Federal Register / Vol. 79, No. 243 / Thursday, December 18, 2014 / Notices 75569 

approved (signed) by the Study Director. For 

example, see Study Start Date in the SEND Trial 

Summary Domain (TSPARMCD = STSTDTC), 

http://www.cdisc.org. 

Federal Register notice must use the 

appropriate FDA-supported standards, 

formats, and terminologies specified in 

the Data Standards Catalog for NDA, 

ANDA, and certain BLA submissions. 

Study data contained in certain IND 

submissions must use the specified 

formats for electronic submission in 

studies with a start date 36 months or 

later after this Federal Register notice of 

availability. 

In section 745A(a) of the FD&C Act, 

Congress granted explicit authorization 

to FDA to implement the statutory 

electronic submission requirements by 

specifying the format for such 

submissions in guidance. Because this 

guidance provides such requirements 

under section 745A(a) of the FD&C Act, 

indicated by the use of the words must 

or required, it is not subject to the usual 

restrictions in FDA’s good guidance 

practice regulations, such as the 

requirement that guidances not establish 

legally enforceable responsibilities. See 

21 CFR 10.115(d). 

II. Paperwork Reduction Act of 1995 

The guidance refers to previously 

approved collections of information that 

are subject to review by the Office of 

Management and Budget (OMB) under 

the Paperwork Reduction Act of 1995 

(44 U.S.C. 3501–3520). The guidance 

pertains to sponsors and applicants 

making regulatory submissions to FDA 

in electronic format for NDAs, ANDAs, 

BLAs, and INDs. The information 

collection discussed in the guidance is 

contained in our IND regulations (21 

CFR part 312) and approved under OMB 

control number 0910–0014, our NDA 

regulations (including ANDAs) (21 CFR 

part 314) and approved under OMB 

control number 0910–0001, and our 

BLA regulations (21 CFR part 601) and 

approved under OMB control number 

0910–0338. 

Sponsors and applicants have been 

voluntarily submitting standardized 

study data in electronic format. Under 

FDASIA, sponsors and applicants will 

be required to make all of these 

submissions electronically in 

compliance with the specified 

standards, formats, and terminologies. 

These requirements will be phased in 

over 2- and 3-year periods after the 

issuance of this guidance. 

For many years sponsors and 

applicants have been submitting 

electronically using the electronic 

common technical document format and 

have included electronic study data in 

both legacy and standardized formats. 

For some sponsors and applicants there 

may be new costs, including capital 

costs or operating and maintenance 

costs, which would result from the 

requirements under FDASIA and this 

guidance, because some sponsors and 

applicants would have to change from 

submissions that have included legacy 

(non-standard) study data to 

submissions in compliance with this 

guidance. FDA estimates that for some 

sponsors and applicants the costs may 

be as follows: 

• Data management (hardware/

software): $350,000–$1,000,000 

• Initial data management operations: 

$500,000–$1,000,000 

• Training: $100,000—$250,000 

III. Comments 

Interested persons may submit either 

electronic comments to http://

www.regulations.gov or written 

comments regarding this document to 

the Division of Dockets Management 

(see ADDRESSES). It is only necessary to 

send one set of comments. Identify 

comments with the docket number 

found in brackets in the heading of this 

document. Received comments may be 

seen in the Division of Dockets 

Management between 9 a.m. and 4 p.m., 

Monday through Friday, and will be 

posted to the docket at http://

www.regulations.gov. 

IV. Electronic Access 

Persons with access to the Internet 

may obtain the document at either 

http://www.fda.gov/Drugs/Guidance

ComplianceRegulatoryInformation/

Guidances/default.htm, http://www.fda.

gov/BiologicsBloodVaccines/Guidance

ComplianceRegulatoryInformation/

Guidances/default.htm, or http://

www.regulations.gov. 

Dated: December 12, 2014. 

Leslie Kux, 

Associate Commissioner for Policy. 

[FR Doc. 2014–29608 Filed 12–17–14; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2011–N–0085] 

Agency Information Collection 

Activities; Submission for Office of 

Management and Budget Review; 

Comment Request; Guidance for 

Industry: Cooperative Manufacturing 

Arrangements for Licensed Biologics 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: 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 January 20, 

2015. 

