7.4

THE FUTURE IN PURIFICATION TECHNOLOGY

7.4.1

NEW FACILITY DESIGN

Viral-based vaccine manufacturing under GMP conditions requires an additional bio-

safety level when compared to the classic mAbs industry. Biosafety level 2 (BSL2) is

often the standard for many viral-based manufacturing. BSL 1 (generally used of mAbs)

focuses on the protection of the product from the operators and the environment,

whereas BSL 2 focuses on containment, protecting the operators and the environment

from the product. Increased biosafety level classification adds manufacturing and facility

complexity and costs. In this respect, having closed processes are essential to mitigate

any possible contamination of the product and also to facilitate the risk assessment

evaluation which has to be performed for any new product introduction into the facility.

Besides the BSL consideration, viral-based vaccine manufacturing and in general

viral vector therapeutics needs facilities that are both modular and flexible to ac-

commodate different virus types and as well as different scales.

Modular facility designs and modular construction are being used in biologics

manufacturing, with a key benefit being faster time from inception to start-up. The

BioPhorum Group hosted an industry collaboration that proposed a standardized,

modular design approach to help advance facility design in the industry [75]. While

the initial project looked at a monoclonal antibody (mAb) facility, it plans to extend

the concept to cell and gene therapy production which is similar in needs to viral-

based vaccine manufacturing [76].

With the modular facility framework, the ballroom concept is a key pillar. The

ballroom approach features a large open operational space where closed processing

equipment can be co-located in the same space. The industry has accepted that the

functionally closed upstream production trains for therapeutic proteins, but not viral

operations, can be deployed using an open ballroom approach. For the operation of

VBVs in a ballroom concept, fully closed systems are required (not only functionally

closed), together with a very thorough risk assessment. This is often challenging to

achieve in many viral-based vaccine processes [77]. To date, processes involving host

cell infection, viral production, purification, and product formulation should be spatially

segregated in a separate room to contain vector particles within a specified zone in the

facility. Regarding heat, ventilation, and air conditioning (HVAC) systems, these

spaces should utilize dedicated air handling units or single-pass airflow to minimize

contamination risks. For multiproduct facilities, processing of multiple VBVs should be

performed either on a temporally segregated campaign basis (with sanitization in be-

tween) or in parallel but completely segregated viral production spaces for each product

campaign produced.

7.4.2

PROCESS INTENSIFICATION

Given the increasing worldwide demand for VBVs, which includes attenuated and

inactivated viral vaccines, as well as viral vector vaccines, faster development times

are required to progress VBVs more rapidly into clinical development and then to

market. This has meant VBV manufacturing is changing and is being driven by the

need for increased speed and greater flexibility. The requirement for greater

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Bioprocessing of Viral Vaccines