Science & Research
Volume III - 6.5 ORA Method Development and Validation Process
Section 6 ORA Method Development and Validation Program
|EFFECTIVE DATE: |
- 6.5.1 Laboratory Method Development and Validation Program (MDVP) Overview
- 6.5.2 Method Development and Validation Program Procedures
The MDVP program supports five project categories:
- Projects are designed to develop and implement new methods.
- Expected Outcome: A new method is implemented within the laboratory or method validation proposal for field wide implementation.
- Projects are designed to evaluate innovator validated methods via peer reviewed assessment and inter-laboratory collaborations.
- Expected Outcome: Validated regulatory method for field wide implementation.
Method Modification, Enhancement, and Extension
- Projects are designed to extend an existing method to one or more additional matrices or analytes; projects designed to improve an existing method.
- Expected Outcome: Modified method implemented within the laboratory or method validation proposal for field wide implementation.
- Projects are designed to investigate and evaluate the usefulness and applicability of new technologies and increase our base expertise in these new technologies.
- Expected Outcome: New technology accepted by one or more publications summarizing experiments performed, data collected, and recommendations.
- Projects are designed to test hypotheses related to FDA mission such as food safety, quality mechanisms, contaminants, analyte/matrix interactions, metabolism studies, degradation/depletion studies, process effects, stability studies. Although method development may be a component of these projects, it is not the primary focus.
- Expected Outcome: Study, results, and impact for FDA described in one or more publications.
The MDVP process is designed to increase flexibility and timely planning of quality projects that benefit the agency. Each ORA laboratory is required to have an ongoing MVDP plan commensurate with their method development and validation time allotment. A good program is mission related and does not duplicate research work being done elsewhere.
Laboratory management, analysts, and Science Advisors have an important role in managing the program. Throughout the year, method development and validation progress and accomplishments are monitored and adjustments made to react to emerging analytical needs as they arise. Laboratories are expected to fully plan and accomplish their assigned method development and validation time.
126.96.36.199 Call for Proposals
ORS issues a request for proposals to ORA Laboratories and Centers for the highest priority method development and validation projects that target validation, development, and enhancement of regulatory methods. Additionally, at that time, laboratories may submit proposals for projects not listed in the call for proposals to be considered for future program needs.
The call for proposals issues at least annually with approximately a thirty (30) day deadline for proposal submission.
188.8.131.52 Proposal Preparation and Submission
NOTE: This section will be revised when CARTS is fully implemented.
The Office of Regulatory Science Call for Proposals issues annually and includes the following information:
- a list of method development and validation projects requested for study;
- FDA Component Automated Research Tracking System (CARTS); and
- Method Development and Validation Program Record (for use when CARTS is unavailable or not accessible to certain users).
1. Method Development and Validation Project Proposal Form
A Method Development and Validation Project (Proposal Form) is completed by the laboratory personnel for those projects requested from ORS. This form is completed electronically (in CARTS if accessible) or by completing the form in Appendix I (if CARTS is not accessible)
- An MDVP proposal shall include the following information:
- project number;
- estimated number of hours and timeline;
- describe the problem the project intends to solve;
- regulatory significance and relevance to the FDA mission;
- literature search and supporting documents;
- current issues and recent accomplishments in the field;
- experimental plan/methods and materials
- describe in detail the experimental approach, methods and materials
- QC/QA controls, validation/extension protocol requirements from the appropriate source (e.g. Laboratory Manual, Volume II, ORA-LAB5.4.5, AOAC, BAM, CVM protocol, CFSAN/ORS microbiology protocol);
- anticipated results
- future plans (e.g. collaborative study, publications);
- safety requirements;
- funding requirements and declaration of funding support; and
- appropriate signatures and endorsement.
- Additional information applicable to the following studies shall be included in the MDVP project record:
Method validation studies
- method validation protocol (e.g. single lab validation, collaborative study)
Method Modification, Enhancement, or Extension
- method description;
technical details of the modification; and
- benefits of the modification.
- identify the accomplishments from the previous project;
- propose a new plan of work or update Experimental Plan/Methods and Materials; and
- update literature review.
All MDVP proposals are received by the Office of Regulatory Science;
- signatures and endorsement.
184.108.40.206 Proposal Review and Project Assignment
Proposals are submitted to ORS. ORS performs the review internally and/or assigns the review to a scientist/science advisor in the Center with expertise in the technology area. Within 30 days of submission a meeting will be held with ORS and science reviewers to determine proper method pathway to follow. The project will either be recommended for the “MDVP Committee Pathway” or the “ORS Research Pathway”(Appendix III).
Proposal review considers, but is not limited to, scientific merit (e.g. objectives are realistic and scientifically sound), mission importance, FDA impact, literature background, budget, timeframe, accuracy completeness of the submission, and likelihood of success.
Assignments will be based on review, FTE distribution, and availability of hours. A Research Project Number (RPN) number, assigned by DFS, is used by the analysts to track their time in FACTS.
Because laboratories have specific capabilities and programs, resources will not be limited to only the high priority projects. Low priority projects will be considered if high and medium priority projects are addressed and resources are still available.
220.127.116.11 Regulatory Pathway Approval
After proposals are received, ORS will organize a meeting with the appropriate Center review scientists to discuss each project. This Review Committee will review each proposal and will either recommend the proposal for one of two pre-defined pathways (the Regulatory Pathway or Non-Regulatory Pathway), or the proposal will be rejected with comments to the investigators. Additionally, The Office of Foods through the Science and Research Steering Committee (SRSC) has developed validation guidelines of analytical food methods for Agency-wide implementation in a regulatory capacity. A Method Validation Subcommittee will have the responsibility to provide guidance and oversight to all Foods Program laboratories during the method development and validation process and will be the responsible authority for recommendations, evaluations and final approval of all validation studies.
