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Part 2 – Chemistry and Manufacture

1. INTRODUCTION

This chapter sets out the requirements and guidelines for submitting chemistry and manufacturing data as part of applications for:

approval of an active constituent
registration of an agricultural chemical product
approval of a label
variations to an approved active constituent or registered agricultural chemical product or approved label
issue of a permit

With respect to the chemistry aspects of s.14(4) and s.14(5) of the Agricultural and Veterinary Chemicals Code Act 1994 (Agvet Code).

Chemistry and manufacture includes aspects of:

the active constituent
the formulated agricultural chemical product
manufacturing process
quality control
specifications
batch analysis
storage stability
analytical methods
packaging and labelling.

2. TYPES OF APPLICATIONS

The nature of the application determines which Part 2 (Chemistry and manufacture) data module will be required. Each module requires a number of chemistry and manufacture data elements.

2.1. Modular categories

The data elements for Modules 2.1, 2.2, 2.3 and 2.4 relate to data requirements for a particular type of application and are related to the nature of the application. The modules are more fully explained in Module levels for modular categories in Volume 3, and also in the individual category chapters in Volume 2 Category requirements and guidelines.

Comprehensive assessment (Module 2.1) requires submission of a full chemistry and manufacture data package, containing all of the data elements listed in the column titled ‘Data required’ in Module levels for modular categories in Volume 3, according to the type of product or application in the column titled ‘Type of application’.

Reduced assessment (Module 2.2) and Limited assessment (Modules 2.3 and 2.4) comprise a sub-set of the data elements contained in Comprehensive assessment (Module 2.1).

2.2. Fixed categories

Applications which are evaluated under a fixed category (eg Category 7) may require submission of chemistry and manufacture data. The level of data corresponds to Module 2.1, 2.2, 2.3 or 2.4, depending on the application category, and is provided in the relevant category chapter in ‘Category requirements and guidelines’ in Volume 2.

Table 1 summarises how the modules relate to broad application types.

Table 1: Module levels and application types

Module level	Type of application
Module 2.1	New product with new active constituent, or new active constituent only (unless included in Module 2.2)
Module 2.2	New biological product with new active constituent, or new active constituent only (except those described in Module 2.1) New product with new active constituent which is used in household or industrial chemicals, or new active constituent only New product with new source of existing active constituent, or new source of an approved active constituent only Permit, new active constituent New product where the active constituent has been previously assessed under permit
Module 2.3	New product with existing approved active constituent
Module 2.4	Variations to chemistry and manufacture details of registered veterinary chemical products Extension of shelf life Extension of in-use shelf life Change to storage temperature/conditions Change to packaging material (immediate container and/or closure system) Other applications where assessment of stability data may be required Permit application where minor chemistry assessment is required

3. APPROVAL OF AN ACTIVE CONSTITUENT

Section 15 of the Agvet Code requires the APVMA to approve active constituent(s) which are contained in an agricultural chemical product intended for distribution, sale or use in Australia. This applies regardless of whether the product is formulated in Australia or overseas.

Section 17 of the Agvet Code requires the APVMA to keep a Record of Approved Active Constituents for Chemical Products and to enter particulars and any conditions of the approval into the Record.

Subsection 42(3)(e) of the Agvet Code Regulations provides that the APVMA may establish standards for approved active constituents. When the APVMA approves an active constituent, a standard, which establishes the minimum purity of the active constituent and the maximum contents of the relevant impurities (particularly those of toxicological significance), will be established by the APVMA. All approved active constituents used in agricultural chemical products for which an APVMA active constituent standard exists must comply with the standard on an ongoing basis as a condition of the active constituent approval.

The APVMA active constituent standards are available in Standards for active constituents on the APVMA website.

3.1. Approval of a new active constituent

Application for approval of a new active constituent may be made under Category 1, 2, 15, 16, or 17.

Data requirements for approval of a new active constituent are described in section 4.

3.2. New source of an approved active constituent

New sources of approved active constituents must be chemically and toxicologically equivalent to the first approval of that active constituent, and will be assessed against the data package used in the risk assessment of the first approval of that active constituent. Application for approval of a new source of active constituent must be made under Category 17 or 24.

The data requirements for a new/additional source of an approved active constituent are described in section 5.

3.3. Variations to the particulars or conditions of approval of an approved active constituent

An application for variation to the particulars or conditions of approval of an approved active constituent, such as changes to quality, specifications, or manufacturing process of an approved agricultural active constituent, must be made under Category 18.

The data requirements for variation to approved active constituent are described in section 6.

4. DATA REQUIREMENTS FOR APPROVAL OF AN ACTIVE CONSTITUENT

This section sets out the chemistry and manufacture data that must be submitted to the APVMA in support of an application for approval of a new active constituent (or as a manufacturing concentrate). These requirements apply to all active constituents prepared by chemical synthesis. The requirements for approval of active constituents derived from a living organism (plants, animals, micro-organism plus organisms that have been genetically modified) are set out in Guidelines for the Registration of Biological Agricultural Products available on the APVMA website.

An active constituent application may precede an application for registration of a new agricultural chemical product. However, the preferred approach is the simultaneous submission of the active constituent approval and agricultural chemical product registration application.

Data held by a third party (eg active constituent manufacturer or product formulator) may be required for the purposes of approval or registration, but may not be available to the applicant for commercial reasons. In this case arrangements should be made with the third party to provide the data directly to the APVMA, preferably at the same time as the application is lodged, with a covering letter including details of the application to which the data relate.

The following information must be provided with each application for active constituent approval. If the applicant believes that the requirement for information is inappropriate or irrelevant, the data heading must still be maintained and the statement ‘No information supplied’ inserted. A brief explanation to justify the absence of the required information must also be provided.

The data package for modules 2.1, 2.2, 2.3 and 2.4 should include whichever of the following data elements are required by the module level for the application.

4.1. Identification of the active constituent

Details of the identity of each active constituent must be provided. The nomenclature required includes the common name, chemical name, chemical structure and Chemical Abstracts Service (CAS) registry number.

Common name

The common name given in the Australian Standard (AS 1719 1994: Recommended Common Names for Pesticides) must be used if this is available.

If Standards Australia (SA) has not published or otherwise approved a name, the International Organization of Standardization (ISO) common name, or proposed ISO common name and where relevant, other proposed or accepted common names (synonyms), including the name (title) of the nomenclature authority concerned, must be provided.

Inquiries may be directed to Standards Australia for approval of new common name for a new active constituent: Projects Manager, Committee CH-005, Standards Australia International, GPO Box 476, SYDNEY, NSW 2001.

Chemical name (IUPAC and CA nomenclature)

The full chemical name, in accordance with both the International Union of Pure and Applied Chemistry (IUPAC) and the Chemical Abstracts (CA) nomenclature, must be provided.

