
[Federal Register Volume 79, Number 129 (Monday, July 7, 2014)]
[Notices]
[Pages 38318-38319]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2014-15810]


=======================================================================
-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2011-N-0085]


Agency Information Collection Activities; Proposed Collection; 
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 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 proposed extension of the 
collection of information concerning cooperative manufacturing 
arrangements for licensed biologics.

DATES: Submit either electronic or written comments on the collection 
of information by September 5, 2014.

ADDRESSES: Submit electronic comments on the collection of information 
to: http://www.regulations.gov. 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: 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: 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.

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.

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 Sec.  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

[[Page 38319]]

introduction of new products or at inspection). The license holder is 
responsible for reporting these changes to FDA (Sec.  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 (BLA) describing the 
manufacturing facilities and operations applicable to the preparation 
of that manufacturer's biological substance or product (Sec.  
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 Sec.  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, and 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 Sec. Sec.  606.121, 606.122, and 
610.40 have been approved under OMB control number 0910-0116; Sec.  
610.2 has been approved under OMB control number 0910-0206; Sec. Sec.  
600.12(e) and 600.80 have been approved under OMB control number 0910-
0308; Sec. Sec.  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; Sec. Sec.  803.20, 803.50, and 803.53 have been 
approved under OMB control number 0910-0437; and Sec. Sec.  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; Sec. Sec.  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.

    Dated: July 1, 2014.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2014-15810 Filed 7-3-14; 8:45 am]
BILLING CODE 4164-01-P


