EXECUTIVE INTERVIEW - Vetter: Successfully Bridging the Innovation Gap in Drug Development & Manufacturing

Pharmaceutical and biotechnology companies are under increasing pressure due to sustained globalization in the industry with the associated risks and the loss of patent protection for many blockbuster drugs, resulting in tremendous competition from generic drugs. Generics are projected to grow from $242 billion in 2011 to $430 billion in 2016, according to an outlook report from IMS Institute for Healthcare Informatics. To lower the overall company risk, large pharma/biotech companies have cut back on their own research and development spending and prefer buying advanced promising candidate technology and compounds from small biotech companies as part of their innovation strategy. This enables them to move new injectable drug developments forward while at the same time, limits their own financial risk. For these companies, however, this strategy demands compliance on the part of the biotech partner with high quality, safety and efficacy standards as a precondition. Only the reliable implementation of these preconditions will enable performing clinical trials and subsequently commercialization efficiently. Due to financial constraints, small biotech firms trying to focus on proving the effectiveness of their drug substance encounter challenges and regulatory obstacles that can impede their efforts. By not maximizing the value of their compound in the early stages of drug development, they miss the major opportunity to attract investors, provide out-licensing opportunities, or in some cases, even outright acquisition by one of the large pharma/biotech companies as mentioned above. Drug Development & Delivery recently interviewed Dr. Claudia Roth, President of Vetter Development Service in Chicago, to discuss how an experienced CDMO can help bridge the gap of different parties’ focal points and be of vital support in the process of injectable drug development.

Q: For our readers who are not yet familiar with your company, can you briefly discuss Vetter and what service portfolio it offers?

A: Vetter is an independent contract development and manufacturing organization (CDMO) headquartered in Ravensburg, Germany, and specializes in the aseptic filling of syringes, cartridges, and vials. We have extensive experience with biologics and other complex compounds, including monoclonal antibodies, peptides, interferons, and vaccines. As a full-service provider, we support our customers’ products throughout their lifecycles, from preclinical development through global market supply. We operate state-of-the-art facilities in the US and in Europe that provide support for early stage drug products, with seamless transfer at Phase III to Vetter Commercial Manufacturing for large-scale production. We are the originator of dual-chamber technology, which enables easier, safer lyophilized drug administration; and are a leader in the use of RABS technology in cleanrooms, which mitigates risk of product contamination throughout the manufacturing process. As a family owned, independent company, we do not manufacture our own drugs, but focus solely on our customers’product success.

Q: Can you identify what you see as some of the key trends in the manufacturing industry today, particularly as it applies to the small biotech firms versus large pharma/biotech companies?

A: The R&D model that we saw in the industry just a few years ago continues to rapidly evolve. These changes have been largely due to the ever-increasing costs associated with drug discovery and development, including the time necessary to do this increasing complicated job from the very start and the tremendously increasing pressure to compete and innovate. In addition, the industry faces stricter regulatory guidelines than ever before. To overcome these hurdles, we have seen a continuing trend toward collaboration between big pharma/biotech companies and small biotechs. In many of these cases, we have observed outright acquisitions or mergers between companies. For the large company, the acquisition of a smaller one with promising injectable drug candidates or advanced technology is an attractive option. It affords them the opportunity to move new drug developments forward while limiting their financial exposure or risk. For the small biotech company with limited resources, access to greater human and financial resources allows them to better focus their attention on pursuing other promising injectable drug candidates. Thus, it can be a win-win for all, each focusing on its core competencies. However, the key to a successful partnership or the key to a successful out-licensing deal will be generating a harmonization of requirements that meet the needs of both parties.

Q: Can you provide insight on how the needs of large pharma/biotech companies differ from the ones of small biotech companies?

A: At first glance, it would seem that both have the same target; develop and bring to market injectable drugs and technologies to help patients, while achieving regulatory compliance. But that is pretty much where the similarities end. Large companies need to minimize their risk and ensure they reward investments from a commercial perspective. That equates to high quality, safety and efficacy standards being a precondition of any partnership or acquisition strategy. Offering innovative solutions that will meet a variety of market needs while achieving packaging and process flexibility is the pathway to success. Also, later product lifecycle management activities for longterm market success are key targets. It is these attributes that small biotech companies often lack in their early approach, potentially creating the formula for a successful partnership or acquisition. With their start-up culture and primarily scientific know-how, they focus on the rapid development of drugs and technology. Having said this, they often lack or have little experience in packaging issues, process development, manufacturing, regulatory, or commercializing the drug. Also the end-user perspective is not yet part of their overall project scope. Furthermore, they are extremely sensitive to any risk in early clinical phases because they are typically less resourced from a personal and a monetary aspect. If the compound performs poorly or fails in drug development, the very survival of the company itself can be imperiled. Thus, little thought in this stage is been given to the later development or commercialization efforts that must be applied to the compound.

Q: You stated earlier that in order to ensure success for both companies, harmonizing their individual requirements is critical. Can you offer some thoughts on which approach small biotech companies often follow in their drug development?

