AOAC ERP Gluten Assays - Dec 2018
AOAC EXPERT REVIEW PANEL GLUTEN ASSAYS
THURSDAY, DECEMBER 6, 2018 ROCKVILLE, MARYLAND USA
AOAC INTERNATIONAL OFFICIAL METHODS OF ANALYSIS SM (OMA) PROGRAM
The Official Methods of Analysis SM (OMA) program is AOAC INTERNATIONAL's premier methods program. The program evaluates chemistry, microbiology, and molecular biology methods. It also evaluates traditional benchtop methods, instrumental methods, and proprietary, commercial, and/or alternative methods. In 2011, AOAC augmented the Official Methods SM program by including an approach to First Action Official Methods SM status that relies on gathering the experts to develop voluntary consensus standards, followed by collective expert judgment of methods using the adopted standards. All methods in the AOAC Official Methods SM program are now reviewed by Expert Review Panels for First Action AOAC Official Methods of Analysis SM status, continuance, repeal, and/or to recommend for AOAC Final Action Official Methods status. The OMA program has undergone a series of transitions in support of AOAC's collaborations, evolving technology, and evolving technical requirements. Methods approved in this program have undergone rigorous scientific and systematic scrutiny such that analytical results by methods in the Official Methods of Analysis of AOAC INTERNATIONAL are deemed to be highly credible and defensible. The methods are published in the Official Methods of Analysis of AOAC INTERNATIONAL and supporting manuscripts are published in the Journal of AOAC INTERNATIONAL . AOAC Official Methods SM program allows for submissions for all proprietary, single and sole source methods. Methods submitted through the PTM-OMA harmonized process also will be reviewed through the O fficial Methods of Analysis SM (OMA) program. Other complementary products and services include expanded consulting services for validation protocol development and AOAC INTERNATIONAL Organizational Affiliate Membership.
AOAC INTERNATIONAL 2275 Research Blvd, Suite 300 Rockville, Maryland 20850 Phone: (301) 924-7077
AOAC INTERNATIONAL ● 2275 RESEARCH BLVD, SUITE 300 ● ROCKVILLE, MARYLAND 20850 USA
EXPERT REVIEW PANEL (ERP) FOR GLUTEN ASSAYS EXPERT REVIEW PANEL CHAIR: TERRY KOERNER
THURSDAY, DECEMBER 6, 2018 1:00 PM EST - 5:00PM EST MEETING ROOM: AOAC INTERNATIONAL BOARDROOM
I.
WELCOME AND INTRODUCTIONS Expert Review Panel Co-Chairs
II. REVIEW OF AOAC VOLUNTEER POLICIES & EXPERT REVIEW PANEL PROCESS OVERVIEW AND GUIDELINES Deborah McKenzie, Senior Director, Standards Development, AOAC INTERNATIONAL
III.
REVIEW OF METHODS FOR AOAC FIRST ACTION OFFICAL METHODS STATUS For each method, the ERP members will present a review of the proposed collaborative study manuscript, after which the ERP will discuss the method and render a decision on the status for each method. 1) OMAMAN-47: Quantification of Wheat, Rye, and Barley Gluten in Oat and Oats Products by ELISA RIDASCREEN® Total Gluten Study Director: Patricia Meinhardt, R-Biopharm Inc, 870 Vossbrink Dr., Washington, MO, 63090 USA
IV. DISCUSS FINAL ACTION REQUIREMENTS FOR FIRST ACTION OFFICIAL METHODS (IF APPLICABLE )
ERP will discuss, review and track First Action methods for 2 years after adoption, review any additional information (i.e., additional collaborative study data, proficiency testing, and other feedback) and make recommendations to the Official Methods Board regarding Final Action status.
V.
DISCUSS UPCOMING MEETINGS AND VOLUNTEER ROLES
VI.
ADJOURNMENT
Page 1 of 1
Official Methods of Analysis SM (OMA) Expert Review Panel MEETING AND METHOD REVIEW GUIDANCE
The AOAC Research Institute administers AOAC INTERNATIONAL's premier methods program, the AOAC Official Methods of Analysis SM (OMA). The program evaluates chemistry, microbiology, and molecular biology methods. It also evaluates traditional benchtop methods, instrumental methods, and proprietary, commercial, and/or alternative methods and relies on gathering the experts to develop voluntary consensus standards, followed by collective expert judgment of methods using the adopted standards. The Official Methods of Analysis of AOAC INTERNATIONAL is deemed to be highly credible and defensible. All Expert Review Panel (ERP) members are vetted by the AOAC Official Methods Board (OMB) and serve at the pleasure of the President of AOAC INTERNATIONAL. In accordance to the AOAC Expert Review Panel Member and Chair Volunteer Role Description all Expert Review Panel members are expected to 1) serve with the highest integrity, 2) perform duties and method reviews, and 3) adhere to review timelines and deadlines.
To assist the ERP Chair and its members, please note the following in preparation for Expert Review Panel meetings and method reviews.
Pre-Meeting Requirements 1. Confirm availability and plan to be present to ensure a quorum of the ERP.
(Please refer to page 25, Quorum Guidelines, Expert Review Panel Information Packet ) 2. Ensure that your laptop, CPU or mobile device can access online web documentation. 3. Be prepared for the meeting by reviewing all relevant meeting materials and method documentation.
In-Person Meeting and Teleconference Conduct 1. Arrive on time.
