Highlights of "EPA Regulatory Update" by Mark Lehr and Francisca E. Liem at the 33rd SQA Annual Meeting, National Harbor MD, 30 March 2017
Stuart Mertz, Jr., PhD, RQAP-GLP
Member, EPA Subcommittee of the GLP Specialty Section
Over the past several years, great organization and hard work by the leadership and membership of the new EPA Subcommittee of the GLP Specialty Section has revived a robust SQA EPA program all year long. Regulatory professionals involved in FIFRA EPA GLP/non-GLP compliance once again have great reasons to become an SQA member and attend the SQA Annual Meeting. Thank you all for these accomplishments!
One of the outstanding program elements at this year’s meeting is reported as follows. Co-author Mark Lehr, EPA Inspector, US EPA GLP Program, presented in person while co-author Francisca Liem, US EPA GLP Program Director, was in Europe at an OECD meeting. Unfortunately the talk slides and audio (EPA Session GG-2) will not be available on the SQA website nor the Library archive, so this summary was written to disseminate highlights to the whole SQA EPA community. With permission of Francisca Liem (who has reviewed much of this article for accuracy) the primary contents of their slides (reformatted here for text reading) are reproduced in their entirety, except as noted below; and this article includes some oral information by Mark Lehr during the talk and some notes from Francisca Liem in response to questions raised. We gratefully appreciate and thank Mark Lehr and Francisca Liem for their comprehensive presentation, and we thank the SQA Program Committee for allocating one hour for it.
A thorough overview of EPA’s GLP Program was clearly presented to orientate/educate the novice as well as the experienced members of the audience. Newsletter space is limited, so details are not reported here for the following topics:
- GLP Program Objective
- Reasons why a national standardized QA system of GLP regulations are needed [GLP EPA FIFRA 40 CFR Part 160 & 40 CFR Part 792; and GLP/non-GLP FIFRA 40 CFR 169.2(k)]
- Number of personnel (3 Field Inspectors, 1 Program Manager) serving over 1400 test sites
- Function is to inspect submitted studies
- Awesome geographic maps showed locations of FIFRA GLP labs inspected in FY2016 as well as the newer process of inspection clusters [2-4 inspections conducted in a week in a small geographic region] to increase the no. of inspections by efficient use of inspector’s resources (e.g., time and travel expenses)
- EPA’s work to establish and harmonize GLP programs around the World through OECD’s MAD program, and in concert with China ICAMA to provide GLP training to Chinese involved with residue studies in tropical commodities
- Itemized updates were provided on new OECD documents and initiatives regarding “harmonization” and “transparency” as well as US congressional action on the proposed Pesticide Registration Enhancement Act of 2017 (PRIA 4; most importantly proposed an additional $500,000 for EPA inspectors/inspections).
Remember that to EPA, “laboratory” is a broad term encompassing all types of test sites (e.g., field or in a building, both GLP and non-GLP). There are around 9,000 studies submitted per year to OPP; only about 1.5% are selected for inspection/audit.
Does your facility need an EPA inspection? Francisca Liem subsequently clarified that a lab may remind her (if a study that includes the lab has been submitted to OPP) that it needs an inspection (e.g., a new lab that has never been inspected, or an existing lab that has not had a re-inspection for a long period of time (5 yrs or greater)). It helps to provide the MRID No and the report title, because sometimes the facility name is not recorded in the OPP database (if the facility was not identified as a performing laboratory).
A total of 68 site inspections were conducted in FY 2016. Because one of the three inspectors was out on medical leave for much of the year, this number of inspections was down 30% from previous years (average 90/yr). A total of 59 sites (87%) had no violations – awesome! and 5 stars/high 5s to the Analytical Chemistry labs, which were 100% in compliance! A total of 131 data audits were conducted. Results by Discipline are summarized in Table 1.
|
Discipline
|
No. Lab Inspections
(% Total Inspect.)
|
% Labs in Compliance (No.Inspections with No Findings)
|
No. Actual Findings -- GLPS SubPart
|
|
|
|
|
|
|
Field Sites
|
19 (28%)
|
95% (18)
|
1-F
|
|
Toxicology
|
10 (15%)
|
90% (9)
|
1-B, 1-G
|
|
Analytical Chemistry
|
9 (13%)
|
100% (9)
|
|
|
Product Chemistry
|
18 (26%)
|
83% (15)
|
3-B, 1-D, 2-E, 4-G, 2-J
|
|
Others*:
|
|
*67% (8)
|
3-B, 2-D, 2-E, 1-F, 4-G
|
|
*Antimicrobial Effic.
|
4 (6%)
|
*
|
*included in Others
|
|
*Insecticide Efficacy
|
3 (4%)
|
*
|
*included in Others
|
|
*Ecotox
|
4 (6%)
|
*
|
*included in Others
|
|
*Seed Treatment
|
1 (2%)
|
*
|
*included in Others
|
|
Total:
|
68 (100%)
|
87% (59)
|
*included in Others
|
Table 1. FY 2016 Inspection Results (%s are rounded; some data added by author for clarity)
Plus Human Exposure studies were inspected. Among the above disciplines, 4 sites were conducting Biotech studies - only 1 lab (25%) had No Violations. For all labs, the distribution of number of violations among the GLPS subparts were as follows: A (0), B (7), C (0), D (3), E (4), F (2), G (9) and J (2). There was 1 lab with deviations per Books & Records Regulations [40 CFR 169.2(k)]; 1 lab with non-GLP deviations; and 2 labs with science issues deviations (see examples in “GLP Topic” section below).
