Pharmaceutical Manufacturing asked the following question to four CMOs: The contract development and manufacturing landscape has changed radically, with the addition of biopharma, virtual companies, niched markets and generics manufacturing. What skills are needed for any contract partner to compete, and be successful, in such a fragmented and challenging market?
Peter Soelkner, Managing Director, Vetter: “Many companies have been using the term ‘CDMO’ to define their business model as it suggests that they can help their customers maximize the potential of their compound from the earliest stages of drug development through to commercialization. But a CMO cannot claim to be a CDMO simply because they work on both the development and the manufacturing side of parenterals with their customers. With, on the one hand, ever-increasing regulations as well as constantly high product quality requested; and on the other, a strong focus on controlling and optimizing costs on the customer side, CDMOs have an ever greater need to focus on the ultimate goal: adding value all along the customer product’s lifecycle. The following six skills are crucial for a contractor partner to compete:
Experience: Ask the prospective contract partner questions such as how long the CDMO has been in business and what is their experience with complex compounds. Is integrated drug development and commercial manufacturing part of its portfolio? A strong knowledge of regulations as well as good working relationships with regulators are as important as having a well-trained team. Finding a CDMO outfitted with experienced project managers who understand their business is essential so that each project is handled properly and that communication channels remain open. Proper documentation of processes and the establishment of joint performance measures that can be easily quantified using objective date will be critical to success.
Meeting international quality standards: Providing high-quality yield of valuable product is the goal. Achieving this goal requires a partner that stays abreast of new regulations and meets ever-increasing quality standards. Investigate whether the CDMO is making continuous investments in the technology of its facilities to enable it to remain cutting edge.
Creativity and flexibility: New drugs are subject to many changes, as dictated by results of clinical testing. Creative and nimble approaches to updating project specifications are essential, combined with the flexibility to address the changing needs of the market. Select a dedicated team that can act quickly and proactively at each stage of drug development.
Integrated project approach for long-term partnership: It is critical to employ a continuous partnering relationship. This can be achieved via a key account management philosophy serving as the core element in a company’s strategy to support customer products move efficiently from early drug development through to long-term commercial manufacturing. This process helps result in an integrated approach to projects and the best possible outcomes.
Financial stability: Because a single drug can take years to travel from clinic to marketplace, drug development is expensive. So be certain that your partner can demonstrate solid financial standing. A company with a history of consistent organic growth will prove to be not only a strong partner, but also a strong ally.
Share the vision: Differences in corporate culture and business models are just a few of the issues that can strain a young relationship and threaten positive outcomes. Enable common future success by partnering with a company that makes communication and a shared vision top priority.
Today, being a trusted and well-respected CDMO requires always being there for your customer throughout all stages of its drug’s development and lifecycle, providing necessary support at all times. This will provide the customer with valuable time and resources to concentrate on research and development as well as the marketing of its products.”
Paul Skultety, Ph.D., Director Pharmaceutical Development, Xcelience: “Choosing a good CMO in today’s fragmented market doesn’t have to be hard. Reputation is essential; ask around. There are a few companies out there that will promise the world and don’t deliver. Your colleagues in the industry can help you weed them out. Once you’ve developed a short list, evaluate the CMO on the following five criteria. A good CMO will:
Tell you its strengths: No one company can be expert in all areas of formulation development and analytical work. It’s simply not possible. A good CMO will be up front with you about its strengths and weaknesses. At Xcelience, if we are asked to work in an area where we lack expertise — such as hot melt extrusion, or spray drying — we will contract with an industry-leading expert in that area, rather than try to sell that capability and risk lowering our standards for quality.
Be flexible: Even with the best planning, a good CMO expects the unexpected. Client needs change; sometimes without warning. This could include such things as changing the strengths at the last minute, or changing the number of tablets needed for the study. In one recent case, our client was going to be late delivering their API and would miss the scheduled time for clinical manufacture. We moved up another client’s manufacture of clinical supplies and pushed back the time slot for when the API would arrive, making both clients happy. We are also flexible in working with clients who like to help design formulation development studies as well as with clients who prefer to leave everything up to us.
Deliver on time and budget: In today’s tight economy, change orders are not just delays; they can lead to significant crippling cost overruns. The worst CMOs bid low and then surprise with a string of “unexpected” costs. Reputation is your guide here.
