Battelle: Offers High Quality and Innovative Bioformulation Development and Regulatory Consultancy, Modelling and GLP Product Safety Testing for Biologicals

″Besides assisting with bioformulation development, Battelle supports our clients with their registration process for both biopesticides and biostimulants. Battelle has a long-standing reputation in the U.S. and in Europe for being a trusted partner for formulating successful regulatory compliance strategies. We provide innovative full-scale registration and re-registration support, as well as expert advice in dossier compilation for conventional crop protection products and biologicals,″ said Inês Rocha，PhD, Researcher Microbiology, Crop Protection Division at Battelle and Dominik Reinhard, MBA, European Head of Commercial Sales, Crop Protection Division at Battelle in a recent interview with AgroPages.

They also shared their views on Battelle’s capabilities in biologicals and bioformulation, the challenges and countermeasures of bioformulation development with some specific cases, the company’s regulatory consultancy service and service strategy, insight into the opportunities and challenges in the biological market, and more.

Inês Rocha PhD, Researcher Microbiology, Crop Protection Division at Battelle	Dominik Reinhard, MBA European Head of Commercial Sales, Crop Protection Division at Battelle

Q1. Could you introduce Battelle’s capabilities in the area of biologicals and in particular bioformulation? What is the business model?

Battelle is a global applied science and technology organization that provides innovative and sustainable scientific solutions to the agrochemical industry. Our scientific research, STEM and philanthropic initiatives provide purpose, support climate resilience, and strive to end world hunger, enabling our clients to develop innovative solutions to agriculture’s most complex challenges. Our contract formulation development lab in Havant, UK offers unique solutions to the biological plant protection industry either based on fee-for-service or innovative, alternative outsourcing models including licensing, co-development, or co-investment.

The agrochemical industry is a sector in transformation with significant needs in finding alternative solutions to conventional plant protection products including the rapidly evolving market of biologicals. Battelle knows that being on top of the latest trends and having the knowledge of how to apply new technologies and methods is critical to solving tough challenges. Battelle’s breadth of services runs deep with decades of biological, bioscience and agrochemical formulation which allow us to provide   solutions to the unique challenges of agricultural bioformulation. We base our innovative and sustainable scientific solutions on an integrated approach to research, development, and regulatory compliance.

Our dedicated team of multidisciplinary experts is comprised of analytical chemists, microbiologists, and formulation chemists, some having 25-40 years of experience with multinationals in Formulations and Bioformulations R&D. The formulation work is largely focused on the amendment selection and screening, optimization, encapsulation techniques, content determination (e.g., analytical and microbiological), seed treatment & on-seed testing, storage stability testing, proprietary technology development, process development and scale-up, manufacturing support, and in-pack storage stability testing. Battelle’s team has experience with various biological active ingredients (AIs) such as botanicals, semiochemicals, and microorganisms. We can develop multi-purpose formulations and types such as SC, WP, WDG, OD, EW, and CS for different applications such as foliar, soil, or seed. Work related with molecular characterization and identification, genomics, proteomics, and metabolomics, as well as high-throughput microbial screening and phenotypic characterization is developed in Battelle’s lab in Columbus, Ohio in the U.S. In both labs, Battelle, develops its own internal R&D to gain knowledge to better support our clients as well as to generate proprietary technology that can be offered commercially.

Furthermore, Battelle provides regulatory support for biological dossier preparation and risk assessments for the world’s most important markets including Europe and the U.S. To round up the service offerings we also provide GLP compliant product safety testing, which is planned to soon include microbial formulations.

Q2. What are the challenges of bioformulation development and countermeasures? Could you share some specific cases? Such as how Battelle is improving stability for microbial formulations?

Microbial products are based on living microbes, either single species, mixture of selected species, or complex consortia. The robustness of microbes varies highly between species and strains. Consequently, maintaining the microbial population and efficacy in distribution and storage can be challenging. One of the objectives of bioformulation development is to find the right balance between keeping the microbes alive and avoiding rapid growth or death.