If the MDVP Review Committee concludes that the project is appropriate for the Regulatory Pathway, the committee will notify the laboratory of its decision. The proposal will either be approved as written or approved with minor revisions. The MDVP Coordinator will grant the proposal research hours and the laboratory will move forward with the accepted project.
Once the project is completed, the data and conclusions will be presented to ORS for final evaluation. ORS will then decide whether to approve the project for validation, or disapprove it pending further research. If disapproved, the researchers can propose further research or discontinue the project.
If approved for validation, ORS will coordinate with the Centers to validate the method according to a recommended validation level, if applicable. After the method is validated at the appropriate recommended level, the method should be submitted for inclusion into a regulatory compendium (i.e AOAC), an approved FDA compliance program, or peer reviewed journal. If a method fails validation, it may be determined not fit for use and terminated or re-proposed for validation by the principle investigators.
18.104.22.168 Non-Regulatory Pathway Approval
If the MDVP Review Committee concludes that the proposal is not appropriate for the Regulatory Pathway, ORS will decide whether the proposal is appropriate for the Non-Regulatory Pathway. ORS will review the proposal to determine its value as a non-regulatory method such as for use as a laboratory screening tool. If ORS determines there is no value in this proposal as a non-regulatory method, the proposal will not be approved and the laboratory will be notified why.
If ORS does determine there is value in the project as a non-regulatory method, the MDVP Coordinator will send the laboratory a review decision as approved or approved with minor revisions. The MDVP Coordinator will grant the proposal research hours and the laboratory will move forward with the accepted project. Once the laboratory completes the research, they will present their data and conclusions to ORS for final evaluation.
ORS will then review the data and conclusions and decide if the project is fit for non-regulatory use. If ORS concludes that the project is not fit for non-regulatory use, the laboratory will be notified that further research is necessary. If ORS does conclude that the project is appropriate for non-regulatory use, ORS and the laboratory will again present the project, along with the new data and conclusions, to the MDVP Review Committee for inclusion into the Regulatory Pathway.
If the MDVP Review Committee concludes that the project is now appropriate for the Regulatory Pathway, the project will proceed down this pathway (see Section 22.214.171.124) at the point of method validation. If the MDVP Review Committee concludes that the project is still not appropriate for the Regulatory Pathway, the laboratory should proceed with publication of the project in a peer-reviewed journal or as a Laboratory Information Bulletin (LIB).
126.96.36.199 Project Execution and Reporting
Projects are managed and executed at the laboratory.
Accurate and timely reporting is provided through FACTS.
- report hours under the Miscellaneous Operation Screen.
- FACTS instructions
- select Navigate
- select Miscellaneous Accomplishment Hours
- select Create
- enter Research Operation Code: 01 or 02
- enter accomplishment dates, district
- enter Reference Number: Research Project Number (if applicable)
- enter Description: "CARTS project #######"
- enter name, hours, applicable PAC code
The recommended timeline and schedule for project completion is:
≤ 500 hours = 6 months
> 500 hours = 12 months
Upon project completion, a final project report, a Laboratory Information Bulletin or article for a peer-reviewed journal is submitted to ORS summarizing results and conclusions.
See Appendix C, Laboratory Information Bulletin for guidelines.
The project status is provided to ORS by laboratory management on a quarterly basis and maintained in a database by the ORS Coordinator. Project updates may be provided by telecom, written report, or by Webex Seminar depending upon the amount of progress that has been made and the current status of the project. The report will also be updated to include regulatory impact, publications, presentations, collaborative studies, adoption as official methods (adoption by other field and headquarters laboratories), and inclusion in compliance programs. The report also assists both the laboratory managers and ORS with future planning.
188.8.131.52 Presentation, Assessment, and Implementation
The basic product of scientific research is information. Dissemination of information ensures others interested in the problem can use the data. To accomplish this, ORA encourages and supports several types of research products.
All MDVP outcomes, at a minimum, should be published as a Laboratory Information Bulletin (LIB), or preferably published in a peer-reviewed journal. Manuscripts for outside publications must be reviewed and approved for technical correctness and adhere to Agency and ORA policy and guidance on review and clearance. See Section 6.6.
Authors are expected to produce manuscripts that are coherent, scientifically sound, and likely to be accepted for publication.
Local management is responsible for funding and ordering reprints. Manuscripts intended for publication as an LIB must be reviewed and approved by the Science Advisor, Laboratory Director, and District Director before submission to ORS.
Results may be presented at scientific meetings as lectures or audio-visual sessions. Review and clearance of the presentations is in accordance with Agency and ORA policy. See section 6.6
If the intellectual property produced by authors has potential for patent application or licensing, the Laboratory Director should submit PHS Employee Invention Form (PHS-6364) with other supporting materials to CRADA for further evaluation. Any publication submission including LIB will be withheld pending the CRADA decision.
Some studies will become basis for new projects (e.g. new methods go on to validation studies) and be listed in the next call for proposals
After the study initiator has performed ruggedness testing or intra-laboratory collaboration to ensure that a method is likely to succeed in a full-scale study, a request, accompanied by the method and collaborative study protocol, is sent to ORS to select collaborators for the study. ORS will review the proposed study for suitability of the method and clarity of the directions as stated in the protocol. ORS issues the call for collaborators and informs the initiator of those who agree to participate. In an AOAC collaborative procedure, the initiator must obtain approval from local management before requesting Associate Referee status from the appropriate AOAC General Referee.
Assessment and Implementation
ORS, in conjunction the appropriate Center or headquarter offices, and with ORA laboratory management input, can determine how methods are to be implemented. Methods can be implemented through compliance programs, FERN tests, and assignments. New or improved methods, validated methods, adoption of new technology or rapid methods can be implemented field wide.