EPA's Safer Choice Supplemental Considerations for Partnership on
Microorganism-based Products
July 2013
Safer Choice's Microorganism Review Checklist (Attachment A) describes the basic
information needed to assess the potential hazards of a microorganism, including
methods for proper species identification, sources for a thorough human health and
ecological effects literature search, and possible exposure patterns based on product
use. Assessment of the risk, which is a function of both potential hazards and exposure,
evaluates whether the microorganism is a potential pathogen—to any of a broad
spectrum of organisms (including humans, other mammals, avian species, aquatic
vertebrates and invertebrates, plants and others), and whether there are any other
adverse effects and the likelihood of those effects that may result from exposure to this
microorganism in the specific use of the product.
• Primary considerations for partnership: The risk assessment concludes that the
microorganism is not pathogenic to any species with which it will come into
contact and will not cause any other adverse human health or ecological effects
(e.g., producing metabolites that are more toxic than the parent) in the specific
use of the product. All non-microorganism ingredients must have an acceptable
health and environmental profile (as per the Safer Choice Standard).
Please note that Safer Choice typically partners with formulators of end-use products.
For microbiological-based products, partnership preference is given to companies who
manufacture the microorganism and formulate products for end use, and thereby
maintain maximum control over product formulation. Safer Choice may also partner with
companies that incorporate a third-party's microorganism into their end-use product,
provided that they are able to fully address all partnership elements.
Safer Choice will consider the following additional elements as part of its decision to
offer partnership to a manufacturer of a microorganism-based product. These elements
may be adapted or modified to fit the specific circumstances of the product review, e.g.,
microorganism type, intended use, and method of application, with special attention to
the potential for human or environmental exposures. (Note: All elements not specifically
addressed in the Partnership Agreement will be incorporated by reference.)

I.	Consistency in Use of the Strain.
The manufacturer must commit to formulating with only those microorganism strains
that were the subject of the risk assessment and Safer Choice review and agreed to in
the Partnership Agreement. These strains must be identified through a rigorous
taxonomic review (including but not limited to 16S rDNA or rRNA sequencing), which
can be provided by a recognized full-service culture collection, whether or not the strain
is part of the collection, or by other appropriate means. Such collections may be
commercial or governmental (US or foreign) but should be listed with the World
Federation of Culture Collections and must offer comprehensive identification services
as one of its products. Alternatively, the strains may be identified by an established
expert in the systematics of the organism used. The strain must not change without
prior Safer Choice notification and review. The manufacturer may not substitute a strain
of different species without first securing a third-party risk assessment and Safer Choice
review and approval. The manufacturer many substitute another strain of the same
species (e.g., a related wild-type or a more productive strain) following a careful
evaluation of the taxonomic designation and a determination that a new risk
assessment is not needed. Consistency in use of strain helps ensure reproducible,
consistent formulations, reliable product performance, and a positive health and
environmental profile.
II.	Product Purity and Quality Assurance.
(A).	Key Elements. Related to consistency of strain is product purity, i.e., measures
taken to ensure that the product does not become contaminated with other
microorganisms during the manufacturing or formulating process. The manufacturer
must have quality assurance/control provisions to ensure product purity both during
manufacture and any subsequent processing. An example of useful principles of quality
assurance/control measures can be found in the test guidelines for microbial pesticides
that the U.S. EPA Office of Pesticide Programs has issued (U.S. EPA Microbial
Pesticide Test Guidelines OPPTS 885.1200 and 885.1300). While these guidelines are
prescriptive and directed toward the specific needs of regulating microbial pesticides,
the elements are informative of the kinds of considerations that can be employed in a
quality assurance program for microorganism production. The pesticide guidelines
include the following:
>	A description of the basic manufacturing process, the starting and intermediate
materials, and the steps taken to limit extraneous contamination, both chemical
and biological;
>	A theoretical discussion on the formation of unintentional components, including
microbial contaminants, with a list of procedures to ensure the purity of
unformulated products; and
>	A demonstration that human or other animal pathogens are not present in the
final product.
(B).	Testing. The purity testing should occur on a periodic basis; at a minimum, the