A: Small biotech companies often lack the knowledge and resources necessary for developing their drug product beyond the current early development phase. This lack leads to a gap that makes it difficult to leverage efficient and lean processes while achieving high quality, safety and efficacy. Small biotechs may believe the simplest solution is a cooperation with a variety of small, local laboratories and filling services or generally speaking, singleservice providers. This can present a problem, however, because the small, local service providers seldom possess essential experience and hands-on practice in dealing with complex drug substances and their special requirements. They may also lack the longterm regulator relationship required for the smoothest possible regulatory approval. In the case of injectable drug filling, the small single-service providers are often limited to manual filling operations, targeted to rapid filling realization. This can harbor risks in terms of both drug quality and safety. As I noted earlier, large companies must ensure that quality and safety standards are met in performing clinical trials to help bring about the eventual efficient commercialization of the drug. Only operating with such standards enables them to successfully perform their strategy: move new injectable drug developments forward while limiting financial risks.

Q: How can a CDMO help?

A: We are noticing that CDMOs are acting more and more as the interface between small biotech firms and large drug manufacturers. This is due to a variety of reasons, including the fact that an internationally leading CDMO by definition has already reacted to the changes in the world of R&D. Such a full-service partner has longterm experience with a variety of compounds, including very complex ones, and has knowledge of the most recent regulatory guidelines. Professional CDMOs have set up specialized development services portfolios in the markets where innovation is happening, and often can provide the appropriate capacities and services in the US and Europe. For the small biotech company, partnering with a CDMO affords support in realizing faster and more efficient drug development, and adds critical added value from the earliest stages due to the combination of efficiency, long-term thinking, and high quality and safety. The CDMOs’ packaging, process, and manufacturing know-how as well as the broad compound experience is included right from the start. Lean and streamlined processes with professional project management and success-oriented guidance supports the progress as well as time- and cost-savings. Complete customer-control is included in every development project step due to ongoing direct communication flows between all involved project members. By turning to an experienced CDMO, sponsor companies get support in avoiding obstacles and, at the same time, facilitate a lean and efficient clinical drug development. This helps contribute to the likelihood of out-licensing and in the end, monetary value of their drug products. Larger companies can benefit from this approach when acquiring a drug substance or the small biotech company as a whole. So for both small and large companies then, a CDMO can act as the interface between each other, supporting to align the requirements of both companies, and thus the CDMO being an important key to bridge the gap.

Q: Are there more advantages for cooperating with a leading CDMO for small biotech or large pharma/biotech companies?

A: There are certainly distinct advantages for both the small and large companies when a CDMO is involved. Let us have a closer look at some of the services a CDMO can provide, for example, the aseptic filling procedure. CDMO development services commonly have high-performance production capacities available for clinical filling. Their infrastructure often includes anything from semi-automatic equipment to fully automated filling lines for various drug delivery systems as vials, syringes, or cartridges. This service portfolio offers the small biotech company an opportunity to leverage efficient and lean processes while achieving high quality and safe results. It’s also a way to improve their processes and reduce their time-to-clinic. This, in turn, generates interesting criteria for large drug companies because they can then trust the reliability and high quality of successful drug developments. Having a CDMO as a partner will help not only to cover the actual development phase, but the support of the entire later process as well from approval and subsequent commercial manufacturing, which is already handled by the large company. By supporting the development of injectable drug substances from the start, the potential of expensive and time-consuming knowledge losses from changing single-service partners later is not an issue. The knowledge gained from the early development is kept safe and can be used later on for following processes. As for the large drug company, having a CDMO that has the data and experience from handling the drug substance previously offers enhanced value. For example, following the acquisition of the biotech firm, the large drug manufacturing company can optimize processes themselves and thereby accelerate time-to-market.

Q: From your own perspective, how does Vetter differ from other leading CDMOs?

A: As one of the global leaders in aseptic contract development and manufacturing, Vetter offers a foundation of experience spanning more than 25 years, and dozens of successful pharmaceutical and biotech customer compounds. For Vetter, quality is one of the single most important aspects of our work because patients take into their bodies what we manufacture for our customers. We have passed more than 25 FDA inspections successfully. Our strategic approach can be defined in a single word: alignment. All decisions, both within the company and with our customers, small and large alike, are aligned to clear, specific goals. It is expected that a CDMO partner for injectables offers among other criteria, quality, reliability, flexibility, and punctuality. These are the key factors necessary to achieve a successful partnership. Vetter invests in high-quality materials and aims to achieve the highest possible safety and cGMP standards. Based on our long-term and varied experience, we implement a highly structured project management approach. Combined with ongoing direct communication between all involved parties, this approach serves to reinforce mutual trust. A CDMO has to know and understand the needs of its customers and meet them accordingly. This is why we maintain a close and personal contact with our customers through our key account management organization. For Vetter, it is important to know what their needs are today, but crucial for us to also understand what support they will need in the future with their continuing development. We want to be in the position work with them in partnership to create new solutions.