Gurmeet Singh, Senior Director at West Pharmaceutical Services & Jeff Kyle, Senior Director of Wearable Delivery Systems explore how a focus on containment in early drug discovery can help ease the development process later on.
It may seem counterintuitive to spend time and money on planning for containment and delivery systems for a drug in the earliest stages of discovery when the chances of that molecule making it to market are still quite low. However, starting early can greatly improve the efficiency and speed of the development process.
This is especially true now, with the rise of drug-device combination products that demand sophisticated delivery systems. The growing hospital-to-home trend has motivated drugmakers to convert intravenous medicines into subcutaneous formulations that patients can self-administer. The development of easy to use, intuitive home administration devices, including wearable devices, that can deliver medicines to patients on demand is expanding.
The increasing complexity of drug products has raised concern among pharmaceutical developers. During a 2021 workshop sponsored by West Pharmaceutical Services, 32% of attendees said they were most concerned about generating the right technical data to support their applications to the U.S. Food and Drug Administration (FDA) for approval of drug-device combinations.
Identifying and solving issues related to drug containment and delivery systems is a crucial step in generating the data needed to support regulatory submissions. Many potential problems can be identified early and addressed to ensure the proper solution is in place for clinical trials and, ultimately, for full commercial production.
One major challenge for drug developers in early stages is determining if the container closure system and any drug-contacting materials will be compatible with the medicine. It’s important to ensure, for example, that the containment material doesn’t introduce extractables resulting in leachables in the drug product—chemicals that could potentially alter the drug’s activity or cause toxicity. Compatibility must also be considered in the context of shelf life and specific storage and transportation conditions.
Even if the formulation of the drug is not yet finalised, developers can work with partners to perform analytical tests on its basic ingredients to get an early readout on potential compatibility. Then, as they refine the product from Phase I clinical trials to Phase II, and home in on the final formulation, they can repeat that testing to ensure compatibility.
Never too early
For developers of drug-device combination products, addressing containment and delivery in the early stages can make it easier to meet regulatory requirements down the road. For example, the FDA expects manufacturers of drug-device combinations to define essential performance requirements (EPRs) such as total volume delivered, activation force, and if it’s an on-body delivery system, the adhesion force required to maintain attachment during delivery.
The FDA will require EPR testing on the final combination product, including requirements that are specific to the device’s design and performance. That’s why it’s a good idea to think about that device in early development, keeping the FDA’s view in mind. This should become easier, as the FDA is expected to publish a guidance document on EPRs by end of 2022.
Engaging in extensive testing for containment compatibility, product requirements, and EPRs early in development will understandably raise concerns about cost. Given that only a small percentage of drugs will ultimately make it to market, answering the question of just how much to invest in finding the right containment system—and how early to invest—is never easy.
But waiting too long to assess containment and delivery carries its own risks. When companies have to change their delivery or containment systems late in the development process, the impact on cost, timeline, and the chances of regulatory success are often significant.
Gurmeet Singh is Senior Director at West Pharmaceutical Services, a provider of pharmaceutical delivery and packaging systems. She has more than 15 years of experience in medical device project management and marketing.
Jeff Kyle is Senior Director of Wearable Delivery Systems, R&D at West Pharmaceutical Services. He has 25 years of experience in life sciences operations, delivery systems and new product introduction.