Research Article
Pharmaceutical Biotechnology
Strategies for Setting Patient-Centric Commercial Specifications for Biotherapeutic Products

https://doi.org/10.1016/j.xphs.2020.09.048Get rights and content
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Abstract

Commercial specifications for a new biotherapeutic product are a critical component of the product's overall control strategy that ensures safety and efficacy. This paper describes strategies for setting commercial specifications as proposed by a consortium of industry development scientists. The specifications for some attributes are guided by compendia and regulatory guidance. For other product quality attributes (PQAs), product knowledge and the understanding of attribute criticality built throughout product development should drive specification setting. The foundation of PQA knowledge is an understanding of potential patient impact through an assessment of potency, PK, immunogenicity and safety. In addition to PQA knowledge, the ability of the manufacturing process to consistently meet specifications, typically assessed through statistical analyses, is an important consideration in the specification-setting process. Setting acceptance criteria that are unnecessarily narrow can impact the ability to supply product or prohibit consideration of future convenient dosage forms. Patient-centric specifications enable appropriate control over higher risk PQAs to ensure product quality for the patient, and flexibility for lower risk PQAs for a sustainable supply chain. This paper captures common strategic approaches for setting specifications for standard biotherapeutic products such as monoclonal antibodies and includes considerations for ensuring specifications are patient centric.

Keywords

Monoclonal antibody(s)
Antibody drug conjugate
Regulatory science
Biopharmaceutical characterization
Compendium
Physicochemical
Quality by design

Abbreviations

ADC
antibody drug conjugate
ADCC
antibody dependent cellular cytotoxicity
ADCP
antibody dependent cellular phagocytosis
CDC
complement dependent cytotoxicity
CE-SDS
capillary electrophoresis sodium dodecyl sulfate
CIEF
capillary isoelectric focusing
CQA
Critical Quality Attribute
CZE
capillary zone electrophoresis
DS
drug substance
DP
drug product
ELISA
enzyme-linked immunosorbent assay
EOSL
end of shelf life
FcRn
neonatal Fc receptor
HILIC
hydrophilic interaction chromatography
ICH
International Council for Harmonization
IEC
ion exchange chromatography
IgG
immunoglobulin G
mAb
monoclonal antibody
PQA
product quality attribute
SEC-HPLC
size exclusion chromatography high-performance liquid chromatography
PK
pharmacokinetics
PD
pharmacodymanics
QbD
Quality by Design
RTRT
Real time release testing
RP-HPLC
reversed phase high-performance liquid chromatography

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