Department of Health and Human Services 
OFFICE OF 
INSPECTOR GENERAL 
FDA WARNING LETTERS 
Trends and Perspectives 
JUNE GIBBS BROWN 
Inspector General 
FEBRUARY 1999 
OEI-09-97-00380  OFFICE OF INSPECTOR GENERAL 
The mission of the Office of Inspector General (OIG), as mandated by Public Law 95-452, is to 
protect the integrity of the Department of Health and Human Services programs as well as the 
health and welfare of beneficiaries served by them.  This statutory mission is carried out through a 
nationwide program of audits, investigations, inspections, sanctions, and fraud alerts.  The 
Inspector General informs the Secretary of program and management problems and recommends 
legislative, regulatory, and operational approaches to correct them. 
Office of Evaluation and Inspections 
The Office of Evaluation and Inspections (OEI) is one of several components of the Office of 
Inspector General.  It conducts short-term management and program evaluations (called 
inspections) that focus on issues of concern to the Department, the Congress, and the public.  The 
inspection reports provide findings and recommendations on the efficiency, vulnerability, and 
effectiveness of departmental programs. 
OEI's San Francisco Regional Office prepared this report under the direction of Kaye D. Kidwell, 
Regional Inspector General, and Paul A. Gottlober, Deputy Regional Inspector General.  Principal 
OEI staff included: 
REGION  HEADQUARTERS 
Brad Rollin, Project Leader  Elise Stein, Program Specialist

Robert Gibbons, Program Analyst  Barbara Tedesco, Mathematical Statistician

Scott Hutchison, Program Analyst

Don Loeb, Program Analyst

Steven Zerebecki, Program Analyst

To obtain copies of this report, please call the San Francisco Regional Office at 415-437-7900. 
Reports are also available on the World Wide Web at our home page address: 
http://www.dhhs.gov/progorg/oei  E X E C U T I V E   S U M M A R Y  
PURPOSE 
To determine (1) why the number of Food and Drug Administration (FDA) warning 
letters has decreased in recent years, (2) what accounts for variations in district office 
warning letters, and (3) how firms view the warning letter process. 
BACKGROUND 
The FDA is the Federal agency charged with enforcing the Federal Food, Drug, and

Cosmetic Act and related laws.  At the headquarters level, FDA primarily is comprised of

five centers and the Office of Regulatory Affairs.  The Office of Regulatory Affairs

coordinates compliance activities and oversees FDAs 5 regional offices, 20 district

offices, and 130 resident posts.

The FDA's district offices and resident posts conduct almost all inspections of the firms

that FDA regulates.  When investigators find objectionable conditions, they are required to

provide the firm with their findings using form FDA-483.  If violations uncovered during

an inspection meet a threshold of regulatory significance, FDA also may issue a warning

letter.  Both FDA centers and district offices issue warning letters, depending on the type

of firm and violation.  Some warning letters issued by the district office require

headquarters review and approval.  The warning letter generally represents FDA's first

official notification that it has found one or more products, practices, processes, or other

activities that are in violation of the Food, Drug, and Cosmetic Act.  The warning letter

affords firms the opportunity to voluntarily correct violations prior to the initiation of

formal enforcement action.

In fiscal year 1997, FDA issued 1,175 warning letters.  This reversed a trend during which

the number of warning letters decreased 36.2 percent from 1994 (1,626) to 

1996 (1,037).  District offices issue approximately 80 percent of all warning letters.  The

number of warning letters issued varies greatly, and concerns have been raised about this

variation as well as the decrease in warning letters in general.

We interviewed staff from FDA headquarters, all district offices, and 24 firms that

received warning letters during fiscal year 1996.  We also analyzed warning letter and

district office inspection trends and data as well as FDAs Regulatory Procedures Manual.

