IND Enablement and Drug Product Development – Mitigating Risk and Accelerating Through the “Valley of Death”

Partnering with the right outsourcing provider, such as Coriolis Pharma—a comprehensive one-stop-shop for drug development and analytical services spanning preclinical to commercial stages, including lifecycle management—can streamline the advancement of even the most complex parenteral drug products. Coriolis Pharma stands out by integrating innovative technologies and expertise, focusing on scalability, and proactively addressing CMC and device development needs from the outset.

Overcoming Challenges from Preclinical to Clinical Development

To achieve market approval, drug candidates must meet various critical criteria. Most early-stage companies focus on demonstrating the efficacy and safety of their therapeutic. This task is particularly daunting for treatments targeting complex and debilitating conditions, such as various oncological, hematological, and neurological diseases, making it sensible that those are the top priorities for drug developers during early stages. However, the path to market involves more than proving efficacy and safety; the drug must also be manufacturable. This requires addressing critical chemistry, manufacturing, and controls (CMC) considerations early in development. The biotherapeutic must not only be stable enough for manufacturing but also designed for practical implementation at large scale. Comprehensive data must be gathered to ensure a smooth transition from lab-scale to clinical-scale manufacturing. Additionally, appropriate data must be developed to support the filing of both Investigational New Drug (IND) applications and Biologic License Applications (BLAs). Insufficient CMC information can lead to complete response letters from regulatory bodies during the approval process, prolonging the timeline to commercial launch. These setbacks can deter investors seeking quick returns and increase the risk of program failure. Understanding and managing risk presents another significant challenge, and it is essential to invest in specialized techniques to assess and predict risks associated with a drug candidate. A delicate balance between the time and cost of conducting these assessments and the depth of insight they provide must be struck to facilitate informed decision-making. This balance supports making timely, critical decisions throughout the development process.

Utilizing effective predictive tools, such as developability assessments including benchmarking against commercial products, help comprehensively understand a molecule’s characteristics, which is crucial for advancing through the development stages and successfully meeting key milestones en route to IND submission.

The Importance of Selecting the Right Outsourcing Partner

The successful transition from preclinical to clinical studies is vital not only for the survival of a program but also for the viability of smaller biotech firms. Missing crucial development milestones can jeopardize funding opportunities. Many emerging biotechs lack extensive experience in drug development and often overlook the importance of downstream considerations, focusing instead on immediate needs at the expense of manufacturability and the generation of comprehensive CMC data.

The key to addressing these challenges is choosing appropriate service providers equipped with the necessary tools and expertise to implement the best solutions for specific drug candidates. A frequently observed approach at the preclinical or phase I stages is selecting a partner specialized only in early development phases without the expertise to ensure consideration of more distal needs that will be essential to advance the program further. This often results from a narrow focus on financial constraints and the pressure to minimize initial investments, such as those needed for risk assessments. Such an approach might save investments into the service provider but mean higher costs on the customer side and increased risks of clinical trial delays in later development stages. From the investors’ point of view, this is a not a favored scenario.

A more strategic approach involves selecting a supplier capable of supporting the entire drug development life cycle from early-stage through to commercialization, although such end-to-end integrated providers may lack sufficient specialization in capabilities that are critical to a given development program. For such programs, a better alternative may be a best-of-both-worlds hybrid model, in which a company engages with a small number of specialist providers (e.g., for formulation development, sophisticated analytics, drug product manufacturing, etc.) who have a nuanced understanding of the full scope of program needs and are well positioned to serve as effective bridges connecting earlier and later stages. An outsourcing paradigm built in this way reaps the unique benefits of specialization while avoiding the gaps and bottlenecks that can occur during transition from a contract research organization (CRO) to a contract development and manufacturing organization (CDMO) or from an early-stage CDMO to a commercial manufacturer.

For independent small biotechs, considering the full path to commercialization and establishing such a partnership strategy from the outset can significantly enhance the value of a drug candidate while reducing the risks associated with progressing from preclinical to clinical development and late stage/commercial. Such partnerships are generally favored by investors, who recognize the added value and increased success likelihood these comprehensive suppliers bring to the table.

Strategic Timing in Project Management

Effective management of project timing is crucial for success in drug development. It is particularly advantageous to establish outsourcing partnerships as early as possible, ideally before initiating process and formulation development activities. Establishing an end-to-end outsourcing strategy and initiating strategic partnerships at this early stage allows for optimal utilization of their extensive expertise and experience. This strategic timing ensures that considerations regarding manufacturability and administration or delivery devices are integrated from the beginning.

At this juncture, conducting a feasibility study is vital for determining any additional formulation development needs and for minimizing risk. Such proactive assessment helps to outline the risks associated with a drug candidate and delineates the necessary steps within the development timeline, facilitating effective program planning and helping to prevent potential delays.

However, many companies delay establishing these partnerships until phase I trials are underway, often discovering too late that their formulations are suboptimal. In such situations, it becomes imperative to select a CRDMO with proven expertise in formulation development and problem-solving. Common issues that emerge include inadequate stability testing, insufficient characterization of aggregates and other particulates, and flawed surfactant screening. Addressing these issues early with the right partner can mitigate significant challenges later in the development process.

Prioritizing Device Selection in Drug Development

In drug development, particularly for parenteral products, the trend is shifting from traditional vial filling toward the use of devices that facilitate administration, such as prefilled syringes, autoinjectors, and pens. These products are considered combination products, and it is crucial to develop strategies that encompass both the drug product and the device.

