s posting of comments to public dockets, see 80 FR 56469, September 18, 2015, or access the information at: http://www.fda.gov/ regulatoryinformation/dockets/ default.htm. Docket: For access to the docket to read background documents or the electronic and written/paper comments received, go to http:// www.regulations.gov and insert the docket number, found in brackets in the heading of this document, into the ‘‘Search’’ box and follow the prompts and/or go to the Division of Dockets Management, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. FOR FURTHER INFORMATION CONTACT: FDA PRA Staff, Office of Operations, Food and Drug Administration, Three White Flint North 10A–12M, 11601 Landsdown St., North Bethesda, MD 20852, PRAStaff@fda.hhs.gov. 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 E:\FR\FM\11JYN1.SGM 11JYN1 Federal Register / Vol. 81, No. 132 / Monday, July 11, 2016 / Notices of automated collection techniques, when appropriate, and other forms of information technology. sradovich on DSK3GDR082PROD with NOTICES General Licensing Provisions: Biologics License Application, Changes to an Approved Application, Labeling, Revocation and Suspension, Postmarketing Studies Status Reports, and Form FDA 356h OMB Control No. 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 ensure 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). Section 130(a) of the Food and Drug Administration Modernization Act (Pub. L. 105–115) amended the Federal Food, Drug, and Cosmetic Act (the FD&C Act) by adding a new provision (section 506B of the FD&C Act (21 U.S.C. 356b)) requiring reports of postmarketing studies for approved human drugs and licensed biological products. Section 506B of the FD&C Act provides FDA with additional authority to monitor the progress of postmarketing studies that applicants have made a commitment to conduct and requires the Agency to make publicly available information that pertains to the status of these studies. Under section 506B(a) of the FD&C Act, applicants that have committed to conduct a postmarketing study for an approved human drug or licensed biological product must submit to FDA a status report of the progress of the study or the reasons for the failure of the applicant to conduct the study. This report must be submitted within 1 year after the U.S. approval of the application and then annually until the study is completed or terminated. A summary of the collection of information requirements follows: Section 601.2(a) requires a manufacturer of a biological product to submit an application on forms prescribed for such purposes with accompanying data and information, including certain labeling information, to FDA for approval to market a product in interstate commerce. The container and package labeling requirements are provided under §§ 610.60 through VerDate Sep<11>2014 16:55 Jul 08, 2016 Jkt 238001 610.65 (21 CFR 610.60 through 610.65). The estimate for these regulations is included in the estimate under § 601.2(a) in table 1. Section 601.5(a) requires a manufacturer to submit to FDA notice of its intention to discontinue manufacture of a product or all products. Section 601.6(a) requires the manufacturer 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 BLA 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 revise 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. Sections 601.12(b)(1) and (3), (c)(1), (3), and (5), and (d)(1) and (3) require applicants to follow specific procedures to submit information to FDA of any changes, in the product, production process, quality controls, equipment, facilities, or responsible personnel 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 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 (3) in table 1. 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) through (3) requires applicants to follow specific procedures to report certain labeling changes to FDA. Section 601.12(f)(4) requires applicants to report to FDA advertising and promotional labeling and any changes. PO 00000 Frm 00032 Fmt 4703 Sfmt 4703 44869 Under § 601.14, the content of labeling required in 21 CFR 201.100(d)(3) must be in electronic format and in a form that FDA can process, review, and archive. This requirement is in addition to the provisions of §§ 601.2(a) and 601.12(f). The burden estimate for § 601.14 is minimal and included in the estimate under §§ 601.2(a) (BLAs) and 601.12(f)(1) through (3) (labeling supplements and annual reports) in table 1. Section 601.45 requires applicants of biological products for serious or lifethreatening illnesses to submit to the Agency for consideration, during the pre-approval 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 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 as follows: §§ 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); and 680.1(b)(2)(iii) and (d). In table 1, the burden associated with the information collection requirements in the applicable regulations is included in the burden estimate for §§ 601.2 and/ or 601.12. A regulation may be listed under more than one subsection 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 including: § 640.74(b)(3) and (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), (b), and (c) 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 610.65 or 21 CFR 809.10. Therefore, the burden estimates for these regulations are included in the estimate under §§ 610.60 through 610.65 in table 1. The burden estimates associated with § 809.10 are approved under OMB control number 0910–0485. E:\FR\FM\11JYN1.SGM 11JYN1 sradovich