COVID-19 Complicates Already Challenged FDA Foreign Inspection Program (GAO-20-626T)
Summary
GAO testimony, GAO-20-626T, before the Senate Committee on Finance on June 2, 2020, the statement of Mary Denigan-Macauley, Director, Health Care, on drug safety and the Food and Drug Administration's (FDA) foreign inspection program. It recalls GAO's December 2019 finding that a growing share of FDA's foreign drug manufacturing inspections were in China and India (43 percent in 2018). It states that in fiscal year 2015 FDA for the first time conducted more foreign inspections than domestic inspections. From fiscal year 2016 through 2018, both foreign and domestic inspections decreased, by about 10 percent and 13 percent. The testimony's title states that COVID-19 complicates the already challenged program.
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United States Government Accountability Office
Testimony
Before the Committee on Finance,
U.S. Senate
DRUG SAFETY
For Release on Delivery
Expected at 2:30 p.m. ET
Tuesday, June 2, 2020
COVID-19 Complicates
Already Challenged FDA
Foreign Inspection
Program
Statement of Mary Denigan-Macauley, Director,
Health Care
GAO-20-626T
June 2, 2020
DRUG SAFETY
COVID-19 Complicates Already Challenged FDA
Foreign Inspection Program
Highlights of GAO-20-626T, a testimony
before the Committee on Finance, U.S.
Senate
Why GAO Did This Study What GAO Found
The outbreak of COVID-19 has In December 2019, GAO found that a growing number of foreign drug
called greater attention to the United manufacturing inspections conducted by the Food and Drug Administration
States’ reliance on foreign drug (FDA) were in China and India (43 percent in 2018), where most establishments
manufacturers and further that manufacture drugs for the United States were located. In fiscal year 2015,
highlighted the importance of FDA, for the first time, conducted more foreign inspections than domestic
ensuring a safe pharmaceutical inspections. However, from fiscal year 2016 through 2018, both foreign and
supply chain. Much of the domestic inspections decreased—by about 10 percent and 13 percent,
manufacturing of drugs for treating respectively. FDA officials attributed the decline, in part, to vacancies among
COVID-19 occurs overseas, which is
investigators available to conduct inspections. In March 2020, FDA announced
also true of the majority of other
that, due to Coronavirus Disease 2019 (COVID-19), it was postponing almost all
drugs marketed in the United States.
While the volume of drugs
inspections of foreign manufacturing establishments. While FDA has indicated it
manufactured overseas for the U.S. has other tools to ensure the safety of the U.S. drug supply, the lack of foreign
market is not fully known, FDA inspections removes a critical source of information about the quality of drugs
reports that about 70 percent of manufactured for the U.S. market.
establishments manufacturing active
The 10 Countries with the Most Foreign Drug Establishments Shipping to the United States as
ingredients and more than 50 of March 2019, by Country
percent of establishments
manufacturing finished drugs for the
U.S. market were located overseas,
as of August 2019.
FDA is responsible for overseeing
the safety and effectiveness of all
drugs marketed in the United States,
regardless of where they are
produced, and conducts inspections
of both foreign and domestic drug
manufacturing establishments.
GAO has had long-standing
concerns about FDA’s ability to
oversee the increasingly global
pharmaceutical supply chain, an
issue highlighted in GAO’s High Risk
Series since 2009. In particular:
• GAO recommended in 2008
(GAO-08-970) that FDA GAO also found that FDA had vacancies among each of the groups of
increase the number of investigators who conduct foreign inspections. FDA had 190 investigators in the
inspections of foreign drug United States who conduct the majority of foreign inspections, but an additional
establishments. 58 positions were vacant. At the time of GAO’s December 2019 testimony, FDA
• GAO found in 2010 (GAO-10- was in the process filling 26 of these vacancies, with 32 remaining. However,
961) that FDA continued to according to FDA officials, it could be 2 to 3 years before new staff are
conduct relatively few foreign experienced enough to conduct foreign inspections. FDA also faced persistent
inspections than domestic vacancies among investigators in its foreign offices.
inspections.
View GAO-20-626T. For more information,
contact Mary Denigan-Macauley at (202) 512-
7114 or deniganmacauleym@gao.gov.
United States Government Accountability Office
• GAO found in 2016 (GAO-17- GAO further found in December 2019 that FDA investigators identified persistent
143) that FDA was conducting challenges conducting foreign inspections, raising questions about the
more of these foreign drug equivalence of foreign to domestic inspections. Specifically, GAO found:
inspections, and GAO closed its • While FDA inspections performed in the United States were almost
2008 recommendation to conduct
always unannounced, FDA’s practice of preannouncing foreign
more foreign inspections.
inspections up to 12 weeks in advance may have given manufacturers
However, GAO also reported that
FDA may have never inspected
the opportunity to fix problems ahead of the inspection. Investigators
many foreign establishments from FDA’s China and India offices had conducted some unannounced
manufacturing drugs for the U.S. inspections, but these staff do not perform most of the inspections in
market. these countries (27 percent and 10 percent, respectively).
In addition, in the summer of 2018,
FDA Estimates of the Amount of Notice Provided to Foreign Drug Establishments Prior to
FDA began announcing recalls of Inspection, Fiscal Year 2018
blood pressure medications Amount of
manufactured overseas that were Type of notice Percentage of inspections involving this
tainted with a potential carcinogen, investigator provided investigator type
raising further questions about FDA’s China office 0-5 days Involved in 27 percent of total number of
oversight of foreign-manufactured investigator inspections in China
drugs. India office 0-5 days. Involved in 10 percent of total number of
investigator inspections in India
This statement is largely based on
GAO’s December 2019 testimony
(GAO-20-262T) and discusses U.S.-based Generally 12 Involved in:
investigator weeks • 73 percent of total number of
1. the number of foreign inspections
inspections in China
FDA has conducted,
• 90 percent of total number of
2. inspection staffing levels, and inspections in India
• 100 percent of total number of
3. challenges unique to foreign inspections in other foreign countries
inspections. Source: Interviews with Food and Drug Administration (FDA) officials and GAO analysis of FDA data. | GAO-20-626T
For that testimony, GAO examined
FDA data from fiscal years 2012 • FDA was not generally providing translators on foreign inspections.
through 2018 and interviewed Rather, FDA continued to rely on translators provided by the foreign
investigators from FDA’s 2019 cadre establishments being inspected, which investigators said raised
of investigators (who are based in the questions about the accuracy of information FDA investigators collected.
United States but exclusively conduct For example, one investigator said there was more risk of conflict of
foreign drug inspections) and from interest if the establishment used its own employees to translate. In
FDA’s foreign offices in China and addition, the establishment representative providing the translation may
India. be someone who does not have the technical language needed, which
can make it harder to communicate with establishment staff and
facilitate the inspection.
• The overseas travel schedule can present challenges for FDA’s
domestically based investigators, who conduct the majority of foreign
inspections. Domestically based investigators told us there is little
flexibility for them to extend foreign inspections during an overseas trip.
The inspections they conduct on an overseas trip are scheduled back-
to-back in 3-week trips and may involve three different countries.
Therefore, extending one inspection would limit the amount of time the
investigator has to complete their other scheduled inspections. FDA
officials said that inspections conducted by investigators based in China
or India (and domestic inspections in the United States) are generally
scheduled one at a time and can thus more easily be extended if the
investigator needs additional time to pursue potential deficiencies.
