Accelerating development through manufacturing best practices
The journey to commercialization can be fraught with challenges for organizations developing cell and gene therapy products. While demand for tomorrow’s critical therapies intensifies in the midst of a global pandemic, the manufacturing process can present a sizable bump in the road. Maximizing scalability to meet the needs of patients can prove to be a particular obstacle, which is why a solid regulatory strategy with optimized manufacturing processes for commercial good manufacturing practice (GMP) production should be in place early in the research phase.
Kate Coleman, Senior Director/Principal Consultant, explores manufacturing best practices that can help organizations developing cell and gene therapy products build a robust, repeatable and sustainable process early on to accelerate development and avoid manufacturing transfer-related delays.
Manufacturing life-changing therapies needs a solid framework of guidelines
Making the transition from laboratory-based research to a sustainable commercial operation requires early planning and flexibility for innovator companies. This is particularly relevant with advanced therapy medicinal products (ATMPs), as they’re called in the European Union and the UK, or cell and gene therapy products (CGTPs) as they are called in the United States. For organizations pursuing accelerated regulatory pathways, such as EMA PRIME in Europe or one of the FDA’s expedited development and review pathways, a GMP-compliant plan is a must from the outset.
Fortunately, there is specific guidance regarding the principles that must be applied to ensure the manufacturing of a therapy is safe, efficacious and of the appropriate quality. The “Guidelines on Good Manufacturing Practice specific to Advanced Therapy Medicinal Products”, within Part IV of Eudralex Volume 4, a summary document issued by the European Commission, is recognized as the best current GMP guidance document on the production of ATMPs. These guidelines protect patient safety by ensuring that ATMPs are consistently produced and controlled according to high quality standards.
The FDA has issued several guidance documents on CGTPs, which align with EMA guidelines, establishing a methodology on which to base regulatory and compliance strategy. Additionally, the Pharmaceutical Inspection Cooperation Scheme (PIC/S) is an important resource, aligning inspection practices and GMP standards from 53 regulatory authorities around the world. However, although there are standards in place, ATMPs are renowned for their diversity in terms of manufacturing platform, which makes it difficult to have a single guidance that will apply to every facet of manufacturing for every ATMP and CGTP.
Start with 5 priority areas
Given the diversity that exists within the sector, consider these 5 priority areas when making the transition to commercial manufacturing.
- Prepare for operational readiness. Moving from bench to full-scale manufacturing must be carefully considered. Assess every aspect of the potential manufacturing process and identify any risks that could arise during scale-up to commercial production. This will allow mitigation actions to be identified and implemented before any issues threaten to increase cost or delay time to market.
- Determine how your product will be manufactured. This is a huge consideration. Will you build your own manufacturing facility? Would it be preferable to work with a contract manufacturing organization/contract development manufacturing organization (CMO/CDMO)? In a recent survey of roughly 150 ATMP industry leaders, almost three quarters were working with a CMO or CDMO in some capacity, most often as part of a hybrid in-house/CMO model. A report from the survey notes that this gives flexibility to innovators by letting them own the development of their process without significant cost outlay on dedicated facilities and manufacturing expertise. If building yourself, you would need to consider the requirements for the design, operation and maintenance of a classified cleanroom facility. When using a CMO, consideration should be given to oversight and ensuring knowledge gained during commercialization is retained in-house.
- Prioritize safety. It goes without saying that in an environment designed to manipulate human cells and genetic material, the consequences of a mix-up or cross-contamination event could be disastrous. A sound Contamination Control Risk Assessment and resulting Contamination Control Strategy is needed to address the facility, material and personnel flows, cleaning and decontamination protocols, the way utilities are set up and contamination controls. Fully understand the minimum requirements for contamination control, for product development and for production and quality control as they relate to GMP principles— from respective starting materials through to production of the finished product. The Contamination Control Strategy is underpinned by the Quality Risk Management (QRM) Strategy, ensuring that the risk to the patient is at the center of all activities and decisions taken. The optimal QRM strategy protects the workforce, product and, most importantly, the patient.
- Build in flexibility. Novel, life-changing therapies necessitate thinking about potential obstacles or issues that have never been faced before—and that demands flexibility. Being flexible enough to adapt and integrate new technologies or processes can enhance efficiency. Nimbly resolving unexpected challenges can keep costs in check and timelines intact.
- Respond with agility. With patients’ lives and investors’ expectations hanging in the balance, developers of cell and gene therapies must do what they can to speed up the process from bench to market. Instead of the several years it used to take to get a new biopharma facility designed, built and licensed, the focus today is on innovative design-build solutions that can move project delivery from concept to operation in just a year or two. With timelines that much shorter, careful and comprehensive preparation is more critical than ever.
An early deployed strategy pays off
Successfully navigating the manufacturing process and avoiding landmines is entirely possible with a well-constructed strategy that is devised and implemented early on. This can, in turn, minimize contamination risk and operating costs, safeguard reliable production and smooth the regulatory approval process.
Interested in learning more about manufacturing best practices? Download our white paper, The Future of Advanced Therapies: Strategies to Evolve Global Health in a Post-COVID World.