on DSK3GDR082PROD with NOTICES 44870 Federal Register / Vol. 81, No. 132 / Monday, July 11, 2016 / Notices 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) until after licensing the product for use in adults. Section 601.27(c) provides that an applicant may request a full or partial waiver of the requirements under § 601.27(a) with adequate justification. The burden estimates for § 601.27(a) are included in the burden estimate under § 601.2(a) in table 1 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 to the Center for Drug 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 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. If the postmarketing studies were required or agreed to, the status of these studies is to be reported under § 601.70 rather than under this section. Sections 601.33 through 601.35 clarify the information to be submitted in an application to FDA to evaluate the safety and effectiveness of radiopharmaceuticals intended for in vivo administration for diagnostic and monitoring use. The burden estimates for §§ 601.33 through 601.35 are included in the burden estimate under § 601.2(a) in table 1 since these regulations deal with information to be provided in an application. Section 601.70(b) requires each applicant of a licensed biological product to submit annually a report to FDA on the status of postmarketing studies for each approved product VerDate Sep<11>2014 16:55 Jul 08, 2016 Jkt 238001 application. Each annual postmarketing status report must be accompanied by a completed transmittal Form FDA 2252 (Form FDA 2252 approved under OMB control number 0910–0001). Under § 601.70(d), two copies of the annual report shall be submitted to FDA. Sections 601.91 through 601.94 concern biological products for which human efficacy studies are not ethical or feasible. Section 601.91(b)(2) requires, in certain circumstances, such postmarking restrictions as are needed to ensure the safe use of the biological product. Section 601.91(b)(3) requires applicants to prepare and provide labeling with relevant information to patients or potential patients for biological products approved under part 601, subpart H, 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 subpart H are subject to the postmarketing recordkeeping and safety reporting applicable to all approved biological products. Section 601.94 requires applicants under subpart H to submit to the Agency for consideration during preapproval review period copies of all promotional materials including promotional labeling as well as advertisements. Under §§ 601.91(b)(2) and 601.93, any potential postmarketing reports and/or recordkeeping burdens would be included under the adverse experience reporting (AER) requirements under 21 CFR part 600 (OMB control number 0910–0308). Therefore, any burdens associated with these requirements would be reported under the AER information collection requirements (OMB control number 0910–0308). The burden estimate for § 601.91(b)(3) is included in the estimate under §§ 610.60 through 610.65. Section 610.9(a) requires the applicant to present certain information, in the form of a license application or supplement to the application, for a modification of any particular test method or manufacturing process or the conditions which it is conducted under the biologics regulations. The burden estimate for § 610.9(a) is included in the estimate under §§ 601.2(a) and 601.12(b) and (c) in table 1. Under § 610.15(d), the Director of CBER or the Director of CDER may approve, as appropriate, a manufacturer’s request for exceptions or alternatives to the regulation for constituent materials. Manufacturers seeking approval of an exception or alternative must submit a request in writing with a brief statement describing PO 00000 Frm 00033 Fmt 4703 Sfmt 4703 the basis for the request and the supporting data. Section 640.120 requires licensed establishments to submit a request for an exception or alternative to any requirement in the biologics regulations regarding blood, blood components, or blood products. For licensed establishments, a request for an exception or alternative must be submitted in accordance with § 601.12; therefore, the burden estimate for § 640.120 is included in the estimate under § 601.12(b) in table 1. Section 680.1(c) requires manufacturers to update annually their license file with the list of source materials and the suppliers of the materials. Section 680.1(b)(3)(iv) requires manufacturers to notify FDA when certain diseases are detected in source 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) (21 CFR 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. 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 CDER. The application form serves primarily as a checklist for firms to gather and submit certain information to FDA. As such, the form, now entitled ‘‘Application to Market a New or Abbreviated New Drug or Biologic for Human Use,’’ 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. In addition, the form provides key information to FDA for efficient handling and distribution to the appropriate staff for review. The estimated burden hours for nonbiological product submissions to CDER using FDA Form 356h are approved under OMB control number 0910–0001 (an estimated 3,200 submissions × 24 hours = 76,800 hours). E:\FR\FM\11JYN1.SGM 11JYN1 Federal Register / Vol. 81, No. 132 / Monday, July 11, 2016 / Notices For advertisements and promotional labeling (e.g., circulars, package labels, container labels, etc.) and labeling changes, manufacturers of licensed biological products may submit to CBER or CDER Form FDA 2253. 