Considerable attention is being paid to the emerging field of regenerative medicine because of the potential for curative or near-curative benefits, often in a one-time treatment.

At first, the excitement of any emerging biotechnology is focused on the promise of the science. The work to establish the revolutionary science behind regenerative medicines is advancing quickly and the challenges of proving out their promise with compelling evidence of safety, efficacy and long-term outcomes are being overcome. Innovation used to focus on clinical development. There are few unknowns in pharmaceutical and biologic knowledge bases built over decades, including the manufacturing and quality systems known as CMC (Chemistry Manufacturing and Controls).

Regenerative medicines are unlike anything that has come before.

Each category of regenerative medicines – cell, gene and tissue-based – are different and each therapy within the categories is wholly or partially unique. Some are personalized medicines and others, while not bio-matched for one individual, are made for one patient at a time, rather than mass produced. Existing industry operating frameworks for CMC were built for mass market therapies and chronic treatments, not for these unique and complex regenerative therapies.

Novel regenerative therapies require new thinking across the value chain, with particular focus on innovation in CMC.

There are unique challenges in manufacturing regenerative medicines and developers are climbing the steep innovation curve typical in new paradigm-shifting technologies. This learning curve is particularly challenging with tissue-based regenerative medicines, such as Enzyvant’s investigational therapy. Tissue biomaterials are complicated communities of cells with intricate interactions, increasing the complexity of manufacturing and quality systems exponentially. The therapy is manufactured for one patient at a time and handling of the tissue is a meticulous, manual and intensively complicated process that must be precisely-timed. Assays for process validation and quality control testing also must be developed, often not only the tests themselves but also the markers that measure consistency, potency and quality. All of this innovation represents a tremendous scope of work for developers.  Each aspect must be integrated into a comprehensive manufacturing process and total quality system.

Tissue therapies are so rare that while there is some guidance from the U.S. Food and Drug Administration (FDA) on gene-based regenerative medicines there is none yet for tissue. The CMC innovation curve is one that is shared by regulators and biotech companies.  And, the number of CMC-related delays in regenerative medicine development programs suggest that the innovation curve is industry-wide.

Biotech companies and regulators share the purpose to bring needed regenerative treatments to patients as safely and as quickly as possible.

As a condition of approval, company developers making the shift from manufacturing an investigational regenerative therapy used in clinical trials to one that is commercially available must develop and prepare robust manufacturing and quality systems, including processes, tests and measures, people and facilities, that meet rigorous GMP (Good Manufacturing Practices) certification standards of the FDA.  While there is a great deal of innovation work required to get to the standards, striving for the highest quality standards that will ensure consistent and reliable safety and efficacy for patients over time is what matters most.

Speed matters to patients and so does getting manufacturing and quality systems right. Fortunately, company developers can do both.

There is a great deal of urgency in the innovation of regenerative medicines for patients with rare and life-threatening diseases.  The FDA created expedited program designations, such as Breakthrough Therapy and Regenerative Medicine Advanced Therapy (RMAT), that offer faster pathways to approval because regenerative medicines offer extraordinary promise for patients. For development teams at Enzyvant, clocks are a daily reminder that time is running out for families with children facing life-threatening conditions. The urgency is a very tangible driver of the work. Regenerative medicines are in an accelerated innovation environment and the advancements are happening at warp speed.

Enzyvant is on the leading edge of the industry’s work to redefine best development, manufacturing and commercial practices for emerging regenerative medicines.  Development teams across the industry are pushing innovation forward to bring potential breakthrough to patients as quickly and as safely as possible. Every step these teams take not only advances CMC processes and quality systems for this first wave of regenerative therapies for patients with few to no options, it also clears more pathways for future regenerative medicines that will help more patients in urgent need.