[Federal Register Volume 76, Number 152 (Monday, August 8, 2011)]
[Pages 48166-48167]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2011-19958]



Food and Drug Administration

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

Agency Information Collection Activities; Submission for Office 
of Management and Budget Review; Comment Request; 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 
September 7, 2011.

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 e-mailed to [email protected]. 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: Juanmanuel Vilela, Office of 
Information Management, Food and Drug Administration, 1350 Piccard Dr., 
PI50-400B, Rockville, MD 20850, 301-796-7651, 
[email protected].

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.

(1) Notification of All Important Proposed Changes to Production and 

    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 
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 

(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 

(4) Standard Operating Procedures

    In the guidance, we remind the license manufacturer 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 post-approval 
obligations, such as

[[Page 48167]]

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), and (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 0910-0387; 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 March 16, 2011 (76 FR 14405), FDA 
published a 60-day notice requesting public comment on the proposed 
collection of information. No comments were received from the public.

    Dated: August 2, 2011.
David Dorsey,
Acting Associate Commissioner for Policy and Planning.
[FR Doc. 2011-19958 Filed 8-5-11; 8:45 am]