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Manufacturing of Recombinant Proteins Using Quality by Design (QbD) Methodology: Current Trend and Challenges

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Biopharmaceutical Manufacturing

Part of the book series: Cell Engineering ((CEEN,volume 11))

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Abstract

Since the introduction in 2009, the Quality by Design (QbD) is a methodology widely used in the development of therapeutic proteins. The fundamental concept of QbD is that the development of a therapeutic protein starts with the comprehensive understanding of the target product profile in terms of identity, strength, quality, purity, and potency. The manufacturing is then designed to ensure the product produced from the designed process meet the target product profile consistently and reproducible matter. Presently, all marketing application for therapeutic proteins submitted to FDA or EU regulatory agencies require the QbD methodology implemented during their product development and manufacturing stages. Despite of its effectiveness and regulatory requirements, the implementation of QbD concept in its entirety has been limited due to (1) insufficient time to fully characterize the target protein profile in the beginning of development process, (2) complexity of input and output parameters prohibiting the full design of experiments, and (3) challenges in collecting and analyzing the end-to-end product and manufacturing data. In order to overcome those challenges, many efforts are on-going with the most noticeable progress made in the advanced data analytics and machine learning perspective.

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Abbreviations

ADC:

Antibody Drug Conjugate

AI:

Artificial Intelligence

API:

Active Pharmaceutical Ingredient

ATMP:

Advanced Therapy Medical Product

BPOG:

Biophorum Operations Group

CDC:

Complement Dependent Cytotoxicity

CHO:

Chinese Ovary Hamster

cIEF:

Capillary Isoelectric Focusing

CPPs:

Critical Process Parameters

CPV:

Continued Process Verification

CQAs:

Critical Quality Attributes

DoE:

Design of Experiment

DP:

Drug Product

DS:

Drug Substance

ELIZA:

Enzyme-Linked Immunosorbent Assay

GMP:

Good Manufacturing Practice

HMW:

High Molecular Weight

ISPE:

International Society for Pharmaceutical Engineering

LMW:

Low Molecular Weight

ML:

Machine Learning

NOR:

Normal Operating Range

OPLS:

Orthogonal Partial Least Squares

PAR:

Proven Acceptable Range

PAT:

Process Analytical Technology

PC:

Process Characterization

pCPPs:

Potential Critical Process Parameters

pCQAs:

Potential Critical Quality Attributes

PDA:

Parenteral Drug Association

PLS:

Projections to Latent Structures

PPQ:

Process Performance Qualification

QbD:

Quality by Design

QTPP:

Quality Target Product Profile

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Conflict of Interests

The authors declare no conflict of interest.

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Authors and Affiliations

  1. QBDC GmbH, Nusshof, Switzerland

    Younok Dumortier Shin & Karlheinz Landauer

Authors
  1. Younok Dumortier Shin
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  2. Karlheinz Landauer
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Corresponding author

Correspondence to Karlheinz Landauer .

Editor information

Editors and Affiliations

  1. Institute of Bioprocess and Biosystems Engineering, Hamburg University of Technology, Hamburg, Germany

    Ralf Pörtner

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Shin, Y.D., Landauer, K. (2023). Manufacturing of Recombinant Proteins Using Quality by Design (QbD) Methodology: Current Trend and Challenges. In: Pörtner, R. (eds) Biopharmaceutical Manufacturing. Cell Engineering, vol 11. Springer, Cham. https://doi.org/10.1007/978-3-031-45669-5_9

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