Chemical Abstracts Service (CAS) registry number

The CAS number of the active constituent must be provided, if available. If the CAS number has not been allocated, write ‘not yet allocated’.

Manufacturer’s code number(s) and/or synonyms

Manufacturer or laboratory code numbers and/or synonyms must be provided.

Molecular and structural formula and molecular mass

The molecular formula, molecular mass and structural formula of the active constituent must be provided. For active constituents existing as salts or hydrates, the molecular mass of the free base or anhydrous form should also be provided. For polymeric compounds this should include weight average (M_w), number average molecular weight (M_n), molecular weight distribution.

The structural formula should include (where relevant), stereochemical properties of the active constituent eg geometric isomerism (cis/trans, E/Z), number of chiral centers and configuration at each center. Where possible, the structural formula should be given diagrammatically with all known stereochemistry.

Elucidation of structure and other characteristics

Confirmation of chemical structure of the active constituent and impurities must be provided. The elucidation of structure (eg the data and its interpretation) should be based on appropriate physical and chemical test results. This may include the following:

discussion of the synthetic route as evidence of structure
elemental analysis with theoretical values
discussion on ultraviolet (UV) characteristics including pH dependence shifts
infrared (IR) spectra
1H and 13C nuclear magnetic resonance (NMR) spectra
19F and 31P spectral data, where relevant
mass spectrum (MS)
any other related information used to confirm the structure (eg X-ray diffraction).

If elucidation of the structure of the active constituent and impurities present difficulties, the results of studies conducted on structure elucidation of the active constituent are acceptable.

4.2. Physical and chemical properties

All relevant physical and chemical properties of the active constituent and/or manufacturing concentrate must be provided. The information should include, as appropriate:

a general description (eg appearance, colour, odour, physical state)
stereochemical properties of the molecule, eg geometric isomerism, number of chiral centers and configuration at each center
if a new active constituent contains one or more chiral centers, it must be specified whether the active constituent is a pure enantiomer, racemate or fixed combination of non-enantiomeric isomers
if the active constituent is optically active, a specific optical rotation measurement with limits
melting point or range (for solids)
boiling point or range (for liquids)
if melting and/or boiling point cannot be determined because of decomposition or sublimation, the temperature at which decomposition or sublimation occurs
condensation point (for gases)
refractive index (for liquids)
density/specific gravity(for liquids)
UV absorption maxima and molar absorptivity
pH and pKa values
vapour pressure
Henry’s Law Constant
solubility in water expressed as g/L or mg/L, in the neutral range, acidic range (pH 4 to 6) and in the alkaline range (pH 8 to 10)
solubility in various organic solvents expressed as g/L or mg/L
n-octanol/water partition coefficient (Pow or log Pow)
hydrolysis in aqueous solution under acid, neutral and basic conditions
dissociation characteristics, if appropriate
flash point (where the melting point is below 40°C)
flammability including auto-flammability
explosive properties
photochemical properties
oxidising properties
auto-ignition temperature
corrosion characteristics
dangerous goods classification as per the Australian Dangerous Goods Code (ADG Code), the Department of Transport & Regional Services (DOTARS)₄, if applicable.

The purity of the test substance used to generate the physical and chemical properties must be stated. The applicant must also describe the methods used to generate the data provided.

Where the method used is described in a scientifically recognised publication or manual (eg those by Organization for Economic Cooperation and Development (OECD)5, Collaborative International Pesticide Analytical Council (CIPAC)6, the American Society for Testing Materials (ASTM)7, a reference to the relevant publication will suffice.

It is desirable that physical properties such as solubility in water and vapour pressure be determined from tests conducted at ambient temperature (20 25C). However, if data are available at another temperature, these may be provided. The temperature at which these tests were conducted, or other relevant test conditions, must be stated.

4.3. Stability data

Applicants must provide the results of stability studies (long-term and accelerated conditions) conducted on at least one batch of the active constituent.

Stability studies must establish the inherent stability of the molecule, in particular the degradation pathway and the identity of any degradation products, especially toxicologically significant impurities) formed during storage.

For storage stability studies, samples of the active constituent must be stored for a minimum of 14 days at 54°C and/or long term testing for up to 2 years at room temperature (30°C or under normal Australian warehouse conditions). If the active constituent is unstable at 54°C and 30°C, it may be stored at lower temperature (eg 0 - 5°C, between 2 and 8°C).

The active constituent content and, if appropriate, any toxicological significant impurities, must be monitored initially and at sufficient sampling frequency.

Details of the specific analytical test methods used for assay and toxicological significant impurities must be provided. The submission must include the actual stability results (ie raw data) and details of the analytical methods employed and determination of degradation products.

The effect of metal or metal ions on the stability of the active constituent must be provided if there is a likelihood that the active constituent will come into contact with metals/metal ions during its storage or use.

Guidelines suitable for the generation of such data have been prepared by the European Union (EU) and the United States Environmental Protection Agency (US EPA). Either protocol will be acceptable to the APVMA. However, testing must be undertaken in the proposed commercial packaging or smaller packages of the same construction and materials.

4.4. Method of manufacture of the active constituent

Manufacturer and site of manufacture

The name and business address of the manufacturer or manufacturers of the active constituent and the street address of the manufacturing plant(s) in which the active constituent is manufactured must be provided. If a toll or contract manufacturer is involved then their details must also be provided.

Description of the manufacturing process

An accurate description of the manufacturing process and process controls must be provided.

An acceptable description of the manufacturing process will include the following information:

an introductory paragraph detailing the number of chemical steps, whether the process is a batch or continuous process, and significant purification steps
a flow diagram of the synthetic processes that includes molecular formulae, chemical structure of starting materials, intermediates, reagents and chemical equations of the reactions involved reflecting stereochemistry, where relevant
relative amounts of each starting material and their order of addition
reaction conditions (temperature, pressure, pH and reaction times, etc), where these are critical
the duration and yield of each step of the process
information on intermediates which are isolated and purified
description of any purification procedures for the active constituent, including procedures to recover starting materials, intermediates or the final product
if a manufacturing concentrate is produced, details of the final concentration of the active constituent present, methods used to confirm the concentration, details of the diluents and/or any additives used.

The synthetic process must be described in sufficient detail to enable the APVMA to assess the potential presence of impurities of toxicological significance.

Quality control

The following information must be provided on the measures taken to ensure the quality of the active constituent:

specifications/purity for all starting materials, reagents and key intermediate products
measures used to monitor and assess the performance of an on-going manufacturing operation (eg analysis to determine the concentration of reactant or product to check the completion of a reaction)
tests and acceptance criteria (with justification including experimental data) performed at critical steps of the manufacturing process to ensure that the process is controlled
representative data relating to in-process quality control.

Impurities

Information on impurities that are or may be present in the active constituent at levels of greater than or equal to 0.1% must be provided. Note that toxicological significant impurities at any level must be characterised and reported. The submission with respect to impurities must include structural formulae and possibly a scheme for the formation of the impurity, followed by a text discussion of its formation.