Warning Letters--Trends and Perspectives  1  OEI-09-97-00380  FINDINGS 
Changes in FDA policies and practices and better industry compliance have 
contributed to decreases in warning letters 
The FDA has fostered a more cooperative approach to industry compliance, permitting 
districts to find alternatives to warning letters.  Other factors which contribute to the 
decrease include the reorganization of many districts and changes in the scope and type of 
inspections conducted by FDA.  In addition, one-third of district offices believe that firms 
are themselves doing a better job of being in compliance. 
Despite the existence of clear warning letter guidance, differences in district 
office attitudes, experience, and the types of firms in the district affect warning 
letter volume 
From 1994 to 1997, some district offices issued almost five times as many warning letters 
as others.  While the staff size of the district offices has an obvious effect on the number of 
inspections and warning letters, other factors also affect the number of warning letters 
each district issues. 
Firms would like to better understand the warning letter process and suggested 
some minor changes 
The FDAs policies and procedures governing warning letters are unclear to firms.  When 
possible, firms would appreciate advance notice that a warning letter will be issued. 
With some exceptions, firms were satisfied with FDAs customer service during 
the warning letter process 
Firms generally had positive comments about FDA investigators and district offices.  Few 
firms contacted FDA headquarters, and customer service reviews were mixed. 
RECOMMENDATION 
The FDA should (1) continue to improve relations and communication with 
industry and (2) consider issuing guidance that would authorize district offices to 
use FDA-483s and meetings to achieve compliance in lieu of warning letters 
Further development of the FDA/industry relationship is important in preserving fairness. 
A firm should not suffer adverse consequences solely because it is located in a different 
district than another firm.  At the same time, we recognize the need to allow district 
offices considerable discretion. 
Warning Letters--Trends and Perspectives  2  OEI-09-97-00380  AGENCY COMMENTS 
We received comments on the draft report from FDA in which the agency concurred with 
our recommendation.  Where appropriate, we have made revisions in the report in 
response to these comments.  We also have responded to several of FDAs comments in 
the appendix. 
This report is one of two reports concerning FDA warning letters.  A companion report, 
FDA Warning Letters:  Timeliness and Effectiveness (OEI-09-97-00381), determined how 
FDA uses warning letters and the extent to which they result in timely compliance with Federal 
laws and regulations. 
Warning Letters--Trends and Perspectives  3  OEI-09-97-00380  T A B L E   O F   C O N T E N T S  
PAGE

EXECUTIVE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

INTRODUCTION  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

FINDINGS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  11

Reasons for decrease in warning letters  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

Differences among district offices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  14

Firms understanding of warning letters  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

Firms views of FDAs customer service  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

RECOMMENDATION  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  18

APPENDICES

A:  Agency comments  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19

B:  OIG response to agency comments  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24

