Guidance for Industry 

Formal Dispute Resolution: 

Scientific and Technical Issues 

Related to Pharmaceutical CGMP 

U.S. Department of Health and Human Services 

Food and Drug Administration 

Center for Drug Evaluation and Research (CDER) 

Center for Biologics Evaluation and Research (CBER)

Center for Veterinary Medicine (CVM) 

Office of Regulatory Affairs (ORA) 

Pharmaceutical CGMPs 

January 2006

OMB Control Number 0910-0563 

Expiration Date: 05/31/2008 

See additional PRA statement in Section VI of this guidance 
Guidance for Industry 

Formal Dispute Resolution: 

Scientific and Technical Issues 

Related to Pharmaceutical CGMP 

Additional copies of this Guidance are available from 

 Office of Training and Communications 

 Division of Drug Information, HFD-240 

Center for Drug Evaluation and Research 

 5600 Fishers Lane, Rockville, MD 20857 

 Phone 301-827-4573 

Internet: http://www.fda.gov/cder/guidance/index.htm. 

or 

 Office of Communication, Training and 

Manufacturers Assistance, HFM-40 

Center for Biologics Evaluation and Research 

1401 Rockville Pike, Rockville, MD 20852-1448 

Phone 800-835-4709 or 301-827-1800 

Internet: http://www.fda.gov/cber/guidelines.htm

or 

Communications Staff, HFV-12 

Center for Veterinary Medicine 

7519 Standish Place, 

Rockville, MD 20855 

Phone 240-276-9300 

Internet: http://www.fda.gov/cvm/guidance/published.htm

U.S. Department of Health and Human Services 

Food and Drug Administration 

Center for Drug Evaluation and Research (CDER) 

Center for Biologics Evaluation and Research (CBER)

Center for Veterinary Medicine (CVM) 

Office of Regulatory Affairs (ORA) 

Pharmaceutical CGMPs

January 2006
Contains Nonbinding Recommendations

TABLE OF CONTENTS 

I. INTRODUCTION............................................................................................................. 1

II. SCOPE OF THE GUIDANCE ........................................................................................ 2

III. DISPUTE RESOLUTION PROCESS ............................................................................ 3

A. Tier-One Dispute Resolution at the Office of Regulatory Affairs and Center Levels.............4

B. Tier-Two Dispute Resolution with the DR Panel on Scientific and Technical Issues..............5

C. How to Request Formal Dispute Resolution................................................................................6

D. Supporting Information to be Provided by Manufacturers.......................................................8

E. FDA Response to Requests for Dispute Resolution ....................................................................9

IV. SUITABILITY OF ISSUES FOR FORMAL DISPUTE RESOLUTION................... 9

A. Failure to Comply With a Precise Element of CGMP Regulations.........................................10

B. Failure to Comply With a Precise Requirement Established in an Approved Application..11

C. The Regulatory Significance of Failing to Comply With a Precise Requirement..................11

D. Issues Not Raised During the Inspection ...................................................................................12

V. COMMUNICATION OF DISPUTE RESOLUTION DECISIONS .......................... 12

VI. PAPERWORK REDUCTION ACT OF 1995.............................................................. 12

 
Contains Nonbinding Recommendations

Guidance for Industry1 1 

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6 

Formal Dispute Resolution: 

Scientific and Technical Issues Related to Pharmaceutical CGMP 

7 This guidance represents the Food and Drug Administration's (FDA's) current thinking on this topic. It 

8 does not create or confer any rights for or on any person and does not operate to bind FDA or the public. 

9 You can use an alternative approach if the approach satisfies the requirements of the applicable statutes 

10 and regulations. If you want to discuss an alternative approach, contact the FDA staff responsible for 

11 implementing this guidance. If you cannot identify the appropriate FDA staff, call the appropriate 

12 number listed on the title page of this guidance. 

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I. INTRODUCTION 

This document is intended to provide 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) requirements. 