Most Frequent GLP Deviations for Subpart B - Organization & Personnel:
- QA missing master schedule
- Final report does not reflect raw data
- Protocol deviations (i.e.,not clearly written – not a complete understanding of the deviation and, therefore, the impact)
- Training records and job descriptions not accurate
- Lack of temperature monitoring for storage stability study
- Missing raw data
Most Frequent GLP Deviations for Subpart G – Protocol for the Conduct of Study
- Errors in data recording
- Storage temperature not recorded for storage stability study - Missing raw data
- Protocol deviations (i.e, not clearly written – not a complete understanding of the deviation and therefore the impact)
Most Frequent GLP Deviations for Subpart J – Records & Reports
- Final report does not reflect raw data
- Final report missing GLP elements
◦ Missing raw data
In FY2016, a total of 8 studies were rejected for GLP/non-GLP violations as shown in Table 2.
|
Type of Studies
|
No. of Studies
|
Civil Penalty
|
Violations
|
|
Residue Chemistry
|
2
|
$5,720
|
Failure to maintain raw data
|
|
Insecticide Efficacy
|
2
|
$7,150
|
Failure to maintain raw data
|
|
Insecticide Efficacy
|
2
|
$15,000
|
Non GLP: Failure to maintain raw data &
Raw data does not match final report
|
|
Toxicology
|
2
|
$20,020
|
1. Failure to conduct stability testings
2. Failure to maintain raw data
3. Lack of separation between QAU and study personnel
|
|
Total:
|
8
|
$47,890
|
|
Table 2. FY2016 GLP/Non GLP Enforcement Cases
For FYs 2013-2016, 36 studies were rejected for regulatory actions by OPP all of which resulted from raw data violations that were found in ten GLP inspection as shown in Table 3.
|
Type of Studies
|
No. of Inspections
|
No. Studies Rejected
|
Reason for Rejection
|
|
GMO
|
1
|
1
|
Lack of raw data
|
|
Product Chemistry
|
7
|
25
|
Lack of raw data
|
|
Companion (toxicology)
|
2
|
10
|
Original data altered
|
|
Total:
|
10
|
36
|
|
Table 3. Regulatory Actions by OPP FY 2013 – 2016 Resulting from GLP Inspections
Also it was reported that the next OECD inspection of US EPA will be in 2020. EPA is still working through the corrective actions requested in the 2013 GAO audit. And EPA has an SOP on auditing computers (EPA does not use FDA Part 11).
Mark Lehr introduced the new headings of “2016 GLP Topic” (which replaced the “GLP Alerts” heading used in Francisca Liem talks) and “Final Thoughts” to focus our attention on key issues to examine at our facilities. I have numbered (Mark Lehr used bullets) items to facilitate future discussions within our groups.
2016 GLP Topics
- 40 CFR 160.107(d): Test, control, and reference substance handling. The receipt and distribution of each batch is documented. Such documentation shall include the date and quantity of each batch distributed or returned.
- Non routine calculations and formulas should be consistent with EPA’s understanding (method of calculation questioned; OPP requested the inspection)
- Before the final report is submitted to EPA, check with
- Office of Pesticide Programs (OPP)
- Office of Pollution Prevention and Toxics (OPPT)
- Study Director should give an explanation in the final report if test substance is found in the control (untreated group)
- 40 CFR 160.130(e):
- Storage stability testing needs:
- Temperature monitoring and recording
- Stability testing on day 0
Final Thoughts for successful inspections were shared as follows:
- Designate an inspection contact person at lab (for EPA inspector communications)
- Establish procedures for inspections (SOP)
- Discuss with inspector during opening conference
- No waivers or restrictive agreements will be signed by the inspector; they can sign in a visitor log at a facility
- Develop an inspection kit (useful in all types of audits/inspections: e.g., Org. Chart, directions to site/lodging options, site map/floor plans, field maps, SOP Index, appropriate Master Schedule printout)
- Make duplicate copies of everything we request
- Ask questions before/ during/ after the inspections – want “partnership” working together
- Our Common Goal … Working together to Ensure the Highest Quality Science for Good Decision Making
Contact information if you have any questions or need more explanation: [email protected], 303.462.9391, and [email protected], 202.564.2365.