Subvisible (2-100 μm) particle analysis during biotherapeutic drug product development: Part 2, experience with the application of subvisible particle analysis.
Measurement and characterization of subvisible particles (including proteinaceous and non-proteinaceous particulate matter) is an important aspect of the pharmaceutical development process for biotherapeutics. Health authorities have increased expectations for subvisible particle data beyond criteria specified in the pharmacopeia and covering a wider size range. In addition, subvisible particle data is being requested for samples exposed to various stress conditions and to support process/product changes. Consequently, subvisible particle analysis has expanded beyond routine testing of finished dosage forms using traditional compendial methods. Over the past decade, advances have been made in the detection and understanding of subvisible particle formation. This article presents industry case studies to illustrate the implementation of strategies for subvisible particle analysis as a characterization tool to assess the nature of the particulate matter and applications in drug product development, stability studies and post-marketing changes.
Eli Lilly and Company, Indianapolis, IN, USA. Electronic address: corvarivj@lilly.com.
Vincent
V
Corvari
Amgen, Process Development, Thousand Oaks, CA, USA.
Linda O
LO
Narhi
Human Genome Sciences, Inc., Rockville, MD, USA.
Thomas M
TM
Spitznagel
Bristol-Myers Squibb, Molecular and Analytical Development, NJ, USA.
Nataliya
N
Afonina
Amgen, Process Development, Thousand Oaks, CA, USA.
Shawn
S
Cao
MedImmune, Gaithersburg, MD, USA.
Patricia
P
Cash
Merck Serono Guidonia Site, Rome, Italy.
Irene
I
Cecchini
Eli Lilly and Company, Indianapolis, IN, USA.
Michael R
MR
DeFelippis
Boehringer Ingelheim Pharma GmbH & Co. KG, Biopharmaceuticals, 88397 Biberach an der Riss, Germany.
Patrick
P
Garidel
Boehringer Ingelheim Pharma GmbH & Co. KG, Biopharmaceuticals, 88397 Biberach an der Riss, Germany.
Andrea
A
Herre
F. Hoffmann-La Roche Ltd, Pharma Technical Development Europe (Biologics) Analytical Development, 4070 Basel, Switzerland.
Atanas V
AV
Koulov
Janssen R&D LLC, Malvern, PA, USA.
Tony
T
Lubiniecki
F. Hoffmann-La Roche Ltd, Pharma Technical Development Europe (Biologics) Pharmaceutical Development and Supplies, 4070 Basel, Switzerland.
Hanns-Christian
HC
Mahler
BD Medical - Pharmaceutical Systems, 11, rue Aristide Bergès BP4, 38801 CEDEX Pont de Claix, France.
Paolo
P
Mangiagalli
GlaxoSmithKline, King of Prussia, PA, USA.
Douglas
D
Nesta
Genzyme Corporation, Framingham, MA, USA.
Bernardo
B
Perez-Ramirez
MedImmune, Gaithersburg, MD, USA.
Alla
A
Polozova
Merck Serono Guidonia Site, Rome, Italy.
Mara
M
Rossi
F. Hoffmann-La Roche Ltd, Pharma Technical Development Europe (Biologics) Pharmaceutical Development and Supplies, 4070 Basel, Switzerland.
Roland
R
Schmidt
Biogen Idec, Cambridge, MA, USA.
Robert
R
Simler
Pfizer Inc, Chesterfield, MO, USA.
Satish
S
Singh
Biogen Idec, Cambridge, MA, USA.
Andrew
A
Weiskopf
Janssen R&D, Schaffhausen, Switzerland.
Klaus
K
Wuchner
D000388:Air; D000911:Antibodies, Monoclonal / Q000032:analysis; D001691:Biological Therapy; D004339:Drug Compounding; D004340:Drug Contamination; D004349:Drug Packaging; D005612:Freeze Drying; D045423:Microbubbles; D046210:Microfluidic Analytical Techniques; D009391:Nephelometry and Turbidimetry / Q000379:methods*; D010316:Particle Size; D052638:Particulate Matter / Q000032:analysis*; D004364:Pharmaceutical Preparations / Q000032:analysis*; D011994:Recombinant Proteins / Q000032:analysis; D012542:Scattering, Radiation; D012827:Silicone Oils; D013052:Spectrometry, X-Ray Emission; D017550:Spectroscopy, Fourier Transform Infrared
D000911:Antibodies, Monoclonal; D052638:Particulate Matter; D004364:Pharmaceutical Preparations; D011994:Recombinant Proteins; D012827:Silicone Oils
Flow imaging; Light obscuration; Particulate matter; Protein; Silicone oil; Subvisible