Visible Particles – Mechanism and Mitigation of the Formation and the Control Strategy - English

Visible particle control is an important part of the control strategy for biological products. Visible particles testing is required for release and stability testing of biological drug products (Injections). Particles may originate from many sources and can be foreign to the manufacturing process (extrinsic particles), related to the manufacturing process (intrinsic) or known to be a specific for a certain product formulation in its primary container closure system (inherent). Beside measures implemented to reduce the ingress of visible particles, the 100% visual control has the goal to identify any container with intrinsic or extrinsic particles. Each container with a particle needs to be discarded. The AQL test verifies the effectiveness of the 100 % visual control. The visual inspection is probabilistic and and the detection probability depends on many factors (e.g. nature of the particles). In case where particles are observed in an on-going stability study their nature has to be explored. This may inform route cause analysis, further use of the material or the need for any regulatory interaction. 

In recent years, new type of root courses of intrinsic particles formation in biological products attract industry/regulatory attention, e.g. excipients degradation and/or visible particle formation related to residual host cell proteins. Advances in analytical techniques enabled the investigation of these new particle phenomena and contributed to the route cause understanding. This session will introduce the mechanism of intrinsic particles formation in biological products, then the control strategy will be discussed from industry/regulatory point of views. 

Preliminary Key Questions:
- How to set a suitable approach for characterization of visible particles, and to select suitable analytical methods?
- What is known about the mechanism of visible particle formation?
- Which approaches can be taken to mitigate risk of visible particle formation and strengthen the control strategy: e.g. control of raw material and manufacturing process, release and stability testing
- How to set suitable acceptance criteria for visible particles specification of biological products?
- Acceptance criteria of visible particles: Are there differences to implement “Practical free from particle” among JP, USP and Ph.Eur.?

Session Speakers:
16:05 - 16:25
Perspective on Visible Particles in Biopharmaceuticals
Yukiko Shirahata, PMDA-Pharmaceuticals and Medical Devices Agency, Japan

16:25 - 16:45
Proteinaceous Visible Particle in Liquid Monoclonal Antibody Formulations
Satoshi Saito, Chugai Pharmaceutical Co., Ltd., Japan

16:45 - 17:15
Industry Perspective on Polysorbate Degradation and Control Strategy for Biopharmaceutical Products - A view of EFPIA Working Group 
Karoline Bechtold-Peters, Novartis Pharma AG, Switzerland and Klaus Wuchner, Cilag AG, Switzerland