Potential sources of impurities/related substances include:

impurities in the starting materials, from incomplete or side reactions, or isomerisation
residual solvents, reagents and immediate precursors
trace elements arising from the use of catalysts or other sources
degradation of the active constituent that may occur after manufacture.

Impurities of toxicological significance

If there is potential for the formation of toxic impurities and/or by-products this must be declared and quantified.

Details must also be provided of the conditions leading to their formation and steps taken to control the formation of toxic impurities.

Note a general list of toxicologically significant impurities is listed in the APVMA’s active constituent standards under the heading Read the definition of APVMA's Standards for active constituents.

4.5. Declaration of composition (DoC)

A comprehensive DoC for the active constituent must be provided. The DoC must be signed and dated by an Approved Person.

The declaration of composition must include the following information:

the minimum purity of the active constituent (in g/kg or g/L as appropriate on a dry weight basis) as well as the ratio of the content of isomers/diastereoisomers (where relevant)
the maximum content of all impurities present in quantities of 0.1% or more
any toxicologically significant impurities present at any level (including less than 0.1%)
if the active constituent is a manufacturing concentrate, the DoC must include the minimum concentration of the active constituent in the manufacturing concentrate as well as the minimum purity of the active constituent and the maximum content of all impurities on a dry weight (solvent/additive free) basis, and the content of diluents and/or any additives in g/kg
the chemical names, with company code numbers (where applicable), CAS registry numbers (where they exist), empirical formula, molecular weight and structural formula for all identified impurities.

All impurities present at or above 0.1% level must be identified. If identification of an impurity is not feasible, a summary of laboratory studies demonstrating the unsuccessful effort should be included in the application.

Identification of impurities not of toxicological significance below levels of 0.1% is not necessary.

Table 2 provides an example of the DoC for an active constituent.

Table 2: Recommended format for a declaration of composition

Declaration of Composition
Name of active constituent:
Name and address of applicant:			Name and address of manufacturer:
Compound (Chemical Name)	CAS Number	Limits (g/kg, g/L)		Type A: Active I: Impurity T: Toxicologically significant impurity
Compound (Chemical Name)	CAS Number	Upper limit	Lower limit



Name and title of approved person			Signature of approved person

4.6. Batch analysis data

Batch analysis results (analysed within the last five years) must be provided for at least five commercial-scale production batches of the active constituent to demonstrate routine compliance with the DoC.

If data on commercial-scale batches are not available, batch analyses should be provided for pilot-scale batches manufactured using the same process as intended for commercial-scale batches.

The results should include:

batch size, number, date of manufacture and date of analysis
results of the analytical determination for the content of the active constituent and each impurity present at a concentration of 0.1% or more using specific methods. Actual numerical results must be provided rather than vague statements such as ‘within limits’ or ‘conforms’
content of toxicologically significant impurities (present at any level)
information on the analytical methods used to generate the data and validation of these methods
where applicable, chromatograms of the batches showing separation of impurities. Chromatograms must be clearly labelled with batch numbers, peak identity and peak integration data
a copy of all raw data used to generate the final results.

For determination of impurities present in the active constituent, reference standards should be prepared for each of the identified impurities, particularly those known to be toxic, and the concentration of impurities quantitated against their own reference standards.

It is acceptable to use the active constituent as an external standard to estimate the levels of impurities, provided the response factors of those impurities are sufficiently close (≥90%) to that of the active constituent. In cases where the response factor is not close, it may still be acceptable to use the active constituent provided a correction factor is applied.

The sum of the quantitative level of active constituent and impurities is often referred to as the mass balance. Mass balance is an important parameter in the batch analysis to ensure that all major impurities have been detected. The mass balance need not add up to exactly 100%, because of the analytical error associated with each analytical procedure, however the mass balance should be in the range 98-102%.

4.7. Analytical methods

Full details of the test methods used for determining the active constituent, all impurities at or above 0.1% and toxicologically significant impurities (even when present at less than 0.1%) in the active constituent must be provided. The following information must be included in a written analytical method:

principle of the method, method summary, sample preparation techniques, equipment/reagents eg for chromatographic methods details of the column, eluent (including gradients, where applicable), temperature, detector and retention times
purity of reference standards
where chromatographic techniques are used, relevant chromatograms (blank, sample and standard) including retention times, peak assignment and peak integration data
worked examples of the calculations.

4.8. Validation data

Validation data for the method(s) used to assay the active constituent and impurities must be provided. The following parameters must be addressed, where appropriate.

specificity
linearity
precision
recovery (accuracy)
limit of quantitation for impurities.

Further information regarding the validation of analytical methods is available in Guidelines for the Validation of Analytical Methods, available from the APVMA website.

4.9. Analytical reference standards

Applicants for approval of new active constituents must provide the following samples to the Australian Government National Measurement Institute (NMI):

1 gram analytical reference standard of each pure active constituent, or where the active constituent is a mixture of major isomers which can be separated, 1 gram of each isomer
100 grams of active constituent as manufactured (the percentage purity and the method used to determine purity must be provided)

NOTE: Applicants may provide justification that they should supply less than 1 gram analytical reference standard and/or less than 100g of active constituent as manufactured. The APVMA will consider the argument on its merits.

10 mg of analytical reference standards for the toxicologically significant impurities present in the active constituent
100 mg analytical standard for all metabolites identified and for which a maximum residue limit (MRL) applies.

Storage instructions and information on shelf life of the analytical reference standard and active constituent are required, especially if degradation is likely to occur under transport or storage.

The samples should be sent to:

Australian Government National Measurement Institute – Chemical Reference Materials
1 Suakin Street
PO Box 385
PYMBLE NSW 2073
Phone: (02) 9449 0111
Fax: (02) 9449 1653
E-mail: info@measurement.gov.au

Samples must be accompanied by a letter stating:

the reason for submitting the samples
the purity of the materials supplied with the certificate of analysis
storage instructions
acute oral and dermal toxicities of the materials, or the appropriate Material Safety Data Sheet (MSDS).

Care should be taken to ensure that samples are properly packed. Samples that arrive leaking or otherwise damaged will be destroyed and replacement samples will be requested.

Samples must be provided to NMI before approval of a new active constituent. When standards are supplied to NMI, documentation to this effect must be forwarded to the APVMA.

From time to time the APVMA may request replacements for some or all of the above samples, to maintain its inventory.

4.10. Packaging

The packaging or storage/shipping containers must be appropriate for the characteristics of the active constituent.

A description of the packaging materials used for the active constituent and information regarding the corrosive effect, if any, of the active constituent on the packaging materials must be provided. This information is not required if the active constituent is formulated into a product at the site of manufacture.

4.11. Data list

Applicants must provide a Data List, including an entry for all information that meets the definition given in the Data Protection documentation. This requirement applies irrespective of whether an application is eligible for data protection.

