Laws and Regulations

Abstract

ReLEAF's regulatory review identifies three separate questions: how the agricultural output is classified, how the engineered production culture is contained, and which requirements apply to the bioreactor. The most important finding is that a potential regulatory pathway is not an approval. A fertilizer or plant-biostimulant route is being investigated for ReLEAF's cell-free output, while the classification of the engineered Bacillus subtilis culture and the final equipment requirements remain separate questions. For post-Jamboree development, BoPEP4 will also be investigated as a potential gray-mold-control product in Taiwan. This use may trigger a pesticide/fungicide pathway distinct from the fertilizer or plant-biostimulant route.

Our analysis covers Taiwan, the European Union, the United States, and potential Southeast Asian markets. Taiwan is our development and validation environment. Our current commercialization plan prioritizes the Philippines as the first international expansion market, with the European Union considered for a later stage.

The review draws on primary legal sources and an industry briefing from Cheng Han Biotechnology (正瀚生技). It also identifies unresolved questions concerning product composition, residual cells and DNA, efficacy evidence, and applicable contained-use requirements. These gaps are treated as development tasks, not as evidence of regulatory compliance. Regulation is therefore not the final checkpoint of ReLEAF – it is one of the constraints that shape what we build, what we claim, and where we sell it.

Regulation as Product Design

ReLEAF is a three-part system: the bioreactor, the engineered production culture, and the cell-free agricultural output. We examined these components across Taiwan, the European Union, the United States, and potential Southeast Asian markets. The same biological output may be treated differently depending on its composition, intended function, claims, and jurisdiction. We therefore treated regulation as part of product design rather than a final approval step.

Our regulatory analysis follows:

Function → Claim → Classification → Requirement → Market Access

Organic Farming Compatibility

ReLEAF's organic-farming compatibility depends not only on whether viable engineered Bacillus subtilis cells enter the agricultural environment, but also on whether each country's organic standards permit agricultural inputs manufactured using genetically engineered organisms. Although ReLEAF's bioreactor is designed to retain the production bacteria behind a 0.2 µm hollow-fiber membrane and deliver cell-free protective proteins and peptides, this containment design does not automatically establish organic eligibility. The following assessment follows ReLEAF's planned market-entry sequence.

Overall strategy

ReLEAF should initially prioritize conventional agricultural applications while conducting organic-input assessments in parallel with its market expansion. Taiwan and the Philippines provide the first opportunities to obtain jurisdiction-specific guidance; Thailand, Vietnam and Indonesia can be assessed as the Southeast Asian strategy develops. The United States and European Union warrant early legal review because their organic standards explicitly restrict genetic engineering or products produced using GMOs. Malaysia should be assessed before regional commercialization is expanded there.

Across all markets, ReLEAF should maintain documentation of viable-cell retention, membrane integrity, residual genetic material, product composition and manufacturing controls. These data support biosafety and product-quality assessments, but they do not override organic standards that restrict the production method itself. Any claim of organic compatibility should therefore be made only after the relevant authority or certification body confirms that the specific formulation and manufacturing process satisfy the applicable requirements.

Three Components, Three Regulatory Questions

ReLEAF does not enter the agricultural environment as one undifferentiated product; ReLEAF’s innovation is so advanced and niche that we are the first ever team to create a system that delivers protectants to plants in stress on-site with a bioreactor, a strain of bacteria, and some proteins! The project is so nuanced that it’s great as a whole, but commencing it is a bit tangled and abstruse. Therefore, we thought to break the project down into three parts to register for commercialization instead of selling it as a bundle deal.

The hollow-fiber membrane (0.2 µm) retains the production culture and lets the soluble products through. Under Regulation (EU) 2019/1009, PFC 6(B) is the category for non-microbial plant biostimulants, and PFC 6 covers functions including improving plant tolerance to abiotic stress. However, our review has not identified a general numerical residual-DNA limit in the Regulation that can be stated as a PFC 6(B) requirement. ReLEAF should therefore not claim a legal DNA threshold unless a specific provision, applicable delegated act, harmonised standard, conformity-assessment requirement, or competent authority interpretation is identified. Independently of the legal threshold, ReLEAF will validate its cell-free output by testing for viable production organisms and residual recombinant DNA, report the methods and detection limits, and describe the hollow-fiber membrane as “designed to retain cells” until retention has been experimentally validated. Containment is not only an engineering requirement; it determines the exposure pathway that regulators must consider. Separating the engineered production organism from the cell-free output lets regulators assess the two as distinct questions.

