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Particulates in Cell & Gene Therapy Products: A Survey and a Solution


by Dr. Steve Oh, PhD
Independent Cell  Therapy Leader

A webinar presented by the ISCT Process Development and Manufacturing (PDM) Committee

Particulates are everywhere but do they pose a problem in cell and gene therapy products? On the 16 Oct. the Manufacturing Materials Safety & Technology (MMST) organised a webinar which sought to answer this question. A report of the survey reached 97 companies who were Cell Therapy developers and Service Providers From the survey, cell therapy developers’ lead products covered the discovery to Phase 3 clinical stage. There was incomplete or spotty awareness of the 14 documents on particulates from the European Pharmacopeia, USP and ISO standards, the most commonly known standards are shown in the Table below. Administration routes covered all methods, IV, IT, IM, IO, IM and Subcutaneous. Responders were concerned about a wide variety of particulates in their process during manufacturing and packaging. They were aware of visual, microscopy, laser scattering, flow cytometry and RAMAN spectroscopy methods of particle measurements. Following this survey, the latest science methods for particulate detection was  presented by Halo Labs. Panel members from the PDM committee then discussed and fielded questions from the audience on the implications of these findings. As there were so many still unanswered questions, the MMS&T group will be organizing a follow up Panel Discussion at the Vancouver international ISCT meeting (29 May – 2 June 2024). We welcome experts and practitioners to reach out to the committee members if they wish to participate in the panel discussions next year.

The topics that we would like the community to address are:-

Challenge 1: define which particulates are harmful based on route of administration.
Challenge 2: call to action for SUS manufacturers to assess their own manufacturing processes to understand how technology could aid cleaner production.
Challenge 3: develop an appropriate and acceptable limit of particulate based materials used and type of drug being produced. ASTM has drafted a document E3230-20 that attempts to do so. So how do we effectively expand this type of material assessment and where do we collate the data?

Readers may access the recording via this link :

Particulate Guidance Reference Table

Ph.Eur 2.9.20-Particulate Contamination: Visible Particles

Ph.Eur 2.9.19-Particulate Contamination: Subvisible Particles

Ph.Eur 5.17.2-Recommendations on testing of particulate contamination: visible particles.

USP<1>-Injections and Implanted Drug Products

USP<788>-Particulate Matter in Injections

USP<789>-Particulate Matter in Ophthalmics

USP<790>-Visual Particulate in Injections

USP<1788>-Particulate Matter in Injections and Ophthalmic Solutions

USP<1790>-Visual Inspection of Injections

USP<1044>-Cryopreservation of Cells

ISO23565-ISO/TS 23565:2021 Biotechnology — Bioprocessing — General requirements and considerations for equipment systems used in the manufacturing of cells for therapeutic use. Section referencing particulates (7.3.4).

ISO 8536-4-Infusion Equipment for Medical Use – Part 4: Infusion Sets for Single Use

EN 45502-Implants for Surgery – Active Implantable Medical Devices

ANSI/ASTM AT6:2005-Autologous Transfusion Devices

The Chair of the webinar was Dr. Steve Oh, Ph.D. Independent Cell Therapy Leader, Singapore.  ( Survey readout and results were presented by Dr. Nisha Durand, Ph.D. Assistant professor of Regenerative Medicine &  Manager of Process Development Human Cellular Therapy Laboratory - Center for Regenerative Biotherapeutics (CRB) Mayo Clinic, USA. Total particle analysis in complex cell therapies: differentiating the extrinsic, intrinsic, and inherent particles with Aura, was presented Dr. Paul Dyer, Ph.D. Field Application scientist, Halo Labs US. Panel members were Dr. Samuel Molina, American Red Cross and Dr. Dalip Sethi, Terumo BCT.

Readers may access the recording via this link :