5. DATA REQUIREMENTS FOR APPROVAL OF A NEW SOURCE OF AN APPROVED ACTIVE CONSTITUENT

5.1. General information

An application for approval of an active constituent from a new source must be made under Category 17 if the source of active constituent is not included in the Record of Approved Active Constituents for Chemical Products.

The APVMA will do a comparative assessment of the chemistry and quality control data (manufacturing details, DoC, batch analysis results and analytical methods) of the new source of the active constituent against the profile of the first approval of that active constituent. If the active constituent purity and impurity profile (including those of toxicologically significance) are identical or substantially similar and the APVMA is satisfied that the manufacturing process is acceptable, the APVMA may determine that the source is equivalent to that of the first active constituent approval. In this case, the APVMA will grant a new approval and include the new source on the Record of Approved Active Constituents for Chemical Products.

If the APVMA determines the new source of active constituent is not equivalent to the first approval of that active constituent, additional data or an application under Category 25 may be required.

5.2. Data requirements

The following information must be provided in full, with each application for approval of a new source of an active constituent:

confirmation of active constituent identity eg spectroscopic (UV, IR, NMR, MS) data
method of manufacture of the active constituent (eg process, quality control, impurity formation), as specified in paragraph 4.4
a declaration of composition (DoC) as specified in paragraph 4.5
a full five-batch analysis as specified in paragraph 4.6
full details of the analytical method(s) used for the determination of the active constituent, any isomers and the impurities present as specified in paragraph 4.7
appropriate validation data for the analytical methods as specified in paragraph 4.8
description of the packaging or container as specified in paragraph 4.10.

5.3. Reference to previously-submitted data

If the manufacturing process or the analytical methods have been assessed and accepted by the APVMA in a previous application, the applicant may reference the data provided in that application.

A suitable reference can be made to the previously accepted data. The reference should include the active constituent approval number or the file reference number. If necessary, the APVMA may request that the referenced data be re-submitted.

5.4. Data list

6. DATA REQUIREMENTS FOR VARIATION TO AN APPROVED ACTIVE CONSTITUENT

6.1. General information

Application to vary the particulars or conditions of approval of an approved active constituent must be made under Category 18. Examples include changes to the quality of the active constituent, changes to the manufacturing process or inclusion of an additional manufacturing site on a current approval.

It is the responsibility of the active constituent approval holder to ensure that the APVMA is notified of any proposed changes to the manufacturing process and/or impurity profile. The APVMA must assess these changes.

6.2. Data requirements

The following relevant information must be provided, in full, with each application for variation to particulars or conditions of approval of the approved active constituent, where applicable:

method of manufacture of the active constituent (eg process, quality control, impurity formation), as specified in paragraph 4.4
a new declaration of composition (DoC) as specified in paragraph 4.5
a new full five-batch analysis as specified in paragraph 4.6
full details of the analytical method(s) used for the determination of the active constituent, any isomers and the impurities present as specified in paragraph 4.7
appropriate validation data for the analytical method(s) as specified in paragraph 4.8

6.3. Reference to previously-submitted data

If the manufacturing process or the analytical methods have been assessed and accepted by the APVMA in a previous application, the applicant may reference the data provided in that application.

6.4. Data list

7. DATA REQUIREMENTS FOR REGISTRATION OF AN AGRICULTURAL CHEMICAL PRODUCT

7.1. Distinguishing product name

The distinguishing product name is the name by which the product is (or is to be) known, registered, labelled, advertised and sold. It should include such descriptive words or phrases as are needed to distinguish the product from other products and to identify the purpose for which it is to be used. Full information on the requirements relating to the distinguishing name is provided in the Ag Labelling Code in Volume 5.

7.2. Formulator and formulation plant details

The name and address of all manufacturing facilities involved in any step of the manufacture of the product must be provided. This includes toll or contract manufacturers and sub-contractors involved in packaging and labelling, and testing, up to and including release for supply.

7.3. Formulation type

The applicant must indicate the type of the formulation to be registered (eg wettable powder, emulsifiable concentrate, suspension concentrate, soluble concentrate, granule, dustable powder, bait, ultra low volume spray, aerosol).

The list of codes used by the APVMA for different formulation codes is in Appendix B.

7.4. Formulation composition

The formulation composition describes the qualitative and quantitative formulation of the product. The applicant must provide a full description of the formulation of the product to be marketed or supplied for the purposes covered by the application including:

the common or chemical names of the constituents
- trade names alone are not acceptable if common or chemical names exist.
CAS registry number (if available)
concentration of all active and non-active constituents in the formulation.
reference to the quality standards eg APVMA approval number for the active constituent, and manufacturer’s specifications for non-active constituents. In some cases, Material Safety Data Sheets (MSDS) may be submitted in lieu of manufacturer’s specifications. For proprietary non-active constituents, the supplier can supply specifications directly to the APVMA
purpose in the formulation (eg active constituent, surfactant, emulsifier, filler etc).

Based on the actual potency of the active constituent and all non-active constituents, adjustment by calculation of the mass of constituent should be made in formulation composition. For example, if the theoretical batch quantity of an active constituent in a batch of product is 100 grams, and the assay ‘as is’ of the batch of ingredient being used is 92% w/w then the factorised mass of the active constituent to be added would be 100g x 100/92 = 108.7g

Concentrations of active constituents, together with the stated nominal amount of active constituent (and any overage), adjuvants, and inert constituents must be expressed in g/L for liquid formulations and g/kg for solid formulations. If these units are not appropriate for a particular formulation, the applicant must propose suitable units eg a biological unit.

Table 3 is an example of an adequate formulation composition statement.

Table 3: Formulation composition details

Constituent name	CAS Number	Constituent Standard	Concentration (g/L)	Purpose in formulation
(a) Active constituent/s
Ethoxethrin (950 g/kg purity) sufficient to give 275 g/L	12345-67-8	23451 (pending)	289.5	Active constituent
(b) Other constituent/s
Sodium alkyl naphthalene sulfonate	13035-04-6	MS	15	Dispersing agent
Octyl phenyl ethoxylate	9002-93-1	MS	25	Wetting agent
Ethylene glycol	107-21-1	MS	50	Antifreeze
Xanthan gum	11138-66-2	MS	25	Viscosity modifier
20% solution of 1,2-benzisothiazolin-3-one in dipropylene glycol	2634-33-5 25265-71-8	MS	1.0	Biocide
Polydimethylsiloxane	63148-62-9	MS	3	Antifoam
Sulfuric acid (25%)	7664-93-5	MS	0.1	pH adjuster
Water	7732-18-5		to 1 litre	Diluent
TOTAL (w/v)			999
Specific gravity (for liquid products) at 25°C			0.99

7.5. Active constituent standard

The active constituent(s) proposed for use in registered agricultural chemical product(s) must be approved active constituent(s). Active constituent sources included in the Record of Approved Active Constituents for Chemical Products comply with the APVMA active constituent standards and may be used in registered products as per the conditions of registration.