Function → Claim → Classification

Ask not “What molecule is this?” but “What is the product intended to do?” We call these three molecules biostimulants because of what they do in the plant. No authority has classified them, so the column below gives the category we are aiming at. Their intended functions are used to investigate whether a plant-biostimulant pathway could be appropriate for the final cell-free product. Because regulatory classification depends on the final formulation, claims, evidence, and jurisdiction, “Plant Biostimulant (PB)” below represents ReLEAF's current commercialization positioning rather than an approved legal classification.

Our intended function is therefore abiotic-stress resilience rather than control of pathogens, insects, or weeds. The three biostimulants address complementary stress conditions: BoPEP4 is being investigated for salinity tolerance, AtLEA14 for salinity-stress protection, and ACCD for heat-stress mitigation through reduction of stress-induced ethylene. These positions represent ReLEAF's current commercialization strategy, not a final legal classification by any regulatory authority.

Because iGEM Grand Jamboree has a white list for high school teams, GEMS-Taiwan 2026 would not be able to test with gray mold, but instead only to validate on abiotic stress improvements. After the Grand Jamboree, when ReLEAF became a full-time commercialized company, ReLEAF plans to pivot BoPEP4 towards helping farmers with the persistent issue of Botrytis cinerea (gray mold) as well as salinity stress. Additionally, ReLEAF plans to expand AtLEA14’s stress responses to cater to drought, osmotic, and salinity stress because Late Embryogenesis Abundant proteins are established to be one of the many protectants with broad-range stress-alleviation abilities.

Three Target Markets

Taiwan European Union United States

Taiwan

Taiwan: Development and Validation

Taiwan is where we build and test ReLEAF. Our lab work, plant trials and farmer meetings are all here, and it is where we would register first. The main regulatory question for the cell-free output is whether its composition, function, and claims fit an existing fertilizer-related category.

Cell-Free Output

Taiwan's fertilizer specifications recognize 植物生長輔助劑類 (Plant Growth Auxiliary Materials / “Biostimulants”) among its fertilizer categories. However, this does not establish that ReLEAF's protein- or peptide-based formulation automatically belongs in that category. Taiwan's Ministry of Agriculture oversees both routes. The Agriculture and Food Agency registers fertilizers under the Fertilizer Management Act, and the Animal and Plant Health Inspection Agency handles pesticides under the Pesticide Management Act. We would confirm our formulation and claims with the Agriculture and Food Agency.

If registered as a fertilizer, ReLEAF would need a defined and reproducible composition, safety and quality data, efficacy data, labeling and registration information. APHIA told us the review itself takes about 30 days once the file is complete.

Separating Abiotic-Stress and Fungicide Claims: Avoiding Pesticide Positioning

ReLEAF is investigating two distinct application pathways. The first focuses on abiotic-stress resilience, including potential applications of BoPEP4 for salinity tolerance, AtLEA14 for salinity, drought, and osmotic stress, and ACCD for heat-stress mitigation. These applications may warrant investigation under Taiwan’s fertilizer or plant-growth-related regulatory framework, subject to confirmation of the product category and supporting efficacy data.

The second pathway emerged after the Jamboree: investigating whether BoPEP4 can control gray mold (Botrytis cinerea), a fungal plant pathogen. This is a separate research direction and may require assessment under Taiwan’s Agro-pesticides Management Act. We will not assume that the product automatically qualifies as a microbial pesticide or fungicide. Its classification depends on the active substance, final formulation, intended use, and the competent authority’s interpretation.

This distinction matters because ReLEAF’s engineered Bacillus subtilis is intended to remain contained in the bioreactor. The agricultural product under investigation is the cell-free output, not the intentional release of engineered bacteria into the field. We therefore need to clarify whether a cell-free product produced by engineered microorganisms falls within an applicable pesticide category and what evidence would be required.