However, these in-country investigators are not involved in the majority
of FDA inspections conducted in China or India.
United States Government Accountability Office
Letter
Chairman Grassley, Ranking Member Wyden, and Members of the
Committee:
I am pleased to be here today to discuss our work on the Food and Drug
Administration’s (FDA) oversight of drugs manufactured overseas. 1 The
outbreak of Coronavirus Disease 2019 (COVID-19) has called greater
attention to the United States’ reliance on foreign drug manufacturers and
further highlighted the importance of ensuring a secure pharmaceutical
supply chain. Like the majority of other drugs manufactured for the U.S.
market, much of the manufacturing of drugs for treating COVID-19 occurs
overseas.
We have had long-standing concerns about FDA’s ability to oversee the
increasingly global pharmaceutical supply chain, an issue highlighted in
our High Risk Series since 2009. 2 A critical element in FDA’s oversight of
overseas manufacturing is the inspections it conducts of foreign
manufacturing establishments. For more than two decades, we have
raised concerns about FDA’s foreign drug inspection program. In 1998,
and again in 2008, we found that FDA inspected relatively few foreign
drug manufacturing establishments—an estimated 8 percent of those
subject to inspection for our 2008 report—and that challenges unique to
foreign inspections influenced the manner in which FDA conducted such
inspections. 3 In our 2008 report we recommended that FDA increase the
1Drugs are defined to include, among other things, articles intended for use in the
diagnosis, cure, mitigation, treatment, or prevention of disease and include components of
those articles. See 21 U.S.C. § 321(g)(1)(B), (D). An active pharmaceutical ingredient
includes, among other things, any component that is intended to provide pharmacological
activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of
disease. See 21 C.F.R. § 207.1 (2019). In this testimony, we refer both to drug products—
drugs in their finished dosage forms—and to active pharmaceutical ingredients as “drugs.”
Our work focuses on human drugs and not on most biologics, veterinary medicines, or
other items or products for which FDA conducts inspections. (Biologics are materials, such
as viruses, therapeutic sera, toxins, antitoxins, vaccines or analogous products, to
prevent, treat, or cure human diseases or injuries and are derived from natural sources,
such as humans, animals, and microorganisms. See 42 U.S.C. § 262(i); 21 C.F.R. §
600.3(h) (2019).)
2See GAO, High-Risk Series: Substantial Efforts Needed to Achieve Greater Progress on
High-Risk Areas, GAO-19-157SP (Washington, D.C.: Mar. 6, 2019).
3See GAO, Food and Drug Administration: Improvements Needed in the Foreign Drug
Inspection Program, GAO/HEHS-98-21 (Washington, D.C.: Mar. 17, 1998) and Drug
Safety: Better Data Management and More Inspections Are Needed to Strengthen FDA’s
Foreign Drug Inspection Program, GAO-08-970 (Washington, D.C.: Sept. 22, 2008).
Page 1 GAO-20-626T
number of foreign inspections it conducts. 4 In 2010, and again in 2016,
we found that FDA was conducting more inspections of foreign
establishments (inspecting about 11 percent and 21 percent of those
subject to inspection for our 2010 and 2016 reports, respectively).
However, in 2010 we reported that FDA continued to conduct relatively
fewer foreign drug inspections than domestic inspections, and in 2016 we
also reported that many foreign establishments manufacturing drugs for
the U.S. market may never have been inspected by FDA. 5 In addition, in
the summer of 2018, FDA began announcing recalls of blood pressure
medications manufactured overseas that were tainted with a potential
carcinogen, raising further questions about FDA’s oversight of foreign-
manufactured drugs. 6
My remarks today primarily discuss the findings from our December 2019
testimony on FDA’s foreign drug inspection program. 7 Accordingly, this
statement provides observations on:
1. the number of FDA’s foreign inspections,
2. inspection staffing levels, and
3. challenges unique to foreign inspections.
For our December 2019 testimony, we analyzed FDA data from fiscal
year 2012 through fiscal year 2018 on inspections of foreign drug
manufacturing establishments. We also interviewed FDA drug
investigators from FDA’s 2019 cadre of investigators, who are based in
the United States but exclusively conduct foreign drug inspections, and
investigators based in FDA’s foreign offices in China and in India. More
4See GAO-08-970, 43. FDA agreed with our recommendation and then started conducting
more foreign inspections and changed how it selects establishments for inspection to
ensure that foreign establishments be inspected at a frequency comparable to domestic
establishments with similar characteristics. As a result, we closed this recommendation.
5See GAO, Drug Safety: FDA Has Conducted More Foreign Inspections and Begun to
Improve Its Information on Foreign Establishments, but More Progress is Needed, GAO-
10-961 (Washington, D.C.: Sept. 30, 2010) and GAO, Drug Safety: FDA Has Improved Its
Foreign Drug Inspection Program, but Needs to Assess the Effectiveness and Staffing of
Its Foreign Offices, GAO-17-143 (Washington, D.C.: Dec. 16, 2016).
6Food and Drug Administration, FDA Updates and Press Announcements on Angiotensin
II Receptor Blocker (ARB) Recalls (Valsartan, Losartan, and Irbesartan), accessed
December 1, 2019, https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-
and-press-announcements-angiotensin-ii-receptor-blocker-arb-recalls-valsartan-losartan
7See GAO, Drug Safety: Preliminary Findings Indicate Persistent Challenges with FDA
Foreign Inspections, GAO-20-262T (Washington, D.C.: Dec. 10, 2019).
Page 2 GAO-20-626T
detailed information on our objectives, scope, and methodology for that
work can be found in the December 2019 testimony. The work on which
this statement is based was conducted in accordance with generally
accepted government auditing standards. Those standards require that
we plan and perform the audit to obtain sufficient, appropriate evidence to
provide a reasonable basis for our findings and conclusions based on our
audit objectives. We believe that the evidence obtained provides a
reasonable basis for our findings and conclusions based on our audit
objectives.
Background
Globalization of Drug Drugs sold in the United States—including active pharmaceutical
Manufacturing ingredients (APIs) and finished dosage forms—are manufactured
throughout the world. According to FDA, as of August 2019 about 70
percent of establishments manufacturing APIs and more than 50 percent
of establishments manufacturing finished drugs for the U.S. market were
located overseas. 8 As of March 2019, FDA data showed that India and
China had the most manufacturing establishments shipping drugs to the
United States, with about 40 percent of all foreign establishments in these
two countries. (See fig. 1.)
8Janet Woodcock, M.D., Director, Center for Drug Evaluation and Research, Food and
Drug Administration, Securing the U.S. Drug Supply Chain: Oversight of FDA’s Foreign
Inspection Program, testimony before the House Committee on Energy and Commerce,
Subcommittee on Oversight and Investigations, 116th Congress, December 10, 2019.
According to FDA, although the agency has information on the location of drug
manufacturing establishments, it does not have information on the volume of drug
ingredients these establishments manufacture for the U.S. market.
Page 3 GAO-20-626T
Figure 1: The 10 Countries with the Most Foreign Drug Establishments Shipping to the United States as of March 2019, by
Country
Note: This figure includes the 10 countries with the most foreign drug establishments shipping to the
United States and does not include those countries with fewer than 70 establishments. The count of
foreign establishments represents the number of establishments that were known to ship or likely
would ship a drug to the United States as of March 2019. This count excludes about 380
establishments that participate in some aspect of the manufacturing process, such as sterilizers and
analytical labs, but would not ship products to the United States directly. Such establishments are
also subject to inspection.
