Product Contact Items (PCIs)
With the increasing use of single-use/disposable systems in drug manufacturing processes, more attention is being given by companies to the assessment of extractable substances leached from process system components, commonly called Product Contact Items (PCIs).
Intermediate solutions obtained during the FE 999049 drug substance (DS) manufacturing process contact various PCIs including single-use and reusable items containing glass, stainless steel, cellulose, silicone, polypropylene and polyethylene polymers, all of which provide a potential source of leachables into the DS.
The multi-step DS manufacturing process consists of a series of purification and dilution steps; consequently, not all PCI leachables are expected to be present in the DS and those that would be present would be at low concentrations.
Bio-Technology General conducted a multi-step study of 15 PCIs employed in the manufacture of FE 999049 DS to identify, quantify and qualify extractables and leachables (E&L), to assess the safety of the commercial FE 999049 drug product (DP).
Data from this study will be presented at E&L Europe by Leo Brenman, M.Sc., Senior Research Scientist, Development Department, Bio-Technology General. Leo is a senior research scientist at BTG's Development department, where he is responsible for overseeing Extractables and Leachables studies. He is an Analytical Chemist with more than 20 years' experience in leading of chromatographic, analytical science and process improvement activities, both in the Pharmaceutical and Bio Technology Industries.
Drug-Filled Implantable Devices
Drug-Filled implantable devices represent a unique challenge when it comes to evaluating extractables and leachables. As opposed to simple drug-coated implantables, in which both drug and device compounds leach into the body, drug-filled implantables serve as a drug reservoir where the drug elutes through the device rather than off of it. In developing an extractables and leachables testing program for drug-filled implantables, three primary actions must be considered;
- leaching of device related compounds into the body,
- leaching of device related compounds into the drug reservoir and
- leaching of drug-device compound adducts into the body.
In addition, leachables from the device into the drug reservoir may negatively impact the safety and/or efficacy of the drug itself.
In general, the study should incorporate components of ISO 10993, PQRI and USP as well as a simulated-use assessment. Considerations for an extractactable and leachable study design, execution and data interpretation will be presented by Dr James Scull, along with a specific case study for an ophthalmic drug-filled implantable device.
James has more than 27 years of pharmaceutical development experience spanning all areas from discovery support through manufacturing. His current responsibilities include providing strategic scientific and technical leadership with a global perspective to NSF's Health Sciences Division.
Leo Brenman from Bio Technology General and Dr James Scull from NSF Health Sciences will be presenting their case studies on Wednesday 12 November 2014, Conference Day Two