2014-15810. 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, [e-mail].

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 § 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 (BLA) 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, 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 §§ 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.

Dated: July 1, 2014.

Leslie Kux,

Assistant Commissioner for Policy.