Types of Inspections FDA is responsible for overseeing the safety and effectiveness of all
drugs marketed in the United States, regardless of where they are
manufactured. Drugs manufactured overseas must meet the same
statutory and regulatory requirements as those manufactured in the
United States. FDA’s Center for Drug Evaluation and Research (CDER)
establishes standards for the safety, quality, and effectiveness of, and
manufacturing processes for, over-the-counter and prescription drugs.
CDER requests that FDA’s Office of Regulatory Affairs (ORA) inspect
both domestic and foreign establishments to ensure that drugs are
Page 4 GAO-20-626T
produced in conformance with applicable laws of the United States,
including current good manufacturing practice (CGMP) regulations. 9
FDA investigators generally conduct three main types of drug
manufacturing establishment inspections: preapproval inspections,
surveillance inspections, and for-cause inspections, as described in table
1. At times, FDA may conduct an inspection that combines both
preapproval and surveillance inspection components in a single visit to an
establishment. 10
Table 1: Types of Drug Manufacturing Establishment Inspections Conducted by the Food and Drug Administration (FDA)
Type of inspection Purpose of inspection
Preapproval inspections FDA conducts preapproval inspections before approving a new brand name or generic drug to be
marketed in the United States. These inspections are designed to verify the accuracy and
authenticity of drug application data (such as manufacturing records) and assess whether the
establishment can manufacture the product in the application in conformance with applicable
regulations to assure a drug’s identity, strength, quality, and purity.a
Surveillance inspections Surveillance inspections are conducted at establishments when drugs are already marketed in the
United States—either after FDA approval or after marketing for drugs that do not require FDA
preapproval—and focus on compliance with system-wide controls for ensuring that the
manufacturing processes produce high-quality drugs.b Systems examined during these inspections
include those related to materials, quality control, production, facilities and equipment, packaging
and labeling, and laboratory controls. These systems may be involved in the manufacture of multiple
drugs.
For-cause inspections For-cause inspections are conducted to investigate specific issues, such as those raised in
consumer complaints, indications of potential manufacturing problems submitted by the
manufacturers themselves, or to follow-up on previous FDA regulatory action, among other reasons.
Source: GAO analysis of FDA information. | GAO-20-626T
a
When FDA receives an application for drug approval (or a supplement to that application related to a
manufacturing change), officials review the inspection history of each establishment listed on the
application, among other things. According to FDA officials, if an establishment listed on the
application has received a satisfactory good manufacturing practices inspection in the previous 2
years for a similar or more complex product, and the agency has no new concerns, FDA may
consider this inspection sufficient and not perform a preapproval inspection of this establishment.
b
Certain drugs, such as some over-the-counter drugs, may not require FDA approval before
marketing in the United States.
FDA uses multiple databases to select foreign and domestic
establishments for surveillance inspections, including its registration
database and inspection database. Because the establishments are
9CGMPs provide for systems that assure proper design, monitoring, and control of
manufacturing processes and facilities. See 21 C.F.R. pts. 210, 211, 212 (2019). FDA
considers nearly all drug establishment inspections to include an assessment of CGMPs.
10Most combined inspections occur when FDA conducts a surveillance inspection at an
establishment where a preapproval inspection was also being conducted.
Page 5 GAO-20-626T
continuously changing as they begin, stop, or resume marketing products
in the United States, CDER creates a monthly catalog of establishments.
The establishments in the catalog are prioritized for inspection twice each
year.
In our 2008 report we found that, because of inaccurate information in
FDA’s databases, the agency did not know how many foreign drug
establishments were subject to inspection. 11 For example, some
establishments included in FDA’s registration database may have gone
out of business and did not inform FDA that they had done so, or they did
not actually manufacture drugs for the U.S. market. In our report, we
noted that some foreign establishments may register because, in foreign
markets, registration may erroneously convey an “approval” or
endorsement by FDA, when in fact the establishment may never have
been inspected by FDA. 12 We recommended that FDA take steps to
improve the accuracy of this registration information. In our 2010 and
2016 reports we found that FDA had taken steps to improve the accuracy
and completeness of information in its catalog of drug establishments
subject to inspection, such as using contractors to conduct site visits to
verify the existence of registered foreign establishments and confirm that
they manufacture the products that are recorded in U.S. import records. 13
To prioritize establishments for surveillance inspections, CDER applies a
risk-based site selection model to its catalog of establishments to identify
those establishments (both domestic and foreign) that, based on the
characteristics of the drugs being manufactured, pose the greatest
potential public health risk should they experience a manufacturing
defect. This model analyzes several factors, including inherent product
risk, establishment type, inspection history, and time since last inspection,
to develop a list of establishments that FDA considers to be a priority for
inspection. 14 Through this process, CDER develops a ranked list of
foreign and domestic establishments selected for inspection that is
11GAO-08-970.
12Foreign and domestic establishments that manufacture drugs for the U.S. market are
required to register annually with FDA. Establishments provide FDA with, among other
things, their names and addresses and a listing of the drugs that they manufacture for the
U.S. market. 21 U.S.C. § 360(b), (i), (j).
13See GAO-10-961 and GAO-17-143.
14Establishments may also be selected for surveillance inspections for other reasons,
such as FDA’s focus on a particular product.
Page 6 GAO-20-626T
submitted to ORA. To be efficient with its resources, ORA staff may shift
the order of establishments to be inspected on CDER’s prioritized list
based on geographic proximity to other planned inspection trips,
according to FDA officials.
FDA Inspection Workforce Investigators from ORA and, as needed, ORA laboratory analysts with
certain expertise are responsible for inspecting drug manufacturing
establishments. 15 FDA primarily relies on three groups of investigators to
conduct foreign inspections:
• ORA investigators based in the United States, who primarily conduct
domestic drug establishment inspections but may sometimes conduct
foreign inspections.
• Members of ORA’s dedicated foreign drug cadre, a group of
domestically based investigators, who exclusively conduct foreign
inspections.
• Investigators assigned to and living in the countries where FDA has
foreign offices, who include both staff based in the foreign offices full
time and those on temporary duty assignment to the foreign offices.
FDA began opening offices around the world in 2008 to obtain better
information on the increasing number of products coming into the
United States from overseas, to build relationships with foreign
stakeholders, and to perform inspections. 16 FDA full-time foreign
office staff are posted overseas for 2-year assignments. FDA staff can
also be assigned to the foreign offices on temporary duty assignments
for up to 120 days. In fiscal year 2019, there were full-time and
temporary duty drug investigators assigned to FDA foreign offices in
China and India.
Post-Inspection Activities FDA’s process for determining whether a foreign establishment complies
with CGMPs involves both CDER and ORA. During an inspection, ORA
investigators are responsible for identifying any significant objectionable
conditions and practices and reporting these to the establishment’s
management. Investigators suggest that the establishment respond to
15ORA investigators lead inspections and are responsible for performing or overseeing all
aspects of an inspection. ORA laboratory analysts are chemists or microbiologists and
have expertise in laboratory testing. In some instances, staff from CDER, such as subject
matter experts or drug application reviewers, may participate in inspections.