This document is not intended to cover medical devices regulated by the Center for Devices 

and Radiological Health (CDRH) or foods or dietary supplements regulated by the Center 

for Food Safety and Applied Nutrition (CFSAN). 

Disputes related to scientific and technical issues may arise during FDA inspections of 

pharmaceutical manufacturers to determine compliance with CGMP requirements or during 

the Agency's assessment of corrective actions undertaken as a result of such inspections. As 

these disputes may involve complex judgments and issues that are scientifically or 

technologically important, it is critical to have procedures in place that will encourage open, 

prompt discussion of disputes and lead to their resolution. This 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 Panel for Scientific and 

Technical Issues Related to Pharmaceutical CGMP (DR Panel). 

Manufacturers are encouraged to seek clarification of scientific or technical issues with the 

inspection team at any time during an inspection. Although there are existing processes to 

encourage dialogue between FDA and manufacturers, the processes described in this document 

1 This guidance has been prepared by the Dispute Resolution Working Group formed as part of the August 2002 

FDA Initiative, Pharmaceutical cGMPs for the 21st Century: A Risk-Based Approach. The Working Group 

included representatives from the Center for Drug Evaluation and Research (CDER), the Center for Biologics 

Evaluation and Research (CBER), the Center for Veterinary Medicine (CVM), and the Office of Regulatory Affairs 

(ORA).

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Contains Nonbinding Recommendations

apply to CGMP questions raised during inspections and are intended to supplement the dispute 

resolution processes currently in place, including: 

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21 CFR 10.75, Internal Agency Review of Decisions. Allows manufacturers to ask for a 

review of Agency decisions at each successive supervisory level through the chain of 

command, ending with the FDA Commissioner's office. 

CDER/CBER guidance for industry entitled Formal Dispute Resolution: Appeals Above 

the Division Level. Describes procedures a sponsor may use to formally appeal disputes 

to the office or center level on scientific and procedural issues that arise during drug 

development, new drug review, and post-marketing oversight processes. The guidance 

may be found on CDER’s and CBER's Web sites.2

CVM guidance for industry #79 entitled Dispute Resolution Procedures for ScienceBased Decisions on Products Regulated by the Center for Veterinary Medicine (CVM),

July 2005. Describes procedures for handling requests for internal review of scientific 

controversies relating to decisions affecting animal drugs or other products that are 

regulated by CVM. The guidance may be found on CVM's Web site.3

 

Investigations Operations Manual (IOM), Chapter 5, Subchapter 510, Sections 512 

(Report of Observations) and 516 (Discussions with Management). Describes processes 

for discussing inspectional observations with a manufacturer. The IOM is available on 

ORA's Web site.4

For the purposes of this document, the term manufacturer5 includes any domestic or foreign 

applicant or manufacturer of a human or veterinary drug, or human biological drug product 

regulated by the Agency under the Federal Food, Drug, and Cosmetic Act (the Act) or section 

351 of the Public Health Service Act (the PHS Act). 

FDA's guidance documents, including this guidance, do not establish legally enforceable 

responsibilities. Instead, guidances describe the Agency's current thinking on a topic and should 

be viewed only as recommendations, unless specific regulatory or statutory requirements are 

cited. The use of the word should in Agency guidances means that something is suggested or 

recommended, but not required. 

II. SCOPE OF THE GUIDANCE 

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 The CDER/CBER guidance can be found on the Internet at http://www.fda.gov/cder/guidance/index.htm and 

http://www.fda.gov/cber/gdlns/dispute.htm. 

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 The CVM guidance can be found on the Internet at: http://www.fda.gov/cvm/Guidance/published.htm#79. 

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 The IOM can be found on the Internet at: http://www.fda.gov/ora/inspect_ref/iom/iomtc.html. 

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 The activities of a manufacturer encompass the processes and functions described in 21 CFR 207.3(8), 21 CFR 

210.3(12), and 21 CFR 600.3(t). 