2. Advise the Chair and ERP members of any potential Conflicts of Interest at the beginning of the meeting. 3. Participation is required from all members of the ERP. All members have been deemed experts in the specific subject matter areas. 4. The ERP Chair will moderate the meeting to ensure that decisions can be made in a timely manner. 5. Follow Robert’s Rules of Order for Motions. 6. Speak loud, clear, and concise so that all members may hear and understand your point of view. 7. Due to the openness of our meetings, it is imperative that all members communicate in a respectful manner and tone. 8. Refrain from disruptive behavior. Always allow one member to speak at a time. Please do not interrupt. 9. Please note that all methods reviewed and decisions made during the Expert Review Panel process are considered confidential and should not be discussed unless during an Expert Review Panel meeting to ensure transparency. Reviewing Methods Prior to the Expert Review Panel meeting, ERP members are required to conduct method reviews. All methods are reviewed under the following criteria, technical evaluation, general comments, editorial criteria, and recommendation status. These methods are being reviewed against their collaborative study protocols as provided in the supplemental documentation. Note: The method author(s) will be present during the Expert Review Panel session to answer any questions.
Page 1 of 2
Version 1 – OMA ERP Meeting Conduct
Official Methods of Analysis SM (OMA) Expert Review Panel MEETING AND METHOD REVIEW GUIDANCE
Reviewing Methods (Cont’d)
Reviewers shall conduct in-depth review of method and any supporting information. In-depth reviews are completed electronically via the method review form. The method review form must be completed and submitted by the deadline date as provided. All reviews will be discussed during the Expert Review Panel meeting. Any ERP member can make the motion to adopt or not to adopt the method. If the method is adopted for AOAC First Action status, Expert Review Panel members must track and present feedback on assigned First Action Official Methods . Recommend additional feedback or information for Final Action consideratio n. Here are some questions to consider during your review based on your scientific judgment: 1. Does the method sufficiently follow the collaborative study protocol? 2. Is the method scientifically sound and can be followed? 3. What are the strengths and weaknesses of the method? 4. How do the weaknesses weigh in your recommendation for the method? 5. Will the method serve the community that will use the method? 6. What additional information may be needed to further support the method? 7. Can this method be considered for AOAC First Action OMA status? Reaching Consensus during Expert Review Panel Meeting 1. Make your Motion. 2. Allow another member to Second the Motion. 3. The Chair will state the motion and offer the ERP an option to discuss the motion. 4. The Chair will call a vote once deliberations are complete. 5. Methods must be adopted by unanimous decision of ERP on first ballot, if not unanimous, negative votes must delineate scientific reasons. Negative voter(s) can be overridden by 2/3 of voting ERP members after due consideration. 6. All other motions will require 2/3 majority for vote to carry.
Page 2 of 2
Version 1 – OMA ERP Meeting Conduct
9/13/2018
AOAC Expert Review Panels An Orientation
Deborah McKenzie רב Sr. Dir., Standards Development AOAC INTERNATIONAL Staff Liaison ‐ Official Methods Board
1
9/13/2018
As a
,
AOAC INTERNATIONAL advances and ,
members, organizations, and experts dedicated to developing and validating and of
by
Analytical Excellence
AOAC Strategic Goals
Core Programs
2
9/13/2018
AOAC STRATEGIC PLAN
Accessible at AOAC homepage www.aoac.org
Analytical Excellence addresses emerging issues and influence standards development as a global leader in analytical excellence
Standards Development
Official Methods of Analysis SM (OMA) & Performance Tested Methods SM (PTM)
Laboratory Proficiency Testing & Quality Management
Analytical Excellence
Journal of AOAC INTERNATIONAL, OMA, ALACC Guide
3
9/13/2018
AOAC Method Approval Programs
Official Methods of Analysis SM (OMA) • AOAC’s premiere methods program • Approved methods – published in the Official Methods of Analysis of AOAC INTERNATIONAL (print and online) – Manuscripts published in the Journal of AOAC INTERNATIONAL – First Action and Final Action status
Performance Tested Methods SM (PTM) • AOAC’s method certification program • Certified methods – Commercial/proprietary rapid methods (test kits) – Certifications published on AOAC website – Manuscripts published in the Journal of AOAC INTERNATIONAL – Method developers licensed to use certification mark – Annual review & recertification
AOAC Official Methods SM Program
Submit Methods Responding to issued Call for Methods • Adoption of methods as Official Methods is contingent upon standards development activities • No application fee required to submit methods in response to Call for Methods Submit Individual & Sole Source Methods • Adoption of methods as Official Methods is contingent upon data supporting applicability and community based validation guidance information • Including proprietary/commercial methods and harmonized PTM – OMA methods • Application fee required
4
9/13/2018
Status of Official Methods of Analysis First Action, Final Action, Repeal
AOAC Policies & Procedures
Policy on Use of Association Name, Identifying Insignia, Letterhead, Business Cards
Policy on Volunteer Conflict of Interest
Policy on Antitrust
OMA Appendix G ‐ Use of AOAC Voluntary Consensus Standards to Evaluate Characteristics of a Method of Analysis
Expert Review Panel Policies and Procedures
5
9/13/2018
Road to First Action OMA Status
1. PTM – OMA Methods 2. Other Sole Source Methods 3. Response to Call for Methods
Method submitted
Expert Review Panels review all methods submitted methods
Notify Method author
Reject
ERP
Adopt
Published First Action OMA
Road to Final Action OMA Status
Method reproducibility must be demonstrated before Final Action consideration.
