Pesticide Safety: Improvements Needed in EPA's Good Laboratory Practices Inspection Program
Published: 2014-05-15T00:00:00

Fast Facts:

Highlights:
section_title: Why GAO Did This Study
paragraphs: Pesticides used to control weeds, unwanted insects, and fungi contribute to agricultural productivity and public health by preventing crop damage and controlling pests. However, pesticides may also have adverse effects. EPA's OPP reviews applications for pesticide products and registers those that it determines do not have unreasonable adverse effects on health and the environment. EPA's OECA inspects laboratories where these pesticides are tested to ensure that the laboratories followed EPA's GLP regulations. FDA also conducts GLP laboratory inspections. GAO was asked to review EPA's GLP Compliance Monitoring Program. This report examines the extent to which EPA (1) inspects for GLP compliance laboratories that test pesticides and the challenges EPA faces in doing so, (2) uses the information obtained through GLP inspections in its pesticide decision-making process, and (3) collaborates with FDA on GLP inspections. To conduct this work, GAO reviewed relevant agency documents and data, conducted a nongeneralizeable survey of 20 laboratories, and interviewed EPA and FDA officials and laboratory and other stakeholders.
section_title: What GAO Found
paragraphs: The Environmental Protection Agency (EPA) inspects few laboratories that test pesticides for Good Laboratory Practices (GLP) compliance and faces challenges in selecting laboratories to inspect. For fiscal years 2009 to 2013, EPA's Office of Enforcement and Compliance Assurance (OECA) GLP Compliance Monitoring Program inspected from 51 to 80 laboratories annually from an estimated 1,400 that conducted studies used to support applications for pesticide registrations. During the same period, EPA reduced OECA's GLP Compliance Program budget and staff by about half. Laboratory and other stakeholders told GAO that not having GLP inspections can negatively affect a laboratory's business domestically and abroad. OECA prioritizes laboratories for GLP inspections using criteria that reflect, among other things, how long it has been since the last inspection and the number of studies the laboratory has conducted that have been submitted to EPA's Office of Pesticide Programs (OPP) in support of a pesticide registration application. However, GAO found that some laboratory information in the OECA database used to prioritize inspections was either inaccurate or incomplete, making it difficult to target laboratories for inspections. GAO also found that OECA is considering ways the GLP program could be run more efficiently given its recent budget cuts and concerns of stakeholders about the infrequent GLP inspections. For example, OECA officials have informally discussed the possibility of charging user fees that may be used to fund the GLP program, as the U.S. Food and Drug Administration (FDA) and many other countries do, but the agency has not conducted a formal evaluation of user fees. Without formally assessing the need for such fees, EPA cannot determine whether charging and retaining the fees would be possible and whether such fees could help make the inspection program self-sustaining.
EPA rarely uses GLP inspection results in making its initial pesticide registration decisions. An OPP official said that this is because most inspections occur after decisions have been made. OPP officials said they have not denied or revoked any pesticide registrations based on OECA GLP inspections during the past 5 years, but OPP has taken other actions, such as requiring that a study be repeated because of subsequent laboratory inspection information. According to EPA officials, OPP and OECA have communicated on an informal basis about OPP's inspection priorities before a pesticide registration has taken place.
EPA and FDA do not regularly collaborate on laboratory inspections and may be duplicating each other's work at some of these laboratories. In 1984, EPA and FDA entered into an agreement to collaborate on GLP inspections and met quarterly to discuss upcoming inspections; the agreement ended in 2004 although meetings continued until 2007. From fiscal year 2005 to 2012, EPA and FDA conducted a total of 170 GLP inspections of the same 37 laboratories. In 38 of 170 inspections, the agencies inspected the same laboratory during the same fiscal year. EPA and FDA have independent but similar sets of GLP regulations. Officials from both agencies said it would be useful to know which laboratories the other agency was planning to inspect and to have those inspection results, since each agency can only inspect a certain number of laboratories each year. Absent collaboration and information sharing with FDA on planned and completed GLP inspections, EPA will have difficulty efficiently using its limited resources to increase the number of inspections it conducts.
section_title: What GAO Recommends
paragraphs: GAO recommends, among other things, that EPA assess its authority and need for a fee-based inspection system for the GLP Program, determine why the database information to prioritize laboratories is incomplete, and that EPA and FDA develop a process to collaborate and share information on planned and completed inspections. EPA and FDA agreed with GAO's recommendations.

section_title: Letter
paragraphs: Pesticides that are used to destroy or control weeds, unwanted insects,  fungi, rodents, bacteria and other pests contribute to agricultural  productivity by preventing crop damage and improving public health by  controlling disease carrying pests. However, the use of pesticides may  also have adverse effects on human health and the environment. For  example, some pesticides in large doses may contribute to the risk of  cancer and other serious human health problems and may also cause  environmental damage, such as contamination of water supplies or  unintended impacts on species not targeted by the pesticide. The Federal  Insecticide, Fungicide, and Rodenticide Act (FIFRA), as amended,  generally requires registration of pesticides and authorizes the  Environmental Protection Agency (EPA) to limit the distribution and sale  of unregistered pesticides to the extent necessary to prevent  unreasonable adverse effects on the environment. Under FIFRA  implementing regulations, EPA reviews applications for pesticide products  and registers those that it determines will meet the FIFRA statutory  standards for registration. EPA also inspects the laboratories where  these pesticides are first tested for safety. Laboratories must conduct  studies in support of pesticide registration applications in accordance with  regulations called Good Laboratory Practices (GLP), which are intended  to ensure the quality and integrity of data.developed and promulgated in the United States during the late 1970s  and early 1980s in response to fraudulent laboratory activities and poor  laboratory practices that occurred during that time.
To monitor a laboratory’s GLP compliance with these standards, EPA  conducts both an audit of the studies conducted by the laboratory and  submitted to EPA and an on-site inspection of the laboratory; these two  types of reviews together are referred to as a GLP inspection. Office of Pesticide Programs (OPP) reviews studies that support  applications for registration of pesticide products submitted by study  sponsors and makes registration decisions based on whether or not the  pesticide products meet the FIFRA standard for registration. EPA’s  Office of Enforcement and Compliance Assurance (OECA) has a  Compliance Monitoring Program that conducts inspections to ensure that  laboratories comply with the agency’s GLP regulations. If OECA’s  inspectors find a problem with the studies they audit or the laboratories  they inspect, OECA submits this information to OPP for reexamination of  the studies to ensure that the data they generated are valid and reliable to  support pesticide decisionmaking. If OPP determines the data upon which  a registration decision was based are not valid or reliable, it can ask the  manufacturer of the pesticide to repeat a study, or it may initiate steps to  change a registration decision.
A “laboratory” in this report is defined as a facility where a study or part of a study is  conducted. A laboratory can conduct its testing either indoors or outdoors at a field site. and Cosmetic Act (FFDCA) for conducting nonclinical laboratory studies  of investigational drugs, medical devices, food additives, and other  products to ensure the quality and integrity of the safety data.cases, EPA and FDA receive studies from the same laboratories.
Environmental and other groups have raised concerns about OPP’s  pesticide registration program, as we reported in August 2013,recommended that EPA take steps to improve the program. Pesticide  manufacturers have also expressed concern about how infrequently  OECA conducts GLP inspections, which they have stated affects firms’  ability to register and market their products in the United States and  abroad.
You asked us to review EPA’s GLP Compliance Monitoring Program. This  report examines the extent to which (1) EPA inspects for GLP compliance  laboratories that test pesticides and the challenges, if any, EPA faces in  doing so; (2) EPA uses the information obtained through GLP laboratory  inspections in its pesticide decision-making process; and (3) EPA and  FDA collaborate on GLP inspections.