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 that the submission is complete. Form FDA 2253 can also be submitted electronically. Form FDA 2253 is approved under OMB control number 0910–0001. Respondents to this collection of information are manufacturers of biological products. Under tables 1 and 2, the numbers of respondents are based on the estimated annual number of manufacturers that submitted the required information to FDA or the number of submissions FDA received in fiscal year (FY) 2015. Based on information obtained from FDA’s database systems, there are an estimated 391 licensed biologics manufacturers. 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. 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 section 601.6(a), the total annual responses are based on FDA estimates 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. In table 1, FDA is estimating one in case a suspension occurs. Under §§ 601.12(f)(4) and 601.45, manufacturers of biological products may use Form FDA 2253 to submit 44871 advertising and promotional labeling (which can include multiple pieces). Based on information obtained from FDA’s database system, there were an estimated 11,676 submissions using Form FDA 2253 of advertising and promotional labeling from 114 respondents. Under §§ 601.28 and 601.70(b), FDA estimates that it takes an applicant approximately 24 hours (8 hours per study × 3 studies) annually to gather, complete, and submit the appropriate information for each postmarketing status report (approximately two to four studies per report) and the accompanied transmittal Form FDA 2252. Included in these 24 hours is the time necessary to prepare and submit two copies of the annual progress report of postmarketing studies to FDA under § 601.70(d). For FY 2015, there were 139 reports from 82 respondents. Under § 610.15(d), FDA has received no submissions since the implementation of the final rule in April 2011. Therefore, FDA is estimating 1 respondent and 1 annual request to account for a possible submission to CBER or CDER of a request for an exception or alternative for constituent materials under § 610.15(d). There were a total of 2,777 amendments to an unapproved application or supplement and resubmissions submitted using Form FDA 356h. FDA estimates the burden of this collection of information as follows: TABLE 1—ESTIMATED ANNUAL REPORTING BURDEN 1 Number of responses per respondent Number of respondents Average burden per response Total annual responses Total hours 10 sradovich on DSK3GDR082PROD with NOTICES 21 CFR section Form FDA No. 601.2(a) 2, 610.60 through 610.65 3 601.5(a) ........................................... 601.6(a) ........................................... 601.12(a)(5) ..................................... 601.12(b)(1)/(b)(3)/(e) ...................... 601.12(c)(1)/(c)(3) 5 ......................... 601.12(c)(5) ..................................... 601.12(d)(1)/(d)(3) 6/(f)(3) 8 .............. 601.12(f)(1) 7 .................................... 601.12(f)(2) 7 .................................... 601.12(f)(4)/601.45 9 ........................ 601.27(b) ......................................... 601.27(c) ......................................... 601.70(b) and (d)/601.28 ................ 610.15(d) ......................................... 680.1(c) ........................................... 680.1(b)(3)(iv) .................................. Amendments/Resubmissions .......... 356h ................... N/A ..................... N/A ..................... N/A ..................... 356h 2 ................. 356h 2 ................. 356h 2 ................. 356h 2 ................. 2253 ................... 2253 ................... 2253 ................... N/A ..................... N/A ..................... 2252 ................... N/A ..................... N/A ..................... N/A ..................... 356h ................... 28 12 1 537 164 120 7 246 72 60 114 20 12 82 1 9 1 125 1.36 0.75 1 24.41 3.66 4.78 1.14 3.34 1.93 1.82 102.42 16.50 1.08 1.70 1 1 1 22.22 38 9 1 13,108 600 574 8 822 139 109 11,676 330 13 139 1 9 1 2,777 860 ..................... 0.33 (20 minutes) 1 ......................... 1 ......................... 80 ....................... 50 ....................... 50 ....................... 24 ....................... 40 ....................... 20 ....................... 10 ....................... 24 ....................... 8 ......................... 24 ....................... 1 ......................... 2 ......................... 2 ......................... 20 ....................... 32,680 3 1 13,108 48,000 28,700 400 19,728 5,560 2,180 116,670 7,920 104 3,336 1 18 2 55,540 Total ......................................... ............................ ........................ ........................ ........................ ............................ 333,951 1 There are no capital costs or operating and maintenance costs associated with this collection of information. reporting requirements under §§ 601.14, 601.27(a), 601.33, 601.34, 601.35, 610.9(a), 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). 3 The reporting requirements under §§ 601.93(b)(3), 640.70(a), 640.74(b)(3) and (4), 640.84(a) and (c), 640.94(a), 660.2(c), 660.28(a), (b), and (c), 660.35(a), (c through g), and (i through m), 660.45, and 660.55(a) and (b) are included under §§ 610.60 through 610.65. 