April 1, 2014
The biopharmaceutical industry is experiencing a surge of collaborations among large and small companies seeking to develop new drug candidates. Often, such efforts have been a result of a merger or acquisition. But other factors also are pushing the rise in collaborations, including dwindling drug pipelines, increasing generics and biosimilars, rising costs of drug development, and changing regulations that are already complex.
High costs of drug development in particular have created greater risks. That is especially true for small biotechnology companies that have limited budgets to bring new drugs through to completion. Such companies need to focus on core competencies. Conversely, large pharmaceutical companies that depend on promising drug candidates might have resources but lack worthy drug candidates. So they are looking for new ways to replenish their portfolios. Most often, such “replenishing” translates into searching for promising opportunities among small biotechnology candidates.
Small facilities often are extremely sensitive to risk during early development. Unlike large, well-financed biopharmaceutical companies, they can lack financial resources and a critical level of experience in key areas. So a negative event — even minor delay or a small mistake in drug development — can potentially lead to financial ruin. Maximizing the value of a complete drug package (a compound and innovative drug-delivery system) as well as the quality and reputation of a company’s partners in early development stages is of paramount concern.
Taking risk-reducing steps can add significant value both to a drug and its sponsor company. This strategy can help attract a large biopharmaceutical company to assist in financing drug development and add expertise. Frequently, the result is outright acquisition of a drug package or (when proper planning has occurred early in the development process) of the company itself.
The actions required for successful drug development are not a simple undertaking. Success or failure of a compound depends on a number of factors from the start. That is especially true for parenteral drug development, which involves complex feasibility, stability, compound–delivery system interactions, and administration challenges. For small biotechnology companies to win at this game, they must create the most advanced and complete drug candidate package possible. Only early and careful planning for the future will lead to probable success and a winning situation for all parties involved.
So how does early planning help in producing the best drug package possible? And how can small biotechnology companies take the right steps and appropriate actions to ensure a successful outcome in the form of an outlicensing deal or outright acquisition by larger biopharmaceutical companies? The answer can be found by taking a closer look at the process of early drug development.
It is well understood that biologics manufacturing demands significant experience and substantial process planning. Active ingredients based on biological processes are extremely complex substances consisting of large molecules. Such substances react with far greater sensitivity to environmental influences such as light and heat than do others. They also require very high standards in manufacturing and handling for quality and safety.
But as previously noted, smaller bioprocessing companies may lack the resources to focus from the start on a complete drug package. That has unpleasant consequences during outlicensing for late-phase development and commercialization and will probably affect the value of packages to be out-licensed.
One way to overcome the lack of in-house resources is to rely on a number of small, local partners such as contract laboratories and filling services. The risk is that smaller partners often exacerbate the problem because they may not possess essential hands-on experience required in early development of complex drug substances. They also can lack long-term relationships with regulatory agencies, which are critical to moving products forward, as well as corresponding current regulatory know-how.
That vacuum of knowledge inevitably means that many tasks still must be executed by small bioprocessing company employees, which often increases costs and adds risk to an entire process through technology transfer activities — exactly what the company is trying to prevent. Generally speaking, a reduced timeline should improve financial benefits, far in excess of higher development cost spendings. So minimizing the number of service providers throughout a process often improves success rates by retaining product and process knowledge, reducing overall timelines, preventing duplication of activities, and decreasing risk.
Partnering with a trusted contract development and manufacturing organization (CDMO) early in development often can make a difference. Such an experienced partner is qualified to provide the necessary and critical development support needed for complex compounds, including fill–finish operations. A well-chosen CDMO can provide a significant incremental effect in helping to achieve an attractive, high-value drug package. A well-conceived partnering approach will add “luster” to a drug package — and therefore to the sponsoring company. That can raise the likelihood of attracting the attention of a large biopharmaceutical licensor or buyer.
CDMOs today are increasingly acting as an interface between small biotechnology companies and their “big biopharma” counterparts because they understand both sides of a situation, including targets and difficulties. As such, CDMOs play an important role in supporting the successes of both parties over the long-term. They understand the continuous changes in the world of research and development and have set up specialized services in markets where development innovation is happening, thereby creating efficiencies in drug development and lean processeses.