16Currently, FDA has foreign offices in China, Europe, India, and Latin America but does
not have drug investigators in the Europe or Latin America offices.
Page 7 GAO-20-626T
FDA in writing concerning all actions taken to address the issues
identified during the inspection.
Once ORA investigators complete an inspection, they are responsible for
preparing an establishment inspection report to document their inspection
findings. Inspection reports describe the manufacturing operations
observed during the inspection and any conditions that may violate U.S.
statutes and regulations. Based on their inspection findings, ORA
investigators make an initial recommendation regarding whether
regulatory actions are needed to address identified deficiencies using one
of three classifications: no action indicated (NAI); voluntary action
indicated (VAI); or official action indicated (OAI). 17 Inspection reports and
initial classification recommendations for regulatory action are to be
reviewed within ORA. For inspections classified as OAI—where ORA
identified serious deficiencies—such inspection reports and classification
recommendations are to be reviewed within CDER. CDER is to review
the ORA recommendations and determine whether regulatory action is
necessary. CDER also is to review inspection reports and initial
classification recommendations for all for-cause inspections, regardless of
whether regulatory action is recommended by ORA.
According to FDA policy, inspections classified as OAI may result in
regulatory action, such as the issuance of a warning letter. FDA issues
warning letters to those establishments manufacturing drugs for the U.S.
market that are in violation of applicable U.S. laws and regulations and
may be subject to enforcement action if the violations are not promptly
and adequately corrected. In addition, warning letters may notify foreign
establishments that FDA may refuse entry of their drugs at the border or
recommend disapproval of any new drug applications listing the
establishment until sufficient corrections are made. 18 FDA may take other
regulatory actions if it identifies serious deficiencies during the inspection
of a foreign establishment. For example, FDA may issue an import alert,
17FDA officials told us that investigators are responsible for checking on previously
identified deficiencies in any subsequent inspections of the same establishment. Officials
told us that repeated identification of the same deficiency could result in regulatory action.
Inspection classifications are publicly available for some inspections on FDA’s website:
https://www.fda.gov/inspections-compliance-enforcement-and-criminal-
investigations/inspection-references/inspection-classification-database/
18Warning letters are publicly available on FDA’s website:
https://www.fda.gov/inspections-compliance-enforcement-and-criminal-
investigations/compliance-actions-and-activities/warning-letters.
Page 8 GAO-20-626T
which instructs FDA staff that they may detain drugs manufactured by the
violative establishment that have been offered for entry into the United
States. 19 In addition, FDA may conduct regulatory meetings with the
violative establishment. Regulatory meetings may be held in a variety of
situations, such as a follow-up to the issuance of a warning letter to
emphasize the significance of the deficiencies or to communicate
documented deficiencies that do not warrant the issuance of a warning
letter.
The Number of
Foreign Inspections
Declined in Recent
Years, and the
Majority of Such
Inspections Identified
Deficiencies
Total Number of FDA In December 2019, we found that from fiscal year 2012 through fiscal
Foreign Drug Inspections year 2016, the number of FDA foreign drug manufacturing establishment
inspections increased but then began to decline after fiscal year 2016. In
Has Decreased Since
fiscal year 2015, the total number of foreign inspections surpassed the
Fiscal Year 2016 after number of domestic inspections for the first time. However, from fiscal
Several Years of Increases year 2016 through 2018, both foreign and domestic inspections
decreased—by about 10 percent and 13 percent, respectively. FDA
officials attributed this decrease to vacancies in the number of
investigators available to conduct inspections (which we discuss later in
this testimony statement) and to inaccurate data used to select
establishments for inspection in fiscal years 2017 and 2018.
Despite steps taken to improve the accuracy and completeness of FDA
data on foreign establishments, in December 2019, we found that the
data challenges we identified in our 2008 report continue to make it
difficult for FDA to accurately identify establishments subject to
inspection. Specifically, since 2017, FDA had pursued an initiative to
inspect approximately 1,000 foreign establishments that lacked an
19An import alert can apply to specific drugs or all drugs manufactured by an
establishment. Import alerts are publicly available on FDA’s website:
https://www.fda.gov/industry/actions-enforcement/import-alerts.
Page 9 GAO-20-626T
inspection history. As of November 2019, officials said all of these
establishments had either been inspected or were determined not to be
subject to inspection because it was determined they did not actually
manufacture drugs for the U.S. market, or had not recently shipped drugs
to the United States. 20 However, officials told us that this effort contributed
to the decline in the number of foreign inspections conducted because of
how data inaccuracies affected the process for selecting establishments
for inspection. Specifically, after selecting uninspected foreign
establishments for inspection, FDA determined that a sizeable
percentage of these establishments were not actually subject to
inspection (e.g., about 40 percent of those assigned to the China Office in
fiscal years 2017 and 2018). 21 These foreign establishments were thus
removed from the list for inspection for the given year. FDA officials told
us that the next highest priority establishments identified through the risk-
based model to replace those establishments were domestic
establishments. As a result, the number of foreign establishments actually
inspected decreased. As part of our ongoing work, we plan to examine
the accuracy and completeness of information FDA maintains about
foreign establishments and the application of its risk-based site selection
process.
We further found that FDA continued to conduct the largest number of
foreign inspections in India and China, with inspections in these two
countries representing about 40 percent of all foreign drug inspections
from fiscal year 2016 through 2018. (See table 2.) In addition to India and
China, the rest of the countries in which FDA most frequently conducted
inspections has generally been the same since our 2008 report.
20We previously reported that as of 2016, FDA lacked the inspection history of 33 percent
of the foreign establishments in its catalog of establishments subject to inspection.
21FDA officials said that some of these establishments were registered with FDA but did
not actually manufacture drugs for the U.S. market, and others were drug manufacturers
but had not shipped drugs to the United States in the previous 3 years. FDA officials told
us that, once identified, they removed such establishments from the catalog of
establishments subject to surveillance inspection to which the agency applies its risk-
based model each year, but they retained information on these establishments in the
larger inventory of establishments should these establishments begin shipping drugs to
the United States in the future.
Page 10 GAO-20-626T
Table 2: Total Number of FDA Foreign Drug Inspections, by Country, Fiscal Years 2012 through 2018
Country 2012 2013 2014 2015 2016 2017 2018
India 140 110 114 204 207 219 252
China 59 74 113 127 173 165 153
Germany 59 60 72 68 72 69 68
Canada 49 51 39 52 56 72 48
Italy 38 45 50 41 69 46 45
Japan 49 28 47 31 65 46 43
South Korea 4 7 8 5 13 56 40
France 25 37 44 45 55 42 36
Switzerland 23 23 37 31 37 25 32
United Kingdom 29 27 33 43 41 40 12
All other countries 150 175 222 193 247 213 206
Total foreign 625 637 779 840 1,035 993 935
Total domestic 1,184 1,030 897 784 882 772 742
Source: GAO analysis of Food and Drug Administration (FDA) data. | GAO-20-626T
Note: The total number of inspections includes those conducted for preapproval, surveillance, and
for-cause purposes.
