CDMO Education Centre

August 18, 2022

Managing the manufacturing process for cell and gene therapy (CGT) products can be a significant challenge for contract development and manufacturing organizations (CDMOs) and their clients. Time is of the essence, as delays can affect capacity, resource planning and the path to product commercialization.

We have assembled six tips to help speed up the manufacturing of your CGT product and ensure you stay on track to meet development and delivery milestones.

Tip #1: Begin at the end

Plan your manufacturing requirements during the preclinical stage of development and use GMP-compliant and scalable processes and equipment. Estimate required doses for the different phases of trials and calculate and define scales required at every stage of manufacturing (Phase 1, 2, 3 and commercial). Identify and use a representative scaled-down model during process development. Determine the biomanufacturing modality required to achieve the desired scale. Finally, choose and invest in a modality that will support commercial manufacturing.

Talk to your CDMO about process controls and in-process analytics to ensure your process is robust and GMP-ready. The process controls and analytics used during development must be comprehensive to collect the data required to characterize your process. Once you establish your process, establish ranges for parameters within which the process can be controlled. Investing in this type of planning during early development will streamline the eventual transition to manufacturing.

Tip #2: Be realistic about the manufacturing process

CGT developers often underestimate the timelines and requirements of process development, which can critically impact clinical and commercial timelines. Working with an established CDMO can help with developing a realistic critical path.

Before moving forward, ensure you have at least three positive responses to the following questions:

  • Do all raw materials and consumables used in the process meet GMP requirements? 
  • Do you have a closed process to enable aseptic operations in manufacturing?
  • If your process is not fully closed, are you willing to consider alternatives to make your process closed?
  • Do you have all the steps identified and/or completed for your Technology Transfer?

Tip #3: Create contingencies for materials and equipment 

Identify all critical materials and equipment during the development stage. Then, work with your CDMO to create a sourcing strategy for the requisite materials and equipment, such as establishing qualified secondary sources, setting lead times, and ensuring supply chain robustness.

During the initial process development, talk to the experts at your CDMO about all the requirements involved in using GMP-grade materials. Identifying these materials at the outset enables your CDMO to evaluate the testing needs and determine which suppliers can meet your manufacturing needs.

Tip #4: Plan for regulatory requirements 

Work with a regulatory expert at every stage of the development process. Because regulations involving GMP manufacturing of CGT products are open to interpretation, failing to properly follow these requirements can lead to manufacturing delays. A regulatory professional can guide your discussions with the relevant government agencies and provide advice on procedures and documentation to help you create a GMP-ready process that aligns with the regulations of the intended market(s).

Communicating with regulators at the beginning of the process ensures more accurate and timely decision-making. It’s also easier and more cost-effective to make process changes at the earlier stages of development to avoid interference with manufacturing timelines. Maintain communication with regulators throughout the development cycle to identify and address issues before regulatory submission to prevent manufacturing delays. Engage with regulators at key milestones (e.g., at the start/end of different phases and before launching the next phase to resolve issues so that they do not carry over to the next step) and before finalizing late-stage or pivotal studies.

Tip #5: Prepare for technical and operational risks

Technical risks can be unpredictable and affect manufacturing timelines in various ways. Risks can include issues with the process and/or analytical testing (e.g., contamination, process failures). The best way to prepare for technical risks is to acknowledge that every project has risks. Prepare a risk assessment with the experts at your CDMO to identify the procedures/processes to control. Identify your project’s worst-case scenarios and how to deal with them. Work with your CDMO partners early in the process and throughout the project to have procedures in place for communicating and addressing technical problems in a timely manner to minimize the impact on project timelines.

Operational risks involve issues outside the technical realm (e.g., documentation delays, supply chain issues). The client’s product management team can partner with the CDMO experts to identify and address these types of risks. Proactive, frequent and transparent communication between clients and the CDMO is key to managing operational risks.

Tip #6: Pre-qualify raw materials and documentation

Raw materials typically arrive with the vendor’s/supplier’s certificate of analysis (CoA) and/or certificate of conformance (CoC). Quality Units, consisting of the quality assurance (QA) and quality control (QC) teams, use a technical specification document to ensure that the raw materials meet the CoA and CoC specifications and can be used in a GMP facility. This may include additional verification tests.

All materials must go through this process and some will be easier to release than others. To secure the prompt release of raw materials into GMP production and prevent material rejection or quarantine, pre-qualify the materials to ensure they meet the specifications. Also, verify that the materials come with the appropriate documentation. This includes ensuring they are translated into the local language and conform to the receiving facility’s local regulatory requirements.

Contact us to learn more about how our supply chain expertise can help accelerate the manufacturing of your CGT products.

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