GEN: At what point should a company seriously consider engaging the services of a CMO?
Dr. Lambalot: There are several reasons for sourcing from a CMO. For early phase start-up companies, the primary reason may be access to platform technologies, capital equipment, facilities and manufacturing expertise that are beyond their current financial reach. For maturing companies, there may be a need to augment internal early phase capacity with larger scale capacities suitable for supplying larger clinical trials or readying for commercial launch. For established biopharma companies with commercial products, there may be a strategic need to add redundancy to their supply chain to assure supply to a growing patient population.
In all cases, partnering with a competent CMO can add value to a company’s manufacturing strategy and ensure a continued robust supply of clinical or commercial materials.
Mr. Downey: Bluntly, the earlier the better! For example, for a commercial API or drug product, allow:
- Four months for RFP generation, CMO audits/technical due diligence, CMO final selection.
- An approximate technical transfer of anything between 6-12 months, dependant upon formulation.
- Allow a further 3–6 months for regulatory approval.
Then serious engagement should begin 13 (best case)/22 (worst case) months ahead of when you require commercial supply. As a conservative rule of thumb, I would engage, at least, 16 months ahead of first product requirement.
Engaging with a strategic partner, i.e., an already approved key CMO, or a truly integrated CMO (e.g., one that can supply both the API and finished drug product), can significantly reduce this time and cost, also mitigating risk.
Dr. Ruchatz: The decision when to outsource depends on the capabilities and the needs of a product-developing company. Key benefits for using a CMO include tapping into its expertise and taking advantage of its track record and capacity, which enables speed, access to certain technologies, and the option of deferred investment.
Outsourcing is already very often part of an overall strategic plan. Many biotech companies want to show positive results of their compounds as early as possible. Since they do not have the capability to quickly produce GMP-grade products for the clinical stage they use CMO services for cell-line generation and process development as well as supply of GMP Phase I material.
Other companies like large pharmaceutical companies have their own manufacturing capabilities and want to debottleneck their process development or clinical production with an option to retransfer the process back to their own facilities in a later stage of the life cycle.
Big Pharma companies often need flexible access to a second source as risk mitigation or as a contingency approach. This is important especially in the launch phase of a product to guarantee continuous product supply to the patients. The expertise in lean and efficient commercial manufacturing using state-of-the-art plants also makes a CMO a strong long-term partner for companies during the entire life cycle of a product.
Mr. Head: If a company does not have internal R&D capabilities, the full array of services offered by a CMO from cell-line development to finished product should be engaged. Companies with small R&D capabilities should seek the expertise of a CMO once proof of concept is established. This structure will ensure the early identification of problems and the necessary response strategies to address them.
Mr. Weiler: Companies considering outsourcing services to a CMO must first determine whether they need tactical support, strategic support, or both. A relationship often starts with a tactical approach and transforms into a strategic partnership.
On the tactical side, companies start to outsource due to internal capacity constraints or if the projects requires a technology or product outside of their core competency. In this case, the company would look to source that specific piece of business out to a CMO, but keep the total solution in-house.
In the strategic approach, a company would be looking to partner with a CMO when they realize that they can reduce the complexity of their supply chain and focus on their core competence as this will increase their efficiency. Finally, this can also mean outsourcing support for anything from different key materials all the way through to full process development. Unique to this approach is the CMO being fully integrated into the solution.
The point at which the consideration of working with a CMO is made will vary with each customer’s situation. Regardless, the range of CMO experience in providing support and/or creating solutions is expansive and affords the customer with a wealth of opportunity.
Mr. Podesta: This depends on the company, their needs, and the device that they are using to deliver their drug to the patient. If one assumes the required custom device has some modest level of complexity, getting a CMO involved early in Phase II is ideal. Even if there is an existing design team, getting a CMO involved early in Phase II provides the best long-term benefits. Throughout the design phases, decisions are made that have a significant impact on timing and cost.
To create a robust device, one must work closely with the design engineers, leverage user study information, and incorporate sound principles and innovative solutions. Designing for manufacturing becomes more restricted as the device moves along the development life cycle. Thus, it is imperative for the CMO to become involved as soon as possible.
When a project is late into Phase II, the design is typically 90% frozen and acceptance for modifications is extremely limited, even if those modifications can dramatically reduce costs. Most of the changes at that point are usually subtle. The opportunity to make significant impacts, in both cost and timing, is lost.
Using sound design for manufacturing techniques early in Phase II has shown to have the best long-term benefits. It is the best time to consider engaging the services of a CMO. It is the ideal time to consolidate or eliