Chemistry Assessment

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Bernadette Boutin-Muma
Evaluation Officer
Chemistry Evaluation Section
Compliance Laboratory Services and Regional Operations Directorate

Outline of Presentation

• Product chemistry data requirements of technical grade of active ingredient (TGAI) and end-use product (EP)
• Chemistry data assessment (what we look for)
• Actives under re-evaluation
• Common deficiencies associated with the data submitted by applicants
• Challenges/new developments in chemistry evaluation process

Product Chemistry

• Product chemistry is required in order to:
  • comprehensively characterize product composition
  • determine uniqueness of each source of active ingredient
  • assess safety of each pesticide to human health and environment.

What the Chemistry Evaluation Section (CES) Reviews

• We review:
  • Product chemistry of :
    • Conventional pesticides (agricultural, antimicrobial etc.)
    • Non-conventional pesticides (plant extracts, essential oils, commodity chemicals, etc.)
    • Environmental residue methods
• CES does not review product chemistry of microbial pesticides.

Submissions for Review

• Cat A (new active ingredient, major new use)
• Cat B (new source of an active ingredient, new end-use products, amendment to product registration)
• Cat C (minor formulation changes to specifications)
• Cat D (IMEP)

Chemistry Data Requirements

• Full details as required according to:
  • Regulatory Directive DIR98-04: Part 2-Technical Product (TGAI)
  • Regulatory Directive DIR98-03:Part 3-End-use Product (EP)
  • Regulatory Proposal PRO2007-02
    Guidelines for the Registration of Low-Risk Biochemicals and Other Non-Conventional Pesticides

Data Requirements for New TGAI : Cat A

• Data requirements:
  • Product identity
  • Product composition
  • Chemical and physical properties
  • Submittal of analytical standard
• GLP standards (EPA 40 CFR 160, OECD)
• Test guidelines

Product Identity DACO 2.1-2.9

• Applicant's name and address
• Manufacturer's name and address and manufacturing plant location
• Trade, common and chemical names (IUPAC,CAS)
• CAS number
• Structural formula
• Molecular formula and molecular weight

Spiromesifen

CAS: 2-oxo-3-(2,4,6-trimethylphenyl)-1-oxaspiro[4.4]non-3-en-4-yl 3,3-dimethylbutanoate

Product Composition DACO 2.11

• Manufacturing Process
  • Starting materials (specifications, MSDSs)
  • Manufacturing process (chemical pathways)
  • Formation of impurities/impurities of toxicological concern
• Specifications
  • Specifications for active and impurities
  • Specifications vs batch data
  • Statement of Product Specification Form (SPSF) signed and dated
• Methodology/validation data
  • Analytical methods
  • Validation data (precision, accuracy, linear range and selectivity)
  • Batch data (analytical data from five batches, pilot scale/full scale production)
  • Confirmation of identity of active and impurities

Chemical and Physical Properties DACO 2.14

• Provide supportive information on the identity of active ingredients and product (colour, odour, physical state etc.)
• Are used in hazard assessment (pH, flammability)
• Provide supportive evidence in evaluating studies required by other science divisions
  (e.g. environmentally relevant properties: vapour pressure, dissociation constant, water solubility, n-octanol-water partition coefficient)

Data Requirements for New Source of a Registered TGAI: Cat B

• All data listed for new active ingredient (DACO 2.1 to 2.14)
• Chemical equivalence assessment based on:
  • Manufacturing process
  • Specifications
  • Batch analysis
  • Microcontaminant data

Data requirements for End-use Products (EPs) CATs A/B

• Part 3 data (DIR98-03):
  • Product identification
  • Formulation process
  • Specifications
  • Product analysis (enforcement methods)
  • Chemical and physical properties

Cat C Submission Data Requirements

• Submission based on precedent
• Specifications and label are required
• Process streamlined by Cat C section and CES:
  • Review by Cat C section (repack, no change in product specifications)
  • Review by Chemistry section (minor formulation changes)

Re-evaluation (Chemistry)

• The purpose of chemistry re-evaluation:
  • To update the chemistry data to current standard
  • To convert active guarantee from minimum to nominal
  • To address TSMP (Toxic Substances Management Policy) issues, if any

Common Deficiencies/Data Gaps

• Cat. A:
  • No batch data from full-scale production
  • No long-term storage stability study
• Cat. B:
  • Specifications not complete (SPSF)
  • Confirmation of identity not provided
  • Method not specific/Insufficient validation data
  • Specifications not supported by batch data
  • Outstanding data gaps not adequately addressed

Environmental Residue Methods

• CES supports the Environmental Assessment Directorate by reviewing analytical residue methods for parent and major metabolites in soil, sediment and water.
• CES ensures through its assessment that methods are fully validated and suitable for post-registration monitoring purposes.

Challenges/Process Improvements

• Challenges:
  • Cat C submissions
    • Category C eligibility not always evident to applicants.
    • Streamlining of process to expedite review.
• Process Improvements:
  • PRO2007-02: Guidelines for the Registration of Low-Risk Biochemicals and Other Non-Conventional Pesticides.
  • Implementation of DIR2008-01: Registering a New Source of Technical Grade Active Ingredient Under the Protection of Proprietary Interests in Pesticide Data Policy.

Data Quality/Efficiency of Process

• Evaluation process works efficiently for applicant and agency when:
  • original data package is correct and complete
  • applicant responds quickly and adequately to identified data gaps

Summary

• Good quality data package based on the outlined requirements and pre-submission consultation with the agency on appropriate data requirements for a specific product, if needed, will facilitate the chemistry review process.
• Chemistry section intends to address new challenges and make improvements to the process as the need arises.

References

• DIR98-04:Chemistry Requirements for the Registration of a Technical Grade Active Ingredient or and Integrated System Product
• DIR98-03:Chemistry Requirements for the Registration of a Manufacturing Concentrate or an End-use Product Formulation from Registered Technical Grade Active Ingredient or Integrated System Products
• PRO2007-02: Guidelines for the Registration of Low-Risk Biochemicals and Other Non-Conventional Pesticides
• DIR2008-01: Registering a New Source of Technical Grade Active Ingredient Under the Protection of Proprietary Interests in Pesticide Data Policy