To conduct this work, we reviewed relevant laws, regulations, EPA and  FDA guidance, EPA data on pesticide studies, and GLP inspection  results. We interviewed OECA and OPP officials, as well as FDA officials.  We reviewed recent literature related to GLP, including information and  documents found on the websites of a variety of industry, international,  environmental, and academic organizations, and foreign government GLP  inspection programs. To determine the extent to which EPA inspects for  GLP compliance laboratories that test pesticides, we collected and  analyzed documentation from EPA officials on its GLP inspection process  and analyzed EPA laboratory and inspection data, the agency’s use of  the data, and the accuracy and completeness of the data. We determined  that inspection data were sufficiently reliable to present results on the  number of inspections conducted during fiscal year 2009 to fiscal year  2013, based on a comparative analysis of inspection data contained in  two of EPA’s databases and interviews with agency officials. We  determined that data on laboratories’ identification numbers and  addresses were not sufficiently reliable to assess the number and location  of laboratories that had conducted studies submitted to EPA and, as a  result, were subject to a GLP inspection. We determined the data were  not sufficiently reliable, based on our analysis of the data, identification of  erroneous data, and interviews with agency and laboratory  representatives. However, EPA did provide estimates of the number and  percentage of eligible laboratories that were inspected each year, and we  used that information in this report. We obtained opinions on the GLP  inspection program, including potential challenges, by interviewing  individuals representing 25 entities, including laboratories; pesticide  manufacturers; international organizations; environmental and health  organizations; national and trade associations; and foreign government  GLP programs, which we selected based on referrals from various  stakeholders and EPA officials. In addition, we obtained survey  responses from 20 laboratories of a nongeneralizable random sample of  53 laboratories and other entities that had sent supporting studies to OPP  for a pesticide registration application for fiscal year 2010 to fiscal year   (see app. II). If  2012 to determine if they had been inspected by EPAthey had not had a GLP inspection, we asked what impact, if any, they  thought not having a GLP inspection had on their business. Although the  results of this sample are not generalizable, the laboratories were  randomly selected, and the results can illustrate such laboratories’  experiences and challenges with GLP inspections. To assess the extent  to which OPP uses the information obtained through GLP laboratory  inspections in its pesticide registration decision-making process, we  analyzed relevant documents and databases to determine the number of  OECA’s GLP inspections that produced results that were referred to OPP  for reexamination, the time it took to conduct these reexaminations, and  any impact the inspections had on OPP’s pesticide registration decisions.  To determine the extent to which EPA and FDA collaborate on  inspections, we analyzed EPA and FDA GLP laboratory inspection data.  We determined that the inspection data were sufficiently reliable for our  purposes. We also analyzed the 20 survey responses to determine if the  laboratories had conducted GLP tests or studies for submission to both  EPA and FDA since 2008. We reviewed agency documents, such as a  1984 interagency agreement between EPA and FDA to cooperate on  GLP inspections, and we interviewed EPA and FDA officials and  laboratory representatives about the potential for the two agencies to  collaborate. Appendix I contains more detailed information on our  objectives, scope, and methodology.
We conducted this performance audit from November 2012 to May 2014  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.
subsections: section_title: Background
paragraphs: The primary federal laws that govern how EPA regulates pesticides in the  United States are FIFRA and FFDCA. Under FIFRA, EPA registers  pesticides distributed, used, or sold, in the United States and prescribes  labeling and other regulatory requirements to prevent unreasonable  adverse effects on health and the environment. If use of a pesticide  would result in a residue of the substance in or on food, EPA may not  register a pesticide under FIFRA unless, among other things, it can  determine that the residue is “safe” as defined by section 408 of the  FFDCA.permissible pesticide residue in or on food or animal feed that is sold— that meets the FFDCA safety standard set forth in section 408 or may   EPA may establish a tolerance level—the maximum  choose to grant an exemption for a tolerance. To obtain a pesticide  registration, or petition to establish a tolerance level, a registrant  (company or person) submits an application for EPA’s review containing  health and environmental effects data and other information on a  pesticide. In addition to testing conducted in a laboratory, these data  can include studies based on the analysis of data collected from field  applications of the pesticide and other information on the pesticide. The  application is submitted with a pesticide registration fee, with the fee  amount depending on certain factors, such as the type of registration  action that is being requested. According to an OPP official, registrants  are required to provide data relating to the pesticide’s hazard and  exposure levels to accompany a proposed registration. All studies  submitted in support of a product registration are subjected to an initial  screening and regulatory and scientific review by OPP staff to determine  potential human and environmental risks. OPP reviews the applications  and registers those products determined to meet FIFRA’s standards for  registration and other regulatory requirements so that they can be  marketed domestically.
Under FIFRA, when a registrant submits an application for pesticide  products to OPP, the accompanying data to support the registration are  required to be prepared in accordance with the agency’s GLP regulations  to ensure the quality and integrity of the data in the study. Each study  submitted is reviewed by OPP to see if GLP criteria have been met. OPP  staff prepare science reports and/or data evaluation records to address  the quality of each study. If studies submitted in support of this process  contain questionable data, this can result in adverse action by OPP. For  example, according to OPP officials, if OPP finds that a registrant  provided false or inaccurate information about the certified limits of the  active ingredients of a pesticide, or if there is a discrepancy in the number  of formulas used to check concentrations, a study would be rejected, and  OPP might deny such an application or request that it be withdrawn.
OECA’s GLP Program is tasked with monitoring compliance with the GLP  regulations through on-site inspections of laboratories, as well as audits  of the laboratories’ studies. According to EPA officials, the purpose of the  study audit is to ensure that the study was conducted in accordance with  the agency’s GLP regulations and that the study is supported by data  generated by the laboratory. A study’s sponsor or applicant must include  one of the following statements in the submission: (1) that the study was  conducted in accordance with GLP, (2) a detailed description of all the  differences between the practices used in the study and those required by  GLP, or (3) that they do not know if their study was conducted in  accordance with GLP. Laboratories eligible for inspection are those that  have conducted studies submitted to the agency. In some instances, a  single laboratory may have conducted more than one submitted study.  During an inspection, OECA’s GLP Program inspectors will verify the  accuracy of a study’s GLP compliance statement. GLP inspections can  take place while OPP is still reviewing a pesticide registration application  or a petition for a tolerance-setting, or it can take place after a pesticide  has been registered, or the tolerance has been established. Figure 1  summarizes the pesticide registration and tolerance-setting process, as  well as its relationship to OECA’s inspection of GLP laboratories.
EPA and FDA have each developed their own GLP standards to address  problems found with laboratory studies submitted for the agencies’  review. Investigations by these agencies in the mid-1970s revealed that  some studies had not been conducted in accordance with commonly  accepted laboratory practices. For example, according to an industry  representative, one of the first laboratories to attract regulatory and media  attention was Industrial Bio-Test Laboratories (IBT), a contract  toxicological research laboratory that conducted much of the U.S.  toxicological testing at the time. As a result of EPA’s and FDA’s  investigations of IBT, several hundred studies were invalidated because  of deliberate fraud, and hundreds of chemicals had to be retested.  Specific findings included poor recordkeeping, testing conducted by  untrained and unqualified personnel, and data fabrication. For example,  data were submitted on rats that had previously been reported as  deceased. As a result, in 1978, FDA formulated and published GLP  regulations under FFDCA. In 1983, EPA published its GLP standards  for pesticide toxicology studies, and in 1989, EPA extended the  standards’ coverage to include nearly all research data supporting  pesticide registrations under FIFRA. The Organisation for Economic Co- operation and Development (OECD), which includes more than 30  member countries including the United States, published OECD  Principles of Good Laboratory Practices and OECD Guidelines for the  Testing of Chemicals in 1981.
GLP standards cover the proper handling of laboratory test substances,  equipment maintenance and calibration, testing operations, study plans,  quality assurance, recordkeeping and reporting requirements, and facility  management, among other things. For example, when EPA conducts a  GLP inspection, it determines, among other things, whether the laboratory  is of suitable size and construction to facilitate the proper conduct of the  studies. Specifically, an EPA inspection would determine, among other  things, whether the laboratory has a sufficient number of rooms or other  areas for proper separation of species and testing, as well as for the  collection and disposal of contaminants and waste.
In 1981, OECD established the Mutual Acceptance of Data program  designed to obtain international recognition of testing data in support of  pesticide registrations. As of August 2012, there were 31 member  countries, including the United States, and 5 nonmember countries, each  participating on a rotating basis in evaluating each other’s testing  programs compared with OECD test guidelines. EPA has signed  memorandums of understanding with seven countries under the Mutual  Acceptance of Data Program and has a bilateral agreement with China.According to EPA documents, U.S. companies seeking to sell pesticides  in foreign countries and multinational companies seeking registration of  pesticides to sell in the United States must meet two Mutual Acceptance  of Data program criteria: (1) the country where a study was conducted  has a valid and active GLP Compliance Monitoring Program and (2) the  testing facility (or laboratory) was inspected by the country’s GLP  compliance monitoring authority. Some other countries fund their GLP  inspections through fee-based systems, under which the registrant or  laboratory pays a portion or all of the inspection costs. For example,  according to a European Commission official, there are currently 17  European Union member countries that charge some type of fee for  conducting GLP inspections. According to FDA officials, FDA charges  user fees for medical and animal product application reviews; these fees,  together with appropriated funds, provide resources that FDA uses for  conducting GLP inspections related to such products. According to EPA  officials, although the agency charges fees for review of pesticide  applications by OPP, it does not charge a fee for OECA’s GLP laboratory  inspections.
EPA’s GLP inspection process includes three stages: (1) the  preinspection targeting stage, (2) the inspection stage or on-site  inspection of the laboratory, and (3) the postinspection stage.
subsections: section_title: Preinspection Targeting Stage
paragraphs: The preinspection targeting stage includes a series of activities performed  by inspectors before the actual on-site inspection is conducted. OECA’s  GLP Compliance Monitoring Program usually initiates its own inspections  by using a targeting module—referred to as the “Neutral Scheme  Targeting Module”—that automatically searches the GLP Program’s  Laboratory Information and Study Audit (LISA) database to target  potential studies and pesticide test laboratories. The GLP Compliance  Monitoring Program selects laboratories for inspection from among the  population of laboratories that have conducted studies submitted to  OPP. Using the Neutral Scheme Targeting Module, the inspector  identifies laboratories and applies numerical weights to them based on a  set of criteria (e.g., the length of time since the last inspection, the  severity of the last and prior inspection findings, and the number of  submitted studies conducted by the laboratory) to establish a list of  potential laboratories to inspect. Most laboratories are selected for  inspection through the Neutral Scheme Targeting Module. When  laboratories are identified for inspection through use of the Neutral  Scheme Targeting Module, the GLP Program Manager assesses these  laboratories to determine their eligibility for inspection along with the  studies selected for audit. The assessment includes performing a  preliminary review of studies to determine, among other things, whether  the laboratory is still in business and whether any studies conducted by  the laboratory have been rejected by OPP in a review of a pesticide  application. The GLP Program Manager will then prioritize and select the  laboratories for inspection. Criteria for selection can include whether the  eligible laboratories are in the same geographic area. The inspector  determines when the laboratory will be inspected and, 10 days prior to the  inspection, notifies the laboratory of the impending inspection.
Inspections can also be initiated at OPP’s request or that of another EPA  office. For example, as OPP reviews studies, it may have questions or  problems with the supporting data. In those cases, OPP can request that  OECA’s GLP Program conduct an audit of particular studies and inspect  the laboratories used for these studies. In addition, according to EPA  officials, foreign governments can request an EPA inspection if a U.S.  registrant is applying to use its pesticide in a foreign country and that  country requires a GLP inspection of the U.S. laboratories whose studies  are to be used in support of the registration. Finally, according to EPA  officials, OECA can conduct a “for cause” GLP inspection based on a tip  or complaint received through anonymous phone calls, e-mails or letters  about potential GLP violations at a laboratory.
section_title: Inspection Stage
paragraphs: The inspection stage begins with the OECA inspectors, prior to visiting a  laboratory, conducting study audits and evaluating the laboratory studies  submitted to OPP to determine whether they adhere to GLP standards.  GLP Compliance Monitoring Program inspectors previously performed  this data audit during the inspection of the laboratory. In April 2012, EPA  changed its process to have inspectors audit studies before inspecting  the laboratory to save time spent at the laboratory and therefore reduce  travel expenses. However, OECA officials told us that its inspectors follow  the old process if appropriate to the situation. The inspectors are also to  verify that data generated by the laboratory support the conclusions made  in the study.
Next, an inspector travels to the laboratory to perform the on-site  inspection of the laboratory. As part of this inspection, the inspector  performs a walk-through of the laboratory to gain an understanding of its  capabilities. The inspector will ask to see and review inspection  documentation associated with the laboratory, including qualifications and  responsibilities of laboratory personnel, the receipt and storage of test  substances, the laboratory’s standard operating procedures, and animal  rooms. The inspector then conducts a compliance inspection to gauge the  laboratory’s current practices and procedures by selecting one or two  ongoing or recently completed studies from the laboratory’s master  schedule to see whether they adhered to GLP standards. The inspector  also observes a procedure in an ongoing study to determine adherence to  standard operating procedures, the study plan, and GLP, as well as  whether the person performing the procedure has the appropriate  education and experience.
section_title: Postinspection Stage
paragraphs: The postinspection stage involves activities such as preparing an  inspection report that contains a description of the general nature of the  inspection and the laboratory being inspected. Report appendixes cover  the findings from the study audits and the on-site inspection. Inspection  reports are next reviewed by another GLP inspector to ensure the reports  are complete and consistent. According to an EPA official, the GLP  Program Manager then reviews the inspection report and assigns one of  the following categories to the laboratory as specified in the Enforcement  Response Policy for FIFRA GLP Regulations: (1) no GLP deficiencies  noted, (2) minor GLP deviations, or (3) major/significant GLP violations.  For laboratories given ratings in the first two categories, the inspector  closes out the inspection and enters all the inspection information and the  review category into the LISA database. The inspector also enters some  of this information, such as laboratory information, inspection dates,  number of study audits, and potential deficiencies, into OECA’s Integrated  Compliance Information System (ICIS), which is used for OECA-wide  compliance reporting results.
