Biologicals Regulation: The Right Way

Bruce Caldwell & Jane Fife

We talked to Bruce Caldwell, CEO of 3Bar Bio, and Jane Fife, 3Bar Bio’s CTO, about regulating biologicals and what we should be considering as this topic gets more attention. Bruce, with many years in R&D and product development, tends to focus first on the more business-oriented, commercialization issues. Jane, with a PhD in agricultural engineering, naturally comes from a more technical point of view. Together, they lead 3Bar to ensure that the company is an effective design, development, and delivery partner for both biological discovery companies and distributors. 

We engaged in an in-depth discussion about the current climate around EPA regulations in a Q&A format, read below:

What is the current status of federal, state, and local regulation in the U.S.?

Bruce: The US EPA has for over a decade had a fast-track registration process for biopesticides that enables registration within a couple of years and costs under $500K. 

That is significantly faster and cheaper than a traditional chemical pesticide registration process which has become so burdensome that most companies have stopped working on new molecule pesticides. So biopesticides are really the future for control products (insecticides, herbicides, fungicides). 

For non-control products, like biofertilizers and biostimulants, these have not been regulated on a federal basis and are registered in each state’s department of agriculture in a way similar to fertilizers.

Jane: Because plant biostimulants are neither a pesticide nor a fertilizer, they are stuck in a gray area where no law currently exists, and there is confusion about who (EPA or the states) is responsible for regulation. (Plant biostimulants help the plant increase growth or yield by reducing stress and/or improving plant nutrition, and they cover a broad range of products including microbial inoculants, amino acids, humic and fulvic acids, plant extracts, and seaweed extracts.) 

Current US law divides regulation into two categories: pesticides and fertilizers.

FIFRA (Federal Insecticide, Fungicide, and Rodenticide Act) was established in 1958, and includes outdated pesticide laws that are overly broad in scope to include both pesticides and plant growth regulating (PGR) products. US EPA regulates both biopesticides and PGRs under FIFRA.

What is the Plant Biostimulants Act of 2023?

Bruce: This act follows similar work done in Europe and should support more national commerce in these type products since it sets a standard nationally versus letting each state define product requirements. Industry has been involved and asking for this regulation, so it is a good thing.

Jane: The Plant Biostimulants Act of 2023, importantly, provides a federal definition of plant biostimulants and excludes plant biostimulants from regulation under FIFRA.  

Under the bill, plant biostimulants are defined as “a substance, micro-organism, or mixture thereof, that, when applied to seeds, plants, the rhizosphere, soil, or other growth media, act to support a plant’s natural processes independently of the biostimulants nutrient content, including by improving nutrient availability, uptake or use efficiency, tolerance to abiotic stress, and consequent growth, development, quality, or yield.”  The bill also requires the USDA to study the types of plant biostimulants and practices that contribute to soil health. 

How are ag biologicals regulated elsewhere, and what can we learn? 

Bruce: Brazil, France, and Canada have mandatory product registration, with samples analyzed randomly every year.  

  • Brazil is considered a successful model of moderate regulation which has allowed these products to flourish.
  • France/Europe is not considered a successful model. Brussels has created a very bureaucratic and cumbersome system which inhibits commerce.
  • Canada has a more thorough process than the US for biostimulants, and it’s similar for biopesticides.

Jane: For pesticides and fertilizers, regulatory frameworks exist and can be adapted to encompass the biological part.  

However, biostimulants are different and represent a new category. Historically, most countries have put biostimulants under fertilizers.  Formal regulatory environments for biostimulants, with official definitions, approval systems, and consistent labeling, are beginning to evolve, with the European Union (EU) and United States leading the way.

In the European Union (EU), we can see a record of the first governing body to recognize plant biostimulants as a distinct category of agricultural inputs. 

  • In 2019, the EU approved new fertilizer regulation that included a clear definition for biostimulants, and placed plant biostimulants separately under its fertilizer law. 
  • The Regulation (EU) 2019/1009 on fertilizing products defines biostimulants on a functional basis with four functional claims: “nutrient use efficiency, tolerance to abiotic stress, quality traits, and availability of confined nutrients in soil or rhizosphere.”  
  • For microorganisms, only four (4) genera are accepted in the Regulation, and with only four microorganisms accepted, this leaves out many microorganisms with potential plant beneficial effect, limiting innovation and use of biologicals in this area. 
  • In 2022, the EU enacted the Fertilizing Products Regulation (FPR) program that implements Regulation 2019/2009, and allows companies to access the common market of all EU member states.   
  • The EU regulates biopesticides along with chemical pesticides as part of its overarching Plant Protection Products.  The regulatory process is divided into two phases: the active ingredient is regulated at the EU level, whereas the formulated product is reviewed individually at the country level.  Registration of a new biopesticide is long and overly complex, taking 4-5 years or longer if a new microorganism is the active ingredient. 

In Canada, while a formal definition for biostimulants does not currently exist, biostimulants are being regulated as supplements under the Fertilizers Act. 

In Brazil regulates biostimulants separately as biofertilizers, with two categories of microbial inoculants and stimulants or biofertilizers.  

