Good Laboratory Practice Regulations -
NAFTA Biopesticide Registration Workshop
NAFTA Biopesticide Registration Workshop
Introduction: The US Environmental Protection Agency (EPA) has established a set of criteria known as the Good Laboratory Practice Regulations (GLP's) to govern the conduct and reporting of studies submitted to support applications for research or marketing permits for pesticide products. Canada and other nations have also adopted GLP regulations. These regulations, first put into place to combat fraud, have become the international quality standard for non-clinical safety data submitted to support pesticide registrations. Analogous regulations are also utilized as quality standards for non-clinical safety studies in the chemicals and pharmaceutical industries.
Scope: As found in the US Code of Federal Regulations (CFR), the GLP's that pertain to the submission of non-clinical studies on behalf of FIFRA based compounds can be found in 40 CFR Part 160. These regulations apply to studies designed to determine the effects, metabolism, product performance (as provided for in the regulations), environmental fate, chemical fate, persistence and residue or other characteristics, as the EPA deems necessary. The Organization of Economic Cooperation and Development (OECD) established its own set of GLP's. These GLP regulations have been adopted by several participating OECD countries, including Canada. The OECD GLP's provide for the quality standards in developing non-clinical safety data on pharmaceutical products, pesticide products, cosmetic products, veterinary drugs, food additives, feed additives and industrial chemicals. These types of studies may be conducted in laboratories, greenhouses or field environments. The OECD GLP's and the US GLP's are for all practical purposes comparable, with only subtle differences.
The specific types of studies effected by the US GLP's and there for the registration of a biopesticide product can be found in the Harmonized Testing Guidelines Series 880 (Biochemical Test Guidelines) and 885 (Microbial Pesticide Test Guidelines) which can be found on the US EPA's Office of Pesticide Programs web site. A listing of various web sites and reference sources will be provided at the end of this article.
40 CFR Part 160, section 17 states that, AEPA may refuse to consider reliable for purposes of supporting an application for a research or marketing permit any data from a study which was not conducted in accordance with this part. These standards are not guidelines, they are enforceable regulations. The sponsors of studies are ultimately responsible for the compliance of their regulated research and are subject to inspection by the EPA Office of Compliance Assurance's Data Integrity Branch (40 CFR Part 160.15). But, what are the GLP's?
The Good Laboratory Practice Regulations: The GLP regulations are a set of minimal requirements for the conductance of regulatory studies. They provide a framework for defining the responsibilities of key study personnel and the general needs and requirements for testing facilities. The GLP's set forth requirements for the handling, testing and distribution of test, control and reference materials to verify the use and identity of these materials. The GLP's also provide the framework for study planning, conductance, generation of records and reports and the retention of those documents. The GLP's are in essence a management plan providing for the regulated entity to have put into place procedures for planning, conductance, monitoring, reporting and retaining studies submitted to the EPA. This article will provide a brief overview of these requirements and their ramifications.
Subpart A - General Provisions
This subpart delineates the applicability of the GLP's to various studies, provides for requirement to permit EPA inspection, defines the effect of non-compliance and is the location where terminology used in the GLP's are defined. All studies submitted to the US EPA in support of a research or marketing permit are required to be conducted according to the GLP's. All exceptions to the GLP's are required to be noted in the GLP compliance statement.
Can non-GLP studies be submitted to the USEPA? Yes. But, the US EPA can find those studies unreliable and reject them from consideration.
Can the US EPA inspect a study even though it was submitted non-GLP? Yes. Other requirements that are found in FIFRA are still required and can be evaluated as part of an inspection of the study report.
How are these inspections scheduled?
When an entity submits a package for consideration by the US EPA it is assigned an MRID number. This MRID number and the particulars of who, what and where of the study are forwarded to the US EPA’s Office of Enforcement and Compliance Assurance. This office generates a random selection of the studies from their database and selects a certain number of neutral test sites to inspect quarterly.
It is also important to note that not only are their GLP requirement standards in the US, they are also required for safety data submitted to Canada and most EU member countries.
The US EPA has established the Enforcement Response Policy that describes a sliding scale of severity for infractions of the US GLP's. Low, Moderate and High level violations are provided for. The civil and criminal penalties for violation of the regulations are outlined. The Enforcement Response Policy and other documents can be found along with many others at the web sites provided at the end of this article.
