Acronyms & Definitions
What is TAMC and TYMC?
TAMC = Total Aerobic Microbial Count.
TYMC = Total Yeast and Mold Count.
These are parameters for microbial stability testing for Microbial Counts.
We currently put all TPMF reviews in ToRIS?
False — we no longer upload TPMF reviews in ToRIS. We upload TPMFs along side their corresponding review in Rhapsody SharePoint folders.
What are the four regulatory pathways? What is the difference between the 2 common pathways reviewed by microbiology?
SE (Substantial Equivalence)
PMTA (Premarket Tobacco Product Application)
EX (Exemption),
MRTP (Modified Risk Tobacco Product Application)
Under the SE pathway, the applicant must demonstrate that the new product does not raise different questions of public health compared to a predicate product. Under the PMTA pathway, the applicant must demonstrate that marketing the product is appropriate for the protection of public health.
Name at least three product categories that CTP Microbiology commonly evaluates.
Any three of the following: cigars, pipe tobacco, smokeless tobacco (moist snuff, snus), nicotine pouches, heated tobacco products (HTPs), waterpipe tobacco, electronic nicotine delivery systems (ENDS).
What are the three microbial stability parameters evaluated in microbiology reviews?
Water activity (aw), microbial counts (TAMC and TYMC), and TSNAs (NNN and NNK).
What application allows OS to better track the citations used to support marketing decisions?
EndNote is a reference management tool for managing references (citations) when authoring scientific reviews.
aw less than 0.60 supports microbial growth?
False.
It is generally recognized that aw below 0.60 does not support microbial growth.
What pathway applies to product quantity changes in SE Reports where the applicant seeks an exemption from the full SE requirement?
SEPQ — Substantial Equivalence Product Quantity. It applies when the only change is product quantity and the applicant seeks an exemption because the change does not affect characteristics relevant to public health.
What are the two product compositions evaluated in microbiology reviews?
Humectants and Preservatives.
If a shelf life has not been defined by the applicant, what is one approach to providing microbial stability testing data?
Test the products at two distinct timepoints that are a minimum of one month apart.
What tool is built for FDA that can help assist with your work?
ELSA — FDA's AI assistant tool built for official FDA business.
TYMC remaining below the limit of detection throughout a stability study is considered a positive finding from a microbiology perspective.
True.
It indicates that yeast and mold growth did not occur during product storage, which supports the conclusion that the product is microbiologically stable.
An applicant submits additional information to FDA after their original submission has already been filed. This information is not part of the original application but can still be counted in the review evaluation. What is this called, and how does it differ from the original submission?
An amendment. Amendments are additional information submitted by the applicant after the original submission. Unlike the original submission, amendments are submitted separately but are still reviewed and evaluated as part of the overall review process.
What is considered one of the “other features” of tobacco products as defined under section 910(a)(3)(B) of the FD&C Act. FDA needs post-manufacturing product information because microbial communities and constituents in tobacco products change as a function of storage time.
Stability
What does CCS stand for and why is it relevant in microbiology reviews?
Container Closure System. It is relevant in microbiology reviews because changes in CCS can affect water vapor transmission, which can alter the product's water activity and in turn impact microbial growth and TSNA formation over the product's shelf life.
This application allows users to search for keywords or phrases in tobacco product submission-related documents (e.g. applications, amendments, telecons, memos).
CTP Search
Moisture content data can be used as a substitute for water activity data in a stability deficiency response.
False.
Moisture content measures total water (bound and unbound) and is not an accurate indicator of the water available to support microbial growth. Water activity (aw) is the appropriate parameter because it specifically measures free, unbound water available for microbial growth.
What does it mean to have an addendum made on a review?
An addendum is a supplemental addition to an existing document that provides additional detail or clarification to that specific document.
Preservatives are added to prevent ______in the products.
Undesirable microbial growth.
What methods are evaluated by Chemistry that are relied upon for Microbiology?
TSNA (Tobacco-Specific Nitrosamine) methods. Microbiology relies on Chemistry's evaluation of TSNA analytical methods including those used to measure NNN (N-nitrosonornicotine) and NNK (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone). Microbiology's conclusions about TSNA data are dependent on Chemistry's acceptance of the methods used.
What does TPMF stand for, and what is its purpose in the review process?
Tobacco Product Master File. It allows manufacturers or third parties to submit confidential information such as analytical methods, data or ingredient information that applicants can reference in their submissions without disclosing proprietary information directly.
What is the difference between deferrals and referrals. Do they apply to both SE and PMTA reviews?
Deferral means to send to another discipline for their information or further evaluation that is not needed in your review (i.e., a one-way information transfer). Referral means to send to another discipline for their information or further evaluation needed in your review (this cycle or the next); this represents a two-way information transfer. Deferrals and referrals do NOT apply to PMTA review. Rather, the need for another discipline to review information needs to be discussed and clarified in small group meetings.
I provide general process and roles, writing style, terms, template help, formatting text headings tables figures references, software tips & tricks, etc. for all disciplines and all programs.
Reviewer's Job Aid provides supplemental information to help review teams with submission review and those involved in document preparation.
What does LOA stand for, and when is it required in a microbiology review?
Letter of Authorization
It is required when an applicant references a TPMF, authorizing FDA to access the confidential information in that file for the purposes of reviewing the application.
An applicant submits an SE report and references a TPMF for flavor ingredient information but does not include a Letter of Authorization. The reviewer needs to evaluate the humectant and preservative content of the complex flavor. What happens next and why does this matter from a regulatory process perspective?
Without a Letter of Authorization, FDA cannot access the confidential information in the TPMF. This means the reviewer cannot evaluate the ingredient information for the complex flavor, including any humectants or preservatives it may contain. Therefore a deficiency is issued for the lack of LOA.