Submission Pitfalls of Biopesticide Applications at U.S. EPA - BPPD
Biopesticides and Pollution Prevention Division (BPPD)
The "RAL Coffee Club" is a working group of the regulatory action leaders in the Biopesticides and Pollution Prevention Division of EPA's Office of Pesticide Programs. Regulatory action leaders are the staff level risk managers. They are the ones that coordinate the process and are the primary point of contact for applicants and registrants. This presentation has been put together based on a brainstorming session of the RAL Coffee Club in which RALs discussed common pitfalls or problems that they saw in the submissions that come across their desks. It is not meant to be a comprehensive list; but, hopefully, it is a good start.
Following the discussion of submission pitfalls are copies of BPPD checklists for the regulatory review of old active ingredient related submissions. These are internal BPPD guidance documents and items not on these lists may be required of applicants.
Labeling Issues
| • | Label Changes Not Highlighted |
| • | Label Ingredient Statement Does Not Match CSF |
| • | Product Name on Label Does Not Match CSF |
| • | Description of Pictures or Graphics Not Included |
Highlighting changes in product labeling in label amendment submissions helps speed up BPPD's review process. One common labeling pitfall occurs when the label ingredient statement does not match the confidential statement of formula (CSF) nominal concentration in the percentage of active and total inert ingredients. These have to match exactly. Also, the nominal concentration on the CSF has to match what is on the product label. The product name on the label must match the product name on the CSF. Typically, draft labels are submitted in 8 ½ x 11" paper and text format. Although not a requirement, a description of the pictures or graphics assists BPPD's review process.
Confidential Statement of Formula (CSF) Issues
| • | CSF with Original Signature Not Sent |
| • | Manufacturing Use Product Used in End-Use Product Needs to Parenthetically Note the Pure Active Ingredient; e.g. 50% Pure 10 lbs = 5 lbs Pure in End-Use Product |
| • | CSF for Microbial Does Not Include Viability Measure, e.g., CFU/g |
| • | CSF for Microbial Lacks Nationally Recognized Culture Collection Number |
| • | CSF Lists Source as "Commodity" Rather than a Specific Source |
The CSF is an official document and needs to have an original signature (not merely a photocopy).
When a manufacturing-use product (MP) is used to formulate an end-use product (EP), the CSF needs to parenthetically note the pure active ingredient after the percentage of MP in the EP; e.g., an applicant is formulating a product with a 50% pure material and is using 10 pounds. Thus there are five pounds of pure active ingredient in the EP. Applicants must not only describe the certified limits of the MP on the CSF, but also include these for the pure active ingredient.
For microbial pesticides, the CSF must include a viability measure such as colony forming units per gram (CFU/g), or colony forming units per milliliter (CFU/ml), etc. Additionally, microbial pesticide CSFs must have a nationally recognized culture collection number listed for the subject strain.
BPPD requires that all inert ingredients have specific sources listed on the CSF. However, in some cases changes in inert ingredient sources can be made by notification. PR Notice 98-10 indicates that "[i]f the Agency has required that a registrant identify the source of an individual inert ingredient, the identity of which is known to the registrant, the registrant may change the source of that inert ingredient by notification.(Section III.B.1.)" However, the PR Notice also states that an amendment application and written approval by the Agency is required when changing the source of proprietary ingredients (e.g. solvents, surfactants, etc.) and for antifoulant paint, vertebrate control, and bait products (section III.B.4.).
Forms & Administrative Issues
| • | Incomplete Data Matrix - Narrative Describing How Data is Satisfied Helpful |
| • | Missing Forms |
| • | Formatting 86-5 Deficiencies; e.g., GLP Statements and Study Director's Signature |
| • | Duplicate Data Submission Rather than Citation |
| • | Signatures and Dates Missing Where Needed |
| • | Packaging Information is Missing on Application Form |
| • | Written Request for Time Extension Not Submitted |
One of the problems seen with submitted applications is an incomplete data matrix. The data matrix is necessary when an applicant is using a selective method and citing or submitting specific studies. A narrative in the application cover letter which describes how the data requirements are being satisfied greatly improves the quality of the submission and helps answer the big picture question of how you are supporting the application. If an applicant is using a registered source from a source other than their company, a formulator's exemption form is required. Two of the most common PR Notice 86-5² deficiencies that regulatory action leaders mentioned were 1) incorrect GLP statements and 2) absence of the study director's signature.
Sometimes applicants make duplicate data submission rather than a citation. If you have more than one product, cite the data. When a data submitter submits data , they will receive a unique MRID number, a Master Record Index Number, for each piece of data submitted. Once the number is assigned, it is important to cite it where appropriate and not resubmit the same data.
Sometimes signatures and dates are missing where needed.
Package information can be missing on the application form. This information is needed for the product storage and disposal statement review and for a determination as to whether the packaging is appropriate for the product.
When requested, time extensions of regulatory requirements (e.g., data) must be requested in writing.
Data Issues
| • | Scientific Rationale for Data Waiver Requests Missing |
| • | Inappropriate Test Material (TGAI vs. EP) and Test Levels |
| • | QA/QC Data Lacking for Microbial Products |
| • | No Pre-Submission Meeting |
| • | Citations Without Copies of Literature |
| • | Data Submitted Should Make Sense |
When making data waiver requests, a scientific rationale is required.
Sometimes there is an inappropriate test material or test level in a study, particularly in some of non-target organism studies.
For microbial products, quality assurance and quality control data are critical.
A problem that contributes to incomplete submission packages is the lack of a pre-submission meeting. These are quite important, particularly with new active ingredients, new uses, and other complex applications. The pre-submission meetings allow applicants to discuss regulatory strategy prior to submission of the application with the Agency.
The review process is slowed down when citations are provided without copies of the literature. When using citations of published articles to support data waivers, etc., a copy of the cited material should be provided.
Applicants need to make sure the data they are submitting makes sense. The person putting the application package together for submission to BPPD needs to make sure that it makes sense. The data should be looked at between the time it gets back from the contractor laboratory and the time it is sent into the Agency. Study results should be reviewed by the applicant before they are sent in to the Agency.