If the source of the active constituent is not included in the Record of Approved Active Constituents for Chemical Products, applicants should submit an application for approval of a new active constituent or new source of an approved active constituent, respectively.

Product registrants must ensure the active constituent used in an agricultural chemical product complies with the APVMA’s active constituent standards, available from the APVMA website.

The following information about the active constituent must be provided:

the name of the manufacturer and the street address of the manufacturing plant(s), and the approval number, where available
batch analysis data for the batch of the active constituent (analysed within the last five years) to be used in product formulation. The batch must be analysed for active constituent content and impurities listed in the APVMA’s standard for that active constituent.
full details of the analytical methods used for the determination of the active constituent, any isomer and impurities
appropriate validation data for the analytical methods used for the determination of the active contents and relevant impurities.

7.6. Batch records

The product registrant and/or the active constituent supplier are required to maintain analysis records for each batch of the active constituent used in their registered products dependant on the specific conditions of the product registration. The active constituent batch records held by agricultural chemical product registrants may be audited by the APVMA.

7.6.1. Reference to previously submitted batch record data

If the batch record data have been assessed and accepted by the APVMA in a previous application, the applicant may reference the data provided in that application.

A suitable reference can be made to the previously accepted data. The reference should include the active constituent approval number or the file reference number. The APVMA may request that the referenced data be re-submitted if necessary.

7.7. Formulation process and quality control

A description of the method of formulation of the product and the sequence of operations must be provided, plus an indication of the typical size of the production scale batch.

Full details of the quality control procedures used by the formulator to ensure batch-to-batch reproducibility of the product must be provided. Information should include details of the control checks performed at various stages of the manufacture, processing and packaging of the product. The description of the in-process testing should include the specifications and tests for pivotal and key/critical intermediates.

7.8. Physical and chemical properties of the product

The following data on the physical and chemical properties of the product must be provided:

appearance, colour, odour, physical state
acidity, alkalinity or pH value
bulk density (solids)
density/specific gravity (liquids)
viscosity and surface tension (liquids)
relevant characteristics applicable to the particular formulation type (eg wettable powder: acidity/alkalinity or pH, suspensibility, wet sieve test, wettability and persistent foam)
flash point
flammability
explosive properties
oxidising properties
corrosive hazard
dangerous goods classification as per the Australian Code for the Transport of Dangerous Goods (ADG Code, 6th edition), if applicable.

7.9. Potential for the formation of impurities of toxicological concern

Toxicologically significant impurities present in the active constituent and inert ingredients in the product or formed during the formulation of the product and storage or migration of packaging material into the product must be monitored and reported.

Note a general list of toxicologically significant impurities is listed in the APVMA’s active constituent standards.

7.10. Product specifications

Product specifications with suitable upper and lower limits for the active constituent and the relevant physical characteristics of the product must be provided.

The specification limits must take into account the use of any overages in the formulation.

Specifications must address the test parameters for the particular formulation types as outlined in the Guidelines for the Generation of Storage Stability Data of Agricultural Chemical Products, available from the APVMA website as applicable [e.g. EC (emulsifiable concentrate)].

Table 4 is an example of a suitable format for product specifications.

Table 4: Product specifications

Test	Product specifications	Method
Active Constituent	188-212 g/L (± 6% of label claim)	XYZ 1023
Appearance	Clear yellow liquid	Visual
pH	5.5-6.5	CIPAC MT 75.3
Emulsion Characteristics	When diluted at 5% with CIPAC Standard water: maximum 2 mL cream, trace of oil after 30 minutes.	CIPAC MT 36.1, MT 36.2, MT 36.3, MT 173 or MT 183
Persistent foam	Maximum: 25 mL after 1 min.	CIPAC MT 47.2
Density	1.11-1.15 g/mL	ABC 1024

7.11. Content of active constituent – allowable variations

The difference between the stated label amount/concentration and the actual content of the active constituents must not exceed the statutory limits for chemical products.

Section 42(3)(e) of the Agvet Code Regulations establishes the maximum allowable variations for active constituent content based on the nominal label amount/concentration and composition of the product.

Table 5 summarises the prescribed allowable variations.

Table 5: Statutory allowable variations in the declared content of an active constituent in agricultural chemical products

Declared content g/kg or g/L	Tolerance
Up to 25	± 15% for homogeneous formulations (e.g. EC , SC , SL) ± 25% for heterogeneous formulations (e.g. GR, WG)
Above 25 and up to 100	± 10% of the declared content
Above 100 and up to 250	± 6% of the declared content
Above 250 and up to 500	± 5% of the declared content
Above 500	± 25 g/kg or g/L

Further information on requirements relating to active constituent concentration on product label is provided in the in the Labelling Code in MORAG Volume 5.

7.12. Batch analysis data

Results from a current batch of the product are required to demonstrate that the product is formulated within specifications. The data must address all parameters listed for the product specifications.

Note: The initial results from stability trials may be sufficient to cover this requirement.

7.13. Stability data

Data to demonstrate stability during storage for at least one production batch are required for agricultural chemical products. Stability testing must be conducted on laboratory/pilot/production scale batches of the product (stability data generated on batch size of less than 5 kilograms or 5 litres are normally not acceptable). The formulation must be the same as that proposed for registration in Australia. The samples must be stored in the proposed commercial packaging, or in smaller containers of the same packaging material. Agricultural chemical product containers have an important effect on storage stability/shelf life. If the product is corrosive, lids, liners, seals, seams or container sides may be damaged over time causing the contents to leak during storage, transportation, handling and use. The condition of the containers must be examined at the beginning and end of the study to determine any obvious signs of package failure or deterioration. Any adverse effect of formulations on the containers must be noted and discussed in the stability report.

Toxicologically significant impurities: where toxicologically significant impurities are known to increase in concentration as the active constituent degrades upon storage, then the level of these impurities must also be analysed at the commencement and completion of the relevant product storage stability study. The concentrations found after product storage must be in a proportionally appropriate concentration to meet the APVMA standard for the active constituent. Examples of such products are those that are date-controlled (mancozeb, zineb, diazinon, dimethoate). However, where toxicologically significant impurities are the result of ‘carry-through’ from raw materials and/or as a by-product of the manufacturing process for the active constituent and do not increase on storage, then no analysis of these impurities is needed in the relevant product stability study.

Applicants must demonstrate that the product remains within specifications when stored under normal conditions. Typically, agricultural chemical products must remain within specifications for up to 2 years under normal conditions.

Storage stability data from accelerated and/or long-term testing at or above 25°C (ambient testing) must be provided for the product stored in the proposed commercial packaging (or smaller packages of the same construction and material).