The GLP Program Manager sends a letter to the laboratory and the  registrant notifying them of the results of the inspection and, in the case of  any deficiencies, requesting assurances that appropriate action will be  taken to remedy the deficiencies. In the case of a significant violation of  the GLP standards that, in the opinion of the inspector, may have affected  the validity and integrity of studies performed at the laboratory, the GLP  Program Manager will refer this information to OPP for consideration in  their decision-making process and, if appropriate, to OECA’s Office of  Civil Enforcement (OCE), which develops and prosecutes administrative  civil and judicial cases and provides legal support for cases and  investigations initiated in EPA regions. If the violation is criminal in nature,  it will be referred to OECA’s Office of Criminal Enforcement, Forensics  and Training (OCEFT). The inspection will not be closed until OPP or  OECA has made a final determination. Figure 2 summarizes the GLP  inspection process.
section_title: EPA Has Inspected Few Laboratories for GLP Compliance and Faced Challenges in Selecting Laboratories for Inspections
paragraphs: EPA’s OECA has inspected few laboratories on an annual basis that test  pesticides for GLP compliance for fiscal year 2009 through fiscal year  2013 and faced challenges in doing so. Because of resource limitations in  the GLP Compliance Monitoring Program, OECA prioritizes laboratories  for GLP inspections based on a set of criteria. However, our analysis  showed that some laboratory information in the databases used to  prioritize laboratories for inspection was either inaccurate or incomplete,  and these data challenges may negatively affect prioritization. OECA  officials said that budget cuts, among other things, have reduced the  number of inspectors and the number of GLP inspections that can be  performed. Given the concerns of some stakeholders about the infrequent  GLP inspections, OECA is considering other approaches, such as  charging fees or using third parties to review studies, in order to increase  the number of inspections.
subsections: section_title: OECA Inspects Few Laboratories Annually, but Most Laboratories Are Not Regularly Inspected for GLP Compliance
paragraphs: OECA inspected from 51 to 80 laboratories each year for GLP  compliance in fiscal year 2009 to fiscal year 2013, but most laboratories  were not regularly inspected for GLP compliance. During this period,  OECA inspected about 4 to 6 percent of 1,400 eligible laboratories each  year, according to EPA data and officials. In contrast, FDA’s GLP  compliance program guidance manual states that the program’s objective  is to inspect all eligible nonclinical laboratories conducting safety studies  that are intended to support applications for research or marketing of  regulated products approximately every 2 years.member countries under OECD’s Mutual Acceptance of Data (MAD)  agreement conduct inspections of their laboratories for GLP compliance  every 2 years, according to an OECD official we interviewed.
Some laboratory representatives we surveyed stated that their  laboratories were not inspected for GLP compliance by EPA from 2008 to  2013. EPA officials told us they inspect as many laboratories as they can,  given financial constraints. OECA officials explained that a limited number  of inspectors and tight budgets have hindered their ability to perform more  inspections. In fiscal year 2013, according to EPA officials, OECA had  four GLP inspectors to inspect 1,400 eligible laboratories in the United  States. OECA officials acknowledged that their four inspectors cannot  inspect all 1,400 eligible laboratories for GLP compliance every 2 years.  From fiscal year 2009 to fiscal year 2013, EPA reduced its GLP  Compliance Monitoring Program budget and the number of full-time  equivalent staff by approximately 50 percent from eight to four inspectors.  EPA officials said that the reduction in the number of full-time equivalent  staff was due to retirements, an inability to hire new inspectors because  of budgetary constraints, and most importantly, according to these  officials, the inability to find inspector candidates with the requisite skills.  During this same time period, the number of studies conducted by  laboratories that were submitted to OPP has remained relatively constant,  except for an increase in the number of studies submitted in fiscal year  2010. Estimates of the numbers of studies submitted, inspections  conducted, inspection staff and GLP budget data are shown in table 1.
To increase efficiency and to respond to a reduced budget and workforce,  as well as to address concerns from industry and the OECD, OECA  implemented changes to its GLP inspection procedures in fiscal year  2012 to try to increase the number of GLP inspections from the low of 51  conducted in fiscal year 2011. Under its revised inspection procedures,  agency officials consider laboratories’ geographic proximity to each other,  as well as other criteria, when selecting laboratories to inspect. For  example, in February 2013, the agency inspected five laboratories  located in Oregon and, in March 2013, the agency inspected two  laboratories in Texas. OECA officials explained that grouping laboratory  visits geographically saves travel money and staff time. In addition, they  stated that a change in OECA’s inspection procedures to allow inspectors  to audit studies in EPA offices rather than on-site reduced the amount of  time that inspectors spent at a laboratory.
Nevertheless, some stakeholders and international officials we  interviewed expressed concern about the infrequent GLP inspections by  EPA. Pesticide manufacturers and industry associations told us that if  laboratories cannot prove GLP compliance to potential clients or to  countries where their products may be used, their business can be  negatively affected. According to a senior staff person at one U.S.  laboratory, in 2011, the Netherlands rejected a study from a U.S.-based  laboratory because the contractor laboratory that conducted the study  had not been inspected by EPA. This same study had been previously  submitted to EPA. Following the Netherlands’ rejection of this study, the  laboratory had to repeat the study and subsequently contracted with a  European-based laboratory to do so. In addition, two stakeholders we  interviewed said that such rejections by other countries could likely  increase if U.S laboratories could not show that they had a recent GLP  inspection. One laboratory representative said his laboratory may stop  doing GLP testing since many registrants require proof of GLP  inspections, and his laboratory had not been inspected by EPA. In  addition, this laboratory representative said that if U.S. laboratories  cannot show that they have had a GLP inspection, registrants may not  hire them to conduct studies because of the possibility that those studies  may be rejected. In our survey of laboratories, 5 of 14 respondents  reported that EPA could improve its implementation of its GLP  Compliance Monitoring Program by increasing the number and frequency  of inspections to prevent these business consequences. Twelve of 15  respondents from laboratories with study data submitted to OPP since  fiscal year 2008 reported that EPA’s GLP inspections had a positive effect  on their business. Nine of the 12 respondents who reported positive  effects of a GLP inspection indicated that the inspections enabled them to  prove GLP compliance to their customers, such as U.S. and international  pesticide manufacturing companies, as well as to other countries’  governments.
section_title: OECA Prioritizes Laboratories for GLP Inspections, but Data Challenges May Negatively Affect Its Targeting Process
paragraphs: OECA prioritizes laboratories for GLP inspections, but challenges with  some of the data used to determine those priorities may negatively affect  its targeting process. GLP Compliance Monitoring Program inspectors  use the OPPIN and LISA databases to develop a list of the highest  priority laboratories to inspect for GLP compliance in a given year. Once a  list is generated using the Neutral Scheme Targeting Module located in  the LISA database, OECA officials said they try to select laboratories that  are geographically near to one another to inspect. The information used  to develop this priority list is based on data transferred from OPPIN to  LISA. However, our analysis showed that the laboratories’ information in  these databases was sometimes incomplete or inaccurate.
We found that the OPPIN system currently has three categories to  classify an entity’s role in a study: sponsor, performing laboratory, or both.  These categories do not allow EPA staff to differentiate between GLP  laboratories and other entities involved in a study. As a result, we found  some entities were identified in the OPPIN database as “performing  laboratories,” which EPA defines as facilities where a study or part of a  study is conducted, when in fact they were not. For example, of the  respondents to our survey of performing laboratories found in the OPPIN  database, six reported that they were not a laboratory and did not conduct  GLP testing. Of these six, three said they were consultants, two said  they contract with an outside source for laboratory testing, and one was a  pesticide manufacturer. We were not able to determine how or why these  entities were identified as performing laboratories in OPPIN. EPA officials  told us that if the entity that submits the study puts inaccurate information  on a study’s title page concerning who performed the study and where  the study was performed, the information entered by EPA’s contractors  into OPPIN will also be inaccurate. EPA’s documentation describing the  Neutral Scheme Targeting of laboratories states that the entity’s role in a  pesticide study determines whether it is a candidate for inspection. If  entities are inaccurately identified in OPPIN as performing laboratories,  the Neutral Scheme Targeting Module will not consider the correct  universe of laboratories to inspect and, as a result, inspectors need to do  additional manual research to verify that the laboratory selected for an  inspection is indeed an entity eligible for a GLP inspection.
We also found that address information for some laboratories was  missing or inaccurate in OPPIN. For example, we found missing address  information for 23 percent of laboratories listed in OPPIN. In 2008, EPA  updated its 1991 guidance to the contractors responsible for entering data  into OPPIN. The updated guidance states that the agency wants to  capture the physical address for each laboratory because OECA uses  this information to select laboratories for inspection. The guidance  acknowledges that determining the performing laboratory in published  studies is challenging, but the goal is to identify where the actual location  of the research was done. Without accurate address information, there  could be problems determining where the testing was actually conducted.
