Statement of Objectives - Cyanobacteria Toxins.pdf

NIH-OLAO-OD3-RFP-5598931

Development of Certified Matrix Reference Materials for Select Cyanobacteria Species Statement of Objectives (Dec 12, 2019)

A. Purpose The National Institutes of Health (NIH) Office of Dietary Supplements (ODS) seeks to make available natural matrix certified reference material (CRM) which are fit-for-purpose for characterizing the identity, nutrient composition, and/or safety profile of Aphanizomenon flos-aquae and/or Spirulina (Arthrospira plantis and Arthrospira maxima), in particular when these species are used as dietary ingredients. The chemical constituent analytes of interest for certification measurements include select toxins and nutrients.

B. Background Cyanobacteria, also known as “blue-green algae”, are a diverse group of prokaryotes that are found in marine, freshwater, and terrestrial environments. Human exposure to cyanobacteria primarily occurs from swimming in or drinking or eating seafood from water containing algal blooms.

Additionally, certain cyanobacteria such as Aphanizomenon flos-aquae and spirulina (Arthropira plantis and Arthrospira maxima) have a history of use in traditional foods and have recently been used as ingredients in dietary supplements marketed as being a rich source of protein, fatty acids, and certain vitamins. However, some other species of cyanobacteria that can grow along with A.

flos-aquae and spirulina produce potent toxins known to cause illness and even death in humans depending on the route and amount of exposure1. These neurotoxins and hepatotoxins, such as microcystins, cylindrospermosins, anatoxins, saxitoxin, and β-Methylamino-l-alanine (BMAA), can be present in harmful algal blooms (HABs) and might contaminate A. flos-aquae or spirulina sourced from natural habitats for foods or supplements (“wild harvested”). Given these health risks, the methods for detecting these toxins in the environment, food supply, or dietary supplements must be accurate and reliable to demonstrate regulatory compliance and protect public health 2,3,4.

Validated analytical methods and certified reference materials (CRMs) are foundational to establishing the requisite accuracy, precision, and reliability of measurements for identifying cyanobacteria species and quantifying their toxic constituents. In 2001 the NIH ODS established the Analytical Methods and Reference Materials (AMRM) Program to accelerate the creation and dissemination of validated analytical methods and reference materials to characterize dietary supplements and support the broader biomedical research stakeholder communities. NIH ODS seeks to make available CRMs which can be used to support quality assurance of analysis of algae samples for both toxins and nutrients and to provide validation of measurement methods and quality control for chemical analysis in routine monitoring.

1 Codd et al. (1999) Cyanobacterial toxins, exposure routes and human health, European Journal of Phycology, 34:4, 405-415 2 Šulčius et al. (2017) The profound effect of harmful cyanobacterial blooms: From food-web and management perspectives, Science of the Total Environment, 609, 1443–1450 3 https://www.who.int/water_sanitation_health/diseases-risks/diseases/cyanobacteria/en/ 4 https://www.cdc.gov/nceh/hsb/chemicals/pdfs/Facts_Cyanobacterial_Harmful_Algal_Blooms_508.pdf https://www.who.int/water_sanitation_health/diseases-risks/diseases/cyanobacteria/en/ https://www.who.int/water_sanitation_health/diseases-risks/diseases/cyanobacteria/en/ https://www.cdc.gov/nceh/hsb/chemicals/pdfs/Facts_Cyanobacterial_Harmful_Algal_Blooms_508.pdf https://www.cdc.gov/nceh/hsb/chemicals/pdfs/Facts_Cyanobacterial_Harmful_Algal_Blooms_508.pdf

C. Objectives The National Institutes of Health (NIH) Office of Dietary Supplements (ODS) seeks to make available natural matrix certified reference material(s) (CRMs) for characterizing the purity, nutrient composition, and/or safety profile of Aphanizomenon flos-aquae and/or Spirulina (Arthrospira plantis and Arthrospira maxima) when used as dietary ingredients. These certified reference materials must be fit for purpose for use in food and dietary supplement analytical characterization and safety testing. The chemical analytes of interest include:

• Toxins o Total and/or individual microcystins (e.g., microcystin-RR, -YR, -LR, -LA, -LY, -

LW, -LF)

o Total and/or individual anatoxins (e.g., anatoxin-A, dihydroanatoxin-A, epoxyanatoxin-A) o Saxitoxin and/or total saxitoxins o Cylindrospermopsin o β-methylamino-L-alanine (BMAA) o Toxic metals such as arsenic, lead, cadmium, and/or mercury

• Nutrients o Water-soluble vitamins (e.g., B1, B2, and B12) including non-nutritive corrinoids o Fat-soluble vitamins o Essential minerals (e.g., iron, manganese, magnesium, zinc) o Proximates (protein, carbohydrates, and fat) o Amino acids o Fatty acids (selected individual fatty acids)

The targeted toxin analytes should be either naturally incurred in the matrix or engineered to be present (i.e., not achieved through fortification/addition). ODS’s preference is for CRMs with naturally incurred toxins, in order to better represent real-world analytical challenges and better serve the needs of industry analysts and biomedical researchers.

