registration of biological remedies vs. bio- fertilizers ... · efsa (2015; 13(4):3056): conclusion...

Registration of Biological Remedies vs. Bio-Fertilizers in South Africa

15 November 2017CSIR CONFERENCE CENTRE

THILIVHALI NEPFUMBADATECHNICAL ADVISOR ACT 36 OF 1947

ThilivhaliN@daff.gov.za012 319 6979

Agricultural Remedies

An agricultural remedy: is defined as any chemical substance or biological

remedy, or any mixture or combination of any substance or remedy intended or

offered to be used for the destruction, control, repelling, attraction or prevention

of any undesired microbe, alga, nematode, fungus, insect, plant, vertebrate,

invertebrate, or any product thereof (PGRs desiccants and legume inoculants),

but excluding any chemical any chemical substance, biological remedy or other

remedy in so far as it is controlled under Medicines and Related Substances Act

101 of 1965 or the Hazardous Substances Act 15 of 1973

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INPUTS REGULATED UNDER ACT 36

DAFF Act No. 36 of 1947

Fertilizers

Agricultural Remedies

Insecticides

Fungicides

Herbicides

Bio-pesticides and legume inoculants

Swimming pool remediesAnimal Feeds

Stock RemediesWood Preservatives

Plant Growth Regulators

Adjuvants

Scope of Agricultural Remedies Regulated

Scope of Biological Remedies Regulated

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Microbials, PGRs, Legume inoculants

(e.g. fungi, viruses, bacteria)

Macrobials(e.g. Preditory mites & EPNs)

Botanical/Plant Extracts

(e.g. Sea weed extract)

Semiochemical/Hormones

(e.g.Auxins & gibberellins)

Novel Technologies

(e.g. RNAi)

• Fortune Magazine 2003 “Biotech’s Billion Dollar Breakthrough”

• The process was discovered in the 1990’s and additional research in the area led to winning a Nobel Prize for their work in 2006 by Drs. Andrew Fire and Craig Mello.

• (RNAi) is a natural process cells use to turn down, or suppress the activity of specific genes (dimer switch). It was previously known as (co-suppression, post transcriptional gene silencing or quelling).

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Ribonucleic Acid Interference (RNAi Novel Technology – History

• Agricultural Uses: (SAFETY?)

• RNAi has been used to generate male/female sterility, which is valuable inthe hybrid seed industry and public health uses i.e. vector control.

• Introduce novel plant traits and increase crop yield.

• Modification of metabolic pathway to enhance plant nutrients uptake and thepossibility to reduce toxins production.

•• Ability to apply a single liquid with multiple uses in plants i.e. drought

tolerance, plant stress adaptation, disease/PEST control and plant nutritioncombined in one.

• Plant growth regulatory effects, color formation or alter oil content inoilseed.

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RNAi USE PATTERNS

Section 3: 2 (a) of Act 36 of 1947,

agricultural remedy in respect of which registration is applied for should be suitable and sufficiently effective for the purposes of which it is applied for.

Complies with prescribed requirements.

It should not be contrary to the public interest (Bill of Rights).

The establishment where it is manufactured must be suitable.

Why Register Agricultural Remedies?

OTHER LEGISLATIONS IMPACTING ON IMPORTATION OR REGISTRATION OF BIOLOGICAL ORGANISMS

• Non Proliferation of Weapons of Mass Destruction Act, 1993(Biological weapons).

• National Environmental Management: Biodiversity Act, 2004(Alien and invasive species).

• Agricultural Pest Act,1983).• Genetically Modified Organisms Act, 1997.• Animal Disease Act, 1984.• National Health Act, 2003.• Medicine and Related Substances Control Act, 1965• Food stuff, cosmetics and disinfectant act, 1972• etc

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INTERNATIONAL STANDARDS/CONVENTIONS FOR PHYTOSANITORY MEASURES

1. FAO Guidelines for export, shipment, import and release of biologicalcontrol agents and other beneficial insects (2005)

NB: The scope of this standard does not include living modified organisms,issues related to registration of biopesticides, or microbial agentsintended for vertebrate pest control.