In addition, we found that some laboratory identification numbers were  not reliable. In its November 1991 guidance, OPP states that laboratories  should be assigned a unique laboratory identification number. For example, we found that one laboratory that was given a ranking in fiscal  year 2013 as second highest priority for a GLP inspection had an  identification number that was the same as four other laboratories in four  different states, making it unclear which of those five laboratories was  actually the one selected for inspection.
The agency maintains two different databases to track GLP inspections,  ICIS and LISA. The LISA database is used by the GLP Compliance  Monitoring Program, while the ICIS database is used EPA-wide,  according to officials. Because of technical problems EPA has been  experiencing with the LISA database, inspection data have been entered  only into ICIS since July 2011, according to officials. We reviewed  inspection data contained in both databases for fiscal year 2008 to fiscal  year 2013 in an effort to determine the total number of GLP inspections  OECA conducted, but we were not able to match the inspection  information contained in the two databases. While LISA uses laboratory  identification numbers, ICIS does not. As a result, OECA may not be able  to track if, or when, a specific laboratory had been inspected because the  systems do not both use identification numbers. In addition, the laboratory  names are not always the same in the two databases. We were also  unable to match up the inspections in the two databases. Without  accurate data on which laboratories have been inspected, OECA’s  Neutral Scheme Targeting Module scoring of laboratories most in need of  inspection may be inaccurate and, therefore, manual research is required  to ensure that OECA is targeting the laboratories most in need of  inspection.
Based on the incomplete or inaccurate data in ICIS, LISA, and OPPIN, it  is not always possible for GLP Compliance Monitoring inspectors to  identify where the testing was conducted without making telephone calls  to individual laboratories. The data issues also impede the agency’s  ability to efficiently track which laboratories need inspecting. The officials  said GLP inspectors must spend time manually verifying laboratory data  before deciding which laboratories to inspect. In the absence of reliable  data, EPA may not have the data it needs to prioritize laboratories to  inspect efficiently or effectively.
section_title: OECA Is Considering Other Implementation Approaches to Increase Inspections
paragraphs: OECA is considering other approaches to address laboratory  representatives’ and others’ concerns about infrequent GLP inspections,  such as using third parties or charging fees to increase the number of  inspections. In August 2012, OECA developed a Budget Adjustment Plan,  which provided general information on potential future approaches to the  GLP Compliance Monitoring Program, including ways the program could  be run more efficiently given its recent budget cuts and inability to hire  GLP inspectors. In its Budget Adjustment Plan, EPA states that OECA  will evaluate other implementation approaches, such as the use of a third  party to conduct GLP inspections. EPA officials told us that they have  also conducted internal and informal discussions regarding the possibility  of using user fees for the GLP program, but the agency has not  conducted a formal evaluation of user fees. Without formally assessing  the need for such fees, EPA cannot determine whether charging and  retaining the fees would be possible and whether such fees could help  make the inspection program self-sustaining.
In 2012, we concluded that federal user fees and charges are generally  related to some voluntary transaction or request for government goods or  services beyond what is normally available to the public, such as fees for  patent applications and customs inspections. In 2012, the federal  government collected nearly $300 billion in user fees from the public. In  2008, we found that well-designed user fees can reduce the burden on  taxpayers to finance those portions of activities that provide benefits to  identifiable users. As we mentioned earlier, FDA charges user fees for  medical and animal product application reviews, and these fees, together  with appropriated funds, provide resources that FDA uses for conducting  GLP inspections related to such products. In addition, some other  countries, such as some that are members of the OECD, fund their GLP  inspections through fee-based systems, whereby the registrant or  laboratory pays a portion or all of the inspection costs.
According to Office of Management and Budget (OMB) Circular A-25,  every 2 years, agencies should review programs that are not currently  funded by user fees (such as the GLP program) to determine whether  fees should in fact be assessed for government services.  Once user fees are implemented, revenue from the fees will be credited to the  general fund of the U.S. Treasury as miscellaneous receipts unless  otherwise specified by law. Circular A-25 also states that it may be  appropriate for an agency to request authority to retain the fee revenue if  the user fees offset the expenses of a service that is intended to be self- sustaining. The OMB guidance states that agencies are to discuss the  results of the biennial fee reviews and any resulting proposals in their  Chief Financial Officers (CFO) Annual Report required by the Chief  Financial Officers Act of 1990. In its most recent CFO Annual Report  (EPA Agency Financial Report) EPA discussed its biennial review of its  existing user fee programs. However, it did not discuss reviewing the GLP  program—or any of its other programs that are not currently funded by  fees—to determine whether fees should be assessed. Moreover, in  March 2014, the EPA Office of Inspector General (OIG) reported that  EPA did not conduct thorough biennial user fee reviews for fiscal year  2008 to fiscal year 2009 and for fiscal years 2010 to 2011, and it did not  review all agency programs to determine whether they should assess  fees for government services they provided. Among the OIG’s  recommendations were that the EPA CFO discuss biennial user fee  results in the EPA Agency Financial Report, coordinate with programs  that claimed an exception to charging fees and costs and help determine  whether fees should be assessed. Without assessing the need for user  fees, EPA cannot determine whether fees could help make the laboratory  inspection program self-sustaining.
When asked about user fees, representatives of 8 of 12 laboratories and  pesticide manufacturers told us they would support EPA user fees for  GLP inspections, and they cited more frequent GLP inspections as a  possible benefit of such user fees. Representatives from the remaining 4  laboratories did not support user fees, and some of these expressed  concern that a user fee system might be burdensome to smaller  laboratories. However, as we previously reported, the amount of a user  fee reflects the cost of providing the service, which may differ among  users.
section_title: EPA Rarely Used GLP Inspection Results in Initial Pesticide Registration Decisions but Sometimes Used Them for Later Reexamination
paragraphs: EPA rarely used GLP inspection results in making its initial pesticide  registration decisions. An OPP official told us that this is because most  inspections occur after those decisions have been made. According to an  OPP official, pesticide registration decisions are required by statute to be  made within 3 to 24 months of receipt of the pesticide application. For  example, new pesticide products that are identical in their uses and  formulation to one or more products already registered usually require a  registration decision within 3 months. the GLP Monitoring Program staff cannot set up and conduct inspections  of many of the laboratories involved within those time frames.
The Pesticide Registration Improvement Act of 2003 (PRIA) provides a schedule of  covered applications and registration service fees, including the category or type of  application, the amount of the pesticide registration service fee, and the corresponding  decision review timeframe in which the agency is to make a decision. There are 189 fee  categories or types of applications, each with a fee and decision review time frame. Pub.  L. No. 108-199, div. G, tit. V, § 501(f)(2), 118 Stat. 419, 422 (2004) (codified as amended  at 7 U.S.C. § 136w-8). last 6 to 12 months when performing inspections under the Neutral  Scheme Targeting Module in fiscal year 2013; and (3) OECA audit  specific categories of studies that OPP officials considered critical to their  pesticide approval decisions. An OECA official told us that as of March  2014, OECA inspectors had completed all of the eight OPP-requested  inspections. An OPP official told us that OPP would like to continue to  provide input to OECA prior to the beginning of each fiscal year to  increase the opportunity for OPP to react to findings before a product is  registered. The two offices appear to be communicating and prioritizing  laboratories for GLP inspections informally, but according to an EPA  official, there are no documented procedures that define the  responsibilities of each office in coordinating and prioritizing GLP  inspections. EPA has stated that formal procedures are not needed and  that the current method of communication and coordination is  satisfactory. However, by relying on informal coordination mechanisms,  OECA and OPP are depending on relationships with individual officials to  ensure effective coordination, and these informal relationships could end  once personnel turnover occurs. Without documented procedures for  effective coordination between the two offices, there is no assurance that  the two offices will consistently coordinate on GLP inspections in the  future. Under federal standards for internal control, agencies are to clearly  document internal controls, and the documentation is to appear in  management directives, administrative policies, or operating manuals.