  • In 2020, the Decree No. 10.375 was established as a simplification on the registration of biofertilizers and biopesticides.  Under the Decree, Brazil created the National Bioinputs Program to expand and strengthen bioinputs use, including biopesticides, microbial inoculants and biofertilizers.
  • Biopesticides are regulated following the same legislation as chemical pesticides.  The regulatory approval process for pesticides takes approximately 3-4 years and involves three Brazilian Ministries. 

What has been the result of those regulations? Have they dampened or encouraged new discoveries? 

Bruce: In Brazil, the regulations have encouraged new discoveries, and in the EU, regulations have discouraged innovation.

What do you recommend as the U.S. considers regulation and registration?

Bruce: We need to make sure any federal oversight of biostimulants does not become overly expensive or bureaucratic as this will favor only the large multinationals, and it would make it difficult or impossible for small innovative companies to commercialize.

Specifically for microbial products, the application of some minimum requirements around concentration (CFU/ml or CFU/gr) and also around eliminating or minimizing contaminants is necessary. In a similar manner, it is important for both small and large companies that are thinking about commercializing products in the space should to be consulted.

What are cautions that should be considered? and what agency/organization should regulate/register this? 

Bruce: If we let the regulation process get too expensive and bureaucratic, like EPA pesticide registrations, the segment will suffer and be dominated only by the big multinational corporations. I would not favor the EPA taking the lead; potentially, the USDA is best positioned to provide national registration.

Do you favor federal/nationwide standards? 

Bruce: The primary benefit of federal standards is to supersede all the state differences so a single product can be sold nationwide. Overall, federal/nationwide standards enable nationwide commerce with a single label versus a multitude of state requirements.

Jane: At the federal level, it will be key to the success of biostimulants to have a defined regulatory pathway and involvement.  Without a distinct regulatory framework in the United States, biostimulant products have been forced into various existing pathways at the state level as soil amendments, additives, fertilizers, etc. which has led to problems with exaggerated performance claims and ‘snake oil’ products on the market. 

As a regulatory framework is being developed, do you foresee pushback and from whom? 

Bruce: The major pushback would be from small companies who do not have large budgets or regulatory departments. As they have potentially the most to lose, if there is a complex and time-consuming process. Small companies will want the process to develop regulation to be slow, well tested, and well thought out. 

Thinking about the more technical details, what challenges do you see in regulating these microbial products?

Jane: Biostimulant v. biopesticide: Many microorganisms have dual properties, offering both plant biostimulant and plant protection traits. Currently, manufacturers are limited in the claims being made depending on the regulatory pathway being pursued.  The ability to claim both biostimulant and biopesticide traits through one registration process and label would be beneficial for product development and marketing. Regulatory programs that include quality monitoring of microbial products are necessary to ensure minimum standards are being met in the marketplace. Otherwise, products will have low performance in the field. 

The quality of the product is based on the presence of the defined strain(s), absence of any other strains that would be considered contaminants, and the number of cells being greater than the minimum guaranteed analysis. Therefore, a product label must clearly define the specific strain(s) and guaranteed number(s) of microbial cells in the package.

Another arranges of challenges is related to shelf-life. Manufactured products must be guaranteed not just at the time of production, but during the whole distribution and shelf-life period until the product is used by the farmer and is something consumers and businesses need to look out for.

Contaminants must also be excluded from the mix. Living microbe products must include viable microbes without the presence of any contaminants that could undermine product performance. For liquid products, the composition of the formulated liquid culture including metabolites, solids, and spent media components needs to be clearly defined with respect to biostimulant and/or biopesticide traits.  

Lastly, regulation needs to clearly differentiate the living microbe and its mode(s) of action from the accompanying “dead” culture components. As well as consortia products involving numerous microbe strains that are difficult to monitor for quality control. The existence and implementation of microbiological and/or molecular methods is essential to confirm the presence of each strain and quantify its guaranteed number of cells. Thank you, Bruce, and Jane, you’ve given us a lot to think about, both from a commercial perspective and a technical perspective. As regulation efforts proceed in the U.S., it will be important for industry to contribute input and for government to establish avenues to accept and evaluate those insights. 

Bruce Caldwell

Mr. Caldwell brings 30 years of customer discovery and product innovation leadership from a career at ScottsMiracle-Gro and Procter & Gamble. As Senior VP of R&D at Scotts, he led a global organization and numerous external partnerships to create easy-to-use agricultural products including a line of biologics and seed coatings. At Ohio State he has served on the advisory board of the College of Food, Agriculture, and Environmental Science and as a mentor in the Fisher College of Business Center for Technology Entrepreneurship. He was previously President of the university spinout NanoMed Inc. Mr. Caldwell earned a BS ChE from Georgia Tech and a MBA from U. Cincinnati.

Jane Fife

Dr. Fife’s research focuses on improving formulation and delivery of biologics for more effective application of beneficial microbes to promote plant growth and biological disease control. Prior to joining 3Bar Biologics, she has more than 15 years of expertise in application technology and agricultural biologics through her leadership role managing technology development in agribusiness at Battelle Memorial Institute. Dr. Fife holds a PhD in Agricultural Engineering from The Ohio State University, where she currently serves as an Adjunct Faculty and teaches courses in engineering design. Her main interests are in applying new technologies for more targeted delivery of agricultural inputs and smarter, more sustainable agricultural production.