Warning Letters--Trends and Perspectives  4  OEI-09-97-00380  I N T R O D U C T I O N  
PURPOSE 
To determine (1) why the number of Food and Drug Administration (FDA) warning 
letters has decreased in recent years, (2) what accounts for variations in district office 
warning letters, and (3) how firms view the warning letter process. 
BACKGROUND 
The Food and Drug Administration 
The Food and Drug Administration (FDA) within the Department of Health and Human 
Services is the Federal agency charged with enforcing the Federal Food, Drug, and 
Cosmetic Act and several related laws.  At the headquarters level, FDA primarily is 
comprised of five centers and the Office of Regulatory Affairs.1  The five centers are: 
<  Biologics Evaluation and Research 
<  Drug Evaluation and Research 
<  Devices and Radiological Health 
<  Food Safety and Applied Nutrition 
<  Veterinary Medicine 
Each center promulgates regulations, oversees the review and approval for the marketing 
of new products, develops policy and compliance standards for regulated industries, and 
undertakes other initiatives to ensure the safety and effectiveness of products under FDA's 
purview.  The Office of Regulatory Affairs coordinates FDA's compliance activities and 
oversees the activities of FDA's 5 regional offices, 20 district offices, and approximately 
130 resident posts. 
On-site Inspections 
Staff from FDA's district offices and resident posts conduct almost all inspections of the 
firms that FDA regulates.2  Section 702(a) of the Food, Drug, and Cosmetic Act 
authorizes FDA to conduct inspections to enforce the provisions of that statute as well as 
other applicable laws.  Inspections focus on manufacturing, laboratory, production, and/or 
1  The FDA also operates the National Center for Toxicological Research in Jefferson, Arkansas and the 
Engineering and Analytical Center in Winchester, Massachusetts. 
2  The FDA contracts with State agencies to conduct some inspections, and headquarters staff sometimes 
participate in inspections of foreign or domestic firms. 
Warning Letters--Trends and Perspectives  5  OEI-09-97-00380  storage processes but may include examining a firm's administrative practices and controls 
as well as collecting samples, labels, and promotional materials. 
The FDA requires investigators to follow a standard protocol when conducting an 
inspection.  Upon arriving at a facility, investigators issue a Notice of Inspection (Form 
FDA-482) to the top management official.  The scope of the inspection generally is 
determined by the type of facility being inspected, the firm's history, general knowledge 
about the industry and its problems, and conditions found as the inspection progresses. 
Investigators are authorized to collect samples or other physical evidence while 
conducting inspections.  Examples include food, drugs, devices, or cosmetics.  Samples 
also may include evidence of violative conditions, such as rodent droppings or any other 
evidence of noncompliance with Federal laws and regulations. 
When investigators find objectionable conditions, they are required to provide the top 
management official with their findings on an Inspectional Observations form (Form FDA-
483).  The FDA-483 should include any observed problems with the facility, equipment, 
processes, controls, products, employee practices, or records.  Some examples of 
reportable observations include: 
<  filthy, putrid, or decomposed substances, unsanitary conditions, or evidence of 
contamination; 
<  careless handling of rodenticides or pesticides; 
<  results of field tests that reveal adulteration; 
<  observations of faulty manufacturing, processing, packaging, or holding of food, 
drug, or device products as related to Good Manufacturing Practice regulations;3 
and 
<  observations indicating noncompliance with medical device reporting 
requirements. 
Some observations require that action be taken by the centers only.  The FDA's 
Investigations Operations Manual instructs investigators to not report observations related 
to most labeling issues, promotional materials, the classification of a cosmetic or device as 
a drug, or the classification of a drug as a new drug on the FDA-483.  These issues are 
referred to the centers for compliance action. 
3  The Good Manufacturing Practice regulations specify FDA's expectations as to how firms should operate in 
manufacturing products regulated by the FDA. The regulation includes provisions related to personnel, quality 
control, facility design and maintenance, equipment, internal controls, production and process controls, packaging 
and labeling, storage and distribution, laboratory process, and reports and record keeping. 
Warning Letters--Trends and Perspectives  6  OEI-09-97-00380  Warning Letters 
What is a warning letter?  The warning letter generally represents FDA's first official 
notification to a firm or individual that FDA has found that one or more products, 
practices, processes, or other activities are in violation of the Food, Drug, and Cosmetic 
Act.  The warning letter affords firms the opportunity to voluntarily take corrective action 
prior to the initiation of formal enforcement action. 
The FDA is not required by law to warn firms or individuals that they are in violation of 
the law prior to initiating a formal regulatory action.4  The FDA believes, however, that: 
...documentation of notice of violative conduct strengthens the agency's 
position in regulatory actions by establishing that responsible individuals 
continued violative conduct despite warnings by the agency.5 
Who issues warning letters?  The FDA centers and district offices issue warning letters. 
In general, district offices issue warning letters to domestic firms based on inspections. 
Some centers issue warning letters for advertising and promotional violations or to foreign 
firms marketing products in the United States.  Others, such as the Center for Veterinary 
Medicine, issue few or no warning letters at all. 
At the district office level, although some warning letters can be issued at the discretion of 
the district director without center or other headquarters review or concurrence, FDA's 
Regulatory Procedures Manual lists numerous specific program area violations that 
require review by the appropriate center.  Centers are required to review and approve the 
issuance of warning letters within 15 days of receipt.  Despite this layer of review, the 
decision to initiate the warning letter process rests solely with the office that conducted 
the inspection. 
The following table illustrates how many warning letters the centers and district offices 
issued from fiscal years 1994 to 1997.  The district office tally includes all warning letters 
sent under district directors' signatures, including those that underwent center review: 
4  One exception to this statement is a requirement that when acting under the authority of the Radiation Control 
for Health and Safety Act, FDA is required by law to provide a written notification to manufacturers when the 
agency discovers products that fail to comply with a performance standard or that contain a radiation safety defect. 
5  FDA Regulatory Procedures Manual, Chapter 10, Subchapter  Prior Notice. 
Warning Letters--Trends and Perspectives  7  OEI-09-97-00380  District offices annually issue approximately 
80 percent of all warning letters 
Year  Total  District office-issued  Center-issued 
1994  1,626  1,282 (78.8%)  344 (21.2%) 
1995  1,501  1,175 (78.3%)  326 (21.7%) 
1996  1,037  841 (81.1%)  196 (18.9%) 
1997  1,175  1,003 (85.4%)  172 (14.6%) 
In fiscal year 1997, FDA issued 1,175 warning letters.  This reversed a trend during which

the number of warning letters decreased 36.2 percent from 1994 (1,626) to 

1996 (1,037).  More warning letters are issued for devices and radiological products than

for any of FDA's other product areas.  In fact, from 1994 to 1997, the Center for Devices

and Radiological Health issued more warning letters than any district office.  The district

offices issuing the most letters in 1997 were San Francisco (96), Florida (88), and Dallas

(74).  The district offices issuing the fewest warning letters in 1997 were Boston (16),

Detroit (19), and Nashville (20).

