Module 9 2021

19/03/2021

Virus Clearance Validation Standardised Process for monoclonal Antibodies

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Clarified Bulk Harvest

Partitioning by selective adsorption

Affinity capture

• Virus Reduction

Inactivation

Mechanisms (~21 logs retrovirus; 6-14 logs parvovirus <1 VLP per 10^6 patient doses) • Clearance values are product and process dependent

Low pH

Partitioning by charge

Anion exchange

Partitioning by hydrophobicity

Hydrophobic interaction

Partitioning by charge

Cation exchange

Partitioning by size exclusion + Inactivation (shearing)

Nanofilter

Formulation

Drug Substance

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Facility risk assessment

Engineering Controls and Facility Design

HEPA-filtered air and environmental conditions- temperature and humidity are closely controlled and monitored.

Define the Virus Control Framework with Stakeholders

Surfaces are designed for highest degree of cleanability.

People, Gowning and Material Flow

Personnel regularly sanitize their hands and practice good aseptic behaviors throughout work which protects against viruses. Operator Health Policy to mitigate infected individuals in facility Personnel gowned in clean scrubs, hairnet and beard cover, surgical mask and clean facility-dedicated footwear for access to the GMP Facility. Contractors are subject to the same gowning and are supervised at all times

Control by Performing annual review of mitigations, check currency and seek input from the Broader Industry

Measure the Current State

Virus Control Framework

Process and Product Controls

Functionally Closed Processing and single use equipment

In vitro and in vivo virus testing of cell banks and intermediates and Virus Clearance validation.

Improve by defining the necessary mitigations and manage actions to completion through a risk management system

Analyze by performing a GAP Analysis and Risk Assessment

GMP areas subject to routine disinfection and a sporicidal as needed confirmed effective against viruses. Materials that enter the GMP facility are certified and enter via controlled routes and are disinfected with bleach and/or 70% isopropyl alcohol solutions effective against viruses.

Equipment cleaning, sterilization and gamma irradiation

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