Use of Pilot-Scale Data to Register Multiple Sites for New Active Ingredients

September 12, 2017

Purpose

The purpose of this memo to applicants and registrants is to communicate changes to the Pest Management Regulatory Agency (PMRA) process for registering multiple manufacturing sites for new active ingredients.

Background

The PMRA's Guidance for Developing Datasets for Conventional Pest Control Product Applications - March 2016 requires that each manufacturing site proposed for a technical-grade active ingredient (TGAI) or integrated system product (ISP) be supported by batch data. In particular, DACO 2.13.3 Batch Data specifies that:

• The composition of a minimum of five batches of the product manufactured at the site proposed for registration … must be provided to support the specifications.
• These batches may initially represent pilot plant production from the proposed site; however, once commercial production commences (either at the same location or at a different facility), data from an additional five batches that correspond to the commercial-scale location/process will be required under a separate application to support the specifications.
• If multiple manufacturing sites are proposed at once, batch data are required for each site.

Currently, this means that an applicant for a new active ingredient (i.e., one that has never been registered by PMRA or by any other country) may not have access to commercial-scale production until after approval is obtained. In this situation, pilot-scale equipment which is identical to that ultimately proposed for commercial production - but on a smaller scale - can be used to develop the manufacturing process and simulate future conditions. Such pilot-scale data may be used to support an initial manufacturing site, but other sites - which may be the intended locations for commercial production - may not be approved for several years or more. The time required for a registrant to initiate commercial production, obtain analysis of five batches, generate the corresponding report, and submit it to the PMRA, followed by the Agency's review and approval, can significantly delay the use of the commercial TGAI material for formulating manufacturing concentrates or end-use products.

PMRA has carried out an analysis of data on file for technical products and has concluded that, when certain conditions are met, pilot-scale data will be acceptable for the initial registration of multiple manufacturing sites for technical-grade products. Commercial-scale data will ultimately be required for all sites, as per DACO 2.13.3.

Changes to Batch Data Requirements for New Active Ingredients

If an applicant has no commercial-scale production in place because a new active ingredient has not yet been approved in any country, and wishes to register multiple sites for this active based on one 5-batch set of pilot-scale data from a single site, this must be made clear in the cover letter for the application. In addition, the letter must include the following attestations:

• the manufacturing process used for the pilot-scale production and associated batch data will be the same as that used after scale-up at the commercial-production site(s), including the starting materials, proportions of reactants used, reaction conditions and equipment (i.e., the pilot-scale equipment is comparable to - but a smaller version than - the commercial equipment)
• commercial-scale batch data will be provided as soon as available for each of the sites ultimately used for this purpose, via a Category B.4 application; sites not pursued will be removed from the product's registration via notification
• the upper certified limit (UCL) for any impurity of concern (as defined in PMRA's Guidance for Developing Datasets for Conventional Pest Control Product Applications - March 2016, DACO 2.13.4) present in the pilot-scale material will not be exceeded in material produced at the commercial-production sites

Note 1:

Lab-scale data will not be acceptable for this purpose as the manufacturing conditions are not sufficiently similar to those present in commercial production.

Note 2:

The applicant will be requested to provide expected dates of submission for the batch data supporting each of the proposed sites; these dates cannot exceed 4 years from the time of initial approval.

Note 3:

The outstanding commercial-scale data required for each proposed site will be identified to the registrant via a Section 12 notice immediately after the technical product receives its first registration. Sites for which such data are not provided by the deadline will be removed from the registration.

Note 4:

The same Good Laboratory Practice (GLP) requirement currently in place for all chemistry data, including DACO 2.13.3, applies regardless of whether pilot- or commercial-scale data are being generated.

Scope and Implementation

This revised process to approve TGAI manufacturing sites applies only to new applications to register new active ingredients (not new sources of existing active ingredients), where commercial-scale data are not available because the active has not received initial approval in any country. Complete guidance for preparing chemistry data packages is available from PMRA.

Update 2018-09-07

This initiative has been expanded to include existing TGAIs.  To obtain initial approval for a new site that is not yet producing technical material, a Category C.1.1 application may be employed to add the site to an existing TGAI registration, by referring to historical pilot-scale data already reviewed by PMRA for that TGAI. The following criteria apply:

• The cover letter must include all the above attestations and clearly identify the new site as well as the TGAI registration to which the site is being added.
• A new SPSF must be included, whose specifications by definition will be identical to the SPSF provided for the original pilot-scale data.
• The cited pilot-scale data must be less than 10 years old.
• All the above conditions apply, including the 4-year limit for providing commercial-scale data in response to the section 12 requirement that will be issued following approval of the new site.

Questions / Contact

Any questions should be directed to the PMRA Information Service.