There is significant pressure to reach the first clinical milestones as quickly as possible – and it is often the first opportunity for drug developers to be rewarded for years of research and work. However, it is also important to not get ahead of yourself; you will have invested a significant amount up to this point, and the intricacies required to maintain a drug’s quality must be prioritized during the development of the first batch for clinical trials – regardless of speed. Producing high-quality clinical trial material (CTM) under cGMP takes time, with many developers choosing to work with a CDMO.
Arguably the most important step in producing your successful first batch is establishing realistic timelines based on product complexity and regulatory requirements. You need a comprehensive strategic plan. Supply chain logistics can be out of your control, so it is important to leverage the expertise of all partners (who should clearly understand the regulatory landscape in different countries) to proactively forecast potential delays and maintain compliance throughout. Begin by creating a schedule that accounts for both aseptic filling and cGMP compliance steps and plan for a batch size that accommodates extra testing, destructive sampling and analyses – making sure to factor in enough material for the first stability studies that are key at this stage to show prolonged product quality. Anticipating and addressing critical planning issues early in the process is a preventative measure against potential pitfalls.
Credit: Author supplied
As a product transitions to a manufacturing facility for the first time, regulatory agencies and your CDMO require detailed knowledge about the product to confirm readiness for release to trial sites. To effectively scale the production of your API, a well-defined formulation is imperative. Your CDMO needs detailed instructions on how to produce the API and “build” the formula so that they can understand how to handle the drug substance safely and identify all the required ingredients. You’ll also need to evaluate which technology and processes are best suited for handling the API, which a CDMO can advise on.
Characterizing the product – with the specific combination of equipment and expertise that will be used to fill it – is a fundamental step to monitor the entire process from API handoff to product release. This step includes assessing filling machinery, sterilization equipment, container types, tubing, and more. Selecting the most suitable container is a common starting point.
Remember that anything you know about your product’s particular sensitivities can be vital to aid your CDMO in making the right choices – first time. This includes selecting and confirming the appropriate filter(s) for the product, establishing locked-in testing methods for multiple points in the process, and asking key questions about analytical methods early on to establish quality safeguards. Also, keep in mind that the critical steps in the validation process (which start during process design), often require a certain amount of drug substance beyond what is needed to produce the CTM, so this must be accounted for in the initial batch size calculations.
When communicating with a CDMO partner, it is important to ask about their approach to analytical method validation and whether they can monitor and verify product quality. Asking these questions early on can help ensure that quality safeguards are in place from the beginning. Comprehensive documentation of the manufacturing process can prove invaluable on the backend, potentially averting the need for re-manufacturing of CTM if regulatory authorities raise concerns or have questions later in the process.
To confirm that the final project outputs meet regulatory requirements and support patients as intended, it is necessary to qualify equipment and manufacturing teams, develop and validate processes, and document every step along the way for the highest quality. A CDMO should demonstrate this approach through meticulous qualification and validation processes that maintain consistency and reliability, leading to successful product development, commercial launches, and lasting partnerships.
Taking the time to get the first batch right will ultimately save you money – and stress – during a critical period during your product’s development.
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