ERP determines if sufficient evidence merits a recommendation for Final Action status or repeal. • Only the OMB promotes a method to “Final Action” status or repeal the method. • Methods that did not meet the bar would be repealed. • Same for all method submissions
6
9/13/2018
PTM Overview for PTM‐OMA Harmonized Process • Administered by the Research Institute in 2003. • Well established and streamlined • Original approved by consensus with the OAs, OMB, RI Board of Directors and AOAC INTERNATIONAL Board of Directors. • ERP may be formed during Consulting Service. • Criterion for OMA: manufacturer’s method claims.
Recruiting Experts and Methods • AOAC issues – Call for Methods (Stakeholder affiliated methods) – Call for Experts • Sole Source/Individual Method Submissions – Individually completed Application not associated with an open Call for Methods
7
9/13/2018
Qualifications for ERP Membership Candidate must meet one of the following: • Demonstrated knowledge in the appropriate scientific disciplines. • Demonstrated knowledge regarding data relevant to adequate method performance.
• Demonstrated knowledge of practical application of analytical methods to bona fide diagnostic requirements.
Candidate application package includes: • Statement of Expertise • Current Abridged CV or Resume
ERP Member Vetting Process
Approved roster sent to AOAC President for volunteer appointment
Candidate submits application package
Reviewed by AOAC staff with recommendation to OMB
Reviewed by OMB and roster approved
• All members serve at the pleasure of the AOAC President • OMB assigns a representative to serve as a resource for every ERP
8
9/13/2018
Candidate Method Assignments A minimum of primary and secondary reviewers may be assigned to every method. In depth review via review form Prepare to attend and speak on the method and make a recommendation for ERP discussion and consideration. Review forms are completed and returned to AOAC staff in advance of the meeting. An email is sent with information on how to access the candidate methods and how to submit reviews
Members of both Committee on Safety and Committee on Statistics serve as advisory resources for all ERPs
Candidate Method Reviews
In your judgment, does the method sufficiently meet the Standard Method Performance Requirements (SMPR) or community‐based guidance?
In your judgment, is the method scientifically sound and can be followed? In your judgment, what are the strengths and weaknesses of the method? In your judgment, how do the weaknesses weigh in your recommendation for the method? In your judgment, will the method serve well the stakeholder community that will use the method? In your judgment, what additional information may be needed to further support the method meeting the SMPR or community‐based guidance? Members of both Committee on Safety and Committee on Statistics serve as advisory resources for all ERPs
9
9/13/2018
ERP Meetings ERPs can meet in person at a minimum of twice a year and up to four times per year*: AOAC Mid‐Year meeting (DC metro area) AOAC Annual Meeting. *2 additional designated times for proprietary method Organziational Affiliates At the ERP meeting: Reviews will be presented and the reviewers can make a motion to the ERP whether to adopt the method as First Action OMA. ERP discusses the method. ERP renders a decision on First Action status. ERP renders decisions on modifications to Official Methods . If the method is adopted ERP decides on what additional information is needed to recommend the method for Final Action status
ERP Teleconferences • Only after the initial in‐person ERP meeting for First Action consideration of methods • Possible for some method modifications • Possible for First Action to Final Action ERP recommendations
10
9/13/2018
ERP Meetings
Quorum
Presence of 7 vetted ERP members
Presence of 2/3 vetted ERP members
OR
WHICHEVER IS GREATER IF NO QUORUM, NO OFFICIAL MEETING
Method Review Overview
Method authors may be invited to make a presentation on their method REVIEWERS PRESENT THEIR REVIEWS AND MAY INITIATE A MOTION TO ADOPT THE METHOD IF THEY CHOOSE Chair recognizes each reviewer Reviews are presented.
If in favor, reviewers may make and second a motion to adopt adopt the method Chair can then entertain discussion on themethod Chair can call for a vote once deliberation is complete
11
9/13/2018
Consensus – First Action Adoption
First Action Official Methods status is granted:
Method must be adopted by unanimous decision of ERP on first ballot, if not unanimous, negative votes must be based on scientific reasons.
Negative voter(s) can be overridden by 2/3 of voting ERP members after due consideration.
Method becomes First Action on the date when ERP decision is made.
Consensus – First Action to Final Action
The ERP may then reach consensus on any additional information that it needs to review to be able to make a recommendation for Final Action Official Methods status.
This is a separate motion.
12
9/13/2018
ERP Meetings – Review for First Action METHOD AUTHOR: present any method and any resulting changes to the method since submission for review, summary of SLV and/or reproducibility evaluation, any recognitions (from AOAC or external) and, final draft of method proposed for decision
ERP CHAIR & MEMBERS: present reviews and discuss any resulting issues or questions on the method, review and agree upon final draft of method proposed for decision, and chair calls for ERP decision in accordance to procedures.
CONSENSUS: Method must be adopted by unanimous decision of ERP on first ballot. If not unanimous, negative votes must delineate scientific reasons. Negative voter(s) can be overridden by 2/3 of non‐ negative voting ERP members after due consideration. Abstentions do not count towards vote; in case of multiple abstentions the results will need to be evaluated. Staff will monitor and record consensus voting.
STAFF: Will organize and coordinate meeting, record ERP actions and decisions, draft ERP report and distribute after chair approval, work with chair and OMB liaison to complete checklist and assemble recommendation package for OMB.