Since we last reported on this issue, FDA announced in March 2020 that,
due to COVID-19, it was postponing most inspections of foreign
manufacturing establishments. Only inspections deemed mission-critical
would still be considered on a case-by-case basis. 22 According to the
announcement, while the pandemic has added new complexities, FDA
has other tools to ensure the safety of the U.S. drug supply. For example,
FDA announced that it was evaluating additional ways to conduct its
inspectional work that would not jeopardize public safety and would
protect both the establishments and the FDA staff. Such ways, according
to FDA, could include reviewing the compliance histories of
establishments, using information shared by foreign regulatory partners,
and evaluating establishment records in lieu of an onsite inspection. In
addition, the FDA Commissioner’s May 11, 2020 press statement stated
that while FDA’s regulatory oversight is vital to the long-term health of
America, product safety and quality are ultimately the establishment’s
22According to FDA, the agency’s assessment of mission-critical drug inspections includes
consideration for whether the products are innovative breakthrough products or are
considered medically necessary. FDA indicated that both for-cause and pre-approval
inspections can be deemed mission critical
Page 11 GAO-20-626T
responsibility. 23 Most firms, according to FDA, strive to reliably provide
quality products and maintain the integrity of the supply chain. However,
the lack of foreign inspections removes a critical source of information
about the quality of drugs manufactured for the U.S. market.
It is not clear when FDA will resume regular inspections. The agency
originally announced the postponement would last through April 2020.
However, on May 11, 2020, it stated that the postponement would
continue. According to FDA, the agency continues to closely monitor the
global situation. FDA stated that it remains in contact with its foreign
regulatory counterparts and would work with the Centers for Disease
Control and Prevention to develop a process that would govern how and
where to return to on-site facility inspections as conditions improve.
Most Foreign Inspections In December 2019, we found that each year from fiscal year 2012 through
Were for Surveillance 2018 at least 50 percent of FDA’s foreign inspections were surveillance
inspections. In contrast to preapproval inspections, surveillance
inspections are used to ensure drugs already on the market are
manufactured in compliance with FDA regulations. In recent years, the
proportion of foreign surveillance inspections has increased. As figure 2
shows, in fiscal year 2012, 56 percent of foreign inspections were
surveillance-only inspections; in contrast, from fiscal year 2016 through
2018, about 70 percent of foreign inspections were surveillance-only,
which was comparable to the percentage for domestic inspections during
that period. This is a significant increase from the 13 percent of foreign
inspections that were surveillance-only when we made our 2008
recommendation that FDA inspect foreign establishments at a
comparable frequency to their domestic counterparts (85 percent of which
were surveillance-only at that time). 24
23Food and Drug Administration, Coronavirus (COVID-19) Update: FDA Updates on
Surveillance Inspections during COVID-19, FDA press announcement (May 11, 2020)
24See GAO-08-970, 27.
Page 12 GAO-20-626T
Figure 2: Percentage of FDA Foreign and Domestic Drug Inspections Conducted for
Surveillance Purposes, Fiscal Years 2012 through 2018
Note: FDA conducts surveillance inspections to monitor the ongoing compliance of establishments
manufacturing drugs that are already on the market. This figure depicts surveillance-only inspections.
FDA conducted additional inspections that had a surveillance component combined with another type
of inspection.
In our December 2019 testimony, we also reported that FDA implemented
changes to its foreign drug inspection program since our 2008 report that
may have contributed to the increase in surveillance inspections. Prior to
2012, FDA was required to inspect domestic establishments that
manufacture drugs marketed in the United States every 2 years, but there
was no similar requirement for foreign establishments. As a result, and as
we reported in 2008, foreign inspections were often preapproval
inspections driven by pending applications for new drugs. FDA thus
conducted relatively few surveillance-only inspections to monitor the
ongoing compliance of establishments manufacturing drugs that were
already on the market, with just 13 percent of foreign inspections
conducted for surveillance purposes at the time of our 2008 report.
However, in 2012, the Food and Drug Administration Safety and
Innovation Act eliminated the 2-year requirement for domestic
inspections, directing FDA to inspect both domestic and foreign
Page 13 GAO-20-626T
establishments on a risk-based schedule determined by an
establishment’s known safety risks, which was consistent with our 2008
recommendation. 25
FDA Identified In December 2019, we found that from fiscal year 2012 through 2018,
Deficiencies during the FDA identified deficiencies in approximately 64 percent of foreign drug
manufacturing establishment inspections (3,742 of 5,844 inspections).
Majority of Foreign
This includes deficiencies necessitating a classification of VAI, or the
Inspections more serious OAI, as described in the text box.
Inspection Classifications
Based on their inspection findings, FDA investigators make an initial recommendation
regarding the classification of each inspection:
• No action indicated (NAI) means that insignificant or no deficiencies were
identified during the inspection.
• Voluntary action indicated (VAI) means that deficiencies were identified during
the inspection, but the agency is not prepared to take regulatory action, so any
corrective actions are left to the establishment to take voluntarily.
• Official action indicated (OAI) means that serious deficiencies were found that
warrant regulatory action.
Source: GAO. | GAO-20-626T
About 59 percent of domestic inspections (3,702 out of 6,291) identified
deficiencies during this time period. (See fig. 3.) This proportion is similar
to what we found when we last looked at this issue in 2008, when FDA
identified deficiencies in about 62 percent of foreign inspections and 51
percent of domestic inspections from fiscal years 2002 through 2006. 26
25Pub. L. No. 112-144, § 705, 126 Stat. 993, 1066 (2012) (codified at 21 U.S.C. 360(h)).
This established a comparable inspection frequency for foreign and domestic
establishments with similar characteristics, consistent with our 2008 recommendation.
26In our 2008 report we found that FDA’s data did not provide reliable information about
the number of foreign inspections with serious deficiencies classified specifically as OAI.
Therefore, we reported data on the percentage of inspections classified as either VAI or
OAI together. See GAO-08-970, 29. We recommended that FDA correct this issue, and
they did so beginning in October 2011, but, for comparison purposes, we continue to
report combined VAI and OAI inspection data here.
Page 14 GAO-20-626T
Figure 3: FDA Inspection Classifications for Foreign and Domestic Drug
Establishments by Type of Classification, Fiscal Year 2012 through 2018
Notes: Based on their inspection findings, FDA investigators make an initial recommendation
regarding the classification of each inspection: NAI means that insignificant or no deficiencies were
identified during the inspection; VAI means that deficiencies were identified during the inspection, but
the agency is not prepared to take regulatory action, so any corrective actions are left to the
establishment to take voluntarily; and OAI means that serious deficiencies were found that warrant
regulatory action, such as issuing a warning letter or import alert.
The analysis presented in this figure is based on 5,844 foreign inspections and 6,291 domestic
inspections conducted from fiscal year 2012 through 2018. Totals do not sum to 100 due to rounding.
Some classifications were not yet available at the time of our analysis (1 percent of both foreign and
domestic inspections). Finally, less than 1 percent of both foreign and domestic inspections received
another interim classification, which is not reflected in this figure.
Our December 2019 analysis showed that serious deficiencies identified
during foreign drug inspections classified as OAI—which represented 8
percent of inspections from fiscal year 2012 through 2018—include
CGMP violations such as those related to production and process
Page 15 GAO-20-626T
controls, equipment, records and reports, and buildings and facilities. 27
For example:
• Failure to maintain the sanitation of the buildings used in the
manufacturing processing, packing, or holding of a drug product
(21 C.F.R. § 211.56(a) (2019)). At an establishment in India producing
finished drug products, the investigator reported observing a live moth
floating in raw material used in the drug production, and that the
facility staff continued to manufacture the drug products using the raw
material contaminated by the moth, despite the investigator pointing
out its presence.
