The 6-step clinical manufacturing checklist for injectable drug products

For emerging drug developers, the shift from lab to clinic is a transition that can lay the groundwork for success at many future milestones – from key early regulatory submissions to future partnerships and investment rounds. It’s an especially critical step for parenteral molecules: The aseptic fill-finish process adds many new strategic, operational, and compliance dimensions to the development pathway, all of which needed to be navigated starting with the first batch of clinical trial materials (CTM).

With finite funding and make-or-break milestones ahead, early-stage drug developers need to take a smart, strategic approach to this key clinical manufacturing project. These 6 key steps that should be part of it.

Step 1: Make a clear, proactive game plan.

Once you’ve decided to launch an in-human trial, it’s time to build a detailed roadmap to your first-patient-in date – including every complexity or question that can potentially impact that milestone. To ensure your CTM batch is available on time, factor in:

• Timelines: Including how they may be impacted by your molecule type, delivery format, and additional development work that may be needed to start filling your CTM.
• Regulatory guidance: Especially early input on your first submissions and compliance strategy. Proactively reach out to relevant authorities for feedback.
• Existing team knowledge: In particular, their familiarity with cGMP and ability to extrapolate small-scale study results into compliant processes and methods.
• API and formulation: How your molecule is produced and handled, including precursors, excipients, and any special physical properties or sensitivities.
• Supply chain: The resources you need and how you’ll source them, especially if your product needs any long-tail materials or non-standard components.

Be honest and realistic: It will help you avoid costly downstream roadblocks or delays.

Step 2: Lock in your container, key components, and raw materials

Choosing a container is a key step in getting an injectable product to the clinic, but it’s also a decision you should always make with future plans in mind. Carefully consider each of the three typical options:

• Vials: A standard go-to-market starting point, but one that offers a less desirable end user experience.
• Prefilled syringes: A more complex format to manufacture, but one that adds valuable ease-of-use to your product profile (especially in an autoinjector).
• Cartridges: Another format that requires specialized filling services, but also one that’s essential to the multi-dosing convenience of an injector pen.

This choice is especially important if your product may one day make the increasingly popular leap to a delivery device. Discuss that possibility with your manufacturing partner as early as possible so they can help guide you to the right option.

Whichever format you select, waste no time identifying the components and raw materials that need to be sourced to fill your CTM – including both your primary packaging and API. If some of those resources are rare, difficult to source, or backordered, you’ll want to know as soon as possible to keep your project on track.

Step 3: Get all scopes and contracts in place.

Outsourcing components of a CTM project is often a smart move for emerging drug developers. Whether that means hiring consultants or partnering with a CDMO, lock in that support as early as possible to ensure that all your contractors, suppliers, and service providers are moving toward the same goals from the outset.

Planning ahead for audits is especially important. In the run-up to in-human trials, regulators often want to evaluate manufacturing facilities, fill-finish processes, and cGMP compliance by both internal and external teams. Book the necessary resources in advance to ensure you’re ready for any surprise visits from your regulators.

Step 4: Align with quality best practices

The quality approach you take with your CTM project won’t just be important to regulators. Future licensees, investors, and strategic partners will also pay close attention to this key component of your development path.

To pave the way for future success, put a firm early focus on:

• Establishing a robust process development approach, data integrity framework, and knowledge transfer process.
• Aligning your production processes with ICH quality and transferability guidelines.
• Embedding quality-by-design in your product profile through properties like Critical Quality Attributes (CQAs) and Critical Process Parameters (CPPs).

If your internal team needs guidance on these best practices, a specialized fill-finish CDMO will be a critical resource.

Step 5: Assess your API needs

When it’s time to fill CTM, most early-stage drug developers have a limited amount of API that needs to be stretched as far as possible. To accurately calculate the amount you need, be sure to factor in both your target volume of CTM and the many other steps, activities, and tasks that will also require some amount of API. Those can include:

• Technical runs: Preparatory steps to test and optimize your manufacturing processes.
• Destructive sampling: Small amounts of product needed for lab tests and other quality checks that will render the material clinically unusable.
• Rejected product: Typical amount of product that falls out of specification and needs to be discarded.
• Line losses: Trace amounts of product that can potentially be lost during the fill finish process, even with state-of-the-art technology

Accounting for each of these needs will help you ensure your project yields enough CTM supply to sustain your clinical trial.

Step 6: Find a strategic CDMO partner.

For many emerging drug developers, partnering with a specialized manufacturer is often the best and most efficient way to navigate these steps.

To find that partner for your drug product, look for a combination of relevant expertise, deep experience, and well-established processes. When evaluating candidates, ask these questions early:

• Do they specialize in aseptic filling?
• Do they have experience with molecules like yours?
• Can they safely handle your API?
• Does their Quality Management System meet your quality team’s expectations?
• Do they have available fill slots when you need them?

If the answer to these questions is “yes”, then you may have found a strong partner who can confidently and efficiently fill your batch of CTM.

These six steps can put you on the path to success.

Filling your CTM batch can be a complex and technically demanding project, especially at a time when there is still much to learn about your molecule. But with the right planning and the right partners, it’s also a process that can support valuable results: not just on-time trial initiation, but also downstream partnership and licensing opportunities. Follow these 6 proven steps, and you’ll have a strong head start toward all those important goals.