ADDRESSES: 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: FDA Desk Officer, FAX: 

202–395–7285, or emailed to oira_

submission@omb.eop.gov. All 

comments should be identified with the 

OMB control number 0910–0629. Also 

include the FDA docket number found 

in brackets in the heading of this 

document. 

FOR FURTHER INFORMATION CONTACT: FDA 

PRA Staff, Office of Operations, Food 

and Drug Administration, 8455 

Colesville Rd., COLE–14526, Silver 

Spring, MD 20993–0002, PRAStaff@

fda.hhs.gov. 

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. 

Guidance for Industry: Cooperative 

Manufacturing Arrangements for 

Licensed Biologics—(OMB Control 

Number 0910–0629)—Extension 

The guidance document provides 

information concerning cooperative 

manufacturing arrangements applicable 

to biological products subject to 

licensure under section 351 of the 

Public Health Service Act (42 U.S.C. 

262). The guidance addresses several 

types of manufacturing arrangements 

(i.e., short supply arrangements, divided 

manufacturing arrangements, shared 

manufacturing arrangements, and 

contract manufacturing arrangements) 

and describes certain reporting and 

recordkeeping responsibilities, 

associated with these arrangements, 

including the following: (1) Notification 

of all important proposed changes to 

production and facilities; (2) 

notification of results of tests and 

investigations regarding or possibly 

impacting the product; (3) notification 

of products manufactured in a contract 

facility; and (4) standard operating 

procedures. 

mstockstill on DSK4VPTVN1PROD with NOTICES

75570 Federal Register / Vol. 79, No. 243 / Thursday, December 18, 2014 / Notices 

1. Notification of All Important 

Proposed Changes to Production and 

Facilities 

Each licensed manufacturer in a 

divided manufacturing arrangement or 

shared manufacturing arrangement must 

notify the appropriate FDA Center 

regarding proposed changes in the 

manufacture, testing, or specifications of 

its product, in accordance with § 601.12 

(21 CFR 601.12). In the guidance, we 

recommend that each licensed 

manufacturer that proposes such a 

change should also inform other 

participating licensed manufacturer(s) 

of the proposed change. 

For contract manufacturing 

arrangements, we recommend that the 

contract manufacturer should share 

with the license manufacturer all 

important proposed changes to 

production and facilities (including 

introduction of new products or at 

inspection). The license holder is 

responsible for reporting these changes 

to FDA (§ 601.12). 

2. Notification of Results of Tests and 

Investigations Regarding or Possibly 

Impacting the Product 

In the guidance, we recommend the 

following for contract manufacturing 

arrangements: 

• The contract manufacturer should 

fully inform the license manufacturer of 

the results of all tests and investigations 

regarding or possibly having an impact 

on the product; and 

• The license manufacturer should 

obtain assurance from the contractor 

that any FDA list of inspectional 

observations will be shared with the 

license manufacturer to allow 

evaluation of its impact on the purity, 

potency, and safety of the license 

manufacturer’s product. 

3. Notification of Products 

Manufactured in a Contract Facility 

In the guidance, we recommend for 

contract manufacturing arrangements 

that a license manufacturer cross 

reference a contract manufacturing 

facility’s Master Files only in 

circumstances involving certain 

proprietary information of the contract 

manufacturer, such as a list of all 

products manufactured in a contract 

facility. In this situation, the license 

manufacturer should be kept informed 

of the types or categories of all products 

manufactured in the contract facility. 

4. Standard Operating Procedures 

In the guidance, we remind the 

license manufacture that the license 

manufacturer assumes responsibility for 

compliance with the applicable product 

and establishment standards (21 CFR 

600.3(t)). Therefore, if the license 

manufacturer enters into an agreement 

with a contract manufacturing facility, 

the license manufacturer must ensure 

that the facility complies with the 

applicable standards. An agreement 

between a license manufacturer and a 

contract manufacturing facility normally 

includes procedures to regularly assess 

the contract manufacturing facility’s 

compliance. These procedures may 

include, but are not limited to, review 

of records and manufacturing deviations 

and defects, and periodic audits. 