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Contains Nonbinding Recommendations

The policies and procedures described in this guidance document cover all disputes on scientific 

or technical issues related to CGMP that arise as the result of CGMP and preapproval 

inspections (PAI) for manufacturers of veterinary and human drug products, including related 

Active Pharmaceutical Ingredients (APIs). For disputes that arise during prelicense and 

preapproval inspections for human biological drug products regulated by CBER or for 

application review issues that arise during PAI inspections for human or veterinary drug 

products, the existing CDER/CBER and CVM guidances listed in Section I of this document 

should continue to be used. 

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This guidance does not cover disputes over procedures or administrative matters that may arise 

during the inspection process. At any time, a manufacturer may informally raise a procedural or 

administrative matter with ORA or with the CDER, CBER, or CVM Ombudsman, in accordance 

with 21 CFR 10.75. The procedures described in this guidance do not apply to such informal 

dispute resolution through the CDER, CBER, or CVM Ombudsman. 

If a dispute involves a combination product including a device component, the dispute may be 

addressed through CDRH's dispute resolution process, depending on the nature of the dispute.6

 

III. DISPUTE RESOLUTION PROCESS 

During inspections of manufacturers, investigators are expected to make every reasonable effort 

to discuss observations relating to manufacturing quality as they are observed, or on a daily basis 

to minimize surprise, errors, and misunderstandings when a Form FDA 483 is issued. At the 

conclusion of an inspection, investigators will normally meet with the manufacturer's

management to again discuss observations and solicit views and additional relevant information. 

These processes are described in detail in the Investigations Operations Manual (IOM), Sections 

512 and 516, as listed in Section I of this document. 

When a scientific or technical issue arises during an inspection, we recommend that a 

manufacturer initially attempt to reach agreement on the issue informally with the investigator. 

A manufacturer should discuss with the investigator any observation that the manufacturer 

believes is not justified from a scientific or technical standpoint. As appropriate, the investigator 

can consult with FDA management or program officials, or appropriate product or technical 

experts. The investigator may invite the company to participate in certain consultative 

discussions. If agreement on the issue is not reached with the investigator prior to issuance of 

the Form FDA 483, a manufacturer can formally request dispute resolution after the investigator 

issues the Form FDA 483. 

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 a Form FDA 483, manufacturers can use the formal 

two-tiered dispute resolution process described in this guidance. 

6 CDRH guidance document, Resolving Scientific Disputes Concerning the Regulation of Medical Devices, A Guide 

to Use of the Medical Devices Dispute Resolution Panel; Final Guidance for Industry and FDA, July 2, 2001.

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Contains Nonbinding Recommendations

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Tier one of the formal dispute resolution process refers to scientific or technical issues 

raised to the ORA and center levels. 

Tier two of the formal dispute resolution process refers to scientific or technical issues 

raised to the DR Panel. 

These processes are described in detail in the following subsections. 

A. Tier-One Dispute Resolution at the Office of Regulatory Affairs and Center 

Levels 

Pharmaceutical manufacturers can formally dispute the scientific or technical basis for CGMP 

inspectional observations after issuance of a Form FDA 483. In such cases, the formal dispute 

resolution process starts in the appropriate ORA unit7

 as listed below and may advance to the 

applicable center. 

For domestic manufacturers of veterinary and human drugs, the formal dispute resolution 

process begins in the appropriate district office, ORA. 

For foreign manufacturers of veterinary and human drugs, the formal dispute resolution 

process begins in the Division of Field Investigations, ORA. 

For domestic or foreign manufacturers of human biological drug products inspected by 

Team Biologics, the formal dispute resolution process begins in the Office of 

Enforcement, ORA. 

A manufacturer should seek clarification of a disputed scientific or technical issue within 30 

days of issuance of the Form FDA 483. (FDA defines days to mean calendar days throughout 

this guidance.) FDA may refuse to address a dispute resolution request not raised during this 

time frame. The Agency, at its discretion, may contact the manufacturer to obtain additional 

information and/or seek clarification. 

