Thresholds you can confidently trust
With thousands of rigorously prepared threshold documents under our belt, you can place your trust in our expertise to deliver accurate and compliant exposure limit determinations that inspire confidence.
Experienced toxicologists
Leverage the expertise of our seasoned team of toxicologists ensuring you receive accurate and trusted guidance in the critical area of safety margin determination.
Official ICH Q3E Supplier
As an official supplier for the ICH Q3E workgroup, our services guarantee you industry-leading standards and authoritative insights, ensuring your projects align with the highest benchmarks in the field.
High-volume capacity
Drawing on our extensive experience in handling large-scale projects, our company is adept at processing high-volume orders of up to 1000 PDEs, ensuring accuracy and timeliness every time.
210+
clients from 24 countries
2000+
thresholds established
20
years of experience
Where we can help
Permissible daily exposure (PDE)
PDE is used predominantly in the pharmaceutical industry, particularly in cleaning validation processes for shared facilities where both the API (Drug Substance) and Drug Product (DP) are manufactured, but it also helps to understand potential toxicological risks of extractables and leachables from process-related equipment or container closure system. It represents a substance-specific dose that is unlikely to cause an adverse effect if an individual is exposed at or below this dose every day for a lifetime. Hence, it specifies the maximum amount of a residue (like residual solvents) that can be present on manufacturing equipment without posing a risk to human health. PDE is calculated based on comprehensive toxicological data and is expressed in terms of milligrams per day. It provides a scientific basis for setting cleaning validation acceptance criteria to ensure patient safety.
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We can assist you in understanding how to calculate and apply PDE in your cleaning validation protocols.
Acceptable Daily Exposure (ADE)
ADE is tailored specifically for assessing patient safety in the context of pharmaceuticals. The ADE represents a dose that is unlikely to cause an adverse effect if an individual is exposed, by any route (e.g., intrathecal, inhaled), at or below this dose every day for a lifetime. Hence, it defines the maximum amount of a specific API residue that a patient can be exposed to daily over a lifetime without a significant risk of adverse effects. ADEs are often used in the cleaning validation of shared facilities where multiple APIs and DPs are manufactured to ensure that cross-contamination does not pose a risk to patient health.
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We can assist you in deriving ADEs for your pharmaceutical products, ensuring they are in line with regulatory guidelines and best practices.
Health based exposure limit (HBEL)
HBEL is a term that is broader in scope and is commonly employed in Quality Risk Management (QRM). HBELs should be established for all medicinal products, including those produced in shared facilities since PDE / ADE is a form of HBEL. HBELs plays a role in determining cleaning limits but goes beyond justification of cleaning limits. If control measures cannot adequately ensure that potential contamination is consistently controlled to levels below the HBEL, the products in question should be manufactured in dedicated facilities. HBELs should be established by a person who has appropriate expertise and experience in toxicology/pharmacology, familiarity with pharmaceuticals, and experience with the determination of HBELs such as occupational exposure levels (OELs) or PDE /ADEs.
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We have appropriate expertise in establishing HBELs for your facility, considering both scientific and operational factors.
Update existing safety margins
Our safety margin updating service is designed to provide you with peace of mind and ensure the continuous safety of your operations and products. Recognizing that PDE, HBEL, and ADE values may need periodic updates due to changes in toxicological data, regulatory requirements, or production processes, we offer a comprehensive service to regularly update these safety margins on your behalf. By outsourcing this crucial task to our team of experts, you can focus on your core business activities while ensuring that your operations remain compliant, safe, and optimized for success.
Regularly updated safety margins
Continuous regulatory alignment
Access to full team of toxicologists
The process
Briefly describe the process overview and introduce
Request the preparation of one or more PDE, ADE, or HBEL from IASON consulting.
Optional: Meet your consultant and lead writer in an online or on-site kick-off meeting to discuss your API/DP(s), project timelines, review times and and identify the data required for successful completion.
Send us your list of API/DPs.
The toxicologists you have met carefully calculate the requested safety margin for you. If you have any questions or comments during this project, we will be available for you.
Within the designated timeline, you will receive the draft PDEs, ADEs or HBELs for you review. We will incorporate your feedback from review cycles and finalize the documents.
It is done! We will send you the finalized, signed documents. If desired, we debrief the project in a closure meeting.
It was a pleasure to work with you!
Frequently asked questions
Request a quote
We will be happy to answer any questions you might have via e-mail or in a free online kick-off meeting.