1. FDA/ORA/ORS and FERN Update
Ruiqing Pamboukian, Ph.D.
Office of Regulatory Affairs/Office of Regulatory Science
U.S. Food and Drug Administration
AAFCO Mid-Year Meeting
San Antonio, Texas
January , 2015

2. ORA Organizational Chart

3. Office of Operations Office of Operations
Office of Enforcement and Import Operations
Office of Food and Feed Operations
Office of Medical Products and Tobacco Operations
Office of Regulatory Science
Food and Feed Scientific Staff
Medical Products and tobacco Scientific Staff
Laboratory Operations and Support Staff
ORA Regions
Northeast Region
Southeast Region
Central Region
Southwest Region
Pacific Region

4. Office of Regulatory Science (ORS) organizational chart
ORS Director Brian Baker (acting)
Food and Feed Scientific Staff
Director: Michael McLaughlin
Medical Products and Tobacco Staff
Director: George Salem
Laboratory Operations and Support Staff
Director: LCDR Jean Paul
Deputy Director of Food and Feed
Tim McGrath
Deputy Director of Medical Products and Tobacco
Selen Stromgren

5. ORS Website http://inside. fda

6. Winchester, MA Radionuclides
ORA Laboratory Locations MA NY OH MI GA PA AR KS CO CA WA PR
FCC
Cincinnati, OH
Forensic Chemistry
WEAC
Winchester, MA Radionuclides
WEAC performs analyses in support of the Medical Device Program Area and radionuclide chemical as well as microbiological analyses for the Food Program Area.
ORA Regulatory Lab
ORA Regulatory/Specialty Lab

7. Local Structure of an ORA Laboratory
Regional Food and Drug Director (RFDD)
ORA Science Executive at Office of Reg Science
Current line of
command
Future line of command
Lab Director
Quality System
Manager
Chemistry Branch
Director
Microbiology
Branch Director
Drug Chemistry
Supervisor
Food Chemistry
Supervisor
Analysts
Lab Technicians
Micro
Supervisor
Sensory/Filth
Supervisor*
Support Staff:
Admin
Industrial Hygienist
Sample Custodian
Analysts
Lab Technicians
*Sensory/Filth groups
may also appear under
Chemistry Branch in
some labs’ organization.

8. Roles and Responsibilities Food and Feed Scientific Staff
The Food and Feed Scientific Staff (FFSS) responsibilities cover scientific issues (e.g. methodology, lab selection) involving food and feed testing conducted under FDA jurisdiction.
Their testing coordination activities involve the 13 labs in the FDA/ORA network as well as the cooperative agreement laboratories within the Food Emergency Response Network (FERN).
The staff coordinates various testing assignments and programs involving numerous FDA food safety issues as well as FERN activities.

9. Roles and Responsibilities Food and Feed Scientific Staff
Examples include:
Import and Domestic Acidified and Low-Acid Canned Foods
Domestic and Imported Cheese and Cheese Products
Pesticides and Industrial Chemicals in Domestic and Imported Foods
Domestic and Imported Fish and Fishery Products
Infant Formula Program
Deep Water Horizon Testing Program (Reopening of Gulf States fisheries)
FERN: Proficiency testing Program, training program, Cooperative Agreement Program
ISO Laboratory Accreditation Program

10. Roles and Responsibilities Medical Products and Tobacco Scientific Staff
Coordinate all activities related to CDER, CDRH and CTP.
Coordinate analytical response to pharmacy compounding events
Coordinate and provide analytical/compliance strategy for drug/device/tobacco programs and assignments
Solicit research interest from ORA laboratories in new method development/validation to bridge analytical gaps
Manage and prioritize capital equipment budget
Manage workplan projections in drug/device/tobacco arena
Identify new technology platforms to perform program work
Form collaborations with Centers on analytical projects

11. Roles and Responsibilities Laboratory Operations Scientific Staff
Laboratory Information Management System (LIMS)
Electronic Laboratory Exchange (eLEXNET)
Mobile Labs, Chemistry and Microbiology screening labs
FDA web posting Lab Information Bulletins (LIB)
Method Development and Validation Program (MDVP)
Component Automated Research Tracking System (CARTS)
National Sample Distribution (NSD)
Equipment purchasing: VITEK, VIDAS
Technology transfer/development
ORS Science Seminar.
Whole Genome Sequence

