Standardization of Non-Targeted Methods for Food...

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Standardization of Non-Targeted Methods for Food Fraud Detection

Jeffrey Moore, Ph.D. Senior Director – Scientific Strategy & Planning US Pharmacopeia [email protected]

Understanding Food Fraud Globally, Quebec City, April 5, 2017

mailto:[email protected]


USP’s Beginnings

USP was founded in 1820 by 11 physicians, in Washington, D.C.


A global resource for food integrity and safety solutions including science-based standards, tools, and services to improve confidence in

the global food supply chain.

USP’s Food Program

Food Fraud Mitigation Guidance

www.foodfraud.org Training & Advising


Role of testing in food fraud mitigation

What are non-targeted methods and why are they (and why are they not) they being used?

Overview of draft USP guidance on non-targeted methods

Outline


5

Food Fraud Mitigation Approach For Ingredients

Prioritization

Controls

Data

Testing

Horizon Scanning

Other Factors

How to use data to make prioritization decisions

Supply Chain

History


The Challenge of Testing for Food Fraud

Criminal “designs” adulterant to evade existing QA system QA system reacts

by developing new tests


Instead of looking for what should not be there…

Define very carefully the characteristics of

what should be there

Exclude anything that deviates significantly

from those characteristics

A Way to Get Ahead of Fraud Perpetrators


Non-Targeted Methods?


Output U

9

Sample (U)

Reference Set (S1 to Sn)

Analytical Procedure Similarity

Assessment Procedure Output S1

Output S2 Output S3…Sn

Significance Level (α)

Is U Typical or Atypical with respect to Sn?

Typical

Atypical

Example Analytical Procedures

Spectral Chemical Wet-chemical

Example Similarity Assessment Procedures

Multivariate model (e.g. SIMCA)

Univariate model (e.g. CI, HQI)

Subjective criteria (e.g. “principle spots”)

Example Output types

Spectra

Quantitative measurements

Chromatograms

Images, e.g. micro-photographs

Hyperspectral images

5.39%

Essential Elements of a Non-Targeted Method


Slide courtesy of Steve Holroyd, Fonterra

Example of NT Adulterants Detection: Liquid Milk by FTIR (Fonterra)


Charge to Expert Panel:

To develop and validate a “tool-box” of methods and specifications for skim milk powder that will help protect against economically adulterated materials, including the next melamine

USP Expert Panel on NT Methods


USP Expert Panel on NT Methods


nanometers

Rapid detection on melamine in Skim Milk Powder (SMP) by NIR

Study That Sparked USP’s Interest

0.012 to 0.39% dry-blended melamine in SMP

Non-adulterated SMP

0.033 to 0.39% Wet-blended melamine in SMP


Calibration Reference Set 0% Melamine

0.03% WB Melamine 0.09 % WB Melamine 0.30 % WB Melamine 0.33 % WB Melamine 0.39 % WB Melamine

5 10 15 20 25 30

0.4

0.6

0.8

1

1.2

1.4

1.6

1.8

2 x 10 -4

Hotelling T2 (60.95%)

Q R

esid

uals

(39.

05%

)

SIMCA Model

Wet-Blended Melamine Detectable in NT Model (CFSAN-FDA)


Take-Aways from Study

Non-targeted methods beneficial even when you know what adulterant you are looking for

RM’s for “genuinely fake” adulterated foods needed to provide confidence in rapid test methods


Instrumentation and chemometrics advances -> to non-targeted methods.

Used in routine testing as screening methods, followed by more targeted confirmatory methods for “abnormal” samples

Continued significant investments by major food companies, Testing Labs, and European funded R&I projects

Horizon 2020

Market Trends


17

Year

Cou

nt

Pubmed hits for “untargeted OR non-targeted OR nontargeted”

November 16 2016

Advances in, and maturation of, analytical technologies and data processing allowing rapid broad spectrum analysis

Scientific Trends


Many companies already have the infrastructure, but may not know how to implement this novel approach.

Lack of solid information about the generation and application of NT methods, and very little support.

Lack of standardization Terminology: What does “non-targeted” mean, how to validate?

In use, but inconsistent development

Organizational risk tolerance is not always taken into account when developing non-targeted methods

Representativeness of reference / calibration model

Challenges to Implement NT Methods


Name: USP “Guidance On Developing and Validating Non-Targeted Methods For Adulteration Detection”

Aim: Adaptable “framework” for develop. & valid., encourage use of NT methods, reduce confusion

Elaboration: 10 experts since early 2015

Stage: Public comment period closed end March; Anticipated final publication in September

Where to find: http://www.usp.org/guidance-developing-and-validating-non-targeted-methods-adulteration-detection

19

Draft USP Guidance on NT Methods

Send comments to: Dr. Kenny Xie, [email protected]

http://www.usp.org/guidance-developing-and-validating-non-targeted-methods-adulteration-detection




Non-Targeted Method = Method that determines the similarity of a sample (U) to a reference standard or set (Sn) with a binary output – Typical or Atypical compared to Sn Sensitivity = Ability to correctly recognize unacceptable samples/material as Atypical Specificity = Ability to correctly recognize acceptable samples/material as Typical

Definitions


Applicability statement

Method development using reference set

Application of test set to method

Method performance evaluation

Interpret results, monitor and maintain method

Logic flow of USP’s NT Guide


Applicability statement: NT NMR screening method for detecting economically motivating levels of any adulterants (e.g. melamine at 0.1%) in milk powder with sensitivity of 95%, selectivity of 95% at 95% confidence level

Method development: using reference set of 53 commercial milk powders • DMSO-d6 extraction • 600 Mhz NMR • No pre-processing • Conformity index analysis • Boundary drawn at CI =

6.15

Example: NMR screening method


Application to test set: • 16 independent milk powders • 61 adulterant spiked samples


Adulterant Estimated LOD

Melamine <0.005%

Urea <0.05%

DCD 0.05-0.5%

Maltodextrin 0.05-0.5%

Soy protein ND

Specificity = 100%


Applicability statement: NT NMR screening method for detecting economically motivating levels of any small molecule adulterants (e.g. melamine at 0.1%) in milk powder with sensitivity of 95%, selectivity of 95% at 95% confidence level



Method performance evaluation: In-progress



Many analytical techniques lend themselves to non-targeted testing

They can be rapid, inexpensive, and powerful tools for mitigating risks in food ingredient supply chains, even for known adulterants (e.g. wet-blended melamine).

Combined with targeted methods they can be more effective than either individually.

USP is helping to address the standardization gap, seeking public comments on its proposed Guidance for Non-Targeted Methods.

Conclusions on Non-Targeted Methods


USP Expert Panel on Non-Targeted Methods for Milk Ingredients

Kenny Xie (USP)

Steve Holroyd (chair, sub-team on NT guidance)

Anthony Hanlon

Carmen Diaz-Amigo

Acknowledgements

Standardization of Non-Targeted Methods for Food...

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