Until efficacy and classification are confirmed, gray-mold control remains a proposed research application rather than an established product claim or approved use.

Engineered Production Strain

The engineered B. subtilis is assessed separately from the cell-free output. Our current review did not identify a general Taiwan contained-use GMO framework that clearly resolves this specific engineered bacterial production scenario.

We therefore treat the applicable pathway as unresolved. Before commercial deployment, we would seek clarification from the relevant authority concerning manufacture, contained use, storage, transport, and waste handling. We will not describe the system as certified for contained use until the applicable framework and evidence requirements have been confirmed.

Bioreactor

The bioreactor is an equipment rather than the agricultural product itself. Its requirements depend on the final hardware configuration, including electrical systems, pumps, pressure-bearing components, sensors, and fluid-contact materials. The final commercial design would therefore require a separate equipment-safety and conformity assessment.

European Union

European Union: A Market With High-Risk High-Reward

The EU provides a clear framework to investigate ReLEAF's intended function. Under Regulation (EU) 2019/1009, PFC 6 covers plant biostimulants, including non-microbial PFC 6(B). The regulation explicitly includes improvement of tolerance to abiotic stress within the plant-biostimulant function.

ReLEAF’s Potential Pathway

For now, ReLEAF’s experiment data can qualify for microbial fertilizers, biofertilizers, or plant biostimulants where applicable throughout jurisdictions. In the near future, where ReLEAF is given the opportunity to expand its data on proving efficacy across multiple stresses (salinity, drought, osmotic, heat, and B. cinerea), ReLEAF would apply for two different registrations for farmers to choose between: fertilizer or fungicide — the bacteria vials would be sold separately depending on the purchase between our fertilizer product or fungicide product.

Table 5. Questions ReLEAF Needs To Answer To Commerce In the European Union

Question	ReLEAF Consideration
What does the product do?	Improve tolerance to abiotic stress → potential PFC 6(B)
What is the product made from?	Cell-free proteins/peptides → CMC eligibility must be established
Does it work?	Claims must be supported by efficacy evidence
Is it safe and consistent?	Composition, contaminants, stability, and quality require assessment
Can it enter the EU market?	Applicable conformity assessment must be completed

The EU framework therefore creates a direct feedback loop between our wetlab work and regulatory strategy. The intended claim determines the evidence we need to generate: salinity-tolerance evidence for BoPEP4, drought or osmotic-stress protection evidence for AtLEA14, and heat-stress mitigation evidence for ACCD. These experimental results would support the biological rationale for the corresponding claims, but would not by themselves determine the final regulatory classification.

For ReLEAF’s potential abiotic-stress applications, PFC 6(B) under Regulation (EU) 2019/1009 is a pathway worth investigating because it covers non-microbial plant biostimulants. However, this category does not automatically establish eligibility for ReLEAF’s cell-free output. The product’s composition, function, applicable component-material requirements, conformity assessment, and supporting evidence must be evaluated before determining whether this route is viable.

The proposed BoPEP4 application against gray mold (Botrytis cinerea) is a separate regulatory question. A product intended to control a fungal plant pathogen may fall under the EU plant-protection-product framework, including Regulation (EC) No 1107/2009, rather than the plant-biostimulant pathway. Its classification would depend on the product and intended claims.

Accordingly, ReLEAF should assess the abiotic-stress and gray-mold applications separately. We should not assume that a potential PFC 6(B) route for abiotic-stress claims would authorize a fungicidal claim. Any applicable requirements for the active substance, final formulation, safety, efficacy, and market authorization must be confirmed for the relevant route.

Bioreactor and Engineered Culture

The bioreactor and engineered production culture remain separate from the cell-free fertilizing product. Their applicable equipment and contained-biotechnology requirements must be assessed according to the final design and production system.

United States

United States: A Decentralized Pathway

The United States differs from the EU because agricultural-input requirements can involve both federal and state authorities. For ReLEAF, the main questions remain:

1. How is the cell-free product classified?
2. Do its claims trigger pesticide/plant-regulator regulations?
3. Which state-level fertilizer or beneficial-substance requirements apply?
4. How is the engineered production microorganism regulated?