12. ORA Labs Program Work
Work plan – Annual map for allocation of ORA resources (inspectional, collections, analytical
testing) to different areas of concern.
Centers, in dialogue with Field Committees, determine how ORA resources should be distributed.
ORA utilizes analytical capabilities in areas of chemistry, microbiology, radiochemistry, and engineering to perform the designated program work.
ORA supports the various Centers in the following areas of testing.
Product
Areas of Testing/Analytical Activities Performed by ORA
Foods & Feeds
Pesticides, dioxins, mycotoxins, chemotherapeutics, color additives, toxic metals, filth, select radioisotopes
Pharmaceutical Products
Active pharmaceutical ingredient testing, dissolution testing
Devices
Risk-identified products such as infusion pumps, catheters, surgical tools
Tobacco Products
Flavor compounds in cigarettes, contaminants testing, substantial equivalence
Nanotechnology
Method development and research activities
All products
Private lab package reviews
Analysts-on-inspections
Private lab reviews are analytical packages submitted by private labs who get hired by importers that get put on detention by FDA. In order for the importer to get off the detention, they need to show 5 consecutive clean shipments of product as demonstrated by an independent testing body – private labs. FDA has to review the submitted private lab packages for accuracy, authenticity, completeness before it is accepted and counted towards the 5 clean shipment quota for an importer.

13. Main Instrument Platform Representative Picture
ORA Analytical Capability Snapshot
Test
Main Instrument Platform
Targeted Analytes
Representative Picture
Pesticide
Testing
(fresh produce)
GCMSD, LC-MS/MS, GCQQQ
Up to 670 pesticides covered
Melamine Testing
(pet food, dairy products, protein containing processed foods)
GCMSD and LCMSMS
Melamine, cyanuric acid, ammelide and ammeline
Oil Markers Testing
(seafood during Deepwater Horizon Oil Spill)
LC-FLD and LCMSMS
Polyaromatic hydrocarbons (12 total, 7 being carcinogenic), dispersant, toxic metals
napthalene
Persistent Organic Pollutants Testing
(feed, seafood)
GC X GC – TOF, HRMS
40 compounds that include dioxins, PCBs and PBDEs
Radionuclide Testing
(milk, fresh produce after Fuskushima Meltdown)
Gamma counters
Cs-134, Cs-137, I-131

14. Main Instrument Platform Representative Picture
Test
Main Instrument Platform
Targeted Analytes
Representative Picture
Filth Analysis
(bulk ingredients)
Optical Microscopes
Insects, glass shards, metal scraps, etc
Toxic Metals
(candy, dinnerware, seafood, juice, rice)
ICP-MS, portable XRF, HPLC-ICPMS (speciation), ICP-OES
Pb, Hg, Cd, Cr, As, etc
Microbiology
(fresh produce, cheese, seafood, etc)
ELISA tests, selective media, PCR, PFGE, WGS
Salmonella, E. Coli, Shigella, Campylobacter, Cyclospora
Mycotoxins
(grains, nuts, seeds, juice)
LCMSMS, HPLC
Aflatoxin, patulin, deoxynivalenol, fumonisins, ochratoxin A
Aflatoxin
Acidified and Low-Acid Canned Foods
(canned foods)
pH Meters, headspace GCMS
Preservation: pH and water activity

15. Test
Main Instrument Platform
Targeted Analytes
Representative Picture
Color / Food Additives
(processed foods)
TLC, LCMSMS
Banned colors, additives such as rhodamine B, sulfites in shrimp, dried fruits/vegs, coumarin in “vanilla” products, nitrosamines in baby bottle nipples, benzoates in beverages
Cosmetics
(face creams, hair sprays, lipsticks, henna, hair/skin dyes)
TLC, XRF, LCMSMS, ICP-MS, microbiological kits
Metals, microbiological contamination
Forensic Chemistry
(drugs, tobacco, tampered products)
General chemistry, microbiology, molecular methods
Packaging features, product featuers, contaminant profiles, country-of-origin analysis
Economic Adulteration
(honey, maple syrup, pomegranate juice, olive oil, pet jerky treats, juices)
GCMS, LCMSMS, HPLC, isotope ratio MS
Anthocyanin pigment profile, sugar profile, fatty acid profile, protein profile
Veterinary Drug Residues
(seafood, milk)
LCMSMS, LC-QTOF, ELISA Kits
Vet drug residues such as chloramphenicols, fluorquinolones

16. Test
Main Instrument Platform
Targeted Analytes
Representative Picture
Pharmaceutical Survey Testing
(finished dosage forms, raw APIs, parenterals, excipients)
HPLC, dissolution apparati, spectroscopic techniques
Drug potency, content uniformity, split pill testing, impurities testing
Spiked Active Pharmaceutical Ingredients in Dietary Supplements
(dietary supplements with health claims)
LCMSMS
Erectile dysfunction active drugs, weight loss drugs, anabolic steroids, mood-altering drugs
Microbiology testing in drugs (finished dosage forms, injectables, parenteral bags, compounded human/vet products)
Sterility testing equipment, endotoxin test strips
Bacteria, fungi, bacterial endotoxins
Consumer Complaints, Adverse Events and Outbreaks (drugs, foods, pet foods, devices)
All available chemical, microbiological, physical tools
Broad-band investigative testing to identify causative agent: chemical contaminant, microbiological agent, manufacturing defect, etc

17. Test
Main Instrument Platform
Targeted Analytes
Representative Picture
Shelf Life Extension Testing
(finished dosage forms)
HPLC, dissolution apparati, stability chambers
Drug potency, dissolution, pH, water content, physical appearance, functionality tests
Device Testing (thermometers, catheters, intrauterine devices, forceps, tubing, pumps, radiological health)
Various instruments to conduct engineering investigations – fracture/fatigue tests, software tests
Medical devices, radiological health devices
Tobacco Testing
(cigarettes)
LCMSMS, GCMS, Smoking Machines
Flavor compounds, hazardous and potentially hazardous compound testing, nicotine levels, substantial equivalence testing
Nanotechnology (dietary supplements, food packaging, feeds, sunscreens)
Various physical chemistry instruments – TEM, SEM, XRD, DLS
Broad-band testing to characterize nanoparticles and elucidate their physico-chemical properties

18. Internal Collaboration
ORS
CDER
CTP
13 field labs OP
NCTR
EPA
CDC
USDA
Networks:
FERN
ICLN
NATRLN
CBP
ACIL
AAFCO
AFDO
APHL
OFVM
CFSAN
CVM
CDRH
Internal Collaboration
Committees leading collaboration
Scientific Collaboration areas: food and feed, medical device and radiation emitting product, Tabaco and pharmaceuticals
External Collaboration

19. ORA External Collaborations
Food Emergency Response Network (FERN) – State Labs
Areas of interaction:
Sample analysis (complementary capacity, surge capacity)
Intelligence sharing
Data sharing
Augmentation of enforcement authority
Capability sharing/building
FERN labs augmented ORA analytical response in following incidents:
Melamine Contamination in Foods/Feeds (2008)
Deepwater Horizon Oil Spill (2010)
Peanut Butter from Peanut Butter Corporation of America (2008)
Toxic Metals Surveillance ( )
High Volume Microbiology Surveillance – Avocados (2014)

20. ORA External Collaborations
Organization
Interaction
Association of Public Health Laboratories /Association of Food and Drug Officials/Association of American Feed Control Officials (APHL/AFDO/AAAFCO)
Building a mutually reliant food/feed safety network of labs to promote food/feed safety.
American Council of Independent Laboratories (ACIL)
Collaborating on standardizing analytical requirements in submissions from private labs to ORA in preparation for conforming to FSMA mandates.
Science Board to the FDA
ORA is preparing for its cyclical Science Board Review
(performed on a rotating basis for every Center/ORA). ORA has requested that the Science Board review ORA’s investment in FERN and ISO Laboratory Accreditation as a
mechanism to create increased laboratory food safety capacity.
ORA’s last Science Board review occurred in 2008.
Centers for Disease Control (CDC)
Analytical reliance: ORA obtained microbial ID, fungal sequencing training from CDC.
Customs & Border Protection (CBP)
Analytical reliance: CBP obtained training in melamine testing methods from ORA.
North American Tobacco Research Laboratory Network (NATRLN)
Alcohol and Tobacco Tax and Trade Bureau, FDA/CTP, FDA/ORA, Health Canada, CDC, USDA forum to collaborate on setting common tobacco standards: methods, terminology, etc