What does a warning letter say?  The warning letter instructs the firm to correct the

issues noted and to respond in writing within 15 days of receipt of the letter.  District

offices coordinate with the appropriate center to determine whether a firm's response to a

warning letter is adequate.  If the district or appropriate center deems the firm's response

adequate, it will notify other appropriate agency units.  This may require a reinspection of

the firm.

The FDA issues warning letters for regulatory violations, not for violations of

nonregulatory guidance documents.  It states that "the threshold for determination of what

constitutes 'regulatory significance' is that failure to adequately and promptly achieve

correction to the warning letter may be expected to result in enforcement action."

Subsequent Compliance Actions 
The FDA has both administrative and regulatory actions available to it to ensure 
compliance with the Food, Drug, and Cosmetic Act.  Administrative actions include 
detentions, civil penalties, and requesting voluntary recalls.  Regulatory actions include 
license revocations, license suspensions, citations, prosecutions, judicial civil penalties, 
injunctions, and seizures.6 
6  FDA has recall authority only for infant formula, human tissue, and certain medical devices. Recalls of 
other products are voluntary. License suspensions and revocations are regulatory actions taken for biologicals. 
Warning Letters--Trends and Perspectives  8  OEI-09-97-00380  Related Work 
The General Accounting Office (GAO) issued two studies in 1997 that questioned the 
consistency of FDA's inspection and compliance activities: 
<	 In "Blood Supply:  FDA Oversight and Remaining Issues of Safety" 
(GAO/PEMD-97-1, February 1997), GAO found that FDA issued warning letters 
to blood suppliers inconsistently.  The GAO also reported that some inspections 
yielded multiple FDA-483 observations but did not result in a warning letter, while 
other inspections with relatively few or minor observations resulted in the issuance 
of a warning letter. 
<	 In "FDA Mammography Inspections:  While Some Problems Need Attention, 
Facility Compliance Is Growing" (GAO/HEHS-97-25, January 1997), 
GAO questioned the consistency of inspectors who used different criteria in citing 
mammography facilities.  The GAO stated that FDA's monitoring and enforcement 
process did not ensure timely correction of deficiencies in these facilities.  The 
GAO also noted that FDA district offices needed better information systems to 
manage inspections. 
Based on GAOs concerns and the significant decrease in the number of warning letters 
issued from 1994 to 1996, we determined that this inspection was warranted. 
METHODOLOGY 
Interviews with FDA and Regulated Industry 
We conducted either in-person or telephone interviews with each district office.  We asked 
district office staff about their organizational structure, their experiences with warning 
letters, the factors that contributed to their increase or decrease in warning letters, and the 
responsiveness of the centers to their warning letter recommendations.  In addition, we 
analyzed district office inspection and warning letter trend data, reviewed FDAs 
Regulatory Procedures Manual, and interviewed staff from FDA headquarters. 
We selected a simple random sample of 40 firms that received warning letters during fiscal 
year 1996 and completed telephone interviews with 24 of them.  The remaining firms did 
not return phone calls or had gone out of business.  We asked firms about the violations 
that resulted in the warning letter and their experiences with FDA. 
Warning Letters--Trends and Perspectives  9  OEI-09-97-00380  This report is one of two reports on the FDA warning letter process.  A companion report, FDA 
Warning Letters:  Timeliness and Effectiveness (OEI-09-97-00381), describes the results of our 
on-site fieldwork at six FDA district offices where we conducted reviews of warning letter files 
and FDA follow up.  In that report, we found that warning letters are an effective compliance 
tool.  However, their effectiveness depends on committed follow-up attention by FDA.  We also 
found that their timeliness could be improved and numerous discrepancies exist between 
headquarters and district office data. 
Warning Letters--Trends and Perspectives  10  OEI-09-97-00380  F I N D I N G S 
Changes in FDA policies and practices and better industry 
compliance have contributed to decreases in warning letters 
The FDA has fostered a more cooperative relationship with industry 
In recent years, FDA has implemented measures to ensure compliance with Federal laws 
and regulations by offering education and communication in lieu of warning letters.  Many 
district offices now offer meetings to firms who receive FDA-483s.  In addition, FDA 
recently revised its warning letter guidance to include the following instructions: 
In sending the firm a warning letter, the warning letter should 
appropriately acknowledge corrections promised during the inspection, or 
annotated on the FDA-483, or provided to the district in a written 
response. 
A meeting and/or FDA-483 response may be adequate to avoid a warning letter.  In some 
district offices, a meeting and a firms promised corrections can result in a warning letter 
not being issued.  In other district offices, the warning letter is issued regardless of the 
outcome of the meeting. 
