The landscape for E&L assessment has changed over the past two decades. We now have a better understanding of E&L and improved procedures for analyses. The field is still evolving. Currently updates to regulations and standards are ongoing that will influence E&L assessment in the future. The adoption of ICH Q3E will harmonize the various recommendations, sometimes at odds, that exist currently. Re-defining basic terms such as SCT, AET, UF, etc. and harmonized safety thresholds will be implemented. Changes to USP<661>into two chapters USP<661.1> and <661.2> will influence future E&L assessments. Concepts such as migration modelling will be more common. All these changes that will affect E&L will be discussed.
 
Atish Sen, PhD | Director, Analytical Sciences Inhalation Product Development, AstraZeneca

Peilin Fu | R&D Center Director, Shenyang Sinqi Pharmaceutical

N-nitrosamines and similar structural compounds should be paid attention to in elastomer based on domestic and foreign regulations. The migration of nitrosamines from medical packaging elastomers may lead to the presence of nitrosamines in the drug products resulted in health risk. Therefore, it is urgently important to develop a distinctive method to detect nitrosamines from elastomers in pharmaceutical primary packaging. However, no analytical method is provided for biopharmaceuticals. In present work, a salting-out liquid-liquid extraction (SALLE) coupled with liquid chromatography-mass spectrometry (LC-MS) method was firstly presented for the quantification of 13 nitrosamine contaminations in antibody drugs. The method showcased excellent linearity over the range of 0.5-5.0 μg/L with LOQ (limit of quantitation) of 0.5 μg/L for targeted nitrosamines. Moreover, this method was demonstrated to be accurate (recovery in a range of 75.4-114.7%) and precise (RSD ≤ 13.2%) for 13 nitrosamines using spiked samples. In conclusion, we provide a sensitive and reliable method for nitrosamine estimations to ensure the safety of biological medications.
Yangguo Xie | Senior Supervisor E&L Formulation Analysis, Shanghai Henlius Biotechnology Co., Ltd

This speech will introduce the necessity of extractables and leachables (E&L) research from the sources and regulatory requirements of single-use systems (SUS), and focus on the overall process and technical difficulties of E&L research, including risk assessment, extractables Biochemical studies, toxicological assessments, simulated production studies, and the practice of E&L with specific cases.
In addition, it will also discuss how to apply the supplier's research data, in order to provide advice and help to the final preparation manufacturer.
Finally, the future trend of extractables and leachables research of SUS is also prospected.
Hong Chang | Technical Expert of Compatibility Research, Weipu

Weichun Yang | Senior Director of Analytical Service Unit , STA Pharmaceutical

This topic will focus on the introduction and discussion of extractable research approach in industry. By a SUT case, compare the data in different extractable research approach and Leachable to help customer get more understanding E&L Research and do the E&L Research for SUT.
1. Extractable research approach
2. Leachable research approach
3. Case study for a SUT
Zhaodi Zhang | E&L Lab Manger , Pall Validation

• How to Use Extractables Data from SUS Supplier    
• What is Sartorius Extractables Simulator | ExSim    
• Why Need Sartorius Extractables Assessment         

Hovery Yin | Manager of Project Management,Filtration/SUS, Confidence® Validation Services, Sartorius

Logically there should a strong correlation between the list and amounts of leachables and the list and
amounts of extractables. Such a correlation is fortuitous as it serves three useful purposes: (1) verifies the rigor and completeness of the leachables profiling activity (as one does not want to miss leachables during a leachables migration study), (2) allows extractables testing to do the work of leachables testing in activities such as change control (as managing change by testing incoming items for extractables may be simpler and more efficient than testing manufactured drug products for leachables), and (3) supports the premise that extractables data can forecast leachables. However, extractables and leachables correlations can be poor, suggesting (perhaps) that E&L testing was not being practiced with the expected and necessary high level of scientific competence.
 
In this presentation we review of the underlying aspects of study design and implementation that must be recognized and controlled to enable the effective correlation of leachables to extractables and we consider the logical, and perhaps not so logical, reasons why even under the most equitable and well-controlled experimental circumstances leachables may not be correlatable to extractables.
Additionally, the presenter will address concepts associated with the exhaustive extraction of medical devices.
Dennis Jenke | Chief Executive Scientist, Triad Scientific Solutions

• Regulatory environment and relevant regulations
• Interpretation of FDA assessment concerns
• The cases of E&L studies for FDA drug application

Weixing Yang | CTO, STANDARD BIO-PHARMACEUTICAL

Extractable and leachable studies are often complex and time-consuming, with risk of unexpected issues, budget overspend and late delivery. Effective communication can reduce this risk, helping to prepare a robust study plan and creating more control over the project.
 
In this webinar we explore the benefits of taking time and consideration for proactive communication throughout the lifecycle of the study, from design to delivery. We show how early planning of communication channels and assessment of stakeholders ensures that the right people are involved at the right time. This promotes quick decision making, smooth delivery of the data, and potential cost saving by eliminating unnecessary testing, reduction of errors and scope creep.
Ewa Miaskiewicz | Project Manager, Smithers

1. Is it regulatory mandatory to conduct safety assessment after extractables test/leachables test?
2. Currently, the thresholds for safety assessment include SCT, QT, TTC threshold of ICH M7, TTC value of Cramer classification, etc. Which threshold should be used for safety assessment of injections?
3. Does the TTC threshold of ICH M7 and Cramer's TTC threshold need to be converted by certain factors when used for injection or inhalation? Because Cramer and ICH M7 data are mostly based on oral.
4. When multiple extractables/leachables are detected, should the Individual Impurity threshold or multiple impurity threshold of TTC be used for evaluation? Is it possible to pass the declaration if the Individual impurity  passes the threshold, but the sum of the Multiple Impurities fail the thresholds?
5. Can you give some advice on the use of QT threshold for injections? How to confirm which substances can use QT.

Panel Moderator: Hong Haiyan, Analytical & QC & Development manager, Asia, Saint-Gobain
Panelists: Hovery Yin, Manager of Project Management, Filtration/SUS , Sartorius
                 Zhang Leshuai, Toxicologist, Professor, Soochow University
                 Xu Xueping, Toxicologist, Wuxi AppTec
                 Yangguo Xie, Senior Supervisor E&L Formulation Analysis, Henlius Biotechnology