2011-15141. Agency Information Collection Activities; Proposed Collection; Comment Request; Guidance for Industry on Formal Dispute Resolution: Scientific and Technical Issues Related to Pharmaceutical Current Good Manufacturing Practice

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 collection of information resulting from the guidance to manufacturers of veterinary and human drugs, including human biological drug products, on how to resolve disputes of scientific and technical issues relating to current good manufacturing practice (CGMP).

DATES:

Submit either electronic or written comments on the collection of information by August 19, 2011.

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:

Elizabeth Berbakos, Office of Information Management, Food and Drug Administration, 1350 Piccard Dr., PI50-400B, Rockville, MD 20850, 301-796-3792, [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 comment 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 on Formal Dispute Resolution: Scientific and Technical Issues Related to Pharmaceutical Current Good Manufacturing Practice—(OMB Control Number 0910-0563)—Extension

The guidance is intended to provide information to manufacturers of veterinary and human drugs, including human biological drug products, on how to resolve disputes of scientific and technical issues relating to CGMP. Disputes related to scientific and technical issues may arise during FDA inspections of pharmaceutical manufacturers to determine compliance with CGMP requirements or during FDA's assessment of corrective actions undertaken as a result of such inspections. The guidance provides procedures that encourage open and prompt discussion of disputes and lead to their resolution. The guidance describes procedures for raising such disputes to the Office of Regulatory Affairs (ORA) and center levels and for requesting review by the dispute resolution (DR) panel.

When a scientific or technical issue arises during an FDA inspection, the manufacturer should initially attempt to reach agreement on the issue informally with the investigator. Certain scientific or technical issues may be too complex or time consuming to resolve during the inspection. If resolution of a scientific or technical issue is not accomplished through informal mechanisms prior to the issuance of the FDA Form 483, the manufacturer can formally request DR and can use the formal two-tiered DR process described in the guidance.

Tier one of the formal DR process involves scientific or technical issues raised by a manufacturer to the ORA and center levels. If a manufacturer disagrees with the tier one decision, tier two of the formal DR process would then be available for appealing that decision to the DR panel.

The written request for formal DR to the appropriate ORA unit should be made within 30 days of the completion of an inspection and should include all supporting documentation and arguments for review, as described in this document. The written request for formal DR to the DR panel should be made within 60 days of receipt of the tier one decision and should include all supporting documentation and arguments, as described in the following paragraphs.

All requests for formal DR should be in writing and include adequate information to explain the nature of the dispute and to allow FDA to act quickly and efficiently. Each request should be sent to the appropriate address listed in the guidance and include the following:

• Cover sheet that clearly identifies the submission as either a request for tier one DR or a request for tier two DR;
• Name and address of manufacturer inspected (as listed on FDA Form 483);
• Date of inspection (as listed on FDA Form 483);
• Date the FDA Form 483 was issued (from FDA Form 483);
• Facility Establishment Identifier (FEI) Number, if available (from FDA Form 483);
• FDA employee names and titles that conducted inspection (from FDA Form 483);
• Office responsible for the inspection (e.g., district office, as listed on the FDA Form 483);
• Application number, if the inspection was a preapproval inspection;
• Comprehensive statement of each issue to be resolved;
• Identify the observation in dispute:

○ Clearly present the manufacturer's scientific position or rationale concerning the issue under dispute with any supporting data.

○ State the steps that have been taken to resolve the dispute, including any informal DR that may have occurred before the issuance of the FDA Form 483.

○ Identify possible solutions.

○ State expected outcome.

• Name, title, telephone and FAX number, and e-mail address (as available) of manufacturer contact.

The guidance was part of the FDA initiative “Pharmaceutical CGMPs for the 21st Century: A Risk-Based Approach,” which was announced in August 2002. The initiative focuses on FDA's current CGMP program and covers the manufacture of veterinary and human drugs, including human biological drug products. The Agency formed the Dispute Resolution Working Group comprising representatives from ORA, the Center for Drug Evaluation and Research, the Center for Biologics Evaluation and Research, and the Center for Veterinary Medicine. The working group met weekly on issues related to the DR process and met with stakeholders in December 2002 to seek their input.

The guidance was initiated in response to industry's request for a formal DR process to resolve differences related to scientific and technical issues that arise between investigators and pharmaceutical manufacturers during FDA inspections of foreign and domestic manufacturers. In addition to encouraging manufacturers to use currently available DR processes, the guidance describes the formal two-tiered DR process explained earlier in this document. The guidance also covers the following topics:

• The suitability of certain issues for the formal DR process, including examples of some issues with a discussion of their appropriateness for the DR process.
• Instructions on how to submit requests for formal DR and a list of the supporting information that should accompany these requests.
• Public availability of decisions reached during the DR process to promote consistent application and interpretation of drug quality-related regulations.

Description of Respondents: Pharmaceutical manufacturers of veterinary and human drug products and human biological drug products.

Burden Estimate: Based on the number of requests for tier one and tier two DRs received by FDA since the guidance published in January 2006, FDA estimates that approximately two manufacturers will submit approximately two requests annually for a tier one DR and that there will be one appeal of these requests to the DR panel (request for tier two DR). FDA estimates that it will take manufacturers approximately 30 hours to prepare and submit each request for a tier one DR and approximately 8 hours to prepare and submit each request for a tier two DR. Table 1 of this document provides an estimate of the annual reporting burden for requests for tier one and tier two DRs.

FDA estimates the burden of this collection of information as follows:

Table 1—Estimated Annual Reporting Burden ¹

Activity	Number of respondents	Number of responses per respondent	Total annual responses	Average burden per response (in hours)	Total hours
Requests for Tier One DR	2	1	2	30	60
Requests for Tier Two DR	1	1	1	8	8
Total					68
1 There are no capital costs or operating and maintenance costs associated with this collection of information.

Dated: June 14, 2011.

Leslie Kux,

Acting Assistant Commissioner for Policy.