District office and headquarters staff agree that all tools should be used to achieve 
compliance.  Because of this viewpoint, FDA looks at its options with flexibility.  Some 
district office staff acknowledge that, as they become more used to using the warning 
letter, they increasingly look at whether headquarters is prepared to take additional action 
based on a firms subsequent noncompliance.  Because of the resources required to 
implement a civil or criminal proceeding, the answer is increasingly no.  As a result, 
some district offices believe that working cooperatively with the firms is the most effective 
and timely solution. 
The FDA has implemented some recent policy changes to increase firm cooperation. 
These changes have contributed to the decrease in warning letters.  Numerous changes in 
the Center for Devices and Radiological Health, for instance, have brought the industry 
and FDA closer in addressing compliance issues.  For example, FDA now notifies medical 
device firms prior to arriving for inspections.  This allows the firm to prepare the 
documentation that the investigator will request during the inspection.  The FDA is 
currently considering extending this practice to other product areas and continues to 
develop new policies concerning medical device warning letters through its medical device 
Warning Letter Pilot. 
Warning Letters--Trends and Perspectives  11  OEI-09-97-00380  District office reorganizations may contribute to the decrease 
Although several district officials believe that declining resources have contributed to the 
decrease in warning letters, FDA inspection data indicate that the number of inspections 
completed annually remained constant from FY 1994 to FY 1997.  Some staff believe that 
district offices that moved from a traditional structure, with separate compliance and 
inspection branches, to a combined branch structure suffered a temporary or lasting loss of 
productivity.  Slightly fewer than half of the district offices have combined their 
compliance and investigations branches. 
According to staff, the attrition of experienced staff, staff difficulty understanding new 
roles, time required to train staff for their new roles, and the failure of self-directed teams 
to function adequately resulted in a loss of productivity.  We analyzed inspection and 
warning letter trends for district offices that had reorganized as well as those that had 
retained a traditional structure.  As the following table illustrates, district offices that had 
reorganized in the past several years saw their inspection and warning letter numbers 
decrease at higher rates than those that retained a traditional structure: 
Reorganized district offices have seen inspection and warning 
letter numbers decline faster than traditional district offices 
Structure  Inspections, 1994-1997  Warning Letters, 1994-1997 
Reorganized  -6.9 percent  -32.0 percent 
Traditional  -0.6 percent  -15.8 percent 
Other factors may account for these differences.  Offices that have reorganized may have 
implemented other changes that resulted in fewer warning letters.  For example, the 
Kansas City district office has implemented a major educational effort that changes the 
traditional role of the compliance officer to an educator.  In addition, other district offices 
that have reorganized appear to be focusing a great deal of attention on industry education 
and cooperation. 
District offices conduct different types of inspections than in prior years 
According to district office staff, changes in inspection priorities and methods have 
contributed to the overall decrease in warning letters.  Eight district offices and staff from 
FDA centers noted that the role of the district office has changed in recent years.  In 
particular, the scope and type of inspections have changed: 
<	 More inspections are headquarters-directed.  District offices conduct fewer 
routine inspections based on their workplans.  Instead, the centers frequently 
undertake special initiatives that require that the district offices drop everything 
Warning Letters--Trends and Perspectives  12  OEI-09-97-00380  else in order to inspect all industry-specific firms in their jurisdictions.  Recent 
examples include blood suppliers and mammography providers. 
<	 The FDA now conducts more premarket approval inspections, and they do not 
result in warning letters.  The FDA has attempted to streamline its product 
approval process to speed up the introduction of new products into the 
marketplace.  This has included conducting an inspection prior to FDA granting 
approval of a new product. 
<	 Inspections have become more technical and complicated.  Because technology 
has increased the sophistication of new products, the amount of time, work, and 
expertise required to complete an inspection has increased dramatically. 
<	 Inspections have changed in scope.  As the base of scientific knowledge increases, 
FDA has focused on different issues when conducting inspections.  For example, 
district offices are focusing on microbiological issues rather than filth when 
conducting food inspections.  Whereas filth inspections could result in immediate 
warning letter issuance, investigators now collect samples that FDA labs analyze. 
<	 Some district offices focus inspection resources on previously identified violative, 
risky firms.  Violations uncovered during inspections of these firms typically would 
warrant a more serious compliance action than a warning letter. 
