Thermo Fisher Scientific

The pharmaceutical oncology landscape looksvery different today than it did just a decade ago. Advances in the molecular understanding of cancer, an increased focus on developing targeted therapies based on that understanding, and new regulatory pathways for getting novel treatments to market quickly have changed the clinical development paradigm for oncology drugs and introduced unique hurdles.

To shepherd oncology molecules from formulation design to commercialization, pharmaceutical and biotechnology companies must be prepared to overcome bioavailability challenges, handle high-potency materials, optimize the supply chain, and navigate a complex regulatory environment.They must also begin the development process with the end in mind, where “the end” is not only the final drug product, but alsothe cancer patient whose life depends on that drug product.

The oncology drug development landscape

As the fastest-growing, most active sector ofdrug development, oncology has benefited frombreakthroughs inscience and technology thathave advanced researchers’ understanding of thebiology, immunology, and genetics of cancer. This growing body of knowledge has led to thedevelopment of new therapeuticstrategies thatincrease treatment options and improve outcomesfor patients. Many patient populationsthat previouslywere treated with nonselective chemotherapiesare now receiving targeted agents andcancerimmunotherapies that are tailored to the molecularand clinical features of their disease.

In addition to widening the oncology playing field,this shift toward precision medicine has intensified thecompetition. The past decade has seen 169 launchesof novel active substances in oncology, includingnew immunotherapies, next-generation biotherapeutics,and treatments for rare cancers. In 2021, there werenearly 7,000 anticancer drugs in the R&D pipeline, representing a 7 percent increase over 2020 and outpacingthe overall rate of pipeline growth. Almost all of this pipeline is geared toward precision oncology,including therapies such as small molecule angiogenesisinhibitors, immune checkpoint modulators, T cell–engaging antibodies, antibody–drug conjugates,and chimeric antigen receptor (CAR-T) therapies,among others.

By design, precision oncology requires a drugdevelopment framework that can bend to thespecific needs of cancer patients and the uniquegenetic and molecular characteristics of theirtumors. Theinherent heterogeneity means thepath from laboratory to finished product andcommercial launch will be different for every therapy.Building an optimal road map for each requires adeep understanding of those differences and carefulintegration of best practices to meet patients’needs and more quickly bring novel therapiesto market.

From a manufacturing perspective, the implicationsare significant. Matching drug products to clinicaland commercial needs for such a robust pipelineis inherently challenging and doing so in the shadowof a global pandemic increases the complexity byan order of magnitude.Targeted cancer therapies are more complexthan conventional chemotherapies, makingtheir formulation more challenging, and manyare highly potent compounds that requirespecialized facilities, equipment, and handling.Similarly, biologics must be handled, stored,and shipped at low temperatures to ensure thephysical integrity of the doses and cell-basedimmunotherapies have unique logistical obstacles.Coupled with quickly evolvingstandards ofcare across cancer types, accelerated approvalpathways, lower production volumes,shorterproduct lifecycles, and a crowded developmentfield, these considerations add multiple layers ofintricacy to an already complex development model.

Starting at the finish line with predictive modeling

Designing formulations for targeted oncologytherapies—both small molecules and biologics—presents several challenges related to thecomplexity of the substances, the need for noveland sophisticateddelivery routes and productionmethods, new regulatory pathways, andaccelerated timelines for gettingthese productsto market.To reduce the risk that underperformingformulations will slow developmentprograms atany point along the development continuum,formulations must be designed from the outsetto align with the final container and drug-deliverymethod to avoid discordancy between activeingredientsand production materials. In addition, sponsors and strategic partners should maintain a consistent line of sight to the end goal— development ofa safe, effective medication that meets theneeds of the patients who will be receiving it.

Understanding patient and commercializationneeds is critical for defining strategies forstabilization,concentration, and delivery.In addition to the well-established principles offormulation noted above, theuse of creativeand often proprietary formulation technologiesenables development teams to overcome uniqueformulation challenges. The Quadrant 2computational modeling platform is an example. It is an integrated drug formulation program thatencompasses in silicotools, high-throughputscreening, and predictive tools that can integratewith the commercialization process. The program analyzes the specific molecularstructure and chemical characteristics ofcompounds in combination with the unique targetproduct profile to predict the optimalsolubility enhancement technology and excipientcombination at theearliest stage of development.Further modeling can predict stability outcomesfor shelf life andcomponent compatibility, blendingand compression performance, and even productpharmacokineticbehavior to accelerate formulationand process development.

Capabilities and technologies such as these are becoming crucial differentiators. In addition to streamlining developmenttime and mitigating the inherent risks associatedwith trial-and-error experimental approaches, predictive modeling can help identify specific patient populations who might not tolerate certain drugs well or those at greater risk of an adverse drug reaction. They can also help companies better understand how demand will be affected by variables such as regional demographics or economic conditions. This kind of insight ensures the most efficient use of resources, but more importantly, it improves patient access to critical medicines.

The road to success

As researchers continue to develop new methods of targeting cancer cells and more agents reach the market, competition for key targets will become more intense. To be successful, pharma companies active in oncology will need to adopt new development strategies for getting the right drug to the right patient at the right time. Increasingly, this requires shifting to a more patient-centric approach and developing strategic outsourcing relationships to address the unique formulation, manufacturing, regulatory, and supply chain challenges associated with precision oncology therapies.