When OECA’s GLP inspectors find deficiencies at a laboratory, they  share the inspection reports with major or significant violations with OPP.  According to OPP officials, once OPP receives the OECA inspection  report, it sends it to the OPP registration division responsible for the  registration (or pending registration) of products being supported by the  studies audited. The OPP registration division then reviews the report and  conducts a scientific reexamination of the studies that the laboratory in  question conducted and that were submitted in support of the pesticide  registration. Once OPP finishes its reexamination, if it finds that  deficiencies affect a study’s findings, OPP is to reject the study and may  request that the registrant repeat the study, submit other materials that  support that aspect of the registration, or perform other corrective action  deemed satisfactory to OPP. After the reexamination is complete, OPP  informs both OECA’s GLP Compliance Monitoring Program and the  registrant of the outcome.
We found that, from fiscal year 2008 to fiscal year 2012, OECA GLP  inspectors referred for reexamination the inspection results from 26  laboratories and 73 studies to OPP. Table 2 lists the action taken by OPP  as a result of its reexamination of studies, as of March 2014.
Our analysis of EPA data shows that this review process, from the initial  OECA GLP inspection to completion of OPP’s reexamination, takes on  average about 2 years (see table 3).
According to OPP officials, OPP has not denied a pesticide registration or  revoked any registrations based on OECA laboratory inspection  information during the past 5 years, but OPP has taken other actions  because of that information, such as requiring a registrant to repeat a  study or requesting that a registrant voluntarily cancel its registration. For  example, according to data provided by an OPP official, in fiscal year  2012, 15 studies associated with an already registered pesticide product  were found to be “unacceptable” based on OECA inspection information.  For 10 of these studies, EPA informed the registrants that they needed to  repeat the study. For the 5 others, the registrant voluntarily canceled or  suspended its registration associated with the study, or the study was not  a deciding factor in the products registration and therefore EPA took no  further action. In addition, OPP has required that an efficacy claim be  removed from the label of a registered product based on a study  submitted by a laboratory not meeting GLP standards.
OPP officials explained that a single study is not likely to affect the denial  or approval of a pesticide registration because OPP usually bases its  registration decisions on more than one study (although OPP officials  noted their decision depends on, among other things, the type of study).  For example, according to OPP officials, some pesticides are the subject  of more than 30 different studies before a decision is made on  registration. However, these same officials stated that OPP believes that  the GLP inspections are valuable not only to alert OPP to issues with  study data and laboratories but to act as a deterrent to guard against the  improper conduct of studies and submission of fraudulent or incorrect  study data. According to OECA officials, GLP inspections often lead to  positive action being taken by laboratories and pesticide registrants. They  said that registrants have voluntarily withdrawn studies from OPP as a  direct result of inspection notifications and inspection findings.
section_title: EPA and FDA Do Not Regularly Collaborate on Laboratory Inspections and May Be Duplicating Each Other’s Work
paragraphs: EPA and FDA do not regularly collaborate on GLP inspections and may  be duplicating each other’s work by inspecting the same laboratories. In  1984, EPA and FDA entered into an interagency agreement to  collaborate on GLP inspections that was last renewed in 2004. Under the  agreement, the two agencies agreed to collaborate in monitoring testing  laboratories’ adherence to GLP regulations, as well as in auditing of  health-related toxicological test reports and related laboratory records.  The agencies also agreed to exchange information and coordinate  actions concerning active investigations, regulation correspondence, and  legal or administrative action being considered against any laboratory  covered under the agreement. Among FDA’s responsibilities under the  agreement was to conduct a certain number of on-site inspections of  laboratories identified by EPA. From 2000 to 2007, FDA conducted a total  of nine inspections identified by EPA (three in 2000; three in 2001; and  one each in 2002, 2005, and 2007). EPA officials said they also formally  met with FDA officials on a quarterly and annual basis to discuss  upcoming inspections, but that communication ended by 2007 when,  according to EPA officials, FDA began selecting laboratories for  inspection on an annual basis instead of on a quarterly basis as EPA  does. FDA also shifted from having its Office of Regulatory Affairs select  laboratories for inspection to a more decentralized system, whereby its  centers select laboratories for inspection, which made it more difficult for  EPA to learn which laboratories FDA plans to inspect because it has to  coordinate with multiple centers instead of the Office of Regulatory  Affairs, according to EPA officials. EPA officials also said the last year  FDA sent EPA a list of laboratories it planned to inspect was in 2007.  They explained that, in the past, when EPA knew which laboratories FDA  was going to inspect, it would ask FDA to audit a study for them and  would avoid going to the same laboratory in the same year as FDA.  However, since these meetings ended, EPA officials said that they do not  always know if a laboratory was already inspected by FDA until they  arrive on-site. If EPA knew in advance that a laboratory was inspected by  FDA recently, EPA inspectors could use FDA’s inspection results to  inform their decision regarding whether conducting their own inspection  was necessary. If FDA’s inspection results were sufficient for EPA’s  purposes, EPA inspectors could potentially select a different laboratory to  inspect in place of the one recently inspected by FDA, thereby extending  limited resources. It is important to note, however, that, in some  circumstances, it may be necessary for both agencies to inspect the  same laboratory.
EPA officials stated that they occasionally coordinate with one of FDA’s  centers on GLP inspections and stated that the two agencies performed a  joint GLP inspection in 2013. In addition, EPA and FDA officials also said  that both agencies participate in an FDA-led work group focusing on the  modernization of laboratories. Officials from both agencies said that it  would be useful to know which laboratories the other agency was  planning to inspect and to have the results from those inspections. Since  each agency only inspects a certain number of laboratories each year,  sharing such information could help both agencies leverage resources.  This coordination also could increase the number of laboratories that are  inspected for GLP compliance, which in turn would help ensure that the  study data submitted for pesticide registrations were generated in  accordance with GLP regulations. However, the agencies do not regularly  collaborate on or communicate about future inspections or share results  from completed inspections.
FDA conducts two types of laboratory inspections, surveillance  inspections, which are periodic, routine determinations of a laboratory’s  compliance with GLP regulations and include a facility inspection and  study audit, and directed inspections, which are inspections assigned to  achieve a specific purpose, such as verifying the reliability, integrity, and  compliance of critical safety studies. Because the two agencies do not  regularly share GLP inspection-related information, we found that EPA  and FDA may be duplicating each other’s work in some of their GLP  inspections. For fiscal year 2005 to fiscal year 2012, EPA and FDA  conducted a total of 170 GLP inspections of the same 37 laboratories.In 38 of the 170 inspections, the agencies inspected the same laboratory  during the same fiscal year (see app. III.). For example, EPA inspected a  Colorado laboratory in November 2011, and FDA conducted a  surveillance inspection of this same laboratory 7 months later in June  2012. Similarly, although EPA inspected a Utah laboratory in January  2012, FDA conducted a surveillance inspection of this same laboratory 5  months later, in June 2012. According to EPA and FDA officials, the GLP  standards of the two agencies upon which these inspections are based  are largely similar. Moreover, a senior official in OECA’s GLP Compliance  Monitoring Program and representatives from three laboratories that were  inspected by both EPA and FDA told us that the inspections were  comparable.