One-third of district offices believe that firms are doing a better job of being in 
compliance 
Firms dislike warning letters, which can be used by competitors to disparage their 
reputations.  This is especially true in the pharmaceutical industry, where a warning letter 
may cost a firm millions of dollars in HMO contracts.  As a result, district offices believe 
that the threat of a warning letter is strong motivation for firms to be in compliance. 
Several districts suggested that the age of a firm or of a regulation affects industry 
compliance.  Newer firms with less experience may be unaware that certain practices 
violate FDA regulations.  As these firms become more familiar with the rules governing 
their business, they are less likely to unknowingly commit warning letter infractions. 
Similarly, when industry becomes more accustomed to a regulation, violations are less 
likely to occur. 
Warning Letters--Trends and Perspectives  13  OEI-09-97-00380  Despite the existence of clear warning letter guidance, 
differences in district office attitudes, experience, and the 
types of firms in the district affect warning letter volume 
The FDAs warning letter data illustrate the wide variation in the number of warning 
letters issued by different district offices: 
From 1994 to 1997, some district offices issued almost 
five times as many warning letters as others 
Most warning letters, 1994-97  Fewest warning letters, 1994-97 
San Francisco  384  San Juan  82 
Florida  320  Buffalo  96 
New York  303  Detroit  104 
While the staff size of the district offices has an obvious effect on the number of 
inspections and warning letters, this is not the only factor affecting the extent to which 
warning letters are used.  District offices vary in their philosophy and use of warning 
letters.  Some district offices have adopted a collaborative problem-solving approach with 
industry.  These districts have been more likely to use the FDA-483 to achieve 
compliance, take a firms FDA-483 response into consideration, or call the firm in for a 
meeting in lieu of issuing a warning letter.  Other district offices, however, believe it is 
important to put a firms noncompliance on record by promptly issuing a warning letter, 
regardless of a firms FDA-483 response or desire for a meeting. 
While district offices believe that the compliance programs clearly delineate when 
violations meet warning letter thresholds, they also noted the extent to which the 
experience of investigators, supervisory investigators, and compliance officers figures into 
the determination.  This occurs because these staff are well-acquainted with the 
compliance programs, have inspected similar firms multiple times, and are more 
comfortable making a close judgment call. 
The types of firms under a districts jurisdiction play a major role in the number of warning 
letters issued by a district office: 
<	 Districts with large, highly technical industries:  Inspections take longer to 
complete and frequently are complicated because of the advanced technology 
being used by these firms.  In addition, these firms frequently have regulatory 
affairs staff whose sole job is to ensure compliance with FDA.  As a result, a long, 
resource-intensive inspection may uncover no significant violations. 
Warning Letters--Trends and Perspectives  14  OEI-09-97-00380  <	 Districts saturated with smaller, less FDA-savvy firms:  These firms often are not 
used to dealing with a regulatory agency.  They may be service industry firms (e.g., 
tanning salons) or firms that focus more on the distribution rather than the 
production of goods (e.g., importers, warehousers).  These firms frequently are 
not well-acquainted with FDA regulations and do not have employees whose 
primary responsibility is to ensure compliance with FDA.  As a result, a short 
inspection is often likely to expose violations.  In addition, FDA routinely issues 
warning letters to importers that fail to hold a shipment for FDA examination. This 
tends to generate many warning letters in large import districts. 
<	 Center-driven industry-specific inspection efforts:  Centers sometimes mandate 
that district offices conduct industrywide inspections, such as recent efforts 
focused on mammography establishments, blood banks, and seafood firms.  These 
can have periodic effects on warning letter trends.  A district with heavy 
concentrations of those industries may experience a temporary increase or 
decrease in warning letters.  For example, when FDA initiated a nationwide effort 
to inspect mammography establishments, those districts with a large number of 
these firms experienced a surge in warning letters.  On the other hand, FDAs 
recent efforts to implement Hazard Analysis Critical Control Point regulations in 
the seafood industry have focused on the education of firms.  The Center for Food 
Safety and Applied Nutrition has instructed district offices not to issue warning 
letters during implementation of the regulations.  As a result, districts with a high 
concentration of seafood firms are generating few warning letters as they focus 
their inspection resources on these firms. 
Firms would like to better understand the warning letter 
process and suggested some minor changes 
FDA policies and procedures governing warning letters are unclear to firms 
The firms that received warning letters in 1996 are uncertain about what criteria 