Use less API: More and more clients want to start formulation development sooner while cutting expenses by not having to have as much API available. Recently, we were able to do API in capsule for Phase I study to get a client into clinic as fast as possible. At the same time we developed an IR tablet and a controlled release bead, all with a very small amount of API. Formulation development can be adapted to client needs while taking into account the available amount of API.
Have a solid understanding of the regulatory requirements: A good CMO will educate the client on calibration and measurement capability (CMC) process. This is particularly important for smaller companies without in-house CMC expertise. It is critical that the quality by design concepts be included in the development process starting with excipient compatibility and including continuous process improvement during commercial manufacture. The CMO should also be able to work with consultants and develop an agreed upon program. This includes such things as creating a good design of experiments that will help to identify critical parameters and their ranges for the manufacturing process.
For example, we have been able to help clients set up their stability studies by bracketing with a wide enough range that when changes were made to the dosage strengths, the existing stability program covered the new strengths. In another case, a client was working a combination product and was unsure of the strengths they would need for each of the two compounds. We recommended a beaded dosage form. This allowed for development of dosage form with flexibility such that the strength of each active could be adjusted with no changes needed in stability program.
Offer a global perspective: We have recommended clients release their raw materials using both USP and EP regulatory requirements. Then, when it was necessary to include Europe in the clinical trial, there was no need to manufacture additional clinical supplies.”
Brad Larson, VP Contract Services, PL Development: “From our perspective, the role of the contract manufacturing organization has evolved from being a low-cost manufacturing alternative to being a development partner that can help companies expedite research and development capabilities or bring a product to market more quickly. Sure, it’s still about cost, but it’s not just about the cost of manufacturing the product, it’s the total cost of developing a product and bringing it to market.
If a company has limited — or no — capacity, then it can be far more efficient for them to use a CMO that has already invested in the equipment and expertise that can allow them to bring value to all stages of the development process. This starts with drug evaluations, progressing to developing or refining formulations, addressing regulatory issues, then scaling up production to commercial levels and finally, providing packaging, labeling and distribution. With the rise in virtual companies, there is an increasing need for turnkey solutions whereby the CMO can step up and manage the entire process from concept through distribution.
Successful CMOs are moving into more specialized areas: They can provide the in-depth support that companies need. For example, if a customer needs a tablet developed using an ingredient with poorly soluble compounds, they want to work with a CMO that has expertise in drug delivery systems that can address that problem as well as powder blending capabilities, single-sided and double-sided compression equipment and coating capabilities.
Work with a CMO that has a full analytical laboratory, one where the scientists have extensive experience in method development and validation: If they want to develop an OTC, they may look for a partner with a library of private label formulas that can be adapted for their needs, or bring in scientists with the ability to evaluate new formulations or run pre-clinical and clinical studies.
CMOs need to bring collaborative and project management skills to the process: It’s not enough for a contract manufacturer to work for a company to find solutions that are creative and effective; there must be a strong partnering philosophy. Of course, all projects are on a tight deadline, so responsiveness and the ability to meet deadlines are also key.
Packaging and labeling is seeing increased interest: There are many facets to developing packaging that are both eye catching and FDA/FTC compliant. PL Developments can take on the responsibility for designing packaging that addresses drug facts, tamper proof statements, any black box warnings as well as increasing consumer awareness. We also have dedicated high-speed packaging lines and can offer cost-effective, high-quality packaging in bottles, blisters and cartons.
CMOs must have a track record of success: If you are going to become a manufacturing and development partner with pharmaceutical companies, you must demonstrate your ability to provide quality products. While PL Developments is best known for its work in the private label industry, we have been providing contract services for three decades.
Friedrich Nachtmann, Head, Biotech Cooperations, Sandoz: “From my perspective, there are several skills a successful CMO should be able to offer beyond being a technology leader in your area of CMO services, including:
Technology leadership: Be on top of technology in your area of CMO services.
Quality standards: Offer global quality standards with international facility approvals, and be ready for GMP inspections by authorities and customers.
Intellectual property: Protect intellectual property of all clients.
Capacity: Have enough capacity available to handle your customer’s requirements.
Cost effectiveness: Provide lean production, competitive cost structure.
Regulatory support: Experience in global product approvals assisting your customer in filings and pre-approval inspections.
Stick to schedule: Have the ability to perform CMO services within pre-defined timelines.
Effective communication: Establish a good working relationship along all functions with your clients.”