testing should occur at the time of product formulation and at a time that approximates
the end of shelf life. Records of test results should be available to Safer Choice upon
request. Product purity is key to both safety and reliable product performance.
(C).	Modifications to Formula. The product must not be modified in any way without
providing prior notice to Safer Choice (as specified in the Partnership Agreement, sec.
4). Water may be added by a licensed processor according to the manufacturer's purity
specifications, incorporated by reference in the Partnership Agreement. The
manufacturer must document its legal relationship with the processor.
(D).	Product Containers. Manufacturers, and any downstream processors, must have
quality assurance/control provisions to ensure that containers do not contaminate the
formulation. The recyclability of containers is a desirable product attribute.
III. Functionality and Product Performance.
(A).	Utility of Product Ingredients. The manufacturer must demonstrate that each
ingredient contributes to product performance (with evidence of the efficacy of that
performance) and would not compromise product purity in any way. Use of certain
added fillers or carriers might contaminate the approved microbiological blend (i.e., add
foreign bacteria) or otherwise interfere with performance (e.g., impede digestion of
organic waste constituents, cause increased clogging of drainfield soils, pass through
the system to the receiving environment, etc.).
(B).	Product Performance. The manufacturer must provide performance testing that
demonstrates performance that meets its users' needs. In its review criteria of chemical-
based products, Safer Choice outlines several ways to demonstrate performance: by
comparison testing with a market leading product, by using a standard test method
(such as ASTM), or using a non-standard test protocol in cases where standard
methods are not available or not applicable.
Given the lack of standardized testing for biological-based products, a manufacturer
must provide a literature reference that describes the functionally appropriate use of the
relevant microorganism strains (e.g., certain pseudomonads degrade chlorinated
solvents); alternatively, if there is not a literature reference, a manufacturer may use a
non-standard method. An example of the latter might involve the lab scale application of
microorganisms to media or substrates (e.g., sewage sludge), while simulating real-
world conditions (temperature, time, oxygen levels).1 A small-scale test offers several
1 Performance Testing. A Safer Choice product should perform on a par with industry leading products.
Assays should be designed to compare the recognition candidate to a currently recognized product or
industry leader and to replicate use directions and, to the extent possible, real-world application
conditions. The number and type of substrates tested will be left to the manufacturer's discretion, but test
results should support any product performance claims. Degradation of the substrate (e.g., fats, oils,
grease (FOG)) should be measured through an appropriate method, for example, respirometry that
indicates oxygen consumption or evolved carbon dioxide. Representative photographs would provide
helpful documentation to support quantified measurements at various stages of degradation, but are not
required. In all cases, protocols should be submitted to and approved by Safer Choice before any testing

advantages: reproducibility, comparability among microorganisms, and affordability.
Manufacturers of other products for a similar purpose would be held to a comparable
product performance level.
(C). Shelf life. Shelf life should not exceed the period during which microorganisms are
efficacious. The manufacturer orformulator must provide evidence that demonstrates
product efficacy during the period of potential sale.
IV.	Limitations on Product Eligibility
(A).	Products for Use in Indoor Environments. Safer Choice is presently reviewing the
appropriateness of indoor use of microorganism-based products. Until this review is
complete, Safer Choice will not review or consider for partnership microorganism-based
products intended for use on carpets, hard surfaces or other indoor environments.2
(B).	Septic System and Drain Line Applications (including any application where effluent
may be released to a septic system or directly to the environment, for example, holding
ponds or lagoons; products for bioremediation would be an exception). Microorganism-
based products for septic system, drain line, holding pond or similar applications must
contain only live or dormant (i.e., capable of germinating) microorganisms and water
(limited use of Safer Choice-acceptable nutrients, stabilizers, additives, and colorants
would be allowed) and no added emulsifiers (e.g., surfactants or added enzymes) or
other ingredients that might interfere with microbial digestion of wastes and the proper
functioning of the drainage system. Surfactants are poorly degradable in a tank's
anaerobic environment. Many municipalities have prohibited the use of added
emulsifiers in septic or drain line maintenance products for industrial or institutional
applications (e.g., Corpus Christi, TX and Davidson County, TN).
V.	The Partnership Agreement
(A). To obtain Safer Choice recognition for a microorganism-based product, the
manufacturer must comply with the above-listed information elements and enter into a
partnership agreement with Safer Choice. The partnership agreement governs the
relationship between EPA/Safer Choice and its partner, the product manufacturer. It
contains, among other elements, provisions covering the following: full ingredient
is performed.
Note on grease traps: Evidence should be provided that the degradation products would improve drain
operations, for example, are of a more fluid consistency (i.e., less sticky) than the subject substrate.
2 Safer Choice is exploring whether the use of microorganism-based products in these applications raises
a concern for hypersensitivity pneumonitis (HP), a group of immunologically mediated lung diseases in
which repeated exposures to finely dispersed antigens evoke a hypersensitive reaction resulting in
granulomatous inflammations in the distal bronchioles and alveoli. (Note: HP has typically been
considered an adult disease because of its association with occupational exposures, but it has been
shown to occur in children from exposure to antigens in the home.) Repeated exposure to vegetative
Bacillus subtilis cells and spores may result in hypersensitivity pneumonitis.

disclosure; notification of changes in formula and the need for prior Safer Choice
approval; the manufacturer's commitment to continuous product improvement;
limitations and responsibilities regarding use of the Safer Choice recognition and label;
and partnership sunset and opportunity for renewal. A sample partnership agreement is
available on the Safer Choice web site (at www2.epa.gov/saferchoice/boilerplate-
(B).	As a condition for recognition and a provision of the partnership agreement, a
manufacturer must agree to include on product labels and literature, the following
statement: "Product contains live microorganisms."
(C).	Based on the increasing incidence of microbial resistance to antibiotics, the
manufacturer must test the microorganism(s) in its labeled product(s) for resistance to a
representative set of antibiotics, as specified by Safer Choice.
Attachment A: Microorganism Checklist (see companion file).