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The AAPS Journal

, 22:1 | Cite as

Phase-Appropriate Application of Analytical Methods to Monitor Subvisible Particles Across the Biotherapeutic Drug Product Life Cycle

  • Roman MathaesEmail author
  • Linda Narhi
  • Andrea Hawe
  • Anja Matter
  • Karoline Bechtold-Peters
  • Sophia Kenrick
  • Sambit Kar
  • Olga Laskina
  • John Carpenter
  • Richard Cavicchi
  • Ellen Koepf
  • E. Neil Lewis
  • Rukman De Silva
  • Dean Ripple
White Paper
  • 40 Downloads

Abstract

The phase-appropriate application of analytical methods to characterize, monitor, and control particles is an important aspect of the development of safe and efficacious biotherapeutics. The AAPS Product Attribute and Biological Consequences (PABC) focus group (which has since transformed into an AAPS community) conducted a survey where participating labs rated their method of choice to analyze protein aggregation/particle formation during the different stages of the product life cycle. The survey confirmed that pharmacopeial methods and SEC are the primary methods currently applied in earlier phases of the development to ensure that a product entering clinical trials is safe and efficacious. In later phases, additional techniques are added including those for non-GMP extended characterization for product and process characterization. Finally, only robust, globally-accepted, and stability-indicating methods are used for GMP quality control purposes. This was also consistent with the feedback during a webinar hosted by the group to discuss the survey results. In this white paper, the team shares the results of the survey and provides guidance on selecting phase-appropriate analytical methods and developing a robust particle control strategy.

KEY WORDS

subvisible particles protein aggregation control strategy biotech drug product 

Abbreviations

AAPS

American Association of Pharmaceutical Scientists

AC-SINS

Affinity-capture self-interaction nanoparticle spectroscopy

AF4

Asymmetric flow field flow fractionation

AUC

Analytical ultracentrifugation

CD

Circular dichroism

cIEF

Capillary isoelectric focusing

CQA

Critical quality attribute

DLS

Dynamic light scattering

FDA

Food and Drug Administration

FIH

First in Human

FTIR

Fourier-transform-infrared spectroscopy

GMP

Good manufacturing practice

ICH

International Conference of Harmonization

JP

Japanese Pharmacopeia

LO

Light obscuration

MALS

Multi angle light scattering

μDSC

Micro differential scanning calorimetry

nDSF

Nano differential scanning fluorimetry

NTA

Nanotracking analysis

OOS

Out of specification

PABC

Product Attribute and Biological Consequences

Ph. Eur.

European Pharmacopeia

QC

Quality control

RMM

Resonant mass measurement

RP-HPLC

Reversed-phase high-pressure liquid chromatography

SbVP

Subvisible particles

SEC

Size exclusion chromatography

SEM-EDX

Scanning electron microscopy–energy dispersive X-ray

SLS

Static light scattering

TDA

Thermal denaturation assay

TEM

Transmission electron microscopy

TOF-SIMS

Time-of-flight secondary ion mass spectroscopy

USP

United States Pharmacopeia

VP

Visible particles

Notes

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Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  • Roman Mathaes
    • 1
    Email author
  • Linda Narhi
    • 2
  • Andrea Hawe
    • 3
  • Anja Matter
    • 1
  • Karoline Bechtold-Peters
    • 4
  • Sophia Kenrick
    • 5
  • Sambit Kar
    • 6
  • Olga Laskina
    • 7
  • John Carpenter
    • 8
  • Richard Cavicchi
    • 9
  • Ellen Koepf
    • 10
  • E. Neil Lewis
    • 11
  • Rukman De Silva
    • 12
  • Dean Ripple
    • 9
  1. 1.Lonza Drug Product ServicesBaselSwitzerland
  2. 2.Amgen, IncThousand OaksUSA
  3. 3.Coriolis PharmaMartinsriedGermany
  4. 4.NovartisBaselSwitzerland
  5. 5.Wyatt Technology CorporationSanta BarbaraUSA
  6. 6.Molecular and Analytical DevelopmentBristol-Myers SquibbPenningtonUSA
  7. 7.West Pharmaceutical Services, Inc.ExtonUSA
  8. 8.University of ColoradoDenverUSA
  9. 9.National Institute of Standards and TechnologyGaithersburgUSA
  10. 10.Commercial Product Support, Innovation and Investments, Pharmaceutical Development & SuppliesPTD Biologics Europe. F. Hoffmann-La Roche LtdBaselSwitzerland
  11. 11.Mettler-Toledo, Autochem, Inc.RedmondUSA
  12. 12.U.S. Food and Drug AdministrationSilver SpringUSA

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