21. FERN Update – FDA large scale surveillance assignment

22. BACKGROUND OF THE ASSIGNMENT
The Food Safety Modernization Act (FSMA) outlines a new approach to food safety that is risk-informed and preventive in focus
Sampling process - serves as a mechanism to actively identify risks and – when possible – identify areas where preventive controls can be put into place to better protect public health
As FDA increases its understanding of the sources of contamination in high risk commodities/practices, it can more effectively allocate resources to address public health risks through compliance sampling, targeted sampling or other risk mitigation strategies.
Recognizing that sampling can play a greater role in helping the agency prevent contaminated product from reaching consumers, understand risks, and assess the value of strategies to control those risks, FDA has begun the process of rethinking how the agency deploys sampling resources. 22 22

23. WHY AVOCADO?
A CFSAN working group was established to perform a five year review of microbiological sampling data.
Development of a new analytical tool which calculated risk scores of each commodity collected and analyzed over the past five years based on the risk criteria
Based on the ranking results from the analytical tool, the following commodities were selected for FY 2014: sprouts (seeds, spent irrigation water, and finished product), raw milk cheese (aged 60 days), and avocados (whole pit fruit and pulp) 23 23

24. WHY AVOCADO?
FDA ranked foods based on a variety of criteria and identify three foods to serve as surveillance sampling pilot programs.
Food consistently causing illnesses or linked to outbreaks
High consumption level; and/or consumed by a high risk
Ready-to-eat (RTE) food population
Ingredient in ready-to-eat (RTE) products
Food regularly comes in contact with contaminated sources (water, or soil or equipment) during growing, harvesting, processing, or at retail
Food is intended to be cooked by consumer
Processed or manufactured in a manner without a "kill step" 24

25. MORE INFORMATION
CDC reported the rise of guacamole and salsa as common vehicles in foodborne outbreaks Emergence of Salsa and Guacamole as Frequent Vehicles of Foodborne Disease Outbreaks in the United States, 1973–2008
FDA’s limited sampling of avocado indicates the potential for a high incidence of contamination in this commodity.
Avocado products have been associated with six (6) recalls due to the presence of foodborne pathogens from : Salmonella in fresh avocado (n=1) and L. monocytogenes in frozen/processed products (n=5) 25

26. THE ASSIGMENT
To explore new processes and parameters for sample collections and analysis that will enhance the current FDA system - usage of the FERN labs
To fill knowledge gaps of microbiological hazards by determining the prevalence of selected microbiological hazards (Salmonella) in whole pit fresh  avocados and L. monocytogenes in avocado pulp
To take appropriate enforcement action when positive samples and environmental sampling findings are observed
Include “of the Assignment” to the title to match the outline
Replaced “our” by FDA (red)
Italics for L. monocytogenes on second bullet 26 26

27. (FERN labs and FDA staff)
eLEXNET project folder housed all documents related to the assignment
Data reporting:
FERN website – activation module s
FDA FACTS data entry
Communication from ORS to CFSAN, district offices (both import and domestics)
Added “(FERN labs and FDA staff)” to the title
If you could give a brief how we report will be a good example on how intricate and layered the reporting is. Reporting within 3 days for negative samples and 7-10 days for positive confirmed. Sun uploads or send with the excel files. For positives, the full FDA package (20-40 pages) is sent. Once FDA has the results, they enter our data in their system then is distributed to other offices. 27 27

28. RESULTS SUMMARY ~689 samples received ~682 sample analysis completed
Labs
# of POS MN 14 TX
10 (2 SLM) PA 8 WA 7 IL 5 FL 3 OH NC 2 CO VA MI
NMSU 1 NH RI
~689 samples received
~682 sample analysis completed
70 L. mono confirmed and CRO (~18% soak method)
- 1 confirmed L. mono (pulp method)
10 confirmed Salmonella positive (~1.4%)
Italics for Salmonella 28 28

29. FERN LAB SAMPLE DISTRIBUTION
Number of Sample Received
States Receiving Samples 29

30. PFGE/SEROTYPING/WGS
FL serves as the primary Listeria serotyping and PFGE lab
79 Isolates submitted for PFGE
232 Isolates submitted for serology
~106 uploads to the PulseNet Database via CFSAN
WGS: 19 L. mono and 10 Salmonella isolates have been sequenced by FDA Labs.
Italics for Listeria 30 30

31. Questions?