Device Change Control Extractables Characterisation and Case Studies for Parenteral Product Devices

Parenteral drug products represent the largest number of drug products for which extractables and leachables are a significant issue. For a company which is developing devices for use with these types of products, many challenges exist to delivering an end product which will meet Customer and Consumer requirements for extractables and leachables.

Parenteral drug products represent the largest number of drug products for which extractables and leachables are a significant issue. For a company which is developing devices for use with these types of products, many challenges exist to delivering an end product which will meet Customer and Consumer requirements for extractables and leachables.

Regulatory documents such as the ISO (the International Organization for Standardization) 10993 Part 18 "Biological evaluation of medical devices -- Chemical characterization of materials" help to define material equivalence.

The ISO 10993 Part 18 (Annex C) uses verbiage for principles for judging toxicologic equivalency such as:

"The only difference between a proposed material and a clinically established material is the elimination or reduced level of an additive/contaminant/residue in the former compared with the latter as long as the types and amounts of leachable constituents do not change."

and

"The only difference between a proposed material and a clinically established material is the use of processing conditions for the former which results in reduced levels of extractables compared to the latter as long as the relative amounts do not change."

Application of these principles (among others) can be problematic. In addition, one is compelled to incorporate principles of other best practices documents and regulatory guidance as well in order to properly assess potential patient risk.

Alan Hendricker of Becton Dickinson will focus on one of these primary issues: change control. A strategy for testing extractables and performing leachables assessments will be presented for various scenarios in which Supplier driven change to a material occurred. Case studies will be presented for scenarios in which a range of analytical chemical and toxicological testing was used to demonstrate materials equivalency and patient safety. These include: changes to material supplier location, changes to material color, changes to a material formulation ingredient and changes to a material due to discontinuation of production. A comprehensive approach to risk assessment will be presented. This presentation focuses on strategy for both current best practices proposed by Product Quality Research Institute (PQRI) groups as well as ISO-10993 in a practical manner.

Dr. Alan Hendricker is Principal Specialist at Becton Dickinson and has 15 years of experience in extractables and leachables analysis and 25 years of experience with mass spectrometry. He was a co-author on the PQRI Working Group on Leachables and Extractables recommendation "Safety Thresholds and Best Practices for Leachables and Extractables in Orally Inhaled and Nasal Drug Products (OINDPs)." He has been an active member of the PQRI Leachables and Extractables Parenteral Ophthalmic Drug Product (PODP) working group. Since January of 2014, Alan works at Becton Dickinson (BD) as part of the corporate preclinical development group on extractables and leachables studies for BD devices and products.

Also in this session Jianfeng Hong of Fresenius Kabi will present extractable and leachable studies of a pre-filled syringe (PFS) used for delivery of a cancer-treatment drug solubilized with high content of castor oil surfactant and alcohols, and Carsten Worsoe of Novo Nordisk will share with us his research into E&L challenges in infusion pump systems.

The session "Case Studies of E&Ls in infusion pump systems and pre-filled syringes" will be taking place on Tuesday 11 November 2014 - Conference Day One