⇒ ReLEAF therefore cannot transfer an EU classification directly to the United States.

Cell-Free Output

ReLEAF’s potential US pathway must be evaluated according to the identity of the marketed product, the active substance, the intended use, and whether viable engineered microorganisms are present in the product.

For the proposed abiotic-stress applications, the team must first identify the appropriate federal and state regulatory frameworks for the final cell-free formulation and its intended agricultural claims. A fertilizer or plant-biostimulant positioning should not be treated as confirmed until the relevant requirements have been assessed.

For the proposed BoPEP4 gray-mold application, the team must separately investigate the US Environmental Protection Agency’s pesticide framework under Federal Insecticide Fungicide Rodenticide Act (FIFRA). The distinction between a microbial pesticide and a biochemical pesticide may be relevant: the fact that a peptide is produced by bacteria does not, by itself, establish that the marketed cell-free product is a microbial pesticide. The applicable category and authorization requirements must be determined from the final formulation and intended use. Toxic Substance Control Act (TSCA) biotechnology requirements and United States Department of Agriculture Animal and Plant Health Inspection Service (USDA-APHIS) biotechnology rules should likewise be assessed according to their applicability to the specific organism, activity, and product. None of these pathways should be presented as a confirmed clearance route before the relevant classification questions have been resolved.

Engineered B. subtilis

For the contained engineered microorganism, the Environmental Protection Agency (EPA)’s Toxic Substances Control Act (TSCA) biotechnology framework under ‘Title 40 of the Code of Federal Regulations Part 725’ (40 C.F.R. Part 725) is a principal federal framework to investigate. Whether the final ReLEAF strain qualifies for an exemption or requires notification/review must be determined from the final strain and containment conditions.

Equipment

The bioreactor requires a separate equipment-safety assessment based on its final electrical, mechanical, pressure, and installation characteristics.

Table 6. The Three Target Markets Compared

	European Union	United States
Main Regulatory Structure	Harmonized EU fertilizing-products framework	Federal agencies + state requirements
Plant Biostimulants	PFC 6 under Regulation (EU) 2019/1009	No single harmonized federal biostimulant pathway
Product Claims	Important for PFC classification	Important for determining regulatory jurisdiction
Fertilizer Requirements	EU-wide harmonized framework for CE-marked products	Primarily state-specific
Engineered Microorganisms	Separate assessments from final product	Product- and use-specific federal jurisdiction
Market Strategy	EU-level harmonized pathway	Select target states individually

Expansion Markets

After Taiwan and the Philippines, ReLEAF would investigate selected Southeast Asian markets rather than entering the region simultaneously. Here, ReLEAF explores its possible market expansion lineups through categories such as but not limited to: bioreactor, B. sub culture, output laws; farmland mass; smallholder structure; entry ease; technology acceptance; and on-site deployment fitness. Below, Table 7 shows how we ranked them, Table 8 offers the scoring guidelines, and Tables 9 through 14 are the subtables that expands on the Y’s and N’s (Yeses and Noes) of each category used to weigh the markets and what subcategories are entailed within one category. Additionally, each country’s rationale in the market lineup is explained after Table 14.

The United States ranks first in the weighted screening score (32), but its entry-ease score is only 1/5 because of distance and the practical burden of establishing a route across federal and state systems. We therefore prioritize the Philippines as the first international expansion market, followed by Thailand, while treating the United States as a high-value but resource-intensive target. Vietnam and Indonesia remain later-stage candidates under the current scoring model; the EU is a later-stage target for the cell-free output because the engineered production culture raises a separate regulatory barrier. For more detailed information, visit the business plan.

Expansion Market Scoring

Scoring System

The current country rankings primarily compare the feasibility of investigating ReLEAF’s abiotic-stress and cell-free plant-biostimulant applications. They do not constitute a complete assessment of the separate regulatory pathway that may apply to BoPEP4 for gray-mold control. Because pesticide classification, efficacy requirements, and authorization costs may differ substantially from those for plant biostimulants, the rankings should not be interpreted as establishing market-entry feasibility for the proposed fungicidal application. That pathway requires a separate assessment.

