Workshop 2: Extractables & Leachables and Container Closure Integrity Testing

Packaging testing: why is it important?

Over the last few years, the requirements on the assessment of substances that could leach into the drug product over its life cycle have increased significantly. Substances may migrate from different materials and patients may be exposed through different routes of administration. on the other hand, A drug product container-closure system should not release chemicals that can accumulate in the drug product in quantities sufficient to present a risk of toxicity, or affect its stability or efficacy.

Join this workshop to embark on a journey through the pharmaceutical packaging testing. By attending you will be able to implement a successful strategy to ensure the safety of your products.

During this workshop you will learn:

• Regulatory Requirements and expectations on E&L
• How to Prepare a Successful E&L study
• Practical approaches for E&L testing
• Evaluation of E&L data
• Toxicological assessment
• E&L testing for single-use systems
• Container Closure Integrity Testing (CCIT)

Welcome and introduction

Regulatory requirements: Understanding authority perspective and expectations on extractables & leachables:

• Testing strategy on primary packaging, process materials, combination products, medical devices
• General overview on USP chapters <1663>, <1664>, <665>
• Experiences in regulatory submissions: deficiencies, remarks, warning letters
• Risk based approach: creation of a risk assessment and management of risk assessment outcome

Extractables studies:

• Selection of materials and components to be tested
• Selection of extraction conditions
• Selection of extraction solvents
• Analytical methods
• The adequate reporting threshold to be applied (based on total daily intake, safety concern thresholds, uncertainty factors)
• Unidentified compounds management

Toxicological assessment:

• Calculation of the total daily intake of the compounds of potential concern:
  • Derivation of toxicological threshold, TTC, permitted daily exposure (PDE)
  • Derivation of margin of safety and impact to patient
• Case study

Leachables studies:

• The Targeted Leachables screening
• The non-targeted leachables screening
• The Limit Test vs Full method validation for the Products of Concern
• The Fingerprint approach for the management of small changes in the packaging configuration
• The design of the experiment of a leachables study (strategy and time points definitions)
• How to manage the leachables raising between the stability check points

Container closure integrity testing (CCIT):

• The Life cycle risk assessment for the container closure systems
• The probabilistic and deterministic methods of analysis
• The peculiarities and features of the most used CCIT methods (dye ingress, microbial ingress testing, pressure decay, vacuum decay, high voltage Leak detection, laser-based gas head space analyser)
• The choice of the most proper analytical testing based on the product-container coupling
• Method setup and validation
• Case studies

Hands-on training
Attendes will be given space to actively discuss and problem-solve together. Examples of a primary packaging, a single use-system and a combination product will be showcased and their testing strategy will be discussed with the attendees.

Q&A
Closing and network drink

 This workshop is relevant for:

• Pharmaceutical packaging and device engineers
• Analytical chemists that perform E&L testing
• Toxicologists
• R&D Manager
• QC Manager, QA manager
• Regulatory Manager
• Production Manager
• Packaging Manager
• CMC Manager and Validation Manager

Simone Carrara
Simone joined Eurofins BioPharma Product Testing Italy in 2012. he is the Business Unit Manager of the Extractables & Leachables and packaging testing department. He is also E&L Senior Scientific Director in eurofins. Starting from a biotechnology degree at the University of Milan in 2005, he built his experience as a bio-analytical researcher through LC/MS method developing for Pharmacokinetics analysis and ADMET profiling. He has led projects in a wide range of areas of the analytical chemistry including method developing/validation by LC/MS-GC/MS and drug product impurities characterisation. In the last 10 years his job was focused on Extractables & Leachables testing to support drug-manufacturing companies in the fulfillment of the regulatory requirements.

Davide Tartaglione
Davide graduated in Biology applied to Biomedical research in Milan and joined Eurofins where he worked for 6 years as a Project Manager. He then joined a consultancy company and strengthened his expertise in Process validation and Extractable & Leachables. After an experience in a Contract Manufacturing Organisation, supporting customers in commercial manufacturing of Drug products and Biologics, he joined Eurofins again in 2019. Currently he is leading a team of consultancy and regulatory experts with a focus on pharmaceutical products for Eurofins Regulatory and Consultancy Services Italy.

Francesco Tessari
Francesco graduated in Pharmaceutical Chemistry and Technologies with a focus on Analytical Chemistry and method development. he started working in Johnson & Johnson as QC technician. He then moved to Cambridge (UK) working for 4 years in a C.R.O. as an Analytical Specialist and Study Director specialised in Analytical method development and validation. In 2021 he started working as a Project Leader for the E&L department in Eurofins BioPharma Product Testing Italy providing his expertise on Chemical screenings and Analytical techniques. He is currently supporting the E&L department as a Technical Advisor in order to provide Eurofins approaches on E&L studies and upcoming regulatory challenges.

Daniele Zarini
Daniele earned a bachelor's and master's degree in industrial biotechnology (bioinformatics field) in 2014 and 2016, respectively, and he started working as a toxicologist in the electronic cigarette industry from 2017 to 2021. Daniele joined Eurofins in 2021 as a toxicologist in the E&L sector of the pharmaceutical industry, holding also the role of project manager (E&L, biological, chemicals). Daniele is currently team leader for the pharma consulting group.