Department of Health and Human Services 

OFFICE OF 

INSPECTOR GENERAL 

JUNE GIBBS BROWN 

Inspector General 

FEBRUARY 1999 

OEI-09-97-00380 

FDA WARNING LETTERS 

Trends and Perspectives 
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 
EXECUTIVE SUMMARY 

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 FDA’s 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 FDA’s 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 FDA’s 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 FDA’s 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 FDA’s 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 
TABLE OF CONTENTS 

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 FDA’s 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 
INTRODUCTION 

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 FDA483). 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 GAO’s 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 FDA’s 

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 
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 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 firm’s 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 firm’s 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 FDA’s 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 firm’s 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 firm’s noncompliance on record by promptly issuing a warning letter, 

regardless of a firm’s 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 district’s 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, FDA’s 

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 FDA’s 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 [FDA’s] 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 FDA’s

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 investigator’s 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 office’s 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 

FDA’s 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 don’t 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 
RECOMMENDATION 

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 FDA’s 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 FDA’s comments in 

the appendix. 

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APPENDIX A 

AGENCY COMMENTS

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APPENDIX B

OIG RESPONSE TO AGENCY COMMENTS 

We offer the following additional analysis based on FDA’s 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 FDA’s 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. 

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The medical device Warning Letter Pilot will allow FDA to use a firm’s 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 FDA’s website or the Federal Register 

for August 27, 1998. 

With respect to FDA’s 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. 

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