2. FAO: Code of conduct for the import and release of exotic biologicalcontrol agents (1996)

NB. The standard describes the Code of conduct for the import and Releaseof Exotic Biological Control Agents (parasitoids, predetors, parasites,phytophagous arthropods and pathogens) for research and release intothe environment including those packed or formulated as products.Governments that are already fulfilling the objective of this Code byregulation or other means may consider adapting their existing systemsin the light of this code.

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INTERNATIONAL STANDARDS/CONVENTIONS FOR PHYTOSANITORY MEASURES

3. NAGOYA PROTOCOL: Access to genetic resources and their fair andequitable sharing of benefits arising from their utilization to the ConventionOn Biological Diversity (2011)

NB: The scope of the protocol shall apply to genetic resources within the scope ofArticle 15 of the Convention and to the benefits arising from the utilization of suchresources. This protocol also apply to traditional knowledge associated with geneticresources within the scope of the Convention and to the benefits arising from theutilization of such knowledge.

4. International Plant Protection Convention- IPPC (1997)

NB. The purpose of the convention is to secure common and effective action to preventthe spread and introduction of pests of plants and plant products and to promoteappropriate measures for their control.

PREAMLE: Parties should take into account international principles governing theprotection of plant, humans and animal health and the environment.

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SECTORS USING BIOLOGICAL PRODUCTS

• Agriculture (bio-fungicides, bio-insecticides, growth regulators etc)

• Public health (Bt for vector control)

• Forestry (similar to agricultural uses)

• Environmental remediation (e.g. odor suppression – does not fall under the scopeof Act 36)?

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DATA REQUIREMENTS IN GENERAL

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• Locally generated efficacy/phytotoxicity /residues

» A minimum of three efficacy trials per crop done in three bioclimatic zones done in one season or over two seasons

» For residues =, a minimum of five trials done over one season or two seasons

• Toxicology data (OECD GLP accredited lab studies using OECD test guidelines)

» Department of Health Guidance document is available on request- Botanical pesticides-Microbiological pest control agents-Biochemical pest control agents

» Scientific publication submitted as supporting data

REPORTING TOXICOLOGICAL DATA

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Each report should include a copy of Good Laboratory Practice certificate (OECD)

Full description of tests results, test procedures and analytical methods

Test method(s) description should be supplied (OECD, US EPA, CIPAC/AOAC etc)

» Supporting literature studies- A copy of the journal article/publication- Motivation for including such information

BIOCHEMICAL/SEMIOCHEMICALS TOXICOLOGICAL DATA REQUIREMENTS

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Active ingredient(s) and active constituents

Formulation composition/declaration

Kinetics and metabolism studies

Level one: Toxicological data of active ingredient

Formulation toxicology data

Level 2:Supplemental toxicological studies (chronic studies with the active ingredient)

Storage stability test Analytical methods if it is a new product

MICRO ORGANISMS GENERAL DATA REQUIREMENTS

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• Toxicology studies should be submitted (Human and environmental FATE)

• Shelf life and the active ingredients

• If an applicant changes the strain of micro-organism for a registered product, new efficacy data, toxicology must be supplied

• Any known metabolites i.e. primary/secondary must be reported

IDENFICATION OF BIOLOGICALS CONTROL AGENTS

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• Bacteria = (Cultural, microscopic and molecular sequencing technique)

• Fungi = (Morphological, Molecular Techniques (ITS gene region) and DNA bar-cording)

• Insects = (Morphological and DNA bar-cording)

• Nematodes = (Morphological and DNA bar-cording)

• Viruses = (Cultural, microscopic and molecular sequencing technique)

• Plants extracts/Hormones = (Chemical analysis = 5 batch or Certificates of Analysis - COAs)