Discovering the most suitable formulation type for a product is also demanding, but crucial to enhancing the stability, shelf life, and performance of microorganisms in field conditions. As in the case of conventional agrochemicals, microbial products can be formulated as solids or liquids. The choice depends on the intended application mode, microorganism’s mode of action, compatibility with other components (e.g., different AI, water) and, foremost, stability of the microbe AI (e.g., robustness, stable form). Microorganisms can face different challenges when applied as seed treatment, foliar, or directly into the soil. In this case, the selection of additives (e.g., co-formulants, adjuvants) to add to the formulation, is essential for the microorganism’s survivability and efficacy. Additives are needed to provide protection against adverse environmental conditions such as desiccation, UV light, and wash off, as well as to guarantee a good performance and quality to the formulation (e.g., dispersibility, suspensibility, flowability). Nevertheless, co-formulants and adjuvants commonly used in conventional agrochemical formulations are not always compatible with microbes, compliant to desired markets (e.g., organic), or safe. Despite, the evident shift in the range of additives being offered to the biological market, we are still in need for more alternatives, especially options that comply with the requirements of certain markets (e.g., organic market for biostimulants) and that avoid high costs for the final product.

Additionally, other challenges to be taken into consideration are equipment compatibility and packaging. Farmers often need to use the same application equipment as for conventional products. Consequently, chemical compatibility and specific physical properties might be required for the microbial product. The choice of formulation type and technology is key to solve any potential incompatibility. Gas production by the microorganism or need for water exchange may affect pack selection and/or requirements.

Formulation development of a microbial product can be a complex process; however, it is essential to obtain a commercially viable, cost-effective product and to not jeopardize the sector’s reputation.

As previously mentioned, Battelle invests in its own internal R&D to provide solutions to common problems faced by our clients. Examples of our current  R&D that intends to improve the stability of microbial formulations are as follows: testing of microbial compatibility with novel and conventional co-formulants and adjuvants, design of liquid formulations (e.g., SC, OD, and EW) for gram-negative bacteria or gram-positive non-spore forming, investigating seed stickers that can help to replace some of the common polymer-based ones, development of encapsulation technologies to improve microbial compatibility with other AIs, and stability in both liquid form and on-seed.

Q3. Could you introduce Battelle’s regulatory consultancy service? And share some changes of regulation & policy on biologicals of your company's target markets? What is the service strategy in response to evolving changes?

Besides assisting with bioformulation development, Battelle supports our clients with their registration process for both biopesticides and biostimulants. Battelle has a long-standing reputation in the U.S. and in Europe for being a trusted partner for formulating successful regulatory compliance strategies. We provide innovative full-scale registration and re-registration support, as well as expert advice in dossier compilation for conventional crop protection products and biologicals. Our work is supported by a team of multidisciplinary scientific experts with complementary skill sets and various backgrounds from the crop protection, contract research, and regulatory consulting industries and from national authorities. Our team, in the UK and U.S., provide assistance with study design and global registration, data gap analysis, dossier preparation, risk assessment, and submission including advice for product defense.

The latest modifications in the European framework applied for biostimulants (regulation EU No. 2019/1009) and those to be implemented for biopesticides (e.g., new data requirements for approving active substances and new data requirements for authorizing products) seem to be a constructive change to the biologicals market. For biostimulants, the new regulation in force since July 16, 2022, appears to represent an opportunity for companies to invest in a new range of products and access the whole EU market more easily. For biopesticides, the new rules should accelerate the approval and authorization of biological plant protection products containing microorganisms and provide a better direction on test methods and guidance documents to be used. Nevertheless, the consequences and challenges that come with the new regulations are yet to be fully understood, and although the intention is to ease the overall registration process, that might not be the initial result. For this reason, Battelle is developing a new team of regulatory experts that will exclusively focus on the challenges of biological plant protection products. Our key to success is to deliver tailor made solutions to our clients that are deeply anchored around a purely biological mindset.

Q4. How do you see the impact of the EU Fertilizing Products Regulation to the biostimulant industry?

Plant biostimulants are known for their ability to enhance nutrient uptake and efficiency, improve soil quality and consequently crop, as well as increase crops’ tolerance to abiotic stress. The Fertilizing Products Regulation (FPR) (EU) 2019/1009, is the recognition of plant biostimulants’ role in the industry and in its trends towards sustainability.

The positive impact of FPR is noticeable, specifically when recognizing the growing inquiries from clients that want to know how to approach the harmonized marketing process or start developing biostimulants, aware that they have an opportunity to access the EU market.

