Improving ADC Manufacture Means Stricter Containment Requirements and Continuous Advancement of Analytics (INTERPHEX 2024)

Editor's note: this story was originally published on BioPharmInternational.com.

Speaking at the “Advancements and Challenges in Antibody-drug Conjugate Manufacturing” presentation at INTERPHEX this week, Ashley Harp, a process engineer with CRB Group, stated that antibody drug conjugate (ADC) manufacturing nowadays demands much higher containment requirements than in the past.

In particular, Harp discussed current requirements for facility design for ADCs, which have gotten more complex and sophisticated since the first ADC was approved decades ago. “We're now 24 years since the first ADC was approved, and we have 12 marketed FDA-approved ADCs in the [United States],” she remarked. Yet, although there are higher containment requirements today, ADC manufacturing facilities are still relatively typical high-potency API (HPAPI) facilities—with added personnel protection and product containment, she clarifies.

The linker technologies for ADC manufacturing can have many variations, Harp pointed out, such as having a linker that’s conjugated to the drug (payload) or a linker that’s conjugated to the antibody before the drug is added. However, the majority of the ADC products on the market follow a similar process, she said. These ADC facilities must serve the ultimate goal of providing an environment that processes the product correctly and delivers a safe and effective product to the patient. The added containment requirements, however, are to protect the facility personnel, Harp emphasizes.

Another challenging aspect in ADC manufacture is the constant need to develop analytical capabilities for product detection, Harp also said. “Making sure that you are getting the molecule that you expect and also having the capabilities to detect the molecule on surfaces or in the air (to run industrial hygiene testing, for example) [is important],” she said. Today, Harp pointed out, “we are able to detect levels lower than a single nanogram in much of the analytics [that are run], that it is amazing to me.”

Harp also stated that, while biotech companies require knowledge in their design considerations for ADC facilities, there are many “good regulations and guidance available … [that] bring in … local regulations and requirements for personal protection and product protection.”

“Because we are in a GMP [good manufacturing practice] space, once you hit [the] clinical [stage] … [particularly] Phase II and Phase III … and then first [commercial] manufacturing, we can't just make [the products] in a chemical manufacturing facility. These are going to eventually be injected into someone, so we have to always keep that in mind,” Harp stated.

ADC’s have been the subject of focus recently for bio/pharm companies. Bristol-Myers Squibb, Johnson & Johnson, and Genmab entered multi-billion deals all involving pipelines of ADC therapies (1-3).

INTERPHEX is being held in New York City on April 16–18.

References

1. Mirasol, F. Bristol Myers Squibb and SystImmune Enter Global ADC Collaboration Worth Potentially up to $8.4 Billion. PharmTech.com, Dec. 19. 2023.
2. Mirasol, F. J&J Completes $2 Billion Ambrx Acquisition, Boosts Pipeline for Next-Gen ADCs. PharmTech.com, March 7, 2024.
3. Mirasol, F. Genmab Expands ADC Pipeline with $1.8 Billion Acquisition of ProfoundBio. PharmTech.com, April 4, 2024.