LABEL CLAIMS

General label claims not encouraged (e.g. all crops recommendations)

Codex Crop Groups are used

Number of applications

Timing of application

Pre-harvest intervals (normally not an issue with biological products with no dietary requirements or residues)

Shelf life

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Berries(Blueberry

group)

Blackberry or Raspberry;

Blueberry or Currants, etc

Whole group

Stone fruit(Peaches)

Apricots, Nectarines,

Plums, Peaches and

Cherries

Whole group

CODEX CROP GROUPING FOR THE REDUCTION OF COSTS ASSOCIATED WITH DATA

GLOBAL HARMONIZED SYSTEM FOR THE CLASSIFICATION AND LABELLING OF CHEMICALS (GHS)

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Labeling of agricultural remedies

Labeling of fertilizers and bio-fertilizers

» Hazard Classes (WHO Hazard Classes)» OECD testing guidelines (Dosage of 5000 mg/kg /bw for acute studies)

List Of Biological Control Agents vs Bio-FertilizersMultiple use patterns

ORGANISM Function(s)

Agrobacterium radiobacter Plant growth promotion/bio-fungicide

Agrobacterium vitis Plant growth promotion/bio-fungicide

Bacillus subtilils Growth promotion/bio-fungicide

Trichordema harzianum Growth promotion/bio-fungicide

Pseudomonas fluorescens Growth promotion/bio-fungicide

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List Of Biological Control Agents vs Bio-Fertilizers

CATEGORY OVERLAPING FUNCTION STATUSYES/NO

Microbials YES

Legume Inoculants and Growth Promoting Organisms

YES

Plant Extracts/Botanicals YES

Bio-chemicals/HormonalSubstances

(e.g. Auxins and Giberellins)

Yes

Novel Technologies e.g. RNAi(Pesticide and Nutritional Benefits)

Yes

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Toxicological studies

Eco-toxicology and Environmental fateMammalian toxicology

Hazard Versus RiskHazard: ability to cause harm or damageRisk: is the porability for damage or harm to occurHAZARD X EXPOSURE = RISKPesticide X No of applications = Residues riskBiopesticides X NO applications = Contaminants risk

HARZARD VERSUS RISK DEFINITIONS

Toxins/metabolic by-products of toxicological concern

Inerts or formulants of toxicological concern (NPE Surfactants)

Contaminants− Human pathogens (e.g. E-coli, Shingella typhi, Salmonella

dysenteriae and Vibrio cholerae etc)

− OECD RERENCE PAPER (Issue Paper on Microbial Contaminants Limits 2011)

- Carriers

– Heavy metals etc

BIOLOGICAL PRODUCTS RISKS

BIOPESTICIDES REVIEWS BY EFSAEFSA doi: 10.2903/j.efsa.2016.4524 = Risks for public health related to the presence of Bacillus cereus and other Bacillus spp. Including Bacillus thuringiensis in foodstuffs (Toxins and residues limits)

EFSA (2015; 13(4):3056): Conclusion on the peer review of the pesticide risk assessment of the active substance Trichoderma atroviride, strains IMI-206040, T11 (Secondary metabolites)

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Lowest observed effect level

Non observed effect level

Paracelsus 1493-1541(Alle ding sind gift und nichts ohn gift; alein die dosis macht das ein ding kein gift ist)

(All is poison, nothing is without poison; only the dose determines what isnot a poison)

WHAT IS A POISON?

GLOBAL MARKET

TRENDS

RESOURCE TO USE WHEN ATTEMPTING TO APPLY FOR AGRICULTURAL REMEDIES REGISTRATIONS

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OECD test guidelines

SA guidelines (http://www.daff.gov.za/daffweb3/Branches/Agricultural-Production-Health-Food-Safety/Agriculture-Inputs-Control)

Scientific publications

Data sourced from the internet

Legal agreement and authorization to access the data

Laboratory accreditation certificates are required

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THANK YOU