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The right outsourcing partner should open up access to expertise and technical capabilities in a broad range of dosage forms to ensure commercial success.
As the need for innovation in drug development is increasing, so too is the requirement for companies to partner with a contract development and manufacturing organization (CDMO) early on in development. To find out more about the importance of considering the end-user and the role of an outsourcing partner in successful drug development, Pharmaceutical Technology sat down with a panel of experts.
The panel of experts includes Lonnie Barish, vice-president, business development and marketing, Bora Pharmaceuticals; Richard Shook, director, drug product technical services and business integration, Cambrex; Steven Winling, product development technical specialist, Catalent; Manuel Leal, business development director, Idifarma; Frederique Bordes-Picard, manager, business development for innovative products, Capsules and Health Ingredients, Lonza; Rob Lee, president, CDMO division, Lubrizol Life Science Health; Paul Kippax, pharmaceutical sector director, Malvern Panalytical/Amplify Analytics; Jeremy Drummond, senior vice-president, business development, MedPharm; and Torkel Gren, science and technology officer, Recipharm.
PharmTech: How are companies taking the end users’ opinions and preferences into consideration, in terms of drug dosage forms?
Winling (Catalent): When recommending solutions to product development challenges or performing routine release testing, the patient should be at the center of everything. It is important to work with external collaborators to uncover the needs of the patient groups being served. When patient preferences are not known, a patient first culture helps companies ask the right questions from the very beginning of a dosage form development project. It is important to make sure that the needs of the patient and the challenges of the molecule are well understood and taken into consideration when building any development plans. When the product profile has been determined, all scientists working on a development project should understand the patient needs that the formulation they are working on must address.
Kippax (Malvern Panalytical/Amplify Analytics): Once an API that demonstrates appropriate efficacy against the pharmacological target has been developed, a key requirement for getting the product to market is to formulate the API appropriately to maintain its efficacy, whilst taking patient preferences into account. Both patient compliance and the chosen market, and its associated local restrictions and requirements, can impact the selection of a particular dosage form. Complex formulation techniques are crucial for ensuring the maintenance of bioavailability, which often brings significant characterization challenges.
Gren (Recipharm): There are examples of how companies are trying to get a better understanding of user preferences. It has been a common practice to use taste panels for selection of suitable taste-masking for a long time. However, today there is interest in going much deeper than just taste and skin feel. It is important to understand how the product as a whole is perceived by the patient in a realistic dosing situation, which may vary widely for different patient groups. To understand this [perception], it is necessary to form focus groups with patients and use qualitative and quantitative methods to evaluate preferences.
Drummond (MedPharm): The end users’ opinion and preferences are crucial from the start. These factors should be incorporated into the product profile established from the very beginning. That said, the product profile ought to also consider the API, which may limit options for patient suitability. The expertise of the product developer allows them to manage these constraints whilst still delivering a dosage form that patients are happy to use. This knowledge is particularly important for smaller companies, where it is not uncommon for some to not have thought about end users’ preferences, particularly at the early stage of a project. As patient preferences can be fully understood once a project has started, these new insights can be accounted for within the product and incorporated into any project goals.
Shook (Cambrex): Patient compliance should always be a priority when developing a drug dosage form. When developing a new dosage form, pharmaceutical companies should take the targeted patient population into consideration to better understand how the final drug product will be received and dosed.
Barish (Bora): Patient compliance will dictate design of the dosage form. It must be integral/intrinsic to any drug development strategy because compliance and getting the desired effect is paramount. Each dosage form presents its own challenges and that is further complicated by the API. Drug developers should start with the ideal patient delivery for that form and then work on issues with the API to get as close as possible to that ideal delivery. Fortunately, new techniques and mechanisms have or are being developed to deliver challenging APIs towards those ideal forms.
Lee (Lubrizol): More attention is being paid to this area through the formation of user groups, talking to key opinion leaders in the medical profession and then getting feedback from the end-user patient. From a marketing perspective, end-user input is key if the plan is to reposition marketed drugs to be more patient-centric.
Bordes-Picard (Lonza): Manufacturers are more connected to patients than ever through representative associations and discussion forums, which allows companies to better understand patient preferences and limitations. Much of the discussion is focused on chronic diseases, but it could be extended to additional areas such as oncology and respiratory diseases.
Pharma companies are also collaborating more. A notable example of this is the use of connected devices to improve compliance but also to get rapid and direct feedback from the patient. The key for outsourcing partners, if they are to thrive, is to use the data and look at products in a more holistic manner so that they can design and develop the most effective, patient-centric dosage form.
PharmTech: What role can/does an outsourcing partner play in optimizing a drug dosage form?