2 The VerDate Sep<11>2014 16:55 Jul 08, 2016 Jkt 238001 PO 00000 Frm 00034 Fmt 4703 Sfmt 4703 E:\FR\FM\11JYN1.SGM 11JYN1 44872 Federal Register / Vol. 81, No. 132 / Monday, July 11, 2016 / Notices 4 The reporting requirements under §§ 601.12(a)(2) and (b)(4), 600.15(b), 610.9(a), 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), 640.120, and 680.1(d) are included in the estimate under § 601.12(b). 5 The reporting requirements under §§ 601.12(a)(2), 610.9(a), 640.17, 640.25(c), 640.56(c), and 640.74(b)(2) are included in the estimate under § 601.12(c). 6 The reporting requirement under § 601.12(a)(2) is included in the estimate under § 601.12(d). 7 The reporting requirement under § 601.14 is included in the estimate under § 601.12(f)(1) and (2). 8 The reporting requirement under §§ 601.12(a)(4) and 601.14 is included in the estimate under § 601.12(f)(3). 9 The reporting requirement under § 601.94 is included in the estimate under § 601.45. 10 The numbers in this column have been rounded to the nearest whole number. 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 THIRD-PARTY DISCLOSURE BURDEN 1 21 CFR section Number of respondents Annual disclosures per respondent Total annual disclosures Average burden per disclosure Total hours 2 601.6(a) .................................................. 1 20 20 0.33 (20 minutes) ........................ 7 1 There are no capital costs or operating and maintenance costs associated with this collection of information. to the nearest whole number. 2 Rounded Dated: July 5, 2016. Leslie Kux, Associate Commissioner for Policy. [FR Doc. 2016–16352 Filed 7–8–16; 8:45 am] BILLING CODE 4164–01–P DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA–2016–N–0001] Controlling the Progression of Myopia: Contact Lenses and Future Medical Devices; Public Workshop AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public workshop. The Food and Drug Administration (FDA), in cosponsorship with the American Academy of Ophthalmology (AAO), American Academy of Optometry (AAOpt), American Association for Pediatric Ophthalmology and Strabismus (AAPOS), American Optometric Association (AOA), American Society of Cataract and Refractive Surgery (ASCRS), and Contact Lens Association of Ophthalmologists, Inc. (CLAO) is announcing a public workshop entitled ‘‘Controlling the Progression of Myopia: Contact Lenses and Future Medical Devices.’’ The purpose of this workshop is to discuss the increasing prevalence of myopia, as well as suggested clinical trial design attributes for studies using contact lenses or other medical devices to control the progression of myopia. DATES: The public workshop will be held on September 30, 2016, from 8 a.m. sradovich on DSK3GDR082PROD with NOTICES SUMMARY: VerDate Sep<11>2014 16:55 Jul 08, 2016 Jkt 238001 to 6 p.m. Pickup of materials will begin at 7:30 a.m. ADDRESSES: The public workshop will be held at the FDA White Oak Campus, 10903 New Hampshire Ave., Bldg. 31, Conference Center, the Great Room, (Rm. 1503), Silver Spring, MD, 20993. Entrance for the public workshop participants (non-FDA employees) is through Building 1 where routine security check procedures will be performed. For parking and security information, please refer to http:// www.fda.gov/AboutFDA/ WorkingatFDA/BuildingsandFacilities/ WhiteOakCampusInformation/ ucm241740.htm. FOR FURTHER INFORMATION CONTACT: Michelle Tarver, Office of Device Evaluation, Center for Devices and Radiological Health, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 66, Rm. 2504, Silver Spring, MD 20993, 301–796–6884. SUPPLEMENTARY INFORMATION: starting interventions in childhood. The literature suggests that myopia progression is most rapid between 6 and 11 years of age and manipulating peripheral retinal image quality may be a treatment strategy to control axial length and therefore the progression of myopia. The results of studies conducted with specialized contact lenses, both rigid and soft, have indicated that this approach may reduce the rate of myopic progression in children. As research into myopia control is continuing at a rapid pace, accompanying potential safety and effectiveness questions also have emerged. To ensure that the studies conducted provide information that can adequately inform the regulatory review, we are conducting a workshop to answer questions about the appropriate clinical trial design and outcomes for these devices. I. Background The prevalence of myopia in the United States has increased over the past decade with approximately 24 percent (over 30 million) of adults over 40 years of age being affected. Recent studies have found the overall prevalence of myopia to be 1.2 percent among non-Hispanic White children, 6.6 percent in African Americans, 3.7 percent in Hispanic, and 3.98 percent in Asian children. Pathologic myopia is the third most frequent cause of blindness due to retinal detachments or abnormal blood vessel growth. Given these potentially poor outcomes with high myopia, researchers have sought ways to prevent its development by Topics to be discussed at the public workshop include, but are not limited to the following topics: • Myopia Demographics. • Contact Lens Use and Safety in a Pediatric Population. • Contact Lens Behaviors and Hygiene. • Studies Conducted on Myopia Control Devices and Their Challenges. • Regulation of Contact Lenses (Ref. 1). • Patient/Caregiver Perspectives and the Role in Trial Design and Conduct (Refs. 2 and 3). We will also have a panel discussion to address questions related to the design of these clinical trials. PO 00000 Frm 00035 Fmt 4703 Sfmt 4703 II. Topics for Discussion at the Public Workshop E:\FR\FM\11JYN1.SGM 11JYN1