ERP Methods Review & Approval
Methods should be scientifically sound with demonstrating that it will meet the needs of those using the method (evidenced by meeting the standard, or other acceptance criteria)
ERPs have approved methods with evidence of high potential to First Action and request additional work or support be submitted for review prior to ERP convening to recommend an action to OMB
OMB requires a justification or rationale for methods that are deemed acceptable and adopted but may not fully meet the standard set or acceptance criteria.
13
9/13/2018
OMB Expectations for First Action
Safety review needed prior to First Action status
SLV type of supporting information available per the SMPR
• Applicability, Method Performance Requirements Table, System Suitability, Reference Materials, and Validation Guidance
• Documented method performance versus a SMPR • Document reasons for acceptability if method does not meet the SMPR
Comparison to SMPR
Any approved method(s) along with supporting manuscript(s) and documentation sent to AOAC Publications after the meeting.
Method incorporating ERP revisions (preferably in AOAC Format) Method Manuscript incorporating specified ERP revisions (in AOAC Format) Signed AOAC Copyright Authorization form
NO OMA NUMBER ASSIGNED UNTIL ALL DOCUMENTATION SUBMITTED
Publication of First Action Methods
Method and method manuscript prepared for publication in the Official Methods of Analysis of AOAC INTERNATIONAL and in Journal of AOAC INTERNATIONAL Updates on methods approved or status changes are published in the Inside Laboratory Management magazine and on the AOAC website
14
9/13/2018
ERP Meetings – Method Tracking METHOD AUTHOR: present any method feedback obtained and any resulting changes to the method, any reproducibility information, any implemented ERP recommendations, final draft of method proposed for decision ERP MEMBERS: present any method feedback obtained and
discuss any resulting changes to the method, any reproducibility information, any implemented ERP recommendations, review and agree upon final draft of method proposed for decision, and make a recommendation to OMB. CONSENSUS: 2/3 vote in favor of a motion. Abstentions do not count towards vote; in case of multiple abstentions. Staff will monitor and record consensus voting.
STAFF: Will organize and coordinate meeting, record ERP actions and decisions, draft ERP report and distribute after chair approval, work with chair and OMB liaison to complete checklist and assemble recommendation package for OMB.
Documentation Needed
Method Safety Evaluation
Reference Materials
Evidence of Single Laboratory Validation or equivalent
Evidence of Reproducibility Assessment
Published First Action OMA
Method Performance versus SMPR or acceptance criteria
Final draft of First Action OMA to be considered for status update
Rationale or Justification for Repeal or Continuance of First Action OMA
15
9/13/2018
OMB Meeting for Review of ERP Recommendations
OMB Review (renders decision on recommendation)
ERP Chair/or designee (addresses questions/comment)
OMB Liaison (presents recommendation)
Modifications to Official Methods • Types of Modifications – Editorial
– Major – Minor
• Applicable to First Action and Final Action OMA
• Relevant to all ERPs
16
9/13/2018
Editorial Modifications • The applicant must submit a written explanation of the change(s) including a statement that the modification does not alter the validated performance of the method.
• Examples include: Typos or editorial corrections or clarifications that strengthen instruction.
• Methods that have undergone an editorial modification will retain the same number.
Editorial Changes
• Editorial changes to methods only require AOAC staff review and the change is made to the OMA with changes noted in next printed edition of OMA. • A list of the methods with editorial modifications will be published in Inside Laboratory Management and on the Website.
17
9/13/2018
Minor Modifications • Results in no changes to the current validated performance. There is no significant effect to the results. The method will retain the original number. • Supporting data to justify the proposed modification must be submitted. Equivalency data is required unless adequate Justification to exclude this data is provided. • Examples include: Reagent change, a change in a column or consumables that do not impact the validated method performance.
Major Modifications • Results in a change to the current validated performance of the method. • This level of modification will result in a new method as part of AOAC standards development and will receive a new method number. • Examples include: significant change to the technology, sample preparation, or chemistry.
18
9/13/2018
Minor & Major Modifications
Based on AOAC staff review, a public comment period for the proposed modification is required.
Applicant Options
• Following the comment period, any comments are reconciled and recommends a response to the applicant. • The applicant can decide to proceed based on the reconciled comments
19
9/13/2018
Pathways for Minor & Major Modification • If applicant decides to
proceed, an ERP is formed – Level of modification determined by ERP
– Applies to
modifications of First Action and Final Action methods
Documentation and Communication • AOAC carefully documents the actions of Stakeholder Panel, Working Groups, and Expert Review Panels • AOAC will prepare summaries of the meetings – Communicate summaries to the stakeholders – Publish summaries in the Referee section of AOAC’s Inside Laboratory Management • AOAC publishes its voluntary consensus standards and Official Methods – Official Methods of Analysis of AOAC INTERNATIONAL – Journal of AOAC INTERNATIONAL • AOAC publishes the status of standards and methods in the Referee section of AOAC’s Inside Laboratory Management
20
9/13/2018
Requirements for ERP Service
Must have demonstrated expertise in the method, technology, analyte/matrix, etc… Be a subject matter expert. Must be able to attend ERP meetings Must be able to complete assigned reviews on time Must be prepared to speak on the method and share reviews during the meeting Must be proactive in tracking assigned First Action Official Methods Must be able to assist in peer reviewing paper for publication Must sign and submit AOAC Volunteer Acceptance Form
General Expectations for ERPs • You can expect to have a minimum of three weeks to review methods prior to ERP meeting. – You are requested to submit written reviews by specified deadline. Please alert staff if you are not able to complete on time. – You may have individually assigned methods to review or all of the methods to review. Please be prepared to discuss these methods during meeting. – You may use the OMA appendices as guidance for types of validation work that can be expected. If additional information is needed, please ask staff. • ERP Meeting Quorum – If there is no quorum, there is no official meeting. Please alert staff as early as possible if you are not able to attend a meeting. • ERP Consensus – ERP consensus may not reflect your own personal view – There may be times when a method may not meet all of the criteria exactly; however, the ERP can adopt the method.