FDA uses to determine if a warning letter is necessary.  These firms believe that the step

from the FDA-483 to the warning letter was subjective.  One firm that operates in more

than one FDA district claimed that the same violations do not always receive consistent

compliance action from FDA (e.g. a warning letter versus an FDA-483).  Some firms

believe that investigators interpret the regulations differently.  More than one-half of the

firms believe that their violations did not warrant a warning letter, while 38 percent agreed

with FDAs decision to issue a warning letter.

Firms believe that FDA does not provide consistent and accessible guidance on what

warrants a warning letter.  Policy guidance publications exist, but they are not accessible

Warning Letters--Trends and Perspectives  15  OEI-09-97-00380  to some firms, especially those that are smaller and less sophisticated.  A firm official 
summarized the difficulties: 
The industry is in the dark about changes in [FDAs] procedures and 
priorities.  The FDA is not communicating procedure changes but is 
writing up firms who violate the changes.  For example, we were written 
up for new training requirements that were never communicated to us in 
the first place. 
Another firm with a similar viewpoint requested even more guidance from FDA, saying, 
FDA should give suggestions on exactly how to comply with labeling regulations.  A list 
of suggestions would be helpful. 
Firms also do not understand the role of the investigator in the warning letter process. 
One firm believes that the investigator who conducted the inspection was not a part of the 
decision to issue a warning letter. 
When possible, firms would appreciate advance notice that a warning letter will 
be issued 
Some district offices warn firms that the district office is considering sending a warning 
letter or that they have sent a warning letter recommendation to FDA headquarters.  Other 
district offices issue warning letters without prior notice. 
Firms claim that they would respond and comply more quickly if FDA consistently told 
them that a warning letter was imminent.  Most firms (58 percent) did not expect to 
receive a warning letter.  However, almost half of those that did not expect the warning 
letter received it for violations discovered through postinspection laboratory testing, 
making it impossible for FDA to alert the firm during the inspection. 
Firms suggested a variety of methods that FDA could use to prepare them for the warning 
letter.  These include telephone calls, postcards, electronic mail and letters advising the 
firm that the warning letter is forthcoming.  One-half of the firms responded to the 
FDA-483 in writing, including one firm that indicated an adequate response to the 
FDA-483 could preclude the issuance of a warning letter.  The same firm conceded that 
certain violations will always trigger a warning letter and asked that FDA make more 
efforts to publicize those violations. 
Warning Letters--Trends and Perspectives  16  OEI-09-97-00380  With some exceptions, firms were satisfied with FDAs 
customer service during the warning letter process 
Firms generally viewed investigators as helpful and thorough, although some 
firms questioned their objectivity 
The majority of firms who commented on the FDA investigators customer service had 
generally positive things to say.  A total of sixteen firms reported on the investigators 
customer service, and 10 were generally positive, 5 had negative things to say, and 
1 simply said that investigators vary in candor and helpfulness.  Of those who reported a 
positive experience, investigators were most commonly described as helpful and 
thorough.  One firm praised the investigators, saying they made us a better 
organization.  Of the five firms that reported a negative experience with the investigators, 
three complained about what they perceived as an inordinate amount of time the 
investigator spent inspecting them. 
Most firms perceived the district offices in a positive light; however, some 
reported instances of staff apathy 
Three-quarters of the firms that contacted a district office had positive things to say about 
the offices customer service.  Sixty-seven percent of firms had contact with their district 
office following the issuance of the warning letter.  Comments ranged from, they were 
flexible in allowing us to choose the date for our second inspection, to superlatives 
describing staff  as wonderful and excellent.  Three firms mentioned their district 
office was particularly helpful during the warning letter process.  Those firms accepted 
FDAs assistance in drafting letters of recall or resolving a credentialing problem with the 
State. 
While most firms who contacted their district office found the experience positive, the 
remaining 25 percent of firms had negative experiences.  The three firms that complained 
about their district office mentioned difficulty reaching staff, delays in approval of 
imported foods, unhelpful and impolite staff, and either too few employees or employees 
who just dont care. 
Few firms contacted FDA headquarters, and customer service reviews were 
mixed 
Few firms had contact with FDA headquarters.  Four firms (17 percent) contacted 
headquarters during the warning letter process.  Two firms reported positive experiences, 
and two firms reported negative experiences.  One satisfied firm mentioned that they were 
able to get to the right people  and another firm said the FDA headquarters staff were 
great, they followed up well.  Comments from the two firms that had negative 
experiences included, We could get no clear answers, to their questions regarding tissue 
Warning Letters--Trends and Perspectives  17  OEI-09-97-00380  sampling and we got no response to our request to speed up the process of approving 
imported foods, especially holiday-related foods. 
Warning Letters--Trends and Perspectives  18  OEI-09-97-00380  R E C O M M E N D A T I O N  
The warning letter is an effective tool to achieve compliance with Federal laws and 
regulations.  In our companion report, we recommend that FDA improve the timeliness of 
the warning letter process and follow-up activities and revamp its warning letter data 
collection system to ensure accuracy. 
Based on the findings in this report, we believe that FDA also should implement some 
minor improvements to increase fairness among district offices and improve flexibility. 
Specifically, FDA should: 
<  continue to improve relations and communication with industry and 
<	 consider issuing guidance that would authorize district offices to use FDA-483s 
and meetings to achieve compliance in lieu of warning letters. 
District offices vary significantly in (1) experience, (2) how they view the warning letter, 
and (3) their relationships with industry.  As a result, there is a significant difference in 
how district offices handle inspection violations.  While FDA has accepted this variation in 
the past, the move that some district offices have made toward using FDA-483s and 
meetings in lieu of warning letters has focused attention on these variations. 
We believe that FDAs move towards better communication and collaboration with 
industry is appropriate, in light of the National Performance Review and the findings 
presented in this report.  Further development of these relationships is important in 
preserving fairness.  A firm should not suffer adverse consequences solely because it is 
located in a different district than another firm. 
At the same time, we recognize the need to allow district offices considerable discretion. 
Developing guidance on alternatives to the warning letter will allow them to pursue other 
means of achieving compliance. 
We received comments on the draft report from FDA in which the agency concurred with 
our recommendation.  Where appropriate, we have made revisions in the report in 
response to these comments.  We also have responded to several of FDAs comments in 
the appendix. 
Warning Letters--Trends and Perspectives  19  OEI-09-97-00380  APPENDIX A 
AGENCY COMMENTS