Agencies

[Federal Register Volume 81, Number 132 (Monday, July 11, 2016)]
[Notices]
[Pages 44868-44872]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-16352]



[[Page 44868]]

-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2013-N-0578]


Agency Information Collection Activities; Proposed Collection; 
Comment Request; General Licensing Provisions: Biologics License 
Application, Changes to an Approved Application, Labeling, Revocation 
and Suspension, Postmarketing Studies Status Reports, and Form FDA 356h

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 collection of information 
relating to general licensing provisions for biologics license 
applications (BLAs), changes to an approved application, labeling, 
revocation and suspension, postmarketing studies status reports, and 
Form FDA 356h.

DATES: Submit electronic or written comments on the collection of 
information by September 9, 2016.

ADDRESSES: You may submit comments as follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to http://www.regulations.gov 
will be posted to the docket unchanged. Because your comment will be 
made public, you are solely responsible for ensuring that your comment 
does not include any confidential information that you or a third party 
may not wish to be posted, such as medical information, your or anyone 
else's Social Security number, or confidential business information, 
such as a manufacturing process. Please note that if you include your 
name, contact information, or other information that identifies you in 
the body of your comments, that information will be posted on http://www.regulations.gov.
     If you want to submit a comment with confidential 
information that you do not wish to be made available to the public, 
submit the comment as a written/paper submission and in the manner 
detailed (see ``Written/Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
    Mail/Hand delivery/Courier (for written/paper submissions): 
Division of Dockets Management (HFA-305), Food and Drug Administration, 
5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Division of 
Dockets Management, FDA will post your comment, as well as any 
attachments, except for information submitted, marked and identified, 
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No. 
FDA-2013-N-0578 for ``General Licensing Provisions: Biologics License 
Application, Changes to an Approved Application, Labeling, Revocation 
and Suspension, Postmarketing Studies Status Reports and Form FDA 
356h.'' Received comments will be placed in the docket and, except for 
those submitted as ``Confidential Submissions,'' publicly viewable at 
http://www.regulations.gov or at the Division of Dockets Management 
between 9 a.m. and 4 p.m., Monday through Friday.
     Confidential Submissions--To submit a comment with 
confidential information that you do not wish to be made publicly 
available, submit your comments only as a written/paper submission. You 
should submit two copies total. One copy will include the information 
you claim to be confidential with a heading or cover note that states 
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will 
review this copy, including the claimed confidential information, in 
its consideration of comments. The second copy, which will have the 
claimed confidential information redacted/blacked out, will be 
available for public viewing and posted on http://www.regulations.gov. 
Submit both copies to the Division of Dockets Management. If you do not 
wish your name and contact information to be made publicly available, 
you can provide this information on the cover sheet and not in the body 
of your comments and you must identify this information as 
``confidential.'' Any information marked as ``confidential'' will not 
be disclosed except in accordance with 21 CFR 10.20 and other 
applicable disclosure law. For more information about FDA's posting of 
comments to public dockets, see 80 FR 56469, September 18, 2015, or 
access the information at: http://www.fda.gov/regulatoryinformation/dockets/default.htm.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to http://www.regulations.gov and insert the docket number, found in brackets in 
the heading of this document, into the ``Search'' box and follow the 
prompts and/or go to the Division of Dockets Management, 5630 Fishers 
Lane, Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: FDA PRA Staff, Office of Operations, 
Food and Drug Administration, Three White Flint North 10A-12M, 11601 
Landsdown St., North Bethesda, MD 20852, PRAStaff@fda.hhs.gov.