Emerging biotech companies often overlook the importance of device selection during early clinical testing. The primary focus tends to be on achieving early clinical results swiftly, with little attention to the choice of delivery device. This oversight can lead to significant setbacks, as an inappropriate device may need to be replaced. Switching devices can introduce numerous complications, potentially requiring drug reformulation. Such changes can alter the quality target product profile, necessitating process optimization. Additionally, issues like aggregation and other particulate matters may surface, which need to be tackled due to patient safety requirements.

Investing time during early-stage development to carefully select the most suitable device for a drug candidate is critical. This approach can prevent substantial challenges in later stages of development, ensuring smoother progress and reducing the risk of costly delays and modifications.

Comprehensive Support from Coriolis Pharma

Coriolis Pharma is a leading global contract research and development organization (CRDO), offering a complete range of drug product development and analytical services from preclinical stages through to commercialization, including life cycle management, with a specific focus on the injectable sector. We facilitate the development of both liquid and lyophilized drug products, providing high-quality formulation research and development under both R&D (non-GMP) and Good Manufacturing Practice (GMP) conditions, particularly for biologicals and cell and gene therapies. Our track record includes numerous successful market launches.

At Coriolis, innovation is driven by the synthesis of advanced technologies, deep industry knowledge, and extensive experience, all brought together in a collaborative partnership with our clients. We prioritize manufacturability and scalability from the outset of each project, ensuring all development activities consider CMC and device integration requirements. For example, we utilize only excipients that meet pharmaceutical-grade standards and are available at the required scale for drug product manufacturing.

Our expertise extends to reformulating existing products from traditional vials into more patient-friendly formats, such as cartridges, prefilled syringes, and wearable devices, enhancing life cycle management and catering to specific patient needs. This capability allows our customers to streamline development processes, reduce the necessity for extensive tech transfers from clinical phases to commercial production, and smoothly transition into product line extensions that maximize market value. The services we provide complement those offered by traditional drug substance and drug product CDMOs, making Coriolis a comprehensive partner in pharmaceutical development.

Advanced Developability Assessment and Pre-formulation Screening

Coriolis Pharma excels in supporting clients with discovery and preclinical programs through highly efficient developability assessments, formulation sensitivity testing, commercial product benchmarking, and pre-formulation screening. Our innovative techniques are specifically designed to facilitate accelerated development timelines, complemented by specialized reporting capabilities that produce clear, standardized data reports, perfectly aligned with IND requirements.

Our platforms for developability and pre-formulation screening represent streamlined encapsulations of Coriolis’s extensive experience, with over 2,700 successful biologics development projects across all stages, including commercialization. Our science-based developability assessment platform for antibodies focuses on identifying candidates with the most favorable biophysical properties for effective drug product development, scale-up, and market introduction. Additionally, our novel systemic antibody pre-formulation platform thoroughly examines a broad range of excipients from FDA-approved drugs to generate a comprehensive data set. This holistic approach to drug product development ensures systematic exploration of formulation options. Predictive methodologies, coupled with accelerated stress testing of critical quality attributes (CQAs), help pinpoint the most promising formulations for further stability studies and preclinical development.

Coriolis offers a comprehensive, swiftly executed service package, thoughtfully priced to match the development stage’s needs. The depth of knowledge and risk mitigation our services provide, ensure a valuable investment in drug development efficiency and increases the valuation of the molecule, which is impactful for investors.

Leveraging Proprietary Analytical Methods

At Coriolis Pharma, a deep understanding and thorough characterization of biologic candidates are achieved through a diverse array of analytical methods. Our formulation development processes are bolstered by an extensive suite of analytical capabilities, with over 200 methods at our disposal. These include numerous innovative techniques that have undergone rigorous validation by our in-house science and technology group and through collaborations with major pharmaceutical partners. Furthermore, methods developed for early-stage molecule characterization are seamlessly adaptable to GMP environment for essential stability studies and release testing.

A notable example of our pioneering work in analytical methods is our early adoption of microflow imaging (MFI) for particle analysis in biologics. Our in-house research and scientific publications on MFI have been fundamental to establish this method as an industry-wide standard practice for subvisible particle analysis of biologic drug products and is referenced in USP1787. Additionally, we are at the forefront of developing new analytical techniques for biologics and advanced therapy medicinal products, including cell and gene therapies. These efforts are particularly aimed at aiding the clarification of regulatory standards for these cutting-edge treatments.

Prepared for the Future: Staying Ahead in Regulatory Compliance

At Coriolis Pharma, we understand that regulatory expectations for biopharmaceutical products are dynamic, with quality requirements continuously evolving. It is crucial for us as a service provider not only to remain current with new guidelines but also to proactively anticipate future regulatory changes.

To ensure we are at the forefront of regulatory compliance, Coriolis Pharma conducts regular scientific reviews. Our scientific advisory board members actively participate in industry trade organizations that contribute to the drafting of new regulatory guidelines. This involvement allows us to stay well-informed about the latest developments. Moreover, our ongoing participation in IND and BLA filings provides us with direct insights from regulatory authorities, keeping us updated on shifting expectations regarding development approaches.

In our commitment to better serve our global clientele, Coriolis Pharma continues to expand its capabilities and facilities. In May 2024, we launched a new U.S. entity comprising the commercial organization of Coriolis. This expansion allows our North American clients to enjoy the benefits of localized service coupled with our broad international expertise, further enhancing our ability to meet their needs effectively.