If a manufacturer disagrees with the scientific or technical basis for an observation listed by an 

investigator on a Form FDA 483, the following steps may be taken: 

1. The manufacturer may file a written request for formal dispute resolution with the 

appropriate ORA unit as listed above. The manufacturer should provide all supporting 

documentation and arguments for review. 

2. The appropriate ORA unit may evaluate the written request for formal dispute resolution, 

and may include Agency staff not previously involved in the dispute, as appropriate. 

 

7

 For the purposes of Sections III A and B in this document, the phrase ORA unit will refer to the district office, the 

Division of Field Investigations, or the Office of Enforcement, as appropriate. 

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Contains Nonbinding Recommendations

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If the ORA unit agrees with the manufacturer, 

• The ORA unit will issue a written response to the manufacturer within 30 days of receipt 

of the request, noting its agreement with the manufacturer and resolution of the dispute. 

The resolution may take the form of a letter. It may also take the form of an addendum to 

the existing Form FDA 483. 

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All disputes resolved at the ORA level will be copied to the relevant program center for 

information and public dissemination following appropriate redaction. 

If the ORA unit disagrees with the manufacturer, 

The ORA unit will issue a written response to the manufacturer generally within 30 days 

of receipt of the request. Responses that disagree with a manufacturer's position will 

incorporate a review and decision by the relevant program center, which may require 

additional time as described below. 

The written response will be copied to the relevant program center for information and 

public dissemination after appropriate redaction, in accordance with applicable 

requirements. 

If the ORA unit is unable to complete its review of the request and respond within 30 days, the 

ORA unit will notify the manufacturer, explain the reason for the delay (which may include the 

need for an additional 30 days for center review), and discuss the time frame for completing the 

review. 

3. If a manufacturer disagrees with the tier-one decision, the manufacturer can appeal that 

decision to the DR Panel. 

B. Tier-Two Dispute Resolution with the DR Panel on Scientific and Technical 

Issues 

The DR Panel provides a formal way for manufacturers to defend the science in their 

manufacturing and quality control processes before a neutral panel of experts and to appeal an 

ORA and center-level decision concerning the science underlying the inspectional observation. 

The DR Panel resides at the Office of the Commissioner. The DR Panel considers requests for 

tier-two dispute resolution by manufacturers and provides an opportunity for a manufacturer to 

present its case in support of its position on a scientific or technical issue. The DR Panel’s 

membership includes representatives from each of the program centers and ORA, as well as the 

Chair of the FDA Council on Pharmaceutical Quality, but will not include decision makers who 

have addressed the disputed issue at the ORA and center level. 

If a manufacturer disagrees with the tier-one decision in the formal dispute resolution process, 

the manufacturer can file a written request for formal dispute resolution by the DR Panel. The 

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Contains Nonbinding Recommendations

manufacturer should provide the written request for formal dispute resolution and all supporting 

documentation and arguments to the DR Panel for review within 60 days from issuance of the 

tier-one decision. 

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The DR Panel will evaluate the written request for formal dispute resolution. The DR Panel will 

determine whether or not to consider the specific issue in the appeal. If necessary, additional 

internal and external experts, as well as attorneys from the Office of Chief Counsel (OCC), may 

be added to the DR Panel to facilitate evaluation of the specific issue. 

If the DR Panel determines that the request is appropriate for review, it will schedule a meeting 

to discuss the issue within 90 days. The DR Panel may communicate with the manufacturer at 

its discretion and may request the manufacturer to be present during the meeting. 

If the DR Panel agrees with the manufacturer on the issue, 

The executive secretary of the DR Panel will issue a written response to the manufacturer 

within 30 days of the meeting, noting its agreement with the manufacturer and resolution 

of the dispute. 

All disputes resolved at the DR Panel level will be copied to the relevant FDA units for 

their information and public dissemination after appropriate redaction, in accordance 

with applicable requirements. 

If the DR Panel disagrees with the manufacturer on the issue, 

The executive secretary of the DR Panel will issue a written response to the manufacturer 

within 30 days of the meeting, noting its decision on the issue, except as provided below. 