Warning Letters--Trends and Perspectives  20  OEI-09-97-00380  Warning Letters--Trends and Perspectives  21  OEI-09-97-00380  Warning Letters--Trends and Perspectives  22  OEI-09-97-00380  Warning Letters--Trends and Perspectives  23  OEI-09-97-00380  Warning Letters--Trends and Perspectives  24  OEI-09-97-00380  APPENDIX B 
OIG RESPONSE TO AGENCY COMMENTS 
We offer the following additional analysis based on FDAs concerns. 
At the time that this inspection began, there were six regional offices and 21 district 
offices as we stated in the draft report.  The Mid-Atlantic and Midwest regional offices 
have since merged into the Central regional office, and the Buffalo district office has 
merged with the Brooklyn district office. 
The seafood industry was the only industry in our sample that has a seasonal component. 
Analysis of the firms in our sample that market seafood shows that either there was no 
follow-up inspection conducted (most often because it was a failure-to-hold violation) 
or that reinspection was actually more timely than the average.  Hence, reinspection delays 
resulting from the seasonal nature of the industry had either no effect or a diminishing 
effect on the 278-day average that we reported. 
We do not intend to place any value judgments on the number of warning letters produced 
by a district. Our purpose in identifying these extremes is merely to indicate the wide 
variation in warning letter production that exists among the districts. 
Analysis of FDA data indicates that while both the numbers of inspections and warning 
letters decreased from 1994 to 1997 (the range used for our statements in the reports), 
inspections decreased by 3.6 percent while warning letters fell 39 percent.  In other terms, 
in 1994, about 9.1 inspections conducted yielded 1 warning letter.  In 1997, the rate was 
12.2 inspections per warning letter. 
We agree that the prevalence of importers in a district could contribute to the variation in 
number of warning letters issued and have clarified their importance in this report. 
The FDAs opinion that firms will voluntarily correct violations is highlighted in the 
background section of this report. 
Several districts indicated that increased familiarity with FDA regulations leads to better 
industry compliance.  We have clarified this point in this report. 
Our recommendation was not intended to discourage the use of warning letters, but rather 
to encourage FDA to issue guidance which would allow a district office to select the tools 
it feels are most effective in achieving compliance in a given situation. 
Warning Letters--Trends and Perspectives  25  OEI-09-97-00380  The medical device Warning Letter Pilot will allow FDA to use a firms response to an 
FDA-483 or an untitled letter to preempt a warning letter for certain segments of the 
device industry.  More information can be found on FDAs website or the Federal Register 
for August 27, 1998. 
With respect to FDAs comment on Page 11, last paragraph after table of the 
companion draft report entitled FDA Warning Letters: Timeliness and Effectiveness 
(the table and paragraph now appear on page 12), we note that the paragraph below the 
pie chart on page 13 shows that despite the discovery of repeat or new violations on 
reinspection, the warning letter was still effective.  As stated there, investigators believed 
that the violations found on reinspection were minor and that firms had made satisfactory 
progress towards compliance. 
Warning Letters--Trends and Perspectives  26  OEI-09-97-00380