• Failure to perform operations relating to the manufacture,
processing, and packing of penicillin in facilities separate from
those used for other drug products (21 C.F.R. § 211.42 (d)
(2019)). At an establishment in Turkey that manufactured penicillin
and other drugs, the investigator reported that the manufacturer had
detected penicillin outside the penicillin manufacturing area of the
establishment multiple times. According to FDA, penicillin
contamination of other drugs presents great risk to patient safety,
including potential anaphylaxis (even at extremely low levels of
exposure) and death.
Some investigators who conduct foreign inspections expressed concern
with instances in which ORA or CDER reviewers reclassified the
investigator’s initial inspection classification recommendations of OAI to
the less serious classification of VAI.
In December 2019, we found that FDA’s foreign inspection workforce had
FDA Continued to staff vacancies, which FDA officials said contributed to the recent decline
Face Challenges in inspections. As previously mentioned, FDA used multiple types of staff
resources to conduct foreign drug inspections—including ORA
Filling Vacancies investigators based in the United States, members of ORA’s dedicated
among Staff foreign drug cadre based in the United States, and investigators assigned
to FDA’s foreign offices. 28 However, we found that each of these groups
Conducting Foreign had current vacancies. At the time of our December testimony, FDA
Inspections officials told us that the agency was trying to fill vacancies in each of
27The identification of serious deficiencies is not unique to foreign inspections. For
example, at a domestic establishment producing finished drug products, the investigator
observed brown stains, white residues, and brown stagnant water in manufacturing
equipment.
28In addition to these categories, there are a variety of other FDA staff who, on occasion,
may participate in an inspection if certain subject matter expertise is needed.
Page 16 GAO-20-626T
these groups, but the lower staff numbers may limit FDA’s ability to
conduct more foreign inspections.
ORA investigators based in the United States. This group of
investigators conducted the majority of foreign inspections; about 76
percent of foreign inspections in fiscal year 2018 involved an ORA
investigator based in the United States who conducts both foreign and
domestic inspections. 29 FDA officials said that the more experienced
investigators from this group are expected to conduct three to six foreign
inspections per year, and investigators hired using generic drug user fees
are expected to inspect nine to 12 foreign establishments per year. 30 As
of June 2019, there were 190 investigators eligible to conduct foreign
drug inspections, but officials said that as of November 2019, the agency
had an additional 58 vacancies in this group. At the time of our December
2019 testimony, officials said that the agency was in the process of hiring
26 ORA investigators based in the United States to fill these vacancies,
with 32 vacancies remaining. 31
FDA officials attributed the vacancies to multiple factors: investigator
retirements, investigator movement to other parts of FDA, and the need to
hire to additional investigator positions using generic drug user fees.
Officials also said that a reorganization within ORA led to a reduced
number of investigators who conduct drug manufacturing establishment
inspections. While FDA had recently filled several of the vacancies,
officials told us that new investigators are not typically used for foreign
inspections until they have been with the agency for 2 to 3 years.
ORA dedicated foreign drug cadre. About 15 percent of foreign
inspections in fiscal year 2018 involved an investigator from ORA’s
dedicated foreign drug cadre—a group of ORA investigators based in the
United States who exclusively conduct foreign inspections. FDA officials
said that members of the cadre are expected to conduct 16 to 18 foreign
inspections each year. According to FDA, the cadre had 20 investigators
29Inspections can be conducted by one investigator or multiple investigators. Therefore,
investigators from more than one group could be involved with a single inspection.
30Beginning in 2014, FDA began to use the user fees collected from manufacturers of
generic drugs to hire additional investigators focused on inspecting generic drug
manufacturers. According to FDA officials, these investigators have primarily been
assigned to conduct foreign inspections.
31FDA officials indicated that filling these vacancies was a priority for the agency and
noted that their recent implementation of direct-hire authority has helped them fill these
positions.
Page 17 GAO-20-626T
in 2012 and 15 investigators in 2016. However, the cadre had only 12
investigators as of November 2019, out of 20 available slots. At the time
of our December 2019 testimony, FDA officials told us that the agency
was attempting to fill these positions from the current ORA investigator
pool, but officials were not confident that all 20 slots would be filled.
Investigators assigned to FDA’s foreign offices. Approximately 7
percent of foreign inspections in fiscal year 2018 involved investigators
from FDA’s foreign offices. The investigators conducting these
inspections were those based in the China and India foreign offices—the
countries where most drug inspections occur—and also included those
investigators on temporary duty assignment to these offices. 32 According
to FDA officials, these investigators are expected to conduct 15 foreign
inspections each year. We have noted high vacancy rates for these
foreign offices in past reports. 33 While these vacancy rates have
decreased over time, vacancies persist. As of November 2019, FDA’s
China office had three of 10 drug investigator positions vacant (a 30
percent vacancy rate), while FDA’s India office had two of six drug
investigator positions vacant (a 33 percent vacancy rate).
In our December 2019 testimony, we reported that FDA had taken steps
to address vacancies in the foreign offices but continued to face
challenges. In our 2010 report, we recommended that FDA develop a
strategic workforce plan to help recruit and retain foreign office staff. 34
FDA agreed with our recommendation and released such a plan in March
2016, but the long-standing vacancies in the foreign offices raise
questions about its implementation. FDA officials told us that one
challenge in recruiting investigators for the foreign offices is that well-
qualified investigators for those positions need foreign inspection
experience. For example, an official in FDA’s India office told us that
foreign inspections can be challenging, and the India office does not have
the resources to develop or train new investigators. Therefore, it is
important to recruit investigators who have experience conducting foreign
inspections, and such investigators are recruited from ORA. Thus,
32The percentage of inspections involving these groups of investigators do not equal 100
percent because some inspections may involve only non-investigator staff, such as CDER
drug application reviewers.
33See GAO, Food and Drug Administration: Overseas Offices Have Taken Steps to Help
Ensure Import Safety, but More Long-Term Planning Is Needed, GAO-10-960
(Washington, D.C.: Sep. 30, 2010), and GAO-17-143.
34GAO-10-960.
Page 18 GAO-20-626T
vacancies in the other two groups of investigators can influence the
number of staff available to apply for positions in the foreign offices.
Further, according to FDA officials, after employees have accepted an in-
country position, the agency can experience significant delays before they
are staffed in the office due to delays in processing assignments. For
example, an official in FDA’s India office said that investigators need to
complete a week-long security training program and must obtain the
security clearance needed to work at the U.S. Embassy, which is where
FDA’s foreign office is located. However, the official told us that there are
limited availabilities for that training, and background checks for security
clearances can take time. 35 According to this official, FDA investigators
did not usually receive first priority for the training. FDA estimated that it
can take as little as 1 month to over 2 years for an investigator to clear
background and medical checks and arrive at a foreign office. For
example, an investigator in FDA’s China office told us that as a result of
these requirements and other issues, it took nearly 2 years for the
investigator to arrive at the office after FDA had accepted the
investigator’s application. According to FDA’s own strategic workforce
plan for the foreign offices, these types of delays have resulted in staff
changing their decision after accepting a position in the foreign offices.