For shared manufacturing 

arrangements, each manufacturer must 

submit a separate biologics license 

application describing the 

manufacturing facilities and operations 

applicable to the preparation of that 

manufacturer’s biological substance or 

product (§ 601.2(a)). In the guidance, we 

state that we expect the manufacturer 

that prepares (or is responsible for the 

preparation of) the product in final form 

for commercial distribution to assume 

primary responsibility for providing 

data demonstrating the safety, purity, 

and potency of the final product. We 

also state that we expect the licensed 

finished product manufacturer to be 

primarily responsible for any 

postapproval obligations, such as 

postmarketing clinical trials, additional 

product stability studies, complaint 

handling, recalls, postmarket reporting 

of the dissemination of advertising and 

promotional labeling materials as 

required under § 601.12(f)(4) and 

adverse experience reporting. We 

recommend that the final product 

manufacturer establish a procedure with 

the other participating manufacturer(s) 

to obtain information in these areas. 

Description of Respondents: The 

recordkeeping and reporting 

recommendations described in this 

document affect the participating 

licensed manufacturer(s), final product 

manufacturer(s), and contract 

manufacturer(s) associated with 

cooperative manufacturing 

arrangements. 

Burden Estimate: We believe that the 

information collection provisions in the 

guidance do not create a new burden for 

respondents. We believe the reporting 

and recordkeeping provisions are part of 

usual and customary business practices. 

Licensed manufacturers would have 

contractual agreements with 

participating licensed manufacturers, 

final product manufacturers, and 

contract manufacturers, as applicable 

for the type of cooperative 

manufacturing arrangement, to address 

all these information collection 

provisions. 

The guidance also refers to previously 

approved collections of information 

found in FDA regulations at parts 201, 

207, 211, 600, 601, 606, 607, 610, 660, 

801, 803, 807, 809, and 820 (21 CFR 

parts 201, 207, 211, 600, 601, 606, 607, 

610, 660, 801, 803, 807, 809, and 820). 

The collections of information in 

§§ 606.121, 606.122, and 610.40 have 

been approved under OMB control 

number 0910–0116; § 610.2 has been 

approved under OMB control number 

0910–0206; §§ 600.12(e) and 600.80 

have been approved under OMB control 

number 0910–0308; §§ 601.2(a), 601.12, 

610.60 through 610.65, 610.67, 660.2(c), 

660.28(a) and (b), 660.35(a), (c) through 

(g), (i) through (m), 660.45, and 

660.55(a) and (b) have been approved 

under OMB control number 0910–0338; 

§§ 803.20, 803.50, and 803.53 have been 

approved under OMB control number 

0910–0437; and §§ 600.14 and 606.171 

have been approved under OMB control 

number 0910–0458. The current good 

manufacturing practice regulations for 

finished pharmaceuticals (part 211) 

have been approved under OMB control 

number 0910–0139; §§ 820.181 and 

820.184 have been approved under 

OMB control number 0910–0073; the 

establishment registration regulations 

(parts 207, 607, and 807) have been 

approved under OMB control numbers 

0910–0045, 0910–0052, and 0910–0625; 

and the labeling regulations (parts 201, 

801, and 809) have been approved 

under OMB control numbers 0910– 

0537, 0910–0572, and 0910–0485. 

In the Federal Register of July 7, 2014 

(79 FR 38318), FDA published a 60-day 

notice requesting public comment on 

the proposed collection of information. 

We received no comments. 

Dated: December 11, 2014. 

Leslie Kux, 

Associate Commissioner for Policy. 

[FR Doc. 2014–29611 Filed 12–17–14; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2014–D–1953] 

Guidance for Industry on Providing 

Regulatory Submissions in Electronic 

Format—Submissions Under Section 

745A(a) of the Federal Food, Drug, and 

Cosmetic Act; Availability 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA) is announcing the 

mstockstill on DSK4VPTVN1PROD with NOTICES