The executive secretary of the DR Panel will notify the relevant FDA units of the DR 

Panel’s decision for their information and public dissemination after appropriate 

redaction, in accordance with applicable requirements. 

If the DR Panel determines that the request does not qualify for review (see Section IV), the 

executive secretary of the DR Panel will notify the manufacturer in writing within 30 days of

receipt of the appeal and communicate the DR Panel's decision to the program offices. 

If FDA is unable to complete its review of the request and respond within 30 days, the executive 

secretary of the DR Panel will notify the manufacturer, explain the reasons for the delay, and 

discuss the time frame for completing the review. 

C. How to Request Formal Dispute Resolution 

All Agency decisions in the formal dispute resolution process will be based on the 

manufacturer's documentation that was available at the time of the inspection, unless a 

manufacturer can provide a reasonable explanation why it did not present relevant information 

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Contains Nonbinding Recommendations

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during the inspection or the manufacturer was specifically requested to provide new information 

as part of the Agency’s dispute resolution review. Submission of new information may result in 

the dispute being returned to an earlier point in the process, as the Agency deems appropriate. 

The following list of addresses can be used to request formal dispute resolution. 

1. For a tier-one dispute resolution request from domestic manufacturers of veterinary and 

human drugs, the request should be submitted to: 

Director of the district office responsible for the inspection 

The following Internet site lists district office addresses: 

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2. For a tier-one dispute resolution request from foreign manufacturers of veterinary and 

human drugs, the request should be submitted to: 

Director, Division of Field Investigations 

Office of Regional Operations 

Office of Regulatory Affairs 

Food and Drug Administration 

Mail Code: HFC-100 

5600 Fishers Lane, Room 13-64 

Rockville, Maryland 20857 

3. For a tier-one dispute resolution request from domestic or foreign manufacturers of 

human biological drug products inspected by Team Biologics, the request should be 

submitted to: 

Director, Division of Compliance Management and Operations 

Office of Enforcement 

Office of Regulatory Affairs 

Food and Drug Administration 

Mail Code: HFC-210 

5600 Fishers Lane 

Rockville, MD 20857

4. For a tier-two dispute resolution request, the request should be submitted to the 

appropriate center contact as listed below: 

For CDER: 

Formal Dispute Resolution Project Manager (DPRM) 

Office of Compliance 

Center for Drug Evaluation and Research 

Food and Drug Administration 

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Contains Nonbinding Recommendations

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5600 Fishers Lane 

Rockville, MD 20857 

• For CVM: 

Ombudsman 

Office of the Center Director 

Center for Veterinary Medicine 

Food and Drug Administration 

Mail Code: HFV-7 

7519 Standish Place 

Rockville, MD 20855 

For CBER: 

Assistant to the Director for Policy 

Office of Compliance and Biologics Quality 

Center for Biologics Evaluation and Research 

Food and Drug Administration 

Mail Code: HFM-600 

1401 Rockville Pike, Suite 200N 

Rockville, MD 20852

D. Supporting Information to be Provided by Manufacturers 

All requests for formal dispute resolution should be in writing and include adequate information 

to explain the nature of the dispute and to allow the Agency to act quickly and efficiently. Each 

request should include the following: 

1. Cover sheet that clearly identifies the submission in bold, uppercase letters: 

REQUEST FOR TIER-ONE DISPUTE RESOLUTION 

 or 

REQUEST FOR TIER-TWO DISPUTE RESOLUTION (REVIEW BY THE 

DISPUTE RESOLUTION PANEL FOR SCIENTIFIC AND TECHNICAL ISSUES 

RELATED TO PHARMACEUTICAL CGMP) 

2. Name and address of manufacturer inspected (as listed on the Form FDA 483) 

3. Date of inspection (as listed on the Form FDA 483) 

4. Date the Form FDA 483 issued (from the Form FDA 483) 

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Contains Nonbinding Recommendations

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5. FEI Number, if available (from the Form FDA 483) 

6. Names and titles of FDA employees who conducted inspection (from the Form FDA 483) 

7. Office responsible for the inspection, e.g., district office, as listed on the Form FDA 483 

8. Application number if the inspection was a preapproval inspection 

9. 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 

dispute resolution that may have occurred before the issuance of the Form FDA 483. 

