Issue link: https://www.e-digitaleditions.com/i/1468049
Pharmaceutical Technology TRENDS IN MANUFACTURING 2022 eBOOK 19 plasmid supply. There are often long lead times associated with GMP [good manufacturing prac- tice] plasmid production; so, it can be very ad- vantageous for a therapeutics developer to work with a manufacturing partner who can not only manufacture their viral vectors, but also their GMP-grade plasmids, and can supply these in the shortest possible timeframe. There's also variabil- ity in plasmid quality, which can impact the titer and quality of the resulting viral vector. CGT breakthroughs PharmTech: What are significant breakthroughs for manufacturing CGTs? Xu (Thermogenesis): The first human patient to be treated with gene therapy was a four-year-old girl suffering from severe combined immunode- ficiency in 1990 (2). She received treatment for a congenital disease called adenosine deaminase (ADA). Since then, gene therapies have been used to treat diseases, such as cancer, cystic fibrosis, and hemophilia. In 2017, the FDA gave its first ap- proval of a gene therapy called Luxturna, which is used to treat patients with established genetic vision loss that may result in blindness (3). Gene therapies are still being studied and developed, with over 1000 clinical trials currently underway. Chang (WuXi ATU): CRISPR [clustered regularly interspaced short palindromic repeats] technol- ogy presented us with the opportunity to rewrite our genetic code, and for the last 20 years, the vision has been to bring this into the clinical phase and make it possible to alter genetic ab- normalities in vivo. That vision is now extremely close to becoming a reality. But of course, it's not just CRISPR technolog y that has reached this point, but viral vector engineering, too, to ensure specific packaging of CRISPR and Cas9 within AAV [adeno-associated virus] vectors for delivery to the target tissues. Hewitt (Charles River): Gene editing has the po- tential to transform cell therapy manufacturing, making it truly personalized and f lexible. Man- ufacturing GMP plasmid and vector is a time- consuming, expensive process. Moving to gene editing could significantly simplify cell and gene therapy manufacturing while reducing costs. The use of gene editing also provides the ability to target specific sequences for knock-out and spe- cific loci for knock-in. Future cell therapies may be manufactured at the point of care to address specific patient indications using advanced ana- lytics data to identify the specific edit sites and/or antigens required to eliminate tumor cells. Me u r e r (Bi o p h a r m a E xc e l l e nc e): [T]he u s e of i PS [i nduced plu r ipotent stem cel ls] i n t he ma nufacturing of a l logeneic t herapeutics is a n impor ta nt mi lestone. Even t hough t here a re st i l l ma ny const r a i nt s rega rd i ng [t he] large-sca le production of iPS cel ls, it is just a question of time before the manufacturing technology catches up. Durdy (Cell and Gene Therapy Catapult): The devel- opment of CAR T-cell [chimeric antigen receptor T-cell] technology and approval of those [have] opened the way to many clinical trials and thera- pies now in the clinics. Industry, regulators, pay- ers, healthcare providers, and national healthcare systems have all [learned] a lot from CAR T-cell With the potential to cure diseases, CGTs could change the future of treatments for certain conditions.