21
9/13/2018
Ethical Expectations of AOAC Expert Review Panel Members • Respect for your peer ERP members and chair – Each member has been vetted for expertise relevant to the review of the method(s) in the ERP • Be considerate of each others perspectives and points of view • Be considerate of the ERP’s consensus even if you disagree – Inform staff as early as possible if you cannot attend the scheduled ERP meeting • Be considerate in that your absence can impact the quorum of the ERP and its ability to have an official meeting to make decisions – Notify staff and/or disclose in the ERP meeting if you have a direct or perceived conflict of interest for a specific method • Please review AOAC’s policy on Volunteer Conflict of Interest Ethical Expectations of Expert Review Panel Members (con’t) • Respect for Method Authors and Intellectual Property – Each Method Author is encouraged to attend the ERP meeting – Each candidate methods (not yet adopted or published as Official Methods of Analysis of AOAC INTERNATIONAL ) are still the intellectual property of the method author. Therefore, the information is shared only with the vetted ERP members and is available during the meetings. Please do not distribute the information without expressed written permission from an appropriate AOAC staff liaison. – Be clear about and justify how additional recommended work is a requirement for First Action, a requirement for Final Action consideration, or something recommended, but not necessary. – Keep your focus on the science
22
9/13/2018
ERP Chair Responsibilities
Before Meeting
During Meeting
Moderate discussions based on agenda
Work with staff on meeting coordination
Engage staff to encourage members to reach decision points
Review submitted and/or assigned methods
Engage staff on procedural questions
Review method reviews if applicable
Engage discussion on feedback mechanism
Review SMPR(s) and/or relevant guidance and criteria
ERP Chair Responsibilities
Other Efforts and Recognitions Can nominate methods for OMB Award
After Meeting Review Meeting Report and Approve Final Version
Can nominate ERP members for OMB Award
Assist with any follow up on methods
Can assist in identifying methods for review
Assist in Publication Reviews
Can serve as a guest editor for the Journal
23
9/13/2018
Roles and Responsibilities
AOAC Official Methods Board Vet and approve stakeholder panel chair & voting members Vet and approve ERP membership and AOAC Experts Render decisions on status of First Action methods (Final Action, repeal, etc…) Assign a liaison to each stakeholder panel and ERP Coordinate OMB Awards AOAC Expert Review Panels Review methods and meet in person to render decisions on methods for First Action Official Methods SM status. Track First Action Official Methods SM and modify, if necessary Recommend First Action methods after 2 years or less to OMB for Final Action, continuance, or Repeal Participate in Consulting Service and PTM reviews for OMA and harmonized PTM and harmonized OMA method studies AOAC Experts Review and approve PTM validationtesting protocol documentation Peer review of PTM validation manuscript and supporting documentation AOAC Research Institute ‐ PTM Expert Reviewers Peer Review of PTM validationmanuscripts and supporting documentation
AOAC Research Institute Independent Laboratories Conduct independent evaluation of candidate method using AOAC approved testing protocols AOAC Stakeholder Panels Develop voluntary consensus standards Assign working groups to draft standards method performance requirements Voting members demonstrate consensus on behalf of stakeholders AOAC Staff Coordinate method reviews and method approval activities Coordinate OMB meetings Provide trainings and orientations Maintain website and communication Document and publish actions and decisions Coordinate standards development activities Publish standards and methods AOAC Research Institute Technical Consultants Draft validation protocols in Consulting Service for assigned methods
Facilitate PTM evaluation of assigned candidate methods Facilitate comments/responses for assigned OMA reviews
Questions?