In December 2019, we found that FDA continues to face unique
Persistent Challenges challenges when inspecting foreign drug establishments that raise
Unique to Foreign questions about whether these inspections are equivalent to domestic
inspections. Specifically, based on our interviews with drug investigators
Inspections Raised in the dedicated foreign drug cadre and in FDA’s foreign offices in China
Questions about Their and India, we identified four challenge areas related to conducting foreign
inspections, which are described below. Of the four challenge areas
Equivalence to identified, three areas—preannouncing inspections, language barriers,
Domestic Inspections and lack of flexibility—were also raised in our 2008 report. 36
Preannouncing Inspections. As we reported in 2008, the amount of
notice FDA generally gives to foreign drug establishments in advance of
an inspection is different than for domestic establishments. 37 Drug
establishment inspections performed in the United States are almost
always unannounced, whereas foreign establishments generally receive
35We have highlighted timeliness concerns with the government-wide personnel security
clearance process in our High Risk series. See GAO-19-157SP.
36GAO-08-970.
37GAO-08-970.
Page 19 GAO-20-626T
advance notice of an FDA inspection. According to FDA officials, FDA is
not required to preannounce foreign inspections. However, they said the
agency generally does so to avoid wasting agency resources, obtain the
establishment’s assistance to make travel arrangements, and ensure the
safety of investigators when traveling in country.
In our December 2019 testimony, we found that FDA does conduct some
unannounced foreign inspections, particularly if the investigators
conducting the inspection are based in FDA’s foreign offices. However,
FDA officials told us that FDA does not have data on the frequency with
which foreign drug inspections are unannounced, nor the extent to which
the amount of notice provided to foreign establishments varies. According
to FDA officials, this is because FDA does not have a data field in its
database to systematically track this information. 38 However, the officials
estimated that the agency generally gives 12 weeks of notice to
establishments that investigators are coming when investigators are
traveling from the United States. While investigators in FDA’s China and
India offices do conduct unannounced or short-notice inspections, these
staff do not perform most of the inspections in these countries. (See table
3.)
38According to FDA officials, FDA planned to add a new variable to its data to identify
preannounced and unannounced inspections.
Page 20 GAO-20-626T
Table 3: FDA Estimates of the Amount of Notice It Provides to Foreign Drug Establishments Prior to Inspection, by
Investigator Type, and the Percentage of Inspections in Which These Investigator Types Are Involved, Fiscal Year 2018
Percentage of inspections involving
this investigator type in fiscal year
Type of investigator Amount of notice provided 2018a
China office investigator Announcement: 0-5 days Involved in 27 percent of total number of
FDA officials stated that investigators based in FDA’s China office inspections in China
will announce surveillance inspections (those related to drugs
already on the U.S. market) to drug establishments 5 business
days in advance of an inspection. According to FDA officials, for-
cause inspections (those conducted in response to specific issues
or concerns) conducted by investigators based in the China office
are unannounced, meaning that they are not preannounced to the
drug establishments in advance.
India office investigator Announcement: 0-5 days Involved in 10 percent of total number of
FDA officials stated that investigators based in FDA’s India office inspections in India
will announce inspections to drug establishments 3 to 5 days in
advance of an inspection and can conduct short-notice
inspections that are announced 30 minutes before the inspection.
U.S.-based investigator Announcement: generally 12 weeks Involved in:
(Including dedicated FDA officials said that the agency generally announces foreign • 73 percent of total number of
foreign drug cadre) inspections conducted by domestically based investigators about inspections in China
12 weeks in advance. • 90 percent of total number of
inspections in India
• 100 percent of total number of
inspections in other foreign
countries
Source: Interviews with Food and Drug Administration (FDA) officials and GAO analysis of FDA data. | GAO-20-626T
a
These percentages add up to over 100 percent as some inspections may involve more than one type
of investigator.
Our work indicated that preannouncing foreign inspections can create
challenges and raises questions about the equivalence to domestic
inspections. Of the 18 investigators we interviewed, 14 said that there are
downsides to preannouncing foreign inspections, particularly that
providing advance notice gives foreign establishments the opportunity to
fix problems before the investigator arrives. For example, when an
inspection is preannounced, it gives establishments time to clean up their
facility and update or generate new operating procedures ahead of the
inspection. However, establishments are expected to be in a constant
state of compliance and always ready for an FDA inspection, and several
investigators told us seeing the true day-to-day operating environment for
an establishment is more likely during an unannounced inspection.
Of the 18 investigators we interviewed for our December 2019 testimony,
12 said that unannounced inspections are generally preferable to
Page 21 GAO-20-626T
preannounced inspections. One investigator told us that, although they
believed the best way to ensure industry compliance to CGMPs was for
establishments to not know when FDA is coming for an inspection, there
was no data that would allow the agency to evaluate whether
unannounced inspections were better than preannounced inspections. In
addition, some investigators told us that it was still possible to identify
serious deficiencies during preannounced inspections. For example,
investigators could still identify issues by looking at the firm’s electronic
records, including time-stamped data relating to the creation,
modification, or deletion of a record. Three investigators also told us that
in some cases there could be benefits to announcing inspections in
advance. For example, for preapproval inspections, announcing the
inspection in advance gives the establishment time to organize the
documentation and staff needed to conduct the inspection.
Language Barriers. Work for our December 2019 testimony indicated
that language barriers—which we first reported as a challenge to
conducting foreign inspections in our 2008 report—can add time to
inspections and raise questions about the accuracy of information FDA
investigators collect and thus about the equivalence to domestic
inspections. 39 FDA generally does not send translators on inspections in
foreign countries. Rather, investigators rely on the drug establishment to
provide translation services, which can be an English-speaking employee
of the establishment being inspected, an external translator hired by the
establishment, or an English-speaking consultant hired by the
establishment.
Of the 18 investigators that we interviewed, 14 said that language barriers
can be a challenge to conducting foreign inspections and were especially
challenging in parts of Asia, including China and Japan. Seven
investigators told us this issue was less of a challenge for inspections
conducted in other foreign countries, including India and countries in
Europe, because workers at establishments in these countries were more
likely to speak English, and documentation was also more likely to be in
English. Investigators told us that compared to domestic inspections, it
can be more challenging and take longer to complete typical inspection-
related activities, such as reviewing documentation or interviewing
employees, if the investigator needed to rely on translation.
39GAO-08-970.
Page 22 GAO-20-626T
Fourteen of the 18 investigators we interviewed said that there can be
concerns related to relying on establishment staff and independent
translators. Specifically, 11 investigators told us there can be
uncertainties regarding the accuracy of the information being translated,
particularly when investigators rely on the translation provided by an
employee of the establishment being inspected. For instance, one
investigator said that there was more risk of conflict of interest if the
establishment used its own employees to translate. Another investigator
said that they went to a drug establishment in China that told FDA it had
English-speaking employees to translate the inspection, but that was not
the case, and the investigator had to use an application on their phone to
translate the interviews. In addition, the firm representative providing the
translation may be someone who does not have the technical language
needed, which can make it harder to communicate with firm staff and
facilitate the inspection. One investigator told us that the independent
translators hired by firms were sometimes consultants and, in those
instances, it can seem like the consultants are coaching the firm during
the inspection.
FDA officials told us that when they conduct unannounced for-cause
inspections in China, investigators bring locally employed staff who work
in FDA’s China office to act as translators. The investigators we
interviewed said that in such instances, they valued knowing that the
translation they were getting was accurate. However, FDA does not have
the resources to provide locally employed staff on every inspection,
according to an FDA official.