At the end of the project, the offeror would make the CRM(s) available for sale to their customers, provide approximately 15% of the units to the NIH ODS, and make available scientific reports describing the development of the CRMs.

D. Requirements:

ODS seeks a vendor with capabilities to perform the work necessary to produce and distribute certified reference materials (CRMs) fit for the measurement of selected toxic and nutrient constituents of the dietary supplement ingredients Aphanizomenon flos-aquae and/or spirulina

(Arthropira plantis and Arthrospira maxima). The list of analytes of interest (see Section C.

Objectives) is intended as a proposed target list and not as an inclusive requirement of the solicitation, however the offeror’s proposal in response to this solicitation must include measurements of at least three (3) of the five (5) toxin classes listed above. The offeror’s proposal should include as many of the target constituents as the vendor deems would be beneficial to potential customers and would be cost effective in producing the CRM(s). The offeror’s proposal must state which constituents will be included in the proposed CRM(s) and the analytical approach and methods intended to assign the certified values for the constituents of interest.

The preferred form for these CRMs is the specified constituents of interest in a natural matrix relevant to human exposure, for example cyanobacteria biomass (non-viable or otherwise deactivated), processed material, or powdered ingredient. The selection of matrix for the CRM(s) shall be evaluated to ensure stability of the analytes of interest over time.

The product(s) must meet all requirements to be identified and distributed as Certified Reference Materials. These requirements include comprehensive assignment of certified mass fraction and/or mass concentration values based on an appropriate analytical approachmaterial using liquid chromatography (LC), gas chromatography (GC), and/or mass spectrometry (MS). The certified values for the mass fraction/mass concentration values must have a statement of the measurement uncertainty associated with the value.

After producing the CRMs, the offeror will make the material available for sale to the public. The CRMs must be accompanied by a Material Safety Data Sheet (MSDS), where appropriate. The CRMs must be accompanied by a Certificate of Analysis (COA) that states the certified mass fraction and/or mass concentration of the constituents in the matrix. The basis of the value assignment (i.e., analytical techniques used) must be stated in the COA. ODS must be acknowledged in the COA as the source of funding to produce the CRM. Offeror shall provide approximately 15% of the units of the CRM deliverable(s) to NIH ODS for potential use in complementary measurements and/or in analytical educational/training efforts of the AMRM program.

Offeror must demonstrate prior experience in the preparation, production, and certification of reference materials that meet the international requirements to be CRM.

Offeror must demonstrate experience in the sale and distribution of chemical reagents for use in biomedical research or regulatory compliance, as well as demonstrate adherence to any and all applicable U.S. and international regulations which govern distribution activities of potentially hazardous materials.

Offerors must provide evidence of all the following quality requirements:

• The vendor must have the necessary ISO accreditations to produce the highest quality products that can be identified as CRMs including:

o Accreditation to ISO Guide 34 “General Requirements for the Competence of

Reference Material Producers” is intended to ensure competency in the production and manufacture of reference materials and to assure that appropriate international guidelines are followed in the production and assignment of property values.

o Accreditation to ISO/IEC 17025 “General Requirements for the Competence of Testing and Calibration Laboratories” is intended to address technical competency of the testing laboratory including the laboratory’s ability to provide precise and accurate test and calibration results. Accurate test results are critical in the proper chemical characterization of reference materials.

o Certification to ISO 9001:2008 covers general quality practices of all laboratory operations including organic synthesis, chemical standard manufacturing, testing and certification, and customer and technical service.

Offerors must describe briefly their technical approach to achieve the complexity and scope of this project. Offerors must document the roles and responsibilities of the contract team. Proposed staffing for this effort needs to be explicitly spelled out to ensure that the contract team is comprised of members with the requisite skills to meet the project goals. The offeror’s team must include individuals and subject matter experts with documented experience in developing CRMs for chemical composition. Offerors should furnish resumes for all key personnel involved in the development of this CRM. The majority of key personnel should be members of the prime offeror’s team and not sub-contractors. Offerors should submit evidence, via at least three past performance questionnaires, of successful performance on development of organic compound calibration solutions similar in complexity and scope.

E. Deliverables The offeror will produce the CRM in a quantity estimated to provide a 5-year product inventory at a minimum. The CRMs must be accompanied by a Certificate of Analysis (COA) that states the certified mass fraction and/or mass concentration of each of the constituents in the matrix with the appropriate measurement uncertainty and that meets the ISO requirements for content of a CRM COA. The CRM should be made available for sale to public and private sector researchers and analysts at an appropriate cost and be included in the organization’s catalog and online sales platform. After the development of the CRM, the offeror should prepare a manuscript, suitable for submission to an analytical chemistry peer-reviewed journal, describing the development of the CRM and the approach and techniques used to assign the mass fraction/mass concentration values and the associated measurement uncertainties.

F. Place of Performance and Government Responsibilities The work may be performed at the offeror’s location of choice; however, due to the collaborative nature of this project, the Office of Dietary Supplements expects and thus requires that the successful offeror’s project team meet with the ODS project team quarterly (face-to-face or teleconference) to discuss the status of the project.

G. Estimated Period of Performance Base 12-month project period, plus 12-month option to complete.

H. Contract Type Firm fixed price.