Thank you
24
AOAC SMPR® 2017.021 (Revised 8-2018)
Reproducibility (ISO 5725-1). —Variation arising when identical test materials are analyzed in different laboratories by different operators on different instruments. The standard deviation or relative standard deviation calculated from among-laboratory data. Expressed as the reproducibility standard deviation (SD R ); or % reproducibility relative standard deviation (%RSD R ). 5 Method Performance Requirements See Table 1. 6 System Suitability See information on antibodies, cross reactivity, and calibrators in Appendix M. 7 Reference Material(s) Samples of oat flour spiked with wheat, rye, and barley for validation studies are available from USP. Refer to Annex F: Development and Use of In-House Reference Materials in Appendix F : Guidelines for Standard Method Performance Requirements , Official Methods of Analysis of AOAC INTERNATIONAL (2016) 20th Ed., AOAC INTERNATIONAL, Rockville, MD, USA (http:// www.eoma.aoac.org/app_f.pdf) 8 Validation Guidance For all candidate methods, developers must: ( 1 ) Provide antibody information, cross reactivity data, and information on calibrators according to Appendix M ( 2 ) Wherever possible, identify peptide sequences or target epitopes for all antibodies used ( 3 ) Determine and submit estimates for recovery for each gluten source (wheat, rye, and barley) using the oat flour testing materials ( see Reference Material(s) section for source information) For all claimed matrices, developers must submit: ( 1 ) A sample processing procedure for homogenization, particle size reduction, and test portion size ( 2 ) Data and estimates for LOD and LOQ ( 3 ) Precision estimates (RSD r and/or RSD R ) Method developers may use spiked samples to determine the recovery performance of candidate methods for specific claimed matrices. Guidance on spiking for recovery evaluation are provided at: ( 1 ) Koerner et al. (2013) J. AOAC Int . 96 , 1033–1040. doi. org/10.5740/jaoacint.13-043 ( see section on Spiking Methods ) ( 2 ) Estimating Recovery of a Gluten ELISA Kit Method ( see supporting information following this SMPR) ( 3 ) Spiking Materials for Barley and Rye ( see supporting information following this SMPR) ( 4 ) Appendix D: Guidelines for Collaborative Study Procedures to Validate Characteristics of a Method of Analysis , Official Methods of Analysis of AOAC INTERNATIONAL (2016) 20th Ed., AOAC INTERNATIONAL, Rockville, MD, USA (http://www. eoma.aoac.org/app_d.pdf) ( 5 ) Appendix F: Guidelines for Standard Method Performance Requirements , Official Methods of Analysis of AOAC INTERNATIONAL (2016) 20th Ed., AOAC INTERNATIONAL, Rockville, MD, USA (http://www.eoma.aoac.org/app_f.pdf) Approved by the International Stakeholder Panel on Alternative Methods (ISPAM) on September 24, 2017. Final Version Date: November 1, 2017. Revision Date: August 26, 2018.
Standard Method Performance Requirements (SMPRs®) for Quantitation of Wheat, Rye, and Barley Gluten in Oats
Intended Use: Quantitation of Gluten in the Context of Food Manufacturing 1 Purpose AOAC Standard Method Performance Requirements (SMPRs) describe the minimum recommended performance characteristics to be used during the evaluation of a method. The evaluation may be an on-site verification, a single-laboratory validation, or a multi-site laboratory collaborative study. SMPRs are written and adopted by AOAC stakeholder panels composed of representatives from industry, regulatory organizations, contract laboratories, test kit manufacturers, and academic institutions. AOAC SMPRs are used by AOAC expert review panels (ERPs) in their evaluation of validation study data for a method(s) being considered to determine if it meets the requirements for Performance Tested Methods SM or AOAC Official Methods of Analysis SM , and can be used as acceptance criteria for verification at user laboratories. 2 Applicability Quantitation of total wheat, rye, and barley gluten in groats, rolled oats, steel cut oats, oat flour, oat bran, and extruded/cooked/ finished oat products. 3 Analytical Technique Enzyme-linked immunosorbent assay (ELISA) or related binding-based technologies. 4 Definitions Enzyme-linked immunosorbent assay (ELISA) .—For the purposes of this document, ELISA is defined as “an analytical procedure characterized by the recognition and binding of specific antigens by antibodies” [Appendix M: Validation Procedures for Quantitative Food Allergen ELISA Methods: Community Guidance and Best Practices , Official Methods of Analysis of AOAC INTERNATIONAL (2016) 20th Ed., AOAC INTERNATIONAL, Rockville, MD, USA, http://www.eoma.aoac.org/app_m.pdf; J. AOAC Int . 93 , 442–450(2010)]. This definition is not meant to be restrictive and encompasses other related binding-based technologies. Gluten .—Protein fraction from wheat, rye, barley, or their crossbred varieties and derivatives thereof, to which some persons are intolerant and that is insoluble in water and 0.5 M NaCl. Limit of detection (LOD; Appendix M) .—Lowest concentration or mass of analyte in a test sample that can be distinguished from a true blank sample at a specified probability level. Limit of quantitation (LOQ; AppendixM). —Lowest level of analyte in a test sample that can be quantified at a specified level of precision. Recovery .—The fraction or percentage of analyte that is recovered when the test sample is analyzed using the entire method. Repeatability (ISO 5725-1) .—Variation arising when all efforts are made to keep conditions constant by using the same instrument and operator (in the same laboratory) and repeating during a short time period. Expressed as the repeatability standard deviation (SD r ); or % repeatability relative standard deviation (%RSD r ).