We have defined overlap as two or more agencies or programs engaging in similar  activities or providing similar services to similar beneficiaries. communication between the two agencies on which laboratories they plan  to inspect and what they may have found at inspections that were  conducted, although they have communicated this information in the past.  FDA officials said they would welcome a list of inspections planned and  conducted by EPA.
EPA and FDA officials said that, at present, they do not share the results  of completed inspections at facilities that do both EPA and FDA-related  studies, and they do not have a process in place to collaborate on future  GLP inspections. As a result, EPA is not learning about laboratories that  FDA has inspected and at which it may have found deficiencies. Similarly,  FDA is not learning about the results of EPA laboratory inspections. In  addition to potentially duplicating each others’ work, by not collaborating,  the two agencies are missing opportunities to leverage each other’s  resources and expand their inspection coverage. FDA officials told us it  would be helpful to know if EPA had inspected a laboratory and that it  would be particularly useful if EPA shared information if the agency had  found problems during its inspection. EPA officials also said collaborating  and communicating on inspections would be helpful.
In April 2013, we concluded that when executive branch agencies carry  out activities in a fragmented and uncoordinated way, the resulting  patchwork of programs can waste scarce funds, confuse and frustrate  program customers, and limit the overall effectiveness of the federal  effort. The federal government uses a range of mechanisms to  implement interagency collaboration, such as interagency groups, and  interagency agreements and memorandums of understanding. Key  practices state that agencies that articulate their agreements in formal  documents can strengthen their commitment to working collaboratively.  Written agreements are most effective when they are regularly updated  and monitored. As we concluded in April 2013, where federal programs or  activities are fragmented, overlapping, or duplicative, there are  opportunities for agencies to improve the efficiency and effectiveness of  government programs and activities. Moreover, without leveraging its  inspection resources with FDA, EPA may continue to have difficulty  increasing annual GLP inspections of laboratories.
section_title: Conclusions
paragraphs: OECA has taken some steps to increase the number of GLP compliance  inspections of laboratories conducting studies submitted to EPA for  pesticide registration. However, OECA officials acknowledge that their  four inspectors cannot inspect all 1,400 eligible laboratories for GLP  compliance every 2 years, a time frame used by many of the countries  that are members of OECD’s MAD agreement. Because some  laboratories have never had a GLP inspection, laboratory and industry  representatives expressed concern that if OECA continues to inspect so  few laboratories for GLP compliance, U.S. laboratories and  manufacturers will be less competitive with foreign laboratories and  manufacturers. In addition, with so many laboratories going uninspected,  EPA may not have full assurance of the quality and integrity of data used  to make pesticide registration decisions.
OECA officials told us that they have informally discussed the possibility  of instituting user fees for the GLP program, but EPA has not conducted a  formal evaluation of GLP user fees as directed by OMB guidance for  programs not currently funded by such fees and, as recommended by  EPA’s OIG. OECA might be able to increase the number of inspections it  conducts if it were to charge a fee, which may be used to fund GLP  inspections, as FDA does, and as do 17 European countries. Without  assessing its authority and need for user fees, EPA cannot determine  whether fees could make the laboratory inspection program self- sustaining. In addition, we found that the information in EPA databases  used by OECA to set priorities for laboratory inspection is sometimes  incomplete or inaccurate. In the absence of reliable data, EPA may not  have the data it needs to prioritize laboratories to inspect efficiently or  effectively.
We commend OECA and OPP staff for communicating with each other on  GLP inspection matters, including OECA consideration of OPP’s recent  steps to identify laboratories that OPP considers to be priorities for GLP  inspections. Considering OPP’s request is important because most OECA  inspections currently take place after OPP has made its registration  decisions. However, EPA does not have documented procedures that  define the responsibilities of each office in coordinating and prioritizing  laboratories for GLP inspections consistent with federal standards of  internal control. Without such procedures, there is no assurance that the  two offices will consistently coordinate on GLP inspections in the future.
Furthermore, because EPA and FDA do not regularly share inspection- related information, as they did when they had an agreement to  collaborate on GLP inspections, the agencies have inspected some of the  same laboratories since 2007, while other laboratories may have gone  without needed inspections. Without collaboration and information- sharing on planned and completed GLP inspections, EPA and FDA may  duplicate GLP inspections, and EPA will have difficulty efficiently using its  limited resources to increase the number of inspections it conducts.  Officials from both agencies said that collaborating and communicating on  inspections would be helpful. However, absent a formal written  agreement, it is not clear that the agencies would regularly collaborate on  future planned inspections and share results from completed inspections.
section_title: Recommendations for Executive Action
paragraphs: We are making four recommendations in this report.
To improve the OECA GLP inspection process, we recommend that the  EPA Administrator take the following three steps:  1.  Assess the authority and need for a fee-based inspection system, and  if such a system is warranted, establish a user fee system, seeking  additional legislative authority, if necessary, to make the laboratory  inspection program self-sustaining.  2.  Direct OECA and OPP to ascertain the exact causes of inaccurate  and incomplete data in its databases and take action to ensure that  the data, such as identification of performing laboratories and  inspection history, are accurately recorded.  3.  Direct OECA and OPP to develop documented procedures to  coordinate and prioritize laboratories for inspections.
In addition, we recommend that the EPA Administrator and the FDA  Commissioner develop a formal written agreement, such as a  memorandum of understanding, that outlines how the two agencies plan  to regularly collaborate and share information on GLP inspections and  avoid duplication of inspections so that EPA can more efficiently use its  limited resources.
section_title: Agency Comments and Our Evaluation
paragraphs: We provided EPA and HHS with a draft of this report for their review and  comment; EPA provided written comments, which are reproduced in  appendix IV, and HHS provided written comments, which are reproduced  in appendix V.
In its written comments, EPA stated that it agreed with our findings,  conclusions, and all four of our recommendations. In response to our first  three recommendations, EPA agreed  to assess the authority and need for a fee-based GLP inspection  system;   to ascertain the exact causes of inaccurate and incomplete data  and ensure that the data are accurately recorded; and,   that OECA and OPP should develop written procedures to  coordinate and prioritize GLP inspections.
In response to our fourth recommendation, EPA agreed to develop written  procedures that outline how EPA and FDA will collaborate and share  information on GLP inspections. EPA stated that it did not agree that a  formal memorandum of understanding between the two agencies was  necessary. Our recommendation did not prescribe the type of agreement  the agencies should undertake and offered a memorandum of  understanding as one example. We agree that written procedures  developed and agreed to by both EPA and FDA will address the  recommendation.
In its technical comments, EPA noted that, while EPA and FDA have  similar GLP regulations, and in a small number of cases both agencies  may inspect the same laboratory, EPA does not believe the work is  duplicative. However, we define duplication in this report as occurring  when two or more agencies or programs engaged in the same activities  or provided the same services to the same beneficiaries. We continue to  believe that there is a possibility of duplication when both EPA and FDA  are inspecting the same laboratories within a short period of time because  both agencies provide a similar service to the same beneficiaries  (ensuring laboratory compliance with GLP through facility inspections and  study audits). Also in its technical comments, EPA acknowledged the  problems we found with the databases used for targeting GLP inspections  but stated that it does not believe these problems negatively affect  targeting for inspection because OECA is able to gather the necessary  information manually. While we agree that, ultimately, EPA may target the  appropriate laboratories for inspection through its manual research when  the databases are inaccurate or incomplete, we believe that the agency’s  reliance on manual research is not as efficient or effective as using  databases containing accurate information.
In its written comments, HHS also agreed with our fourth  recommendation. HHS also reiterated the point that there are legitimate  reasons why GLP inspections may be conducted by both EPA and FDA  at a single laboratory within a relatively short period of time. For example,  when FDA observes significant violations during for cause or surveillance  inspections, follow-up inspections may be required to verify corrective  actions. HHS also provided technical comments on our report, which we  incorporated as appropriate.