It is important to note that the FPR entered into force as of July 16, 2022, which means that we are still in a period of adaptation. Some matters still need to be addressed and be fully clarified; for instance, the respective guidelines and guidance are still being developed. Additionally, only a limited number of microorganisms are recognized as being safe to use as components of microbial plant biostimulants. In fact, only four genera of microorganisms (Azotobacter spp., mycorrhizal fungi, Rhizobium spp., and Azospirillum spp) are allowed, which excludes many others that are currently being used or developed. Despite the European Commission’s powers to amend the positive list included in CMC 7 of the FPR to include more microorganisms, there is still no formal procedure for this that has been defined by the Commission. Equally important, the FPR does not provide data protection for applicants. Altogether, these are limitations that might lessen the immediate interest of companies and consequently block innovation and deprive Europe of alternatives to a more sustainable agriculture.

Battelle has been keeping contact with competent authorities and DG GROW to provide the best possible support to our clients in strategy development, data gap analysis, data generation support, dossier preparation, submission, and defense.

Q5. How can you describe the current state of the biological market? What and where are the biggest opportunities and challenges for biologicals? What are the factors affecting changes of the biological market?

The current state of the biological market shows a positive demand for both biopesticides and biofertilizers. Importance and status may differ among countries and regions across the globe, but overall, environmental concerns, consumer demand, organic farming, and regulatory pressures on conventional crop protection products are driving the demand.

Benefits of biologicals such as protection against abiotic and biotic stresses, increase of plant nutritional value, and improvement of soil quality are well known. So too are the hurdles and challenges that prevent them from achieving their full potential in the global market. Regulatory, product quality / shelf life and efficacy, formulation development, and cost are among the main obstacles that hamper a stronger positioning of biological products.

Nevertheless, where one sees challenges, others see opportunities. These hurdles that need to be addressed are basically the spur for the change we want to see in the biological sector. The fact is, even if the trend is positive, biological products will only be able to compete or be used in synergy with conventional products if some of these limitations and complexities are solved and better managed.

For instance, regulatory frameworks through the years have been seen by many to be a hindrance for biologicals, not only because of the major difference in the regulatory frameworks, procedures, and data requirements among countries / regions (e.g., US, EU), but also because of the lack of clear distinction between biologicals and chemicals. This, however, has been changing and there is a clear shift from the regulators to better understand biologicals and their importance in the sector (e.g., modifications to the Regulation (EC) No. 1107/2009 and Regulation (EU) 2019/1009). Time and costs for registrations, again very different across the globe, can also pose a major limitation to many companies. Regulators need to respond faster to this issue, to avoid hindering innovation from SMEs, but also to comply with their own demand for alternatives to the conventional products (e.g., EU Farm to Fork initiative).

Biologicals, especially microbial formulations, have been facing skepticism from farmers. Lack of efficacy and versatility, poor product quality, and shelf life are still damaging the image of microbials. However, new technology developments, not only from the private sector, but also from collaborations between national institutes and academia, are changing this view. Currently, biologicals are more effective than they ever have been and better formulated to be integrated into conventional agricultural practices. Products are becoming more versatile in terms of application range, resistant to environmental conditions, able to be formulated in combination with conventional AIs or other biologicals, and have shown better shelf life and storage at different conditions. Even the offer on co-formulants and adjuvants is becoming more diverse, with companies investing in new resources that are more sustainable, innovative, and biocompatible.

Biologicals are not new to the agriculture industry. However, for many years it was hard for them to compete with conventional chemicals. With the new research tools and better understanding of their functions, formulation advances and technologies, as well as the increasing trend for sustainable agriculture, consumer awareness, and supportive regulations, they finally have a chance to thrive as a valuable tool for farmers.

Q6. Could you give some advice for companies which would like to extend or enter into biological field?

The general advice we can give to our clients is to be knowledgeable and realistic about their active ingredient; for example, the strengths, incompatibilities, limitations, biology, and chemistry. Work to guarantee a stable active ingredient before formulating and understand that R&D is a key element to create a robust and quality product. Also have a clear idea of the intention of product use, application, and market (e.g., EU and U.S. market, organic farming to avoid future regulatory hurdles, or the need to re-formulate). These are all notions that can help to ease both the formulation and regulatory journeys, and consequently save costs and time. Finally, be agile enough to pursue different approaches from conventional agrochemicals when formulating a biological product.

In conclusion, Battelle offers complete turn-key solutions for the entire development and regulatory process of biologicals. 

If you'd like to share your company/solutions story, please contact Grace Yuan via: grace@agropages.com