Lack of Flexibility. Work for our December 2019 testimony indicated
that, as we first reported in 2008, the overseas travel schedule can
present unique challenges for FDA’s domestically based investigators—
including both ORA investigators and members of the dedicated foreign
dug cadre—who conduct the majority of foreign inspections. 40 Eight of the
12 dedicated foreign drug cadre investigators that we interviewed for our
December 2019 testimony told us that there is little flexibility to extend
foreign inspections conducted by domestically based investigators,
because the inspections they conduct on an overseas trip are scheduled
40GAO-08-970.
Page 23 GAO-20-626T
back-to-back in 3-week trips that may involve three different countries. 41
This raises questions about their equivalence to domestic inspections.
For instance, extending one inspection would limit the amount of time the
investigator has to complete their other scheduled inspections, some
investigators told us.
In addition, eight investigators told us that domestically based staff are
generally unable to extend the total amount of time spent on an overseas
trip—one investigator told us that an investigator would have to find
something really bad to justify an extension. In contrast, FDA officials told
us that inspections conducted by in-country investigators in China or
India, and domestic inspections in the United States, are generally
scheduled one at a time and can thus more easily be extended if the
investigator needs additional time to pursue potential deficiencies.
However, in-country investigators are not involved in the majority of
inspections conducted in China or India.
Three investigators from the dedicated foreign drug cadre told us that
when they travel overseas, they adjust their inspection approach to help
ensure they finish foreign inspections on time. For example, one
investigator told us that an investigator may start the inspection in an area
of the establishment that was noted as having issues during the last
inspection. However, one investigator said that sometimes it is not
possible to cover everything in depth during a foreign inspection. Another
investigator told us that they focus on identifying the most serious issues
during a foreign inspection, and that less serious issues can be identified
in the establishment inspection report for reference in the next inspection.
Five investigators also noted that they work long hours during their
inspection to ensure they can complete the needed work. 42 While FDA
may assign more than one investigator to an inspection to complete
needed work, one investigator said that FDA does not usually assign
more than one person to an inspection because investigators are
expected to have the experience to conduct inspections by themselves.
41According to FDA officials, investigators in the dedicated foreign drug cadre are
expected to conduct 16 to 18 foreign inspections per year. To meet this expectation, cadre
members travel overseas six times a year, with each trip lasting 3 weeks, and conduct two
or three back-to-back inspections per trip.
42According to FDA officials, members of the dedicated foreign drug cadre can receive up
to 15 hours of overtime per week during an overseas week to complete inspection-related
work. For example, investigators may use overtime hours to extend the amount of time on
site or to review relevant data and documentation when they return to their hotel at night.
Page 24 GAO-20-626T
FDA data show that from fiscal years 2012 through 2018, the majority of
both foreign and domestic inspections were conducted by one person—
77 percent and 66 percent, respectively. 43
Post-Inspection Classification Process. According to FDA officials,
starting in fiscal year 2018, FDA implemented a new post-inspection
classification process: when an ORA investigator recommends an OAI
classification following an inspection, ORA compliance is required to send
that inspection report to CDER for review within 45 calendar days from
the inspection closeout. Among other things, the process was intended to
help ensure FDA can communicate inspection results to domestic and
foreign establishments within 90 days of the inspection closeout, as
committed to under the Generic Drug User Fee Amendments of
2017(GDUFA II). 44 FDA officials told us that the changes also required an
additional ORA review for foreign inspection reports to align that process
with the process for domestic inspection reports. 45 Although the 45-day
reporting time frame for potential OAI classifications is a requirement for
both domestic and foreign inspections, adding the additional level of
review within ORA effectively shortened the amount of time investigators
have to document findings for foreign inspections.
Our work indicated that the post-inspection reporting time frames can
create challenges for domestic investigators who conduct foreign
inspections and raise questions about the equivalence to domestic
inspections. Eight of the 18 investigators we interviewed for our
December 2019 testimony said shortening the time for completing reports
and adding a level of review has made it more challenging to meet
reporting requirements, especially if serious deficiencies are identified
during the inspection. Investigators told us that for a potential OAI
43In addition to the time pressures associated with sending only one investigator on a
foreign inspection, two of the investigators we interviewed from the dedicated foreign drug
cadre expressed a preference for conducting team inspections as it helps reduce risks to
their personal safety.
44Pub. L. No. 115-52, § 301(b), 131 Stat. 1005, 1020 (codified in pertinent part at 21
U.S.C. § 379j-41 note). Prior to each user fee program reauthorization, FDA negotiates
with representatives of the generic drug industry to identify goals for how FDA should
spend those user fees over the next 5-year authorization period.
45Prior to this change, officials told us that all foreign inspection reports, regardless of
classification type, were sent to CDER for review after being endorsed by ORA
supervisors. Under the new process, all foreign inspections are reviewed by ORA
compliance after being endorsed by ORA supervisors. Foreign inspection reports now
only go to CDER compliance for review in certain circumstances, such as if there is an
OAI recommended, which had been the process for domestic inspections.
Page 25 GAO-20-626T
inspection, they now need to send the inspection report to their supervisor
for endorsement within 10 days of the closeout of a foreign inspection,
regardless of when the investigator’s next inspection is scheduled for, or
whether the investigator has to travel from overseas back to the United
States after the inspection. For example, if a domestic investigator finds
serious deficiencies on the first inspection of an overseas trip—thus
indicating an initial OAI classification—the investigator needs to write and
send the related inspection report to the ORA supervisor for endorsement
before returning home from the 3-week overseas trip to meet the required
time frame. One investigator told us that, as a result of the time
pressures, post-inspection reports may be less thorough, and that some
inspection observations could be better supported if investigators had
more time to write the reports.
In conclusion, foreign manufacturing establishments continue to be a
critical source of drugs for millions of Americans, and FDA inspections are
a key tool to ensure the quality of these drugs. Over the years since we
first examined this issue, FDA has made significant changes to adapt to
the globalization of the pharmaceutical supply chain and has greatly
increased the number of inspections it conducts of foreign
establishments. However, we found in December 2019 that the agency
faced many of the same challenges overseeing foreign establishments
that we identified over the last two decades. These included inspector
vacancies and unique challenges when inspecting foreign drug
establishments that raised questions about the equivalence of those
inspections to domestic inspections. Since then, the outbreak of COVID-
19 has added a layer of complexity. It also further highlights the global
nature of our pharmaceutical supply chain.
Chairman Grassley, Ranking Member Wyden, and Members of the
Committee, this completes my prepared statement. I would be pleased to
respond to any questions that you may have at this time.
If you or your staff have any questions about this testimony, please
GAO Contact and contact Mary Denigan-Macauley, Director, Health Care at (202) 512-7114
Staff or DeniganMacauleyM@gao.gov. Contact points for our Offices of
Congressional Relations and Public Affairs may be found on the last page
Acknowledgments of this statement. GAO staff who made key contributions to this testimony
are William Hadley (Assistant Director); Derry Henrick (Analyst-in-
Charge); Katherine L. Amoroso; George Bogart; Zhi Boon; Rebecca
Hendrickson; John Lalomio; Gail-Lynn Michel; Laurie Pachter; and Vikki
Porter.
(104347)
Page 26 GAO-20-626T
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