Kippax (Malvern Panalytical/Amplify Analytics): Optimizing a formulation against delivery requirements is extremely complicated. The use of in-vitro approaches for assessing bioavailability is increasingly becoming accepted, but the physicochemical analysis techniques required are complex, and the specific knowledge required to get the most out of this type of characterization is not always present within pharma development companies. Hence, the increased propensity of organizations to select outsourcing partners who can address these knowledge and capability gaps.
When optimizing the dosage form, it is no longer sensible to simply rely on the data output of a scientific instrument. Coupling an understanding of the requirements of industry analytics with knowledge of how to maximize the output from analytical instrumentation and methods is critical. To increase development efficiency, pharma companies are now able to establish relationships with a wide range of technical partners to generate actionable data and direction they can consistently rely upon. This [capability] allows nonviable molecules or formulations to be eliminated early in the workflow, focusing attention and budget on those candidates most likely to succeed at all points in the pipeline.
Leal (Idifarma): Choosing the right outsourcing partner is essential for the development of many drugs, because both technically and economically, it is the most sensible approach for many pharmaceutical companies that don’t have the knowledge or capabilities in-house. Finding a CDMO that meets the technical requirements of the product to develop as well as being the right fit for the client is not easy. For example, there are cases where working with a smaller, more specialized partner is the best decision, because the projects are managed closely with the client for quicker decision making and less delays.
Shook (Cambrex): A reliable CDMO outsourcing partner should bring a wealth of drug dosage-form experience to the table. They should be able to balance innovative problem-solving with decreased complexity. An expert CDMO can fill manpower, knowledge, and capability/capacity gaps in the drug development process for smaller or virtual companies and offer efficiencies of scale for larger pharmaceutical companies.
Winling (Catalent): A sponsor really benefits from an outsourcing partner when there is an open relationship, allowing for collaboration during the development of a treatment. The outsourcing partner provides the sponsor access to specialized technology and expertise needed to develop novel dosage forms as well as access to a wide range of capabilities.
Barish (Bora): It’s clear that one of the biggest changes to the pharma manufacturing industry is the increasing reliance on external partners. The shift has been positive for the entire pharma supply chain by promoting quality, innovation, and more efficient drug development and commercialization routes.
Pharma is also relying more on CDMOs to develop and manufacture increasingly complex drugs. It’s well known that more experienced project teams can help accelerate go-to-market schedules, and technical/operational mastery is a prerequisite. However, unlocking an API’s therapeutic value requires sound science, experienced technical expertise, and operational excellence to do it well and meet all commercial, financial, and regulatory expectations.
Companies have been engaging international manufacturing partners for a number of reasons. Some of the initial drivers have been access to lower-cost manufacturing and proximity to emerging markets. While managing costs has been a central theme, access to capacity, technical capabilities, and cutting-edge science have also prompted many partnerships, especially for more commoditized and high-volume products. Securing strategic experience and expertise is a big part of this trend.
Lee (Lubrizol): Ideally, your CDMO will have broad experience working with different routes of administration and a variety of different drugs, from a physical and chemical perspective. Experience with a range of dosage forms creates a wider perspective that can add significant value to your project.
Non-traditional dosage forms bring an added layer of complexity to a drug development project, requiring additional technology and expertise. An outsourcing partner’s experience with these kinds of challenges can ensure that technologies work more effectively, and any issues are anticipated early on.
Drummond (MedPharm): For specialist dosage forms, such as topical products for eye, skin, airways, or mucosal membranes, working with an outsourcing partner has many benefits. The requirements for delivery are quite different from oral and intravenous routes of administration and require unique knowledge and experience that the majority of development companies do not have in-house. In particular, the sophistication of in-vitro models using human tissue, in the development of these products has greatly de-risked these development programs. What is also gained with a specialized contract developer is not only the formulation development experience in a specific area but also an in-depth understanding of what it takes to get a product to market, whether it is a new chemical entity, a repurposed drug for a new indication, an over-the-counter product, or a generic.
Gren (Recipharm): CDMOs can provide access to more technology and competence for dosage-form development locally as well as globally. As well as accessing technical capabilities and a global manufacturing network, pharma companies can also access years of development expertise. Outsourcing also provides the organization with more flexibility to focus on core competencies such as further R&D. Those CDMOs that offer both development and commercial manufacturing services can help guide customers’ molecules from concept to market. Developing the dosage form with manufacturability in mind can have many benefits. Working with an end-to-end CDMO can help to reduce complexity and timelines and ensure smoother progress of a drug to market.
Supplement: Outsourcing Resources
When referring to this article, please cite it as F. Thomas, “Opening the Door to Successful Drug Development,” Outsourcing Resources Supplement (August 2020).