© 2018 AOAC INTERNATIONAL
Table 1. Method performance requirements Parameter
Acceptance criteria
Analytical range, ppm
≤5 to ≥15
LOQ, ppm LOD, ppm
≤5 ≤5
Recovery, % a 50 to 200 b a For validation purposes, individually measured as gluten from wheat, rye, and barley spiked individually in the prepared oat flour test samples, calculated from the slope of the dose response curve. A sample series shall consist of one sample of unspiked oat flour; two samples spiked with wheat; two samples spiked with rye; and two samples spiked with barley. Gluten content for wheat, rye, and barley used for spiking will be estimated as follows: See Estimating Recovery of a Gluten ELISA Kit Method for details on procedures for spiking the flour samples ( see supporting information following this SMPR). Sample providers shall develop an SOP for producing, storing, and shipping the materials. b Criteria for recovery are larger than traditionally used for SMPRs. First, method results for gluten in oats are highly variable due to sample inhomogeneity. This lack of homogeneity may result in a wider range of recovery estimates than would normally be expected at ppm levels. Second, the different relative specificities of the antibodies against wheat, rye, and barley make balancing the response difficult. [ Note : The AOAC Working Group on Gluten determined not to set standards for repeatability (RSD r ) or reproducibility (RSD R ) because of the inhomogeneity issue discussed above about the recovery range. Method developers are directed to determine RSD r using standard oat flour samples.] Wheat: Gluten = (Dumas nitrogen content) x 5.68 x 0.80 Rye: Gluten = (Dumas nitrogen content) x 5.68 x 0.60 Barley: Gluten = (Dumas nitrogen content) x 5.68 x 0.60
© 2018 AOAC INTERNATIONAL
AOAC Official Method ####.##
Quantification of Wheat, Rye, and Barley Gluten in Oat and Oats Products
by ELISA RIDASCREEN® Total Gluten: Collaborative Study, First Action ####.##
Authors: Markus Lacorn a , Thomas Weiss a , Paul Wehling b , Mark Arlinghaus b and Katharina Scherf c a R-Biopharm AG, An der neuen Bergstraße 17, 64297 Darmstadt, Germany Phone: +49 6151 8102 464; Fax: ext-40; Email: m.lacorn@r-biopharm.de b Medallion Labs, 9000 Plymouth Avenue North, Minneapolis, MN 55427; USA c Leibniz-Institute for Food Systems Biology at the Technical University of Munich, Lise-Meitner Str. 34,
85354 Freising, Germany
Abstract:
Since its introduction to the analytical community, the R5 method to quantify gluten led to a strong
improvement of the situation for the food industry and celiac patients. During the last years some questions
arose on the use of the Codex Alimentarius factor of 2 to convert from prolamins to gluten, an
overestimation of rye and barley, inadequate detection of glutelins, and the inhomogeneous distribution of
gluten in oats. These limitations of the R5 method, especially when measuring oat samples led to AOAC
Standard Method Performance Requirement (SMPR®) 2017.021, which was approved by stakeholders in
2017. Here we present a collaborative study of a method for the quantitative analysis of wheat, rye, and
barley gluten in oat and oat products, using a sandwich ELISA that is based on four different monoclonal
antibodies including the R5 mAb. The sandwich ELISA detects intact gliadins and related prolamins from rye
and barley, high-molecular weight (HWM) glutenin-subunits (GS) from wheat, HMW-secalins from rye and
low-molecular-weight (LMW)–GS from wheat. It does not detect D-hordeins from barley. Samples are
extracted by Cocktail solution/80% ethanol and analyzed within 50 minutes. The measurement range is
between 5 mg/kg gluten and 80 mg/kg gluten using a calibrator made out of a gluten extract from four
different wheat cultivars. The results of the collaborative test with 19 participating laboratories showed
recoveries ranging from 99 to 137 % for all three grain sources. Relative reproducibility standard deviations
for samples >10 mg/kg ranged from 10 to 53 %. The collaborative study results confirmed that the method is
accurate and suitable to measure gluten from all three grain sources, and has demonstrated performance on
oat matrices which meets the criteria as specified in SMPR® 2017.021.
Page 1 of 24
Introduction:
With a prevalence of 0.4 to 1.2% of the population in Europe, North America, Australia, and the Middle
East (1), celiac disease (CD) is considered to be one of the most common food hypersensitivities. CD is
an immune-mediated inflammatory disease of the upper small intestine in genetically predisposed
individuals triggered by the ingestion of dietary gluten (2). In the context of CD, gluten is defined as a
protein fraction from wheat, rye, barley, or their crossbred varieties and derivatives thereof, to which
some persons are intolerant and that is insoluble in water and 0.5 mol/L NaCl (3). Gluten is composed of
prolamins that can be extracted by 40-70% of ethanol, and alcohol-insoluble glutelins that can only be
extracted under reducing and disaggregating conditions at elevated temperatures. The prolamins from
wheat, rye, and barley are called gliadins, secalins, and hordeins, respectively, and the prolamin content
of gluten is generally taken as 50% (3). The only known effective treatment for CD is a lifelong gluten-
free diet, which is based on the avoidance of gluten-containing cereals and should contain less than 20
mg gluten per day to prevent a relapse of intestinal damage (4). To guarantee the safety of gluten-free
products for CD patients, a threshold of 20 mg/kg gluten for gluten-free foods is recommended by the
Codex Alimentarius and legislation e.g., in the United States by the Department of Health and Human
Services - Food and Drug Administration (5) and in Europe by the European Commission (6). Specific and
sensitive analytical methods are therefore needed for food quality control. Immunochemical methods
are currently recommended for the quantitative and qualitative determination of gluten in foods (3).
Sandwich and competitive ELISA formats (RIDASCREEN® Gliadin R-Biopharm R7001 and RIDASCREEN®
Gliadin competitive R-Biopharm R7021) based on the R5 monoclonal antibody (7) were successfully
validated as AACCI Approved Method 38-50.01 for intact gluten (8) and 38-55.01 for partially hydrolyzed
gluten (9), respectively. Additionally, the R5 Sandwich ELISA RIDASCREEN® Gliadin was endorsed as a
Codex Alimentarius Type I method for the analysis of gluten (10) and has been adopted by AOAC
International as Official Method™ of Analysis 2012.01 Final Action in 2016 (11). The competitive ELISA
RIDASCREEN® Gliadin competitive (R-Biopharm, R7021) has been adopted by the AOAC International as
Official Method™ of Analysis 2015.05 (12). The R5 based Lateral Flow Device RIDA®QUICK Gliadin (R-
Biopharm, R7003) has been adopted as AOAC International Official Method™ of Analysis Final Action
2015.16 for analysis of foods (13) and as AOAC International Performance Tested Method™ 101702 for
surfaces and cleansing waters (14).
