Extractables and Leachables
Supporting your complete extractables and leachables (E&L) risk assessment profile
E&L risk assessment
Due to rapid global advances in materials engineering, device innovations and new manufacturing models, determining chemical migration risk from packaging, processing equipment, or container-closure systems has become a key focus.
Leachables, in particular, can pose various safety risk concerns to patient health, ranging from mutagenicity to general toxicity. With the recently released draft ICH Q3E guideline and regional justifications are only increasing.
To protect patient safety, regulatory bodies require assessments to demonstrate that potential extractable and leachable impurities are identified, assessed, and controlled. This helps ensure that patients can use their medicines safely, without undue risk from packaging-related impurities.
Why choose Consult Lhasa?
Consult Lhasa provides expert extractable and leachable (E&L) risk assessments, using Lhasa Limited science, that can be recognised and trusted by industry and regulatory authorities.
Lhasa Limited has been collaborating with industry and regulatory working groups to drive E&L risk assessment science in line with the latest draft ICH Q3E guideline.
If you need assistance with your complete E&Ls risk assessment, Consult Lhasa.
How can our experts help you assess
Extractables and Leachables?
Could leachables be present in your drug product?
Predicting leachables starts with a theoretical understanding of extractables. We can review your packaging and manufacturing processes to identify potential risks and guide any further experimental evaluation needed. Our approach reflects current best practice and is in compliance with the draft ICH Q3E guideline.
Do you need help defining an acceptable exposure level for your leachable?
The draft ICH Q3E guideline introduces a structured approach for applying safety thresholds and deriving acceptable exposure levels for leachables, including using the point of departure (POD) to derive a permitted daily exposure (PDE) for systemic toxicity, or an acceptable intake (AI) where mutagenicity is a concern.
We assess your leachable impurity using the latest guidance and recommend a suitable acceptable exposure level strategy.
Do you need help evaluating experimental data for your identified leachable?
Where relevant data exists, the robustness of the data needs to be evaluated before it is used in an acceptable exposure level calculation.
We evaluate the quality of available toxicology data to determine whether it can underpin a safety assessment, and identify any gaps that may require additional supporting evidence.
Is there a suitable read-across surrogate for your leachable impurity?
When direct toxicological data are limited, the draft ICH Q3E guideline supports the use of scientifically justified read-across.
We identify potential structural or mechanistic analogues, evaluate their relevance, and determine whether a read-across surrogate can be used to derive a PDE. Our experts provide a clear justification based on multiple toxicokinetic and toxicodynamic factors. We will provide an expert justification for analogue selection and associated acceptable exposure limit.
What if there is no suitable analogue?
If there is no suitable analogue for your leachable impurity and the draft ICH Q3E guidance published limits are unachievable, we can help you to decide on your next steps.
We will review the weight of evidence (WoE) and suggest any additional data that may support the use of a WoE approach.
We provide regulatory support
Draft ICH Q3E guideline
“Our experience with Consult Lhasa has been very positive, resulting in a final report that we are confident will meet the scope required by regulatory agencies. The Consult Lhasa team are knowledgeable about the regulatory needs of the region, particularly Brazil, and provide great support. Their consulting has been invaluable to our company, the technical, scientific and human exchange has been impeccable. We are very satisfied with the collaboration.”
Adriana Tomalino, Head of Regulatory Affairs at Triquim
“We recently had the experience of collaborating with Consult Lhasa to address an EU regulatory deficiency on a potential degradation impurity of the drug substance. Consult Lhasa made an intriguing task look simple in the final report which was based on Zeneth, literature review and expert analysis. Their professionalism and commitment to excellence were truly commendable and their proactive approach made the entire process seamless and ensured that we met the stringent regulatory timelines. Their core scientific knowledge, hands-on experience with the pharmaceutical industry and caliber of their work make them a standout choice. It is evident that they take great pride in what they do, and this pride reflects in the exceptional quality of their work. We strongly recommend Consult Lhasa to anyone seeking expert advice on API degradation profile, drug-excipient compatibility, leachables & extractables, potentially mutagenic and non-mutagenic impurities and most importantly the nitrosamine impurities.”
Muzaffar Khan, Senior General Manager within Regulatory Affairs at Laurus Labs Limited
“We recently had the opportunity to collaborate with Consult Lhasa on the AI/ limit derivation of a new NDSRI. Given the challenge of limited specific data available for the queried nitrosamine, we sought Consult Lhasa’s expertise to enhance the robustness of our Read-Across approach. Their work is referenced in the latest global regulatory updates on nitrosamines, and this high level of scientific rigor was clearly reflected in their deliverables.
We sincerely thank the team for their deep scientific knowledge, timely efforts, and outstanding support.
We highly recommend Consult Lhasa and look forward to another productive collaboration in the future.”
Eleni Politi, Chemistry, Manufacturing and Controls/Safety Toxicologist at Rontis Hellas
Get in touch
If you are interested in discovering how Consult Lhasa could improve your nitrosamine risk assessments, get in touch.