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

[[Page 44869]]

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, 
Postmarketing Studies Status Reports, and Form FDA 356h

OMB Control No. 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 ensure 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).
    Section 130(a) of the Food and Drug Administration Modernization 
Act (Pub. L. 105-115) amended the Federal Food, Drug, and Cosmetic Act 
(the FD&C Act) by adding a new provision (section 506B of the FD&C Act 
(21 U.S.C. 356b)) requiring reports of postmarketing studies for 
approved human drugs and licensed biological products. Section 506B of 
the FD&C Act provides FDA with additional authority to monitor the 
progress of postmarketing studies that applicants have made a 
commitment to conduct and requires the Agency to make publicly 
available information that pertains to the status of these studies. 
Under section 506B(a) of the FD&C Act, applicants that have committed 
to conduct a postmarketing study for an approved human drug or licensed 
biological product must submit to FDA a status report of the progress 
of the study or the reasons for the failure of the applicant to conduct 
the study. This report must be submitted within 1 year after the U.S. 
approval of the application and then annually until the study is 
completed or terminated.
    A summary of the collection of information requirements follows:
    Section 601.2(a) requires a manufacturer of a biological product to 
submit an application on forms prescribed for such purposes with 
accompanying data and information, including certain labeling 
information, to FDA for approval to market a product in interstate 
commerce. The container and package labeling requirements are provided 
under Sec. Sec.  610.60 through 610.65 (21 CFR 610.60 through 610.65). 
The estimate for these regulations is included in the estimate under 
Sec.  601.2(a) in table 1.
    Section 601.5(a) requires a manufacturer to submit to FDA notice of 
its intention to discontinue manufacture of a product or all products. 
Section 601.6(a) requires the manufacturer 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 BLA 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 
revise 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. 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 
601.12(f)(4) in table 1.
    Sections 601.12(b)(1) and (3), (c)(1), (3), and (5), and (d)(1) and 
(3) require applicants to follow specific procedures to submit 
information to FDA of any changes, in the product, production process, 
quality controls, equipment, facilities, or responsible personnel 
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 (3) in table 1.
    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) through (3) requires 
applicants to follow specific procedures to report certain labeling 
changes to FDA. Section 601.12(f)(4) requires applicants to report to 
FDA advertising and promotional labeling and any changes.
    Under Sec.  601.14, the content of labeling required in 21 CFR 
201.100(d)(3) must be in electronic format and in a form that FDA can 
process, review, and archive. This requirement is in addition to the 
provisions of Sec. Sec.  601.2(a) and 601.12(f). The burden estimate 
for Sec.  601.14 is minimal and included in the estimate under 
Sec. Sec.  601.2(a) (BLAs) and 601.12(f)(1) through (3) (labeling 
supplements and annual reports) in table 1.
    Section 601.45 requires applicants of biological products for 
serious or life-threatening illnesses to submit to the Agency for 
consideration, during the pre-approval 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 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 as follows: 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); and 680.1(b)(2)(iii) and (d).
    In table 1, the burden associated with the information collection 
requirements in the applicable regulations is included in the burden 
estimate for Sec. Sec.  601.2 and/or 601.12. A regulation may be listed 
under more than one subsection 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 including: Sec.  
640.74(b)(3) and (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), 
(b), and (c) 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 610.65 
or 21 CFR 809.10. Therefore, the burden estimates for these regulations 
are included in the estimate under Sec. Sec.  610.60 through 610.65 in 
table 1. The burden estimates associated with Sec.  809.10 are approved 
under OMB control number 0910-0485.

[[Page 44870]]