Page 2 of 24
The R5 antibody raised against ω-secalins primarily recognizes the epitope QQPFP, which is present in
gliadins, secalins, and hordeins and occurs in many peptides that are toxic or immunogenic for CD
patients (15-17).
Since its introduction, the R5 method has led to a strong improvement of the situation for CD patients.
The advantages of the method are that its response is well-characterized and well-understood. There is
a deep understanding of the method performance thanks to the comprehensive initial validation and
therefore, limitations of the R5 system are well known. Additionally, with a limit of quantification of 5
mg/kg gluten, the method is sensitive enough to reliably control and regulate gluten-free products.
However, every analytical method has limitations. For the R5 methods these limitations are the
following: [ 1] factor of 2 to convert from prolamins to gluten, which is not accurate in many cases (18),
[2] overestimation of rye and barley, and [3] inadequate detection of glutelins, which are not detected
by the R5 or any other antibody used in commercial kits, except the Skerritt monoclonal antibody (19).
All these limitations led to increased security for CD patients since analytical results tended to be biased
higher than true contamination levels (limitations 1 and 2). Limitation 3, the non-detectability of
glutelins is only important if a food product shows enriched proportions of glutelins to prolamins as e.g.
in wheat starch (20, 21). One additional limitation for all methods that measure gluten that was raised in
the past years was high observed repeatability standard deviations in some oat samples, which has been
attributed to inhomogeneous distribution of gluten in oats. This may lead to an unsecure situation for
CD patients if a laboratory is not able to manage this inhomogeneity by increasing the test portion and
the number of replicates for extraction. Sample inhomogeneity is a sample-intrinsic problem and not a
shortcoming of analytical systems. Nevertheless, it is an issue that needs to be addressed by all
analytical systems quantifying gluten in oats.
Because of these limitations to the R5 method, a group of oat processors and test kit manufacturers
founded an initiative through AOAC International in 2016. The resulting Standard Method Performance
Requirement (SMPR®) 2017.021 was adopted by stakeholders in 2017 (22). The method acceptance
criteria given in the SMPR are that mean recoveries for gluten from wheat, rye, and barley in oats and
oat products must be between 50% and 200%. Another important requirement in the SMPR is the
availability of “reference materials” with wheat or rye or barley gluten concentrations of 10 or 20 mg/kg
in oats including a blank material. These reference materials can be used to make test kits traceable to
the gluten content of these materials and therefore allow for more precise comparison of methods in
the future.
Page 3 of 24
The new sandwich ELISA RIDASCREEN® Total Gluten (R-Biopharm, R7041) presented here employs a
combination of four monoclonal antibodies including the R5 to detect the majority of gluten fractions
from wheat, rye, and barley including glutelins. It is calibrated to a wheat gluten preparation in the
range of 5 mg/kg up to 80 mg/kg. In consequence, no conversion factor of 2 is needed to convert from
prolamin to gluten. For extraction, the test portion was increased to 1 g compared to 0.25 g for OMA
2012.01 to account for inhomogeneity of gluten in oats. The test portion may be increased even more if
needed. When increasing test portion mass, the amount of Cocktail (patented) (R-Biopharm R7006 and
R7016) and ethanol must be increased proportionately. For this new method, Cocktail (patented) and
80% ethanol are incubated simultaneously and not consecutively as for former methods. The recovery
of the reference materials introduced by SMPR 2017.021 was found to be within the acceptance criteria
prescribed in the SMPR. A collaborative test using oats and oat products was performed in September
2018 with 19 participants worldwide (Australia, Austria, Canada, Finland, Germany, Hungary, Ireland,
Italy, Sweden, USA, and United Kingdom). The study was coordinated by Katharina Scherf (Leibniz-
Institute for Food Systems Biology at the Technical University of Munich).
Scope of the method: RIDASCREEN ® Total Gluten is used for the quantitative analysis of wheat, rye, and barley gluten in oat
flour, groats, oat flakes, and oat cereals which are declared as “gluten-free”. The sandwich ELISA detects
intact gliadins and related prolamins from rye and barley, high-molecular weight (HMW) glutenin-
subunits (GS) from wheat, HMW-secalins from rye and low-molecular-weight (LMW)–GS from wheat. It
does not detect D-hordeins from barley. Samples are extracted by Cocktail (patented) solution/80%
ethanol and analyzed within 50 minutes. The measurement range is between 5 mg/kg gluten and 80
mg/kg gluten using a calibrator made out of a gluten extract from a mixture of four wheat cultivars.
Collaborative Study
Study Design
Following the AOAC guidelines which are published as Appendix D (23) and Appendix M (24), an international collaborative study was set up to validate the RIDASCREEN ® Total Gluten for quantitative
gluten measurement in oat and oat-based foods as an Official Method of Analysis of AOAC International
(OMA). It was coordinated by Katharina Scherf (Leibniz-Institute for Food Systems Biology at the
Technical University of Munich). Before the participants were allowed to analyze the collaborative test
samples, they needed to show analytical competency by analyzing three control samples and the buffer
Page 4 of 24
Made with FlippingBook - Online catalogs