This blog entry is about demystifying the world of Pre-manufacturing notification (PMN) submissions!
Preparing and submitting a PMN can be exhilarating and daunting for a new toxicologist in the chemical space. My goal today is to give you a very gentle introduction to the intricacies of PMN submissions with insights, tips, and best practices to help you effectively navigate the terrain. Embark on this journey with me and empower yourself to navigate the path to a successful PMN submission.
The original Toxic Substances Control Act (TSCA) was passed in 1976 and became effective in 1979. During those three years, the EPA identified over 64,000 substances in use when EPA passed the law. These substances were grandfathered into the TCSA program (as part of the first TSCA inventory) without review for health and safety.
Any chemicals that weren't grandfathered in with the original inventory now required the submission of a pre-manufacturing notice (PMN) 90 days (review time) before the manufacture or importation of the chemical. Even with this, there were criteria for specific exclusions from this requirement, i.e., polymers were exempt from review, as were substances undergoing research and development, implications made solely for exportation, etc.
When introducing a new chemical substance in the U.S., searching the publicly available non-confidential chemicals on the TSCA inventory list was the first step. You could also request that the EPA search the confidential portion of the inventory by submitting a bona fide request to the EPA.
Suppose your chemical of interest is not on the TSCA inventory. In that case, a PMN or an exemption application is needed before production can begin.
Under the original TSCA paradigm, there were no data requirements. With no data, many assumptions were being made about these new chemicals and worst-case approaches taken. Also, under the original TSCA, the absence of evidence to support a concern meant that the EPA had no authority to take regulatory action. If the EPA failed to decide on a new chemical within the 90-day review time, the chemical was automatically approved and added to the TSCA inventory.
In 2016, the EPA revised the original TSCA. Technically now called the Lautenberg Chemicals Safety for the 21st Century Act, the revised TSCA replaced the industrial chemicals framework to strengthen the regulatory authority the EPA had, particularly for industrial chemicals. The intention of making these changes to the law was focused on the management of existing chemicals because the EPA had no specific existing chemicals program in place. However, the modifications ended up having a considerable impact on the assessment of new substances as well.
With the revised TSCA, submitters must wait regardless of how long the EPA takes to evaluate a chemical submission.
The EPA can make Five findings after a substance has undergone review. They are:
1. Not likely to present an unreasonable risk.
2. Information is insufficient to permit a reasoned evaluation.
3. Insufficient Information to permit a reasoned evaluation and may present an unreasonable risk.
4. Will present unreasonable risk.
5. Produced in substantial quantities and may reasonably be anticipated to enter the environment in substantial quantities or maybe substantial human exposure.
Remember that TSCA requires evaluating the use of these substances around sensitive sub-populations (e.g., children and chemicals used in children's toys) and often adjust their assessment parameters accordingly. The EPA will also consider "reasonably" foreseen uses of new substances, which can be highly difficult to anticipate. Using patent libraries to identify other potential uses for this new substance you are trying to register could be helpful for you.
Ensure that the notification package is as detailed as possible to ensure you have the highest probability of success with it. Along with reducing delays, doing so can save you money in the long run.
The review process often begins with the basic physical-chemical properties of the substance of interest. These include but are not limited to melting point, Log Kow, water solubility, etc.
The next step is the environmental fate assessment, which looks at the persistence potentials of the substance, how it partitions in the environment, the half-life of the substance, and any bioaccumulation potential it might have in the food chain.
The hazards are assessed for human health and ecological endpoints using acute and chronic exposure data. When the data is unavailable, predicted data or data from an analog substance is used to fill in any knowledge gaps.
Once all that is gathered, an engineering and exposure assessment is done. This step looks at the entire supply chain of a substance and all the different activities that take place within that supply chain that could be a source of exposure or cause some risk.
A decent amount of time is spent on evaluating the supply chain, how a chemical substance is being used, its function in a final product, etc., and a lot of submitters have seen delays in their submissions because in the U.S., under TSCA, the EPA regulates chemicals based on risk, which is a function of inherent toxicity and exposure.
A clear picture of a substance's exposures and releases across the supply chain provides a reasonable assessment of the exposure and release potential for the target substance. The EPA provides guidance documents for assessing discrete chemicals and polymers as the assessment approach between various chemical classes can differ.
Once a final determination is made on the substance of interest, the submitter must submit a "notice of commencement" of the first manufacturing or import within 30 days. The import date starts once the substance crosses customs (if being imported).