CDMOs usually have high-performance production capacities available for clinical filling with the necessary infrastructure, including semiautomatic equipment and fully automated filling lines. That breadth of capacity affords small bioprocessing companies the ability to perform efficient and lean processes while achieving high-quality and safe results. It is also a way to improve bioprocesses and reduce time to clinic. An experienced partner in supporting drug projects through all phases of development equates to extensive know-how in working with different drug substances and substance classes. Significant experience in handling packaging and production processes is also in place. Developers can concentrate on advancing their injectables without worrying about processes.
Qualified CDMO service providers not only can cover the early development phase but — with a large biopharmaceutical company — also support full later development, including launch and commercial production process. Supporting drug substance development from the start eliminates expensive and time-consuming knowledge losses that can occur with changing service providers later on in a process. Knowledge gained is kept safe and can be used for later processes. For many large biopharmaceutical companies, the data and experience gained through previous handling of drug substances offer greater added value. For example, following acquisition of a drug package or even a small company as a whole, a large biopharmaceutical company can optimize processes itself and thereby accelerate time to market.
Below is a case study involving a small biotechnology company and its experienced partner. It can illustrate how partnering with a development/manufacturing service provider can add value to the complete drug package all along the value chain.
A small biotechnology company (“Biotech”) was in the early stages of drug development for a promising monoclonal antibody (MAb). Understanding that it needed to focus on the goals of long-term market success and adding value to its drug package, the company approached a CDMO to assist with clinical trial material entering phase 2 studies. Biotech needed support in liquid filling of the MAb that was to be used in a cancer indication. This small company also required that a placebo solution be filled.
The project kicked off with transfer of a manufacturing process and methods to the CDMO, and batches were produced successfully within a few months. Having completed that task, Biotech then began looking for a partner that could license the drug package. Because it had a promising drug candidate and had combined with an established partner, Biotech felt confident that all key pieces were in place to attract a strong biopharmaceutical company for outlicensing.
Once the best large company to license the product was found, development of the compound continued seamlessly. Why? Fortuitously, the large biopharmaceutical company was already one of the contract partner’s established customers. In addition, the handover from the small biotech company to the large one was smoothed by help from the CDMO. As such, the project was seamless and flawless in its execution.
Of key importance was the fact that scientific expertise related to the project was retained throughout the licensing process. Transfer was facilitated by a consistency of approach and not compromised by the need of switching contractors. Potential benefits of continuing work with the previous product sponsor included eliminating the expense of additional active pharmaceutical ingredient (API) use through the need to reproduce experiments or perform bridging studies, and so on. Furthermore, the partnership decreased risks associated with technology transfer issues and created a solid relationship that could extend into future projects, adding value to the compound, reducing valuable time and overall cost to market.
As illustrated, Biotech was well aware of the benefits of thinking ahead and the need to involve a sophisticated and experienced partner early in the process to achieve the best long-term outcome. By contracting with this partner to help with the many important studies and tests needed for early and later development and scale-up, the CDMO enabled that all work was performed to the satisfaction of both parties.
Although no one can ever truly predict the outcome or future of a drug in early development, it can be safely said that thinking with the goal in mind from the very start can often make the difference in attracting a large company to help with the cost of development or the actual future of a product candidate in terms of an outlicensing deal or even acquisition. Certainly, involving an experienced service partner early in the process adds value and contributes to the monetary value of a biologic overall. A CDMO can support a product from early development phase through to late clinical development, market launch, and subsequent commercial manufacturing, including lifecycle management activities.
The choice is yours. Your potential licensing partner cares a great deal about each element of the drug package you are offering for outlicensing. So isn’t it smarter to think with the end goal in mind right from the start?
Author Details
Paul Nelles, PhD, is vice president of development service at Vetter Pharma-Fertigung GmbH & Co KG, Schuetzenstrasse 87, 88212 Ravensburg, Germany, 49-751-37000; [email protected].
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