The requirements for stability testing include one or more of the following, as appropriate:

7.13.1. Accelerated testing

An accelerated storage stability test is designed to increase the rate of chemical and physical change of a product. The currently preferred method for accelerated storage stability testing is the Collaborative International Pesticides Analytical Council (CIPAC) MT 46.3: accelerated storage procedure.

The CIPAC method examines samples stored at 54°C over a period of 2 weeks unless other temperatures and times are specified in the FAO specifications for particular formulation types. For products, which are unstable at these temperatures, alternative times and temperature regimes are available e.g., 6 weeks at 45°C; 8 weeks at 40°C).

7.13.2. Real time testing

Stability tests at elevated temperatures are designed to increase the rate of chemical degradation or physical change of a product. Data from an accelerated study can give useful indication of a product’s stability but it should be noted that products may pass this test and yet still be unstable on long term storage. Therefore, it is recommended that applicants provide stability data generated at ambient temperatures over a period of 2 years.

Note: Real time data are required for date-controlled agricultural chemical products (see Appendix A).

7.13.3. Cold stability testing for liquid products

Liquid formulations (e.g. emulsifiable concentrates, oil-in-water emulsions, micro-emulsions, soluble concentrates and suspension concentrates) may be adversely affected by storage at low temperatures. Cold stability testing must be carried out at 0±2°C or lower for 7 days (CIPAC method 39.3).

Note: Cold stability testing is not required if the product label contains a warning against exposure to low temperatures.

Samples from all stability tests must be tested before (initial analysis at the start of the study) and after storage for the content of active constituent and the relevant physical properties for the formulation type. Real time stability results must include testing at suitable intervals.

Further information regarding the storage stability testing is available in the Guidelines for the Generation of Storage Stability Data of Agricultural Chemical Products.

7.14. Analytical methods

Applicants must provide a full description of the analytical methods used for testing the product. The methods of analysis must be appropriate for the type of active constituent and the formulation matrix of the product. The applicant must provide the following information to demonstrate the suitability of the analytical methods used to generate data for product registration:

full details of the analytical methods used for determining the active constituent and, where appropriate, relevant toxicologically significant impurities in formulated agricultural chemical products during stability testing
a description and purity of the reference standards
where chromatographic techniques are used; representative chromatograms of the blank, reference standard and product sample. Chromatograms must be labeled with batch number, peak identity and peak integration data
worked examples of the calculations.

7.15. Validation data

Validation data of the methods used for the determination of active constituent and, where appropriate, relevant impurities must be provided. The following parameters must be addressed:

specificity
linearity
precision
recovery (accuracy)
limit of quantitation for relevant impurities.

Further information regarding the validation of analytical methods is available in Guidelines for the Validation of Analytical Methods (PDF, 164kb).

Note: If the analytical methods have been assessed by the APVMA in a previous application, the applicant may reference the data provided in that application. However, if the formulations are not identical, the applicant must provide specificity and recovery (accuracy) data to demonstrate the analytical method is appropriate for use on the new formulation.

7.16. Packaging

Packaging details must include details of the size, shape, construction and lining of suitable containers, which will be used for the product. The integrity of the container must not be impaired by the product it contains nor must the product be adversely affected by the packaging material.

Potential changes to the integrity of the packaging materials must be monitored during the storage stability studies.

7.17. Data list

8. TEMPLATES FOR SUBMISSION OF DATA

8.1. Approval of an active constituent

TABLE OF CONTENTS

OVERALL SUMMARY

IDENTIFICATION OF THE ACTIVE CONSTITUENT

Common name

Chemical name

CAS registry number

Manufacturer’s code numbers and/or synonyms

Molecular and structural formula and molecular mass

Elucidation of structure and other characteristics

PHYSICAL AND CHEMICAL PROPERTIES

STABILITY DATA

METHOD OF MANUFACTURE OF THE ACTIVE CONSTITUENT

Manufacturer and site of manufacture

Description of manufacturing process

Quality control

Impurities

Impurities of toxicological significance

DECLARATION OF COMPOSITION

BATCH ANALYSIS DATA

Batch size, number, date of manufacture and date of analysis

Results of the analytical determination

Content of toxicologically significant impurities (present at any level)

Information on the analytical methods

Chromatograms of the sample and reference standard

All raw data used to generate the final results.

ANALYTICAL METHODS

VALIDATION DATA

ANALYTICAL REFERENCE STANDARDS

PACKAGING

DATA LIST

8.2. Approval of a new source of an active constituent

TABLE OF CONTENTS

OVERALL SUMMARY

METHOD OF MANUFACTURE OF THE ACTIVE CONSTITUENT

Manufacturer and site of manufacture

Description of manufacturing process

Quality control

Impurities

Impurities of toxicological significance

DECLARATION OF COMPOSITION

BATCH ANALYSIS DATA

Batch size, number, date of manufacture and date of analysis

Results of the analytical

Content of toxicologically significant impurities (present at any level)

Information on the analytical methods

Chromatograms of the sample and reference standard

All raw data used to generate the final results

ANALYTICAL METHODS

VALIDATION DATA

PACKAGING

DATA LIST

8.3. Variation to an active constituent

TABLE OF CONTENTS

OVERALL SUMMARY

DECLARATION OF COMPOSITION

BATCH ANALYSIS DATA

Batch size, number, date of manufacture and date of analysis

Results of the analytical determination

Content of toxicologically significant impurities (present at any level)

Information on the analytical methods

Chromatograms of the sample and reference standard

All raw data used to generate the final results

ANALYTICAL METHODS

VALIDATION DATA

DATA LIST

8.4. Registration of a product

TABLE OF CONTENTS

OVERALL SUMMARY

DISTINGUISHING PRODUCT NAME

FORMULATOR AND FORMULATION PLANT DETAILS

FORMULATION TYPE

FORMULATION COMPOSITION

Common or chemical names of the constituents

CAS registry number (if available)

Concentration of all active and non-active constituents in the formulation.

Reference to quality standards

Purpose in the formulation

ACTIVE CONSTITUENT STANDARD

Name of the manufacturer and the street address of the manufacturing plant(s), and the approval number, where available

Analytical methods used for the determination of the active constituent

Validation data for the analytical methods

BATCH RECORDS

FORMULATION PROCESS AND QUALITY CONTROL

PHYSICAL AND CHEMICAL PROPERTIES OF THE PRODUCT

POTENTIAL FOR THE FORMATION OF IMPURITIES OF TOXICOLOGICAL CONCERN

PRODUCT SPECIFICATIONS

BATCH ANALYSIS DATA

STABILITY DATA

Accelerated testing

Real time testing

Cold stability testing for liquid products

ANALYTICAL METHODS

Analytical methods

Purity of the reference standards

Chromatograms of the sample and reference standard

Worked examples of the calculations

VALIDATION DATA

Specificity

Linearity

Precision

Recovery (accuracy)

Limit of quantitation for relevant impurities

PACKAGING

DATA LIST

APPENDIX A: Date-controlled agricultural chemical products

A date-controlled agricultural chemical product is a product containing any of the following active constituents, as prescribed in Schedule 1 of the Agvet Code Regulations:

Organisms (including, in particular, nematodes, bacteria, viruses, algae or protozoa)
Bacillus thuringiensis
Mancozeb
Zineb
Diazinon
Dimethoate

Note: Real real time stability data are required for date controlled agricultural chemical products.