    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) until after licensing the 
product for use in adults. Section 601.27(c) provides that an applicant 
may request a full or partial waiver of the requirements under Sec.  
601.27(a) with adequate justification. The burden estimates for Sec.  
601.27(a) are included in the burden estimate under Sec.  601.2(a) in 
table 1 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 to the Center for Drug 
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 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. If the postmarketing studies were required or agreed to, the 
status of these studies is to be reported under Sec.  601.70 rather 
than under this section.
    Sections 601.33 through 601.35 clarify the information to be 
submitted in an application to FDA to evaluate the safety and 
effectiveness of radiopharmaceuticals intended for in vivo 
administration for diagnostic and monitoring use. 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 since these regulations deal 
with information to be provided in an application.
    Section 601.70(b) requires each applicant of a licensed biological 
product to submit annually a report to FDA on the status of 
postmarketing studies for each approved product application. Each 
annual postmarketing status report must be accompanied by a completed 
transmittal Form FDA 2252 (Form FDA 2252 approved under OMB control 
number 0910-0001). Under Sec.  601.70(d), two copies of the annual 
report shall be submitted to FDA.
    Sections 601.91 through 601.94 concern biological products for 
which human efficacy studies are not ethical or feasible. Section 
601.91(b)(2) requires, in certain circumstances, such postmarking 
restrictions as are needed to ensure the safe use of the biological 
product. Section 601.91(b)(3) requires applicants to prepare and 
provide labeling with relevant information to patients or potential 
patients for biological products approved under part 601, subpart H, 
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 subpart H are subject 
to the postmarketing recordkeeping and safety reporting applicable to 
all approved biological products. Section 601.94 requires applicants 
under subpart H 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. Sec.  
601.91(b)(2) and 601.93, any potential postmarketing reports and/or 
recordkeeping burdens would be included under the adverse experience 
reporting (AER) requirements under 21 CFR part 600 (OMB control number 
0910-0308). Therefore, any burdens associated with these requirements 
would be reported under the AER information collection requirements 
(OMB control number 0910-0308). The burden estimate for Sec.  
601.91(b)(3) is included in the estimate under Sec. Sec.  610.60 
through 610.65.
    Section 610.9(a) requires the applicant to present certain 
information, in the form of a license application or supplement to the 
application, for a modification of any particular test method or 
manufacturing process or the conditions which it is conducted under the 
biologics regulations. The burden estimate for Sec.  610.9(a) is 
included in the estimate under Sec. Sec.  601.2(a) and 601.12(b) and 
(c) in table 1.
    Under Sec.  610.15(d), the Director of CBER or the Director of CDER 
may approve, as appropriate, a manufacturer's request for exceptions or 
alternatives to the regulation for constituent materials. Manufacturers 
seeking approval of an exception or alternative must submit a request 
in writing with a brief statement describing the basis for the request 
and the supporting data.
    Section 640.120 requires licensed establishments to submit a 
request for an exception or alternative to any requirement in the 
biologics regulations regarding blood, blood components, or blood 
products. For licensed establishments, a request for an exception or 
alternative must be submitted in accordance with Sec.  601.12; 
therefore, the burden estimate for Sec.  640.120 is included in the 
estimate under Sec.  601.12(b) in table 1.
    Section 680.1(c) requires manufacturers to update annually their 
license file with the list of source materials and the suppliers of the 
materials. Section 680.1(b)(3)(iv) requires manufacturers to notify FDA 
when certain diseases are detected in source 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) (21 CFR 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.
    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 CDER. The application form 
serves primarily as a checklist for firms to gather and submit certain 
information to FDA. As such, the form, now entitled ``Application to 
Market a New or Abbreviated New Drug or Biologic for Human Use,'' 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. In addition, the form provides key information to FDA for 
efficient handling and distribution to the appropriate staff for 
review. The estimated burden hours for nonbiological product 
submissions to CDER using FDA Form 356h are approved under OMB control 
number 0910-0001 (an estimated 3,200 submissions x 24 hours = 76,800 
hours).

[[Page 44871]]

    For advertisements and promotional labeling (e.g., circulars, 
package labels, container labels, etc.) and labeling changes, 
manufacturers of licensed biological products may submit to CBER or 
CDER Form FDA 2253. 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 that the submission is complete. Form 
FDA 2253 can also be submitted electronically. Form FDA 2253 is 
approved under OMB control number 0910-0001.
    Respondents to this collection of information are manufacturers of 
biological products. Under tables 1 and 2, the numbers of respondents 
are based on the estimated annual number of manufacturers that 
submitted the required information to FDA or the number of submissions 
FDA received in fiscal year (FY) 2015. Based on information obtained 
from FDA's database systems, there are an estimated 391 licensed 
biologics manufacturers. 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. 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 section 601.6(a), the total annual responses are based on FDA 
estimates 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. In table 1, FDA is 
estimating one in case a suspension occurs.
    Under Sec. Sec.  601.12(f)(4) and 601.45, manufacturers of 
biological products may use Form FDA 2253 to submit advertising and 
promotional labeling (which can include multiple pieces). Based on 
information obtained from FDA's database system, there were an 
estimated 11,676 submissions using Form FDA 2253 of advertising and 
promotional labeling from 114 respondents.
    Under Sec. Sec.  601.28 and 601.70(b), FDA estimates that it takes 
an applicant approximately 24 hours (8 hours per study x 3 studies) 
annually to gather, complete, and submit the appropriate information 
for each postmarketing status report (approximately two to four studies 
per report) and the accompanied transmittal Form FDA 2252. Included in 
these 24 hours is the time necessary to prepare and submit two copies 
of the annual progress report of postmarketing studies to FDA under 
Sec.  601.70(d). For FY 2015, there were 139 reports from 82 
respondents.
    Under Sec.  610.15(d), FDA has received no submissions since the 
implementation of the final rule in April 2011. Therefore, FDA is 
estimating 1 respondent and 1 annual request to account for a possible 
submission to CBER or CDER of a request for an exception or alternative 
for constituent materials under Sec.  610.15(d).
    There were a total of 2,777 amendments to an unapproved application 
or supplement and resubmissions submitted using Form FDA 356h.
    FDA estimates the burden of this collection of information as 
follows:

                                                     Table 1--Estimated Annual Reporting Burden \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                    Number of
            21 CFR section                   Form FDA No.           Number of     responses per   Total annual     Average  burden per      Total hours
                                                                   respondents     respondent       responses            response              \10\
--------------------------------------------------------------------------------------------------------------------------------------------------------
601.2(a) \2\, 610.60 through 610.65    356h....................              28            1.36              38  860....................          32,680
 \3\.
601.5(a).............................  N/A.....................              12            0.75               9  0.33 (20 minutes)......               3
601.6(a).............................  N/A.....................               1               1               1  1......................               1
601.12(a)(5).........................  N/A.....................             537           24.41          13,108  1......................          13,108
601.12(b)(1)/(b)(3)/(e)..............  356h \2\................             164            3.66             600  80.....................          48,000
601.12(c)(1)/(c)(3) \5\..............  356h \2\................             120            4.78             574  50.....................          28,700
601.12(c)(5).........................  356h \2\................               7            1.14               8  50.....................             400
601.12(d)(1)/(d)(3) \6\/(f)(3) \8\...  356h \2\................             246            3.34             822  24.....................          19,728
601.12(f)(1) \7\.....................  2253....................              72            1.93             139  40.....................           5,560
601.12(f)(2) \7\.....................  2253....................              60            1.82             109  20.....................           2,180
601.12(f)(4)/601.45 \9\..............  2253....................             114          102.42          11,676  10.....................         116,670
601.27(b)............................  N/A.....................              20           16.50             330  24.....................           7,920
601.27(c)............................  N/A.....................              12            1.08              13  8......................             104
601.70(b) and (d)/601.28.............  2252....................              82            1.70             139  24.....................           3,336
610.15(d)............................  N/A.....................               1               1               1  1......................               1
680.1(c).............................  N/A.....................               9               1               9  2......................              18
680.1(b)(3)(iv)......................  N/A.....................               1               1               1  2......................               2
Amendments/Resubmissions.............  356h....................             125           22.22           2,777  20.....................          55,540
                                                                ----------------------------------------------------------------------------------------
    Total............................  ........................  ..............  ..............  ..............  .......................         333,951
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.
\2\ The reporting requirements under Sec.  Sec.   601.14, 601.27(a), 601.33, 601.34, 601.35, 610.9(a), 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).
\3\ The reporting requirements under Sec.  Sec.   601.93(b)(3), 640.70(a), 640.74(b)(3) and (4), 640.84(a) and (c), 640.94(a), 660.2(c), 660.28(a), (b),
  and (c), 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 610.65.

[[Page 44872]]

 
\4\ The reporting requirements under Sec.  Sec.   601.12(a)(2) and (b)(4), 600.15(b), 610.9(a), 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), 640.120, and 680.1(d) are included in the estimate under Sec.   601.12(b).
\5\ The reporting requirements under Sec.  Sec.   601.12(a)(2), 610.9(a), 640.17, 640.25(c), 640.56(c), and 640.74(b)(2) are included in the estimate
  under Sec.   601.12(c).
\6\ The reporting requirement under Sec.   601.12(a)(2) is included in the estimate under Sec.   601.12(d).
\7\ The reporting requirement under Sec.   601.14 is included in the estimate under Sec.   601.12(f)(1) and (2).
\8\ The reporting requirement under Sec.  Sec.   601.12(a)(4) and 601.14 is included in the estimate under Sec.   601.12(f)(3).
\9\ The reporting requirement under Sec.   601.94 is included in the estimate under Sec.   601.45.
\10\ The numbers in this column have been rounded to the nearest whole number.

    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 Third-Party Disclosure Burden \1\
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                                                                        Annual
                 21 CFR section                      Number of     disclosures per    Total annual      Average burden per disclosure    Total hours \2\
                                                    respondents       respondent      disclosures
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601.6(a)........................................               1               20               20   0.33 (20 minutes).................               7
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.
\2\ Rounded to the nearest whole number.


    Dated: July 5, 2016.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2016-16352 Filed 7-8-16; 8:45 am]
 BILLING CODE 4164-01-P