Our intended sequence, based on the chart, is therefore:

Taiwan → Philippines → Thailand → United States → Vietnam / Indonesia → European Union → Malaysia

Rationale by Market

Case Studies (Kelpak / Sagarika) & the Cheng Han Biotechnology Briefing

Kelpak Sagarika

Kelpak

Kelpak provides a useful case study for understanding why ReLEAF cannot assume that one regulatory classification will apply globally. Kelpak is a seaweed-derived agricultural biostimulant whose regulatory treatment differs across markets, even though the underlying product remains substantially the same. This makes it particularly relevant to ReLEAF, where the same cell-free protectant output may encounter different legal definitions, registration requirements, and evidence standards depending on the destination market.

Table 15. The 3 Big Markets and Regulatory Treatment of Kelpak

Market	Regulatory Treatment of Kelpak	What This Demonstrates
European Union	CE-marked EU fertilizing product	Harmonized plant-biostimulant framework
Taiwan	Registered fertilizer product	National fertilizer classification
United States	Agricultural input with organic-input approval; requirements can also depend on state	Decentralized regulatory system

The table shows the pattern: Kelpak does not change when it crosses a border, but its pathway does. We therefore treat each target market as a separate regulatory assessment. In the European Union, Kelpak is positioned within the EU fertilising-products framework, demonstrating how a harmonized regional system can provide a defined pathway for plant-biostimulant products. In Taiwan, its registration as a fertilizer illustrates how the same type of agricultural input can instead be evaluated through a national fertilizer classification system. In the United States, Kelpak's market position demonstrates the more decentralized nature of agricultural-input regulation, where federal considerations, organic-input requirements, and individual state requirements can all affect market access.

The contrast is important for ReLEAF because regulatory classification depends not only on the biological material itself, but also on its formulation, intended function, claims, and jurisdiction. Kelpak therefore serves as the main regulatory case study for our project: the product does not change simply because it crosses a border, but the regulatory pathway governing that product can change substantially. ReLEAF consequently treats each target market as a separate regulatory assessment rather than assuming that approval or classification in one jurisdiction automatically transfers to another.

Sagarika

Sagarika is a useful example of a seaweed-derived plant biostimulant, rather than a confirmed microbial biostimulant. IFFCO describes Sagarika Liquid as a concentrated extract of red and brown marine algae (28% w/w), containing naturally occurring plant-growth substances and nutrients. Its official product information therefore supports describing it as a seaweed-extract product; the sources reviewed do not establish that the marketed product is itself a microbial inoculant. Sagarika is relevant to ReLEAF as a comparison for how an agricultural biostimulant is formulated, positioned, and regulated, but it is not a direct biological analogue for ReLEAF's engineered production culture or purified/cell-free protein output. India's regulatory framework for biostimulants was amended through Notification S.O. 882(E) of 23 February 2021, which added biostimulants to the Fertiliser Control Order, 1985, including Clause 20C and Schedule VI.

For ReLEAF, this reinforces the importance of establishing product identity, composition, efficacy, safety, traceability, and containment early.

Industrial Perspective: Cheng Han Biotechnology (CH Biotech)

Where Does ReLEAF Sit?

The three components therefore form one manufacturing system but do not necessarily share one regulatory identity.

Exploring the Gray

A Dual-Track Regulatory Strategy

ReLEAF’s regulatory strategy separates its abiotic-stress applications from its proposed gray-mold application.

Track 1) Abiotic-stress applications. The team will investigate appropriate plant-biostimulant or fertilizer pathways for the cell-free output intended to support plant tolerance to abiotic stress. Potential claims include BoPEP4 for salinity tolerance, AtLEA14 for salinity, drought, and osmotic stress, and ACCD for heat-stress mitigation. Each claim requires relevant efficacy evidence, a defined product specification, and confirmation of the applicable regulatory category.

Track 2) BoPEP4 for gray mold. Following the Jamboree, the team will investigate whether BoPEP4 can control Botrytis cinerea and whether the resulting cell-free formulation falls within Taiwan’s agro-pesticide/fungicide framework. This track requires separate efficacy studies and regulatory consultation. We will not assume that the output is legally a microbial pesticide simply because engineered bacteria produce it.

Future Regulatory Requirements