Issue link: https://www.e-digitaleditions.com/i/1526741
24 BioPharm International ® Emerging Therapies eBook September 2024 www.biopharminternational.com Development etc.," says Pinaud. "Development costs are also very much dependent on the number of patients required for clinical development and the dose." Gene therapies, which are also complex, bring in a new or modified gene, turn off a gene, or replace a gene, according to Pinaud. "Most are delivered using viral vectors, which are costly to produce due to challenges with scalability, productivity, and overall recoveries. Limited availability of some raw materials (e.g., plas- mids for transient transfection) is also an issue. Fortu- nately, progress is being made along many fronts, with contract development and manufacturing organiza- tions (CDMOs) taking a lot of the lead in investing in development of optimized and flexible platform man- ufacturing processes and stable producer cell lines." A new cel l or gene t herapy may requi re ma ny years and high costs, according to Macedone, with cost varying from indication to indication. Often rare diseases also impact children, which might involve f undra ising a nd pat ient foundat ions, Macedone points out, which may aid in costs. "There is always a balance, and every program has its idiosyncrasies. This is where the power of a well-designed modular platform comes into play," says Macedone. Logistics, such as tech transfer, also vary depend- ing on the therapy that's being developed. "For in- stance, tech transferring a partial or nearly complete process will focus development time on compara- bility while a new preclinical process will leverage a manufacturer's existing platform approach," says Macedone. Having process development and analyti- cal development teams in the same space can stream- line comparability testing, according to Macedone. In addition, f lexible and modular platforms to select process parameters may ensure successful develop- ment and manufacturing. Partnering for success Biotechnology partnerships are important, specifies Pinaud, with more data sharing and talent pooling being used than has been previously seen in the phar- maceutical industry. "Particularly when we look at the newer modalities like cell therapies and gene therapies, there is limited practical knowledge that will have to be shared to continue making progress. One of the easiest ways to do this is to leverage manu- facturing platforms through outsourcing/collabora- tion with expert groups such as CDMOs to accelerate timelines and reduce CMC [chemistry, manufactur- ing, and controls] development costs." The need for treatments for rare diseases has cre- ated a variety of communities, according to Mace- done. "The rare disease community is ver y active, especially as patients join groups to share their ex- periences," says Macedone. "They and their families often build relationships with clinicians and trans- lational researchers at hospitals or universities, as well as charitable organizations and even with drug developers and manufacturers." New facilities for new therapies Establishing manufacturing needs and then working backward to plan options for meeting timelines is a good place to start when creating a manufacturing facility for emerging therapy production, according to Pinaud. He also suggests including partners to help with strategy and design. "Site selection is ver y important and will be im- pacted by many factors like proximity to headquar- ters, the surrounding labor market, and even ta x incentives. Depending on where you are starting at (greenfield, brownfield, existing facility), just getting a facility online can take a lot of time and money," says Pinaud. "Timelines also need to account for equipment lead times and building materials as well as commissioning and qualification. Engineering runs and media fills need to be considered, too. A phased building approach is necessary to meet cur- rent requirements, and when possible, leave room for expansion or evolution of the site." "Complying with GMP [good manufacturing prac- tices] requirements is not negotiable, so setting up the physical and electronic systems for proper risk manage- ment and record keeping is compulsory. Understanding the requirements for the flow of people and materials through a manufacturing plant as well as those for sterility are essential parts of the equation. Having ex- perienced personnel and operators is critically import- ant," says Macedone. Designing a facility from scratch instead of retrofitting an existing facility may be more expensive, but it may be easier to implement GMPs. "There will always be the tradeoffs of cost and time, but the basic features required for compliance are the first and last considerations to ensure a safe and quality product for the patient," says Macedone. A phased building approach is necessary to meet current requirements, ... — Michael Pinaud, Ascend Advanced Therapies