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Bacteriophage Manufacturing: From Early Twentieth-Century Processes to Current GMP

Abstract

Recent clinical progress in the field of phage therapy has led to an increased demand for pharmaceutical grade bacteriophages, manufactured under Good Manufacturing Practices (GMP) conditions and approved by regulatory agencies. However, even if the development of a common standardized process for phage production seems rational, there are no guidelines to pave to way for manufacturing. This chapter reviews phage therapy through the lens of modern medicinal guidelines. It lists manufacturing strategies that can be used for phage production. Finally, it stands quality controls that can be applied to release phage-based drug products in compliance with the latest regulatory requirements.

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Authors and Affiliations

Authors

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Correspondence to Jérôme Gabard .

Editor information

Editors and Affiliations

Glossary

ANSM

Agence National de Sécurité des Médicaments et des produits de santé. French drug regulation agency

CFR

Code federal regulations in the USA

CFU

Colony-forming unit

CRO

Contract research organization

DLS

Dynamic light scattering

DP

Drug product, i.e., the final product used in clinical trials or for commercialization

DS

A component of a drug product, such as a phage type in a cocktail

EMA (previously EMEA)

European Medicine Agency

EOP

Efficiency of plating

EudraLex

The body of European Union legislation in the pharmaceutical sector compiled in Volume 1 and Volume 5 of the publication “The rules governing medicinal products in the European Union”

FDA

Food and Drug Administration

GLP

Good Laboratory Practices

GMO

Genetically modified organism

GMP or cGMP

Good manufacturing practices with “c” standing for current, i.e., the latest updated version

GRAS

Generally recognized as safe is a FDA product status (sections 201 and 409 of the Federal Food, Drug, and Cosmetic Act) for food substances or additives, which is delivered according to their safety data package

HCP

Host cell proteins

ICH

International conference on harmonization, leading to international guidelines or procedures, for instance, in the field of technical requirements for registration of pharmaceuticals for human use

IMPD

The investigational medicinal product dossier is the basis for approval of clinical trials by the competent authorities, such as regulatory agency(ies) end ethics committee(s) in the EU

IND

In the USA, the investigational new drug dossier is the basis for approval of clinical trials, emergency use (in a situation that does not allow time for submission of an IND in accordance with 21CFR) or treatment (for experimental drugs showing promise in clinical testing for serious or immediately life-threatening conditions, while the final clinical work and the data review take place) by FDA

IEX

Ion exchange

IU or EU

International unit or enzyme (endotoxin) unit

MHRA

The Medicines and Healthcare Products Regulatory Agency of the United Kingdom

MCS

Master bacteria cell stock

MPB

Master phage bank

NGS

Next-generation DNA/RNA sequencing

NIAID

National Institute of Allergy and Infectious Diseases

NIH

National Institutes of Health

PCR

Polymerase chain reaction

PFU

Plaque-forming unit

QA

Quality assurance is a systematic process to ensure that QC tests are properly performed

QC

Quality control is set of tests to ensure that quality (conformity) of a product is respected. When a drug product belongs to a pharmacopeia, this set of tests and procedures is already precisely described

RE

Restriction enzyme

RFLP

Restriction fragment length polymorphism

RAPD

Random amplified polymorphic DNA

SEC

Size exclusion chromatography

TEM

Transmission electronic microscopy

UF

Ultrafiltration is the filtration of a fluid in order to get rid of the particles that it could contain in suspension

WHO

World Health Organization

WCS

Working bacteria cell stock

WPB

Working phage bank

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Regulski, K., Champion-Arnaud, P., Gabard, J. (2018). Bacteriophage Manufacturing: From Early Twentieth-Century Processes to Current GMP. In: Harper, D., Abedon, S., Burrowes, B., McConville, M. (eds) Bacteriophages. Springer, Cham. https://doi.org/10.1007/978-3-319-40598-8_25-1

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  • DOI: https://doi.org/10.1007/978-3-319-40598-8_25-1

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