Identify possible solutions. 

State desired outcome. 

10. Name, title, telephone and fax number, and e-mail address (as available) of manufacturer 

contact. 

E. FDA Response to Requests for Dispute Resolution 

FDA will respond in writing to all requests for dispute resolution filed under the procedures 

described in this guidance. The written response should specifically agree or disagree with the 

outcome desired by the manufacturer, agree or disagree with parts of the proposed outcome, or 

indicate a resolution that is different from that proposed by the manufacturer. If the Agency does 

not agree with the manufacturer’s position, the response should include reasons for the 

disagreement. 

The Agency official responsible for replying to a request for dispute resolution should make all 

reasonable efforts to resolve the dispute and provide a written response to the manufacturer 

according to timelines suggested above in Section III. A and B. 

The Agency may, under appropriate circumstances, take regulatory action while a request for 

formal dispute resolution is pending. 

IV. SUITABILITY OF ISSUES FOR FORMAL DISPUTE RESOLUTION 

Any dispute involving a scientific or technical issue related to CGMP regulations that arises 

during an FDA inspection, as discussed above, may be suitable for the dispute resolution process 

described in this guidance. 

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Contains Nonbinding Recommendations

The following text provides examples concerning the appropriateness of several issues for the 

dispute resolution process detailed in this guidance. 

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A. Failure to Comply With a Precise Element of CGMP Regulations 

According to 21 CFR 211.100(a), a manufacturer producing a finished pharmaceutical product 

must have written procedures for production and process controls, and these written procedures 

must be designed to ensure that the drug has the identity, strength, quality, and purity it purports 

or is represented to have. 

Failure to have written procedures for production and process controls would be a 

failure to comply with a precise element of the CGMP regulations and would not be 

appropriate for the formal dispute resolution process described in this document. 

 

However, observations pertaining to the adequacy of the process and production 

control design activities could be subject to scientific debate and may be appropriate 

for dispute resolution as described in this guidance. 

Another example relates to the regulatory provisions governing the testing and approval or 

rejection of components, drug product containers, and closures (21 CFR 211.84), which require 

appropriate sampling, testing, or examination of each lot of components, drug product 

containers, or closures. 

Failure to conduct testing or examination of each lot would be failure to comply with 

a precise element of the regulations and would not be appropriate for the formal 

dispute resolution process described in this guidance. 

However, the appropriateness of a particular test or sampling scheme could involve 

the exercise of scientific judgment. A disagreement between a manufacturer and an 

investigator concerning the adequacy of a particular test or sampling scheme could be 

subject to scientific debate and may be appropriate for dispute resolution as described 

in this guidance. 

A third example relates to the CGMP regulation requirements that a manufacturer thoroughly 

investigates any unexplained discrepancy associated with its review of product production and 

control records (21 CFR 211.192). 

Failure to investigate an unexplained discrepancy would be a failure to comply with a 

precise element of the CGMP regulations and would not be appropriate for the formal 

dispute resolution process described in this guidance. 

However, the extent or adequacy of the investigation could be subject to scientific 

debate. Observations pertaining to the adequacy of an investigation into an 

unexplained discrepancy may also be appropriate for dispute resolution as described 

in this guidance. 

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B. Failure to Comply With a Precise Requirement Established in an Approved 

Application 

If, as part of the conditions established in an approved application, a manufacturer is required to 

conduct a particular test on a finished product and the manufacturer fails to conduct that test, this 

failure represents a failure to comply with a precise requirement established in an approved 

application. Any disagreement about the need for such a test should be raised in the application 

review process. Such disagreement is not appropriate for the dispute resolution process 

described in this guidance, but may be raised using the processes described in the CDER/CBER 

and CVM guidances listed in Section I of this document. 

