cell and gene therapy, viral vector

Bream and Salzmann featured in BioProcess International

May 12, 2021

CRB’s Allan Bream and Brita Salzmann are featured in BioProcess International’s co-authored article, “The Difficulties of Manufacturing Cell and Gene Therapies At Scale.” With advanced therapy medicinal products (ATMP) developing at lightning speed, it is no secret or surprise that commercially manufacturing these products mounts several challenges. Bream and Salzmann look to survey data from the 2020 Horizons: Cell and Gene Therapy report of nearly 150 industry leaders to further explore these growing pains.

The ATMP commercial manufacturing pipeline

Today, over 1,000 gene and cell therapy clinical trials are diligently pursuing a path to commercial manufacturing, providing hope to the world of incurable disease and a roadmap of uncertainty for biomanufacturing operations.

“Despite the excitement about ATMP potential, developers and manufacturers are facing sizable difficulties” - Bream & Salzmann

A lack of ATMP commercial good manufacturing practice (GMP) capacity is just one of the many challenges afoot. The commercial roll-out of cell and gene therapies also faces process optimization uncertainty, automation risks, and the need to scale open and manual operations in the near term.

“Our study data were collected from nearly 150 industry leaders and reflect the need for manufacturers to design and construct flexible facilities that can adapt to future process improvement and technologies that continue to change every two to five years. That evolving optimization will enable biomanufacturers to prepare for scale-up or scale-out to GMP commercial manufacturing to meet future demand,” Bream and Salzmann explain.

In-house or outsourced, ATMP GMP capacity challenges are the same

“Nearly three-quarters of respondents are partnering with contract manufacturing organizations (CMOs) or contract development and manufacturing organizations (CDMOs) to overcome those obstacles, citing a lack of GMP manufacturing capacity as their main reason to outsource.”

However, the difficulties of commercially manufacturing cell and gene therapies are not exclusive to in-house production. Limited ATMP GMP capacity is even causing lengthy wait times among outsourced CMOs.

Additionally, a skilled workforce shortage is affecting both sides of the industry. “Getting products off benches and into cleanrooms takes highly skilled, highly trained people. CDMOs can provide that expertise, but they also are faced with the task of building a skilled workforce,” adds Bream and Salzmann.

Technology for aseptic manufacturing

Given the extreme sensitivity and precision needed, aseptic manufacturing is an easy target for industry anxiety.

“Because cell therapies are introduced intravenously and cannot be terminally sterilized, the whole-cell processing that they require during manufacturing must be performed under aseptic conditions to prevent cross-contamination between products and culture contaminations from manufacturing environments. Any slight process alteration or human error can jeopardize a batch”

“A need for aseptic manufacturing is driving the most impactful technology advancements, according to survey respondents.”

Eliminating risks of contamination with closed cell-processing systems registered as equally important. “Although closed cell-processing systems in grade C cleanrooms now account for 25% of cleanroom environments, we anticipate that number to increase to nearly 75% within a few years.”

Most concerning: process development and optimization

Rapid advancements in technology continue to shape and reshape the development process, creating uncertainty around future needs. “Adopting new techniques requires an influx of expertise and equipment that biomanufacturers still are trying to understand and perfect,” shared Bream & Salzmann.

“The speed of change in this sector gives biomanufacturers only a couple of years to learn and adopt current innovations.”

“To scale up or scale out from open, manual processes for clinical production to commercial manufacturing would require a substantial increase in headcount and floor space at prohibitive costs.”

“Nearly 80% of survey respondents ranked process development and optimization among their top three commercial manufacturing challenges across both cell and gene therapy platforms”

Accelerated need for flexibility

Addressing biomanufacturing challenges, Bream and Salzmann articulate the need to plan with flexibility in mind. “A forward-thinking approach to commercial design will allow biomanufacturers to adopt breakthrough technologies and new automation solutions strategically. Thus, developers would have both the control and flexibility needed to shape the future of cell and gene therapies.”

Read the full article here: The Difficulties of Manufacturing Cell and Gene Therapies At Scale