As agreed with your office, unless you publicly announce the contents of  this report earlier, we plan no further distribution until 30 days from the  report date. At that time we will send copies to the EPA Administrator and  the FDA Commissioner, the appropriate congressional committees, and  other interested parties. In addition, the report will be available at no  charge on the GAO website at http://www.gao.gov.
If you or your staff members have any questions about this report, please  contact me at (202) 512-3841 or neumannj@gao.gov. Contact points for  our Offices of Congressional Relations and Public Affairs may be found  on the last page of this report. GAO staff who made key contributions to  this report are listed in appendix VI.
section_title: Appendix I: Objectives, Scope and Methodology
paragraphs: Our objectives were to examine the extent to which (1) the Environmental  Protection Agency (EPA) inspects for GLP compliance laboratories that  test pesticides and the challenges, if any, EPA faces in doing so, (2) EPA  uses the information obtained through Good Laboratory Practices (GLP)  laboratory inspections in its pesticide decision-making process, and (3)  EPA and the U.S Food and Drug Administration (FDA) collaborate on  GLP inspections. To address these objectives, we reviewed relevant  federal statutes and regulations, EPA program and guidance  documents, federal internal control standards, Office of Management  and Budget circulars, and previous GAO and EPA Inspector General  reports. We also reviewed EPA’s fiscal year 2011-2015 strategic plan;  EPA’s fiscal year 2011, 2012, and 2013 annual agency financial reports;  and EPA Office of Enforcement and Compliance Assurance (OECA)  fiscal year 2012 Budget Adjustment Plan. In addition, we interviewed  EPA’s Office of Pesticide Programs (OPP) and OECA officials and  reviewed documentation they provided to obtain further information and  clarification on EPA’s pesticide registration process and how it relates to  the GLP process, and we interviewed FDA officials and reviewed  documentation they provided on FDA’s GLP process. Furthermore, we  reviewed recent literature related to GLP, including information and  documents found on the websites of a variety of industry, international,  environment, and academia organizations, and foreign government GLP  inspection programs. We interviewed about 25 representatives from these  organizations. We selected these individuals based on referrals from  EPA, and industry and environmental stakeholders.
To examine to what extent EPA inspects for GLP compliance laboratories  that test pesticides; and the challenges, if any, EPA faces in doing so, we  collected and analyzed documentation from OECA officials on its GLP  inspection process and analyzed EPA laboratory and inspection data, the  agency’s use of this data , and the accuracy and completeness of the  data. Specifically, we obtained information on how OECA determines  which laboratories to inspect and how EPA’s Office of Pesticide Programs  Information Network (OPPIN), Laboratory Information and Study Audit  (LISA), and Integrated Compliance Information System (ICIS) databases  are used to assist inspectors in making these decisions, as well as the  type of inspection data that are entered into these databases. Regarding  inspection data, we requested OECA to provide us with several data  elements contained in its LISA database for the years 2000 to 2013,  including name and location of laboratory inspected, reason for  inspection, number and type of inspections conducted, and number and  name of studies associated with the laboratory inspected. We determined  that inspection data were sufficiently reliable to present results on the  number of inspections from fiscal year 2009 to fiscal year 2013 as a  range. Since data, such as laboratories names and addresses, as well as  information on studies contained in OECA’s LISA database are  transferred from OPP’s OPPIN, we also requested OPP provide  information from OPPIN on the number of studies associated with  performing GLP laboratories from fiscal year 2008 to fiscal year 2012. We  analyzed this study data for accuracy and completeness. However, we  determined that data for “performing laboratories,” identification numbers,  and addresses were not sufficiently reliable to assess the number and  location of laboratories that had submitted studies to EPA. As a result, we  were not able to define the universe of laboratories subject to a GLP  inspection. However, EPA did provide estimates of the number and  percentage of eligible laboratories that were inspected each year, and we  used that information in this report.
To determine the views on EPA’s GLP Compliance Monitoring Program,  we interviewed individuals representing 25 entities, including laboratories,  pesticide manufacturers, international organizations, environmental and  health organizations, national and trade associations and foreign  government GLP programs, which we selected based on referrals from  various stakeholders and EPA officials. Specifically, we spoke with  representatives of nine laboratories and conducted site visits to four of  these laboratories located in Maryland and Illinois. We also conducted a  Web-based survey of performing laboratories. For our survey, we drew a  randomly selected sample of 80 performing laboratories included in the  OPPIN database that sent study data to OPP from fiscal year 2010 to  fiscal year 2012. Because OPPIN does not contain e-mail addresses, we  searched for laboratories’ e-mail addresses and found them for 53 of the  80 laboratories that we sampled. We sent the Web-based survey to these  53 laboratories. We obtained responses from 26 laboratories and other  entities. However, 6 of these 26 respondents stated that they were not a  laboratory and did not conduct GLP testing. Therefore, we received  usable survey responses from 20 laboratories. Not all respondents to our  survey, however, answered every question. Our survey asked if the  laboratory had conducted GLP testing for EPA or FDA, experienced a  GLP inspection by EPA, what was the effect of having an inspection, and  what improvements they thought could be made to EPA’s GLP Inspection  Monitoring Program. The survey results are not generalizeable to all  laboratories that are covered by the GLP program, but they were  randomly selected, and the results can provide examples of such  laboratories’ experiences and challenges with GLP inspections. We were  not able to select a representative sample because some data in the  OPPIN database was not sufficiently reliable.
To assess the extent to which OPP uses the information obtained through  GLP laboratory inspections in its pesticide decision-making process, we  analyzed relevant documents and databases to determine the number of  OECA’s GLP inspections that produced results that were referred to OPP  for reexamination, the time it took to conduct these reexaminations, and  any impact the inspections had on OPP’s pesticide registration decisions.
To determine the extent to which EPA and FDA collaborate on  inspections, we analyzed EPA and FDA GLP laboratory inspection data  and determined that the inspection data were sufficiently reliable for our  purposes. We also analyzed the 20 laboratory survey responses to  determine if they had conducted GLP tests or studies for submission to  both EPA and FDA since 2008. We reviewed agency documents, such as  a 1984 agreement entered into by EPA and FDA to cooperate on GLP  inspections and FDA’s Compliance Program Guidance Manual. We  interviewed EPA and FDA officials, laboratory representatives and other  stakeholders about the potential for the two agencies to collaborate.
We conducted this performance audit from November 2012 to May 2014  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.
section_title: Appendix II: Web-Based Survey to Laboratories
section_title: Appendix III: Laboratories Inspected for GLP Compliance by EPA and FDA, FY 2005-2012
paragraphs: Our analysis of Environmental Protection Agency (EPA) and U.S. Food  and Drug Administration (FDA) Good Laboratory Practices (GLP)  inspections data identified the following instances where laboratories  were inspected by both agencies (see figure 3). We do not know the  reason for every inspection. In some instances, EPA and FDA may have  needed to conduct their own inspection.
section_title: Appendix IV: Comments from the Environmental Protection Agency
section_title: Appendix V: Comments from the Department of Health and Human Services
section_title: Appendix VI: GAO Contact and Staff Acknowledgments
subsections: section_title: GAO Contact
section_title: Staff Acknowledgments
paragraphs: In addition to the individual named above, Anne K. Johnson, Assistant  Director; Cheryl Arvidson; Mark Braza; Greg Carroll; Cynthia Grant;  Angela Miles; and Patricia Moye made key contributions to this report.  Richard Johnson, Stuart Kaufmann, Anna Maria Ortiz, and Dan Royer  also made important contributions.