APPENDIX B: Formulation types

(Source: Croplife International codes for technical and formulated pesticides)

Solid formulations

Code	Solid formulations for direct use	Description
DP	Dustable powder	A free-flowing powder suitable for dusting.
DS	Powder for dry seed treatment	A powder for application in the dry state directly to the seed.
GR	Granule	A free-flowing solid formulation of a defined granule size range ready to use.
DT	Tablet for direct application	Formulation in the form of tablets to be applied individually and directly in the field, and/or bodies of water, without preparation of a spraying solution or dispersion.

Code	Solid formulations for direct use	Description
WP	Wettable powder	A powder formulation to be applied as a suspension after dispersion in water.
WS	Water dispersible powder for slurry seed treatment	A powder to be dispersed at high concentration in water before application as slurry to the seed.
WG	Water dispersible granule	A formulation consisting of granules to be applied after disintegration and dispersion in water.
WT	Water dispersible tablet	Formulation in the form of tablets to be used individually, to form a dispersion of the active constituent after disintegration in water.
EG	Emulsifiable granule	A granular formulation, which may contain water-insoluble formulants, to be applied as an oil-in-water emulsion of the active constituents(s) after disintegration in water.
EP	Emulsifiable powder	A powder formulation, which may contain water-insoluble formulants, to be applied as an oil-in-water emulsion of the active constituent(s) after dispersion in water.

Code	Solid formulations for direct use	Description
SP	Water soluble powder	A powder formulation to be applied as a true solution of the active constituent after dissolution in water, but which may contain insoluble inert ingredients.
SS	Water soluble powder for seed treatment	A powder to be dissolved in water before application to the seed.
SG	Water soluble granule	A formulation consisting of granules to be applied as a true solution of the active ingredient after dissolution in water, but which may contain insoluble inert ingredients.
ST	Water soluble tablet	Formulation in form of tablets to be used individually, to form a solution of the active ingredient after disintegration in water. The formulation may contain water-insoluble formulants.
GW	Water soluble gel	A gelatinized formulation to be applied as an aqueous solution.

Liquid formulations

Code	Simple solutions	Description
SL	Soluble concentrate	A clear to opalescent liquid to be applied as a solution of the active constituent after dilution in water. The liquid may contain water-insoluble formulants.
LS	Solution for seed treatment	A clear to opalescent liquid to be applied to the seed either directly or as a solution of the active constituent after dilution in water. The liquid may contain water-insoluble formulants.
OL	Oil miscible liquid	A liquid, homogeneous formulation to be applied as a homogeneous liquid after dilution in an organic liquid.
UL	Ultra low volume (ULV) liquid	A homogeneous liquid ready for use through ULV equipment.

Code	Solutions for dispersion	Description
EC	Emulsifiable concentrate	A liquid, homogeneous formulation to be applied as an emulsion after dilution in water.
DC	Dispersible concentrate	A liquid homogeneous formulation to be applied as a solid dispersion after dilution in water. (Note: there are some formulations, which have characteristics intermediate between DC and EC).

Code	Emulsions	Description
EW	Emulsion, oil in water	A fluid, heterogeneous formulation consisting of a solution of pesticide in an organic liquid dispersed as fine globules in a continuous water phase.
ES	Emulsion for seed treatment	A stable emulsion for application to the seed either directly or after dilution.
ME	Micro-emulsion	A clear to opalescent, oil and water containing liquid, to be applied directly or after dilution in water, when it may form a diluted miro-emulsion or a conventional emulsion.

Code	Suspensions	Description
SC	Aqueous suspension concentrate	A stable suspension of active constituent(s) with water as the fluid, intended for dilution with water before use.
FS	Suspension concentrate for seed treatment	A stable suspension for application to the seed, either directly or after dilution.
CS	Aqueous capsule suspension	A stable suspension of capsules in a fluid, normally intended for dilution with water before use.
OD	Oil-dispersion	A stable suspension of active constituent(s) in water-immiscible fluid, which may contain other, dissolved active constituent(s), intended for dilution with water before use.

Code	Dual character formulations	Description
SE	Aqueous suspo-emulsion	A fluid, heterogeneous formulation consisting of a stable dispersion of active constituent(s) in the form of solid particles and fine globules in a continuous water phase.

Formulations prepared as devices

Code		Description
MC	Mosquito coil	A coil which burns (smoulders) without producing a flame and releases the active constituent into the local atmosphere as a vapour or smoke.
MV	Vaporising mats	A mat made from pulp, or other suitable inert materials, and impregnated with an active constituent. The mat is intended for use in a heating unit designed to produce slow volatilisation of the active constituent.
LV	Liquid vaporiser	A liquid formulation in a cartridge/bottle, designed to fit a suitable heating unit, from which the formulation passes up a heated wick and evaporates into the local atmosphere.

9. GLOSSARY

Active constituent

The substance or substances in a product, which is/are primarily responsible for the biological or other effects that make the product an agricultural/veterinary chemical product.

Additive

An ingredient (such as a wetting agent, emulsifying agent, dye etc.), which is intentionally added to a product, to improve its physical characteristics, e.g. sprayability, solubility, spreadability.

Analytical reference standard

A substance of established quality and purity.

APVMA approved active constituent

An active constituent that has been approved by the APVMA for use in an agricultural /veterinary chemical products in Australia.

APVMA Standard

The standard determined by the APVMA to which an active constituent contained in chemical products must comply.

Batch

A defined quantity of material produced in a single series of operations.

Batch number

A distinctive combination of numbers and/or letters which specifically identifies a batch and from which the production history can be determined.

5-Batch analysis

A five-batch analysis is analysis for active constituent, isomers and impurities content carried out on five separate batches of production material. The five-batch analysis provides evidence that the material conforms to the specifications i.e., it is within the certified manufacturing limits.

Biological product

A product with an active constituent that is a living organism or derived from a living organism.

Declaration of composition (DoC)

A statement (signed and dated by the Approved person) stating maximum and minimum level of purity of the active and maximum levels of impurities present in the active constituent.

Equivalence

A comparative assessment of the full impurity profile of active constituent produced by different manufacturers against the profile of the active constituent used in the first approval of that active constituent. If the impurity profiles are similar, the active constituent from the new sources can be considered equivalent to the original active constituent.

Evaluation

A written assessment of study reports or other data examined in the course of an appraisal by the APVMA for the granting or refusing of an application or other consideration.

