By William Wei Lim Chin, Ph.D., Global Scientific Affairs Manager, Science & Technology, Catalent
To be commercially successful, new oral solid dose treatments must offer superior real-world outcomes, and provide market differentiation. Achieving development milestones is obviously critical to progressing molecules to, and through the clinic, but this does not always translate to commercial success, or better outcomes for patients and stakeholders. Decisions that are taken during a product’s design and development must be made to deliver the best results for the patients who depend upon their therapies, and outsourcing partners with access to a wide range of technology platforms and development expertise can be invaluable in accelerating the development of a successful drug product.
Partnering with experts as early as possible in a program and throughout development can reduce the overall timeframes of a project and help mitigate program risks. From the concept stage and evaluating the needs of all stakeholders, to API selection, formulation and dose form design, all the way to having robust, reliable manufacturing operations, leveraging an experienced partner can be invaluable. This ensures the correct decisions are made at the appropriate times in a project and can dramatically improve the chances of a molecule’s success.
Stakeholder needs
Each stakeholder has specific needs in a drug. It is important that these are all taken into account, both at the design stage and as the project progresses and adjustments potentially need to be made.
For the developer, time is a key factor as it will primarily influence the cost of a project, and the potential returns from commercialization. Finding a partner that can offer integrated services and parallel development in different areas can reduce the costs significantly. The goal in any program is to create the “best” treatment possible, with the drug product being efficacious, stable, easy for a patient to administer, and resulting in good patient compliance and outcomes.
For a prescriber, a product must offer optimal clinical outcomes – with excellent absorption and drug load, with minimal patient variability. Additionally, it should offer minimal side effects, have minimized food effects, and ideally have a reduced dosing frequency and burden on the patient.
Payers need to see improved clinical outcomes and patient adherence, which can in turn lead to better economic outcomes through consistent disease and symptom resolution.
Most importantly, drug products must be patient-focused so that their experiences are enhanced. For drugs to be effective, patients must not be put off by administration, so drugs that are convenient to take, and do not present a burden to patients’ lifestyles will lead to greater compliance. The experience can be enhanced through a number of proven technologies such as smaller, easier to swallow dose forms, and those that reduce the potential pill burden.
Target Product Profile and Dose Design
Establishing the needs of a drug and pairing those needs with delivery technologies can influence a drug’s success greatly. There are a wide range of advanced drug delivery technologies available to overcome a variety of challenges including dose loading, taste masking, drug release, food effects, and others that can match in with the needs of stakeholders.
Softgels provide a patient-preferred solution and optimal drug release profiles through targeted delivery, modified release, coated and fixed dose combinations. Although the technology has existed for many decades, innovations have been made in this space that allow the oral delivery of macromolecules, reduce the dose form size, and produce products that are both vegetarian and vegan approved, as well as GMO-free. Softgel capsules can also be designed to contain semi-solid matrices for modified release of poorly soluble and/or poorly permeable drug compounds to solve unique drug delivery challenges.
To design a dosage form that is convenient and easy to take, and fit in with patient lifestyles, goes a long way to improving and increasing patient compliance and adherence. Orally disintegrating tablets (ODTs), which can be taken without water and disperse almost instantly in the mouth offer many advantages, especially for patients that have issues with swallowing – such as the elderly or very young – and can also be used in specialized situations, including to ensure patients with psychiatric disorders receive the medicines that they need. Delivery of a drug by an ODT can also have other benefits such as the rapid onset of action and reduced side effects by avoidance of food effects and first pass metabolism, as the drug can be absorbed before entering the patient’s stomach. Over-the-counter drugs that are available as an ODT form include analgesics, allergy relief and travel sickness medication.
Partnering for Success
Developing a drug product with a partner has many advantages: as previously noted, the experience in the process can be invaluable in ensuring mistakes are avoided, and correct decisions are made at the appropriate times. By engaging an integrated development partner at the beginning of the program that has the capabilities to collaborate through to commercial launch, there are opportunities to accelerate the timeframes, mitigate risks, and reduce costs by eliminating duplicate work involved in working with multiple service providers.
Development partners with multiple delivery and technology options have the advantage of being agnostic in terms of potential development options – it is vital that the molecule and the needs of the program decide the delivery method, rather than determining the dosage form and attempting to manipulate the drug molecule to fit. Screening and modeling can assist in the determination of what the most viable options in terms of dosage form may be, and then by evaluating these against the drivers and stakeholder needs of the project, a potentially successful product can result. Choosing a partner with a broad range of delivery options and formulation tools widens the options available to an API molecule and to potential solutions. It is important to remember that there is no one-size-fits-all approach to development, and although experience is valuable, each program is unique and needs to be treated as such.
Using an integrated company with the experience, tools and capabilities to bring a drug molecule through to commercialization, allows a true collaboration to be built between innovator and development partner. Where partners were once considered to be “contract manufacturers”, companies now bring their experiences and provide input into programs, and in the case of integrated development companies, can be thought of as extensions of the innovators. Fewer partners and service providers involved in a program means less risk for innovators through multiple handoffs through different vendors between product phases, and reduced management of contracts, auditing, harmonizing procedures and tech transfer. Having a single project manager allows streamlined communication, and ensures issues and potential problems can be dealt with effectively and swiftly.
There is no set method for achieving a successful orally-delivered drug, but by evaluating the needs of each stakeholder within a program, and evaluating these needs against the options available in terms of formulation, dose form design and delivery method, and using these as a framework, a molecule increases its potential to reach the patient, and bring potentially life-changing effects.