C. The Regulatory Significance of Failing to Comply With a Precise 

Requirement 

The CGMP regulations require that all changes to production and process control procedures be 

approved by the quality control unit (21 CFR 211.100(a)). If a manufacturer makes a change in 

production and process control procedures, but does not obtain approval of those procedures by 

the manufacturer’s quality control unit, this would be a failure to comply with a precise 

requirement of the CGMP regulations. The manufacturer may contend that the failure in this 

particular case was not significant because it did not have an adverse effect on product quality 

and may convey this contention to the Agency through existing informal communication 

channels, including Form FDA 483-response correspondence. 

In such a case, the significance of this observation would not be appropriate for dispute 

resolution as described in this guidance, as the observation concerns a failure to comply with a 

precise requirement of the regulations. The regulatory significance of an observation is 

determined by the Agency after considering all relevant information, including the 

manufacturer's response to the inspectional observations. The Agency encourages manufacturers 

to provide all information relevant to the regulatory significance of an observation as part of this 

response, but such disputes are not within the scope of this guidance on scientific and technical 

disputes concerning the interpretation and application of CGMP requirements. 

Manufacturers must have internal written production and process control procedures (21 CFR 

211.100(a)) and, as part of these procedures, manufacturers often establish procedural action 

limits that are tighter than release specifications. When the action limits are exceeded, the 

internal written procedures may call for some type of investigation to determine if the process is 

drifting toward a loss of control, or the procedures may call for other assessments to determine if

the product will meet appropriate specifications throughout its expected shelf life. If a 

manufacturer's internal written procedures require certain actions when action limits are 

exceeded, failure to follow these written production and process control procedures is a failure to 

comply with 21 CFR 211.100(b). The manufacturer may contend that this failure is not 

significant in that the product met all regulatory specifications when released. As discussed 

above, this contention about significance is not appropriate for the formal dispute resolution 

process described in this guidance. 

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D. Issues Not Raised During the Inspection 

If, during an inspection, an investigator notes what appears to be an objectionable condition and 

a manufacturer disagrees with that observation, the manufacturer should voice its disagreement 

with the investigator. By doing so, the investigator has the opportunity to evaluate the 

manufacturer's position and consult, as needed, with Agency experts. The Agency may not 

accept a request for dispute resolution concerning a disagreement that was not initially raised by 

the manufacturer during the inspection unless a manufacturer can provide a reasonable 

explanation why it did not present relevant information during the inspection. 

V. COMMUNICATION OF DISPUTE RESOLUTION DECISIONS 

FDA believes that decisions made in the dispute resolution process, along with all supporting 

documentation, should be publicly available consistent with FDA’s disclosure regulations (21 

CFR Part 20) and applicable statutes, unless the decisions involve information that would 

otherwise be withheld under these regulations and statutes. The Agency will redact, as 

appropriate, any documents requested through the Freedom of Information process. 

When appropriate, a summary of the relevant issues and Agency views will be provided in a 

question and answer format and posted on the FDA Web site with all identifying information 

excluded. Information gained from these decisions should promote consistent application and 

interpretation of pharmaceutical CGMP requirements. 

VI. PAPERWORK REDUCTION ACT OF 1995 

This guidance contains information collection provisions 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 time required to complete this information collection is estimated to average 30 hours to 

prepare and submit each request for tier-one dispute resolution and 8 hours to prepare and submit 

each request for tier-two dispute resolution. This includes the time to review instructions, search 

existing data resources, gather the data needed, and complete and review the information 

collection. Send comments regarding this burden estimate or suggestions for reducing this 

burden to Edward M. Sherwood, Center for Drug Evaluation and Research (HFD-3), Food and 

Drug Administration, Rockwall II, Rm. 7231, 5515 Security Lane, Rockville, MD 20857, 

301-594-2847. 

511 An agency may not conduct or sponsor, and a person is not required to respond to, a collection of 

512 information unless it displays a currently valid OMB control number. The OMB control number 

513 for this information collection is 0910-0563 (expires 05/31/2008). 

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