Subpart B - Organization and Personnel
This subpart details and defines the roles and responsibilities of personnel, Testing Facility Management, Study Director and the Quality Assurance Unit. The responsibilities outlined in this section are specific to the individual titles presented above. While management may designate duties associated with the successful completion of the tasks associated with these responsibilities, the ultimate legal and enforceable responsibility will also reside with the entities as defined in this section.
Subpart C - Facilities
This subpart describes the various requirements as they pertain to testing facilities, test system care, test system supply facilities, facilities for handling test, control and reference substances, laboratory operation, specimen and data storage.
Subpart D - Equipment
This subpart provides for the requirements involved with equipment design and the maintenance and calibration of equipment used in GLP studies.
Subpart E - Testing Facility Operation
The requirements and need for Standard Operation Procedures is provided for in this subpart, along with the requirements involving reagents and solutions, and animal or other test system care.
Subpart F - Test, Control and Reference Substance
The characterization of test, control and reference substances, their handling and the handling of mixtures of substances with carriers is provided for in this section of the GLP's.
Subpart G - Protocol for and Conduct of a Study
The minimal elements of the protocol are described in this section, along with the requirements for the conduct of the study. There is also a section that covers the physical and chemical characterization requirements for test, control and reference substances.
Subpart J - Records and Reports
This section covers the reporting of study results, storage and retrieval of records and their retention requirements.
GLP Definitions: The basic definitions provided for in subpart A of these regulations provide a fundamental starting point for the GLP's. Basic definitions are presented as follows:
| • | Sponsor - The entity that pays the bills and holds registration -not a management company or consulting company |
| • | Study director - Individual responsible for the overall conduct of a study |
| • | Quality Assurance Unit - Any person except the study director, management or other individuals involved in the study, designated by testing facility management to perform the duties relating to quality assurance of the studies |
| • | Test Facility Management - management where the study director resides |
| • | Testing Facility - person who actually conducts a study, i.e., actually uses the test substance in a test system |
| • | Study - Any experiment at one or more test sites, in which a test substance is studied in a test system under laboratory conditions or in the environment to determine or help predict its effects, metabolism, Product performance, environmental and chemical fate, persistence and residue, or other characteristics in humans, other living organisms, or media. Does not include basic exploratory studies. |
| • | Person - individual, partnership, corporation, association... or any legal entity |
| • | Standard Operating Procedure - Written, approved procedures that describe in detail standard and repetitive procedures |
| • | Protocol - Approved, written document that clearly indicates objectives, study design and all methods to be used in conducting the study |
| • | Test System - the entity that the test substance is tested in or added to |
| • | Test Substance/Article - Any material or device administered to a test system |
| • | Reference Substance - Any chemical substance or mixture, analytical standard, or material other than a test substance, feed, or water, administered to or used in analyzing the test system to establish basis for comparison. |
| • | Control Substance/Article - Any material other than a test substance, feed, or water, administered to the test system during the study. |
| • | Study Dates: |
| • Study Initiation Date - date protocol is signed by the study director. | |
| • Study Completion Date - date final report is signed by the study director. | |
| • Experimental Start Date - first date the test substance is administered/applied to the test system.* | |
| • Experimental Completion Date - last date data are collected for the study.* | |
| *EPA | |
| • | Raw Data - Any laboratory worksheets, records, memoranda, notes, or exact copies, that are the result of original observations and activities of a study and are necessary for the reconstruction and evaluation of the report of that study. |
| • | Computer Data - Define as either magnetic media or first hard-copy printout - data cannot be overwritten or erased. |
| • | Archives - Area used for the orderly storage and expedient removal of all raw data, documentation, protocols, specimens, and interim and final reports. |
Ms. Frances Liem, Branch Chief of the Agriculture Division’s, Laboratory Data Integrity Branch |
www.sqa.org National Education Committee Training Regional Chapters Training |
Useful GLP Related links on the World Wide Web
With links to public web sites for Finland, Ireland, South Africa, Switzerland, US and the European Union
These sites have multiple links that will hyperlink you
to other Societies and their regional chapters involved with GLP's
and Quality Assurance, resource web pages
| Society of Quality Assurance | www.sqa.org |
| British Society of QA | www.barqa.com |