Formulation

An agricultural chemical product preparation containing active constituent(s) and formulant(s) in a form suitable for use.

Formulation site

Any site/s associated with the formulation/packaging of the agricultural chemical product.

Formulation change

A formulation change in relation to a chemical product means:

a variation in the concentration of one or more of the active constituents, or other constituents of the product; or
the addition to the product, or removal from the product, of one or more of the active constituents, or other constituents, of the product.

Formulant

see additive.

Impurity

Any constituent other than an active constituent or an intentionally added non-active constituent. Impurities include intermediates, reaction products, degradation products, contaminant or chemicals added for purposes of extraction or purification.

Manufacturer of active constituent

Any person or organisation involved in any stage of the manufacturing process and responsible for the quality of the active constituent.

Manufacturing concentrate

A form of an active constituent, which contains an intentionally added inert ingredients, such as stabilisers or solvents.

Manufacturing site

The physical location of the site where the active constituent is manufactured.

Material safety data sheet (MSDS)

Data sheet produced by manufacturer/importer, which provides the information needed to allow the safe handling of hazardous substances.

Maximum residue limit (MRL)

The maximum concentration of a chemical residue that is legally permitted in or on a food or feed commodity when that chemical is applied according to good agricultural practice (GAP) or good practice in the use of veterinary drugs (GPVD).

New active constituent

An active constituent that has not previously been approved for use in an agricultural /veterinary chemical product in Australia.

Non-active constituent (excipient)

Any ingredient, other than an active constituent, which is part of a product formulation. Non-active constituents are added at the time of manufacture for various reasons including improving formulation characteristics such as stability, solubility and spreadability (see also additive).

Quality assurance

Those procedures and controls, including inspections and audits, designed to monitor studies to assure the quality of the data.

Overage

The excess of active constituent deliberately added to a formulation to compensate for manufacturing loss or loss during storage.

Product

A formulation containing one or more active constituents, and possibly non-active constituent(s), which is intended for application, with or without dilution prior to use, and which is labelled with directions for use.

Raw data

All original records and documentation, including verified copies thereof, which are the result of original observations and activities in the study.

Record of approved active constituents

The record of the active constituents that the APVMA approves.

Relevant impurity

An impurity that is toxicologically significant to human beings or environment, is phytotoxic to treated plants, affect the stability of the active constituent or cause any other adverse effect (see also toxicologically significant impurity).

Shelf life

Period of time during which the product remains suitable for use and within the approved shelf-life specifications, provided that it is stored under the conditions specified on the label in the proposed container and closure.

Specifications and test methods

Specifications describe the requirements to which materials should conform. Specifications for the active constituents and products include a list of tests, references to analytical procedures, and appropriate acceptance criteria, which are numerical limits, ranges, or other criteria for the tests described. Active constituents and products, when tested according to listed analytical procedures, must meet the listed acceptance criteria.

Toxicologically significant impurity

An impurity that is very highly toxic or sensitising to mammals at very low concentrations.

10. REFERENCES

Agricultural and Veterinary Chemicals Code Act 1994 (Agvet Code)
Agricultural and Veterinary Chemicals Code Regulations 1995 (Agvet Code Regulations)
Standards Australia International, Australian Standard, AS1719-1994, Recommended Common Names for Pesticides, (Available from Standards Australia, GPO Box 5420, Sydney, NSW 2001)
The Australian Dangerous Goods Code (ADG Code), the Department of Transport & Regional Services (DOTARS).
Organization for Economic Cooperation and Development 1994, OECD Guidelines for the Testing of Chemicals, OECD 101-117; OECD, Paris , France , ISBN 92 6414018 2.
Collaborative International Pesticides Analytical Council Limited, CIPAC Handbooks, Black Bear Press Ltd, King’s Hedges Road, Cambridge, CB4 2PQ, UK, ISBN 0 902951 15 7.
American Society for Testing and Materials, Annual Book of ASTM Standards, ASTM, 1916 Race Street, Philadelphia , PA 19103 , U.S.A.
European Union, EU: The Official Journal of the European Communities, No. L 230, Volume 34 ( 19 August 1991), Plant Protection Products Directive (91/414/EEC).
United States Environmental Protection Agency (US EPA), Pesticides Assessment Guidelines, Subdivision D, Product Chemistry, EPA 540/09-88-048 and 540/09-82-018 , United States Environmental Protection Agency (US EPA), The Office of Prevention, Pesticides and Toxic Substances, Product Properties Test Guidelines (830 Series); US Government Printing Office, Washington, DC, US 1996, and United States Environmental Protection Agency (US EPA), EPA Manual of Chemical Methods for Pesticides and Devices, 2 nd Edition; AOAC, Arlington, VA, US 1992.
Global Crop Protection Federation, Catalogue of Pesticide Formulation Types and International Coding System, Technical Monograph No 2, 5 th Edition, March 2002, Brussels, Belgium.
Pest Management Regulatory Agency, Health Canada Regulatory Directive Dir 98-04, Chemistry Requirements for the Registration of a Technical Grade of Active Ingredient or an Integrated System Product and Pest Management Regulatory Agency, Health Canada Regulatory Directive Dir 98-03, Chemistry Requirements for the Registration of a Manufacturing Concentrate or an End-use Product Formulated from Registered Technical Grade of Active Ingredient or an Integrated System Product.

11. ABBREVIATIONS

APVMA	Australian Pesticides and Veterinary Medicines Authority
ASTM	American Society for Testing and Materials
AQIS	Australian Quarantine and Inspection Service
BSI	British Standards Institute
CA	Chemical Abstracts
CAS	Chemical Abstracts Service
CIPAC	Col laborative International Pesticides Analytical Council
DoC	Declaration of Composition
EU	European Union
FAO	Food and Agriculture Organization of the United Nations
GMO	Genetically Modified Organism
IR	Infra-red
ISO	International Organization for Standardisation
IUPAC	International Union of Pure and Applied Chemistry
MORAG	Manual of Requirements and Guidelines
MRL	Maximum Residue Limit
MS	Mass Spectrometry
MSDS	Material Safety Data Sheet
NMI	National Measurement Institute
NMR	Nuclear Magnetic Resonance
OECD	Organization for Economic Co-operation and Development
OGTR	Office of the Gene Technology Regulator
PMRA	Pest Management Regulatory Agency, Health Canada
SA	Standards Australia
SUSDP	Standard for the Uniform Scheduling of Drugs and Poisons
US EPA	United State Environmental Protection Agency
UV	Ultra-violet
WHO	World Health Organization of the United Nations

REVISION HISTORY

Revision Date	Description of Revision
1 July 2005	First edition first MORAG edition—unchanged from the original Ag Requirements Series.
1 October 2005	Second edition no changes.
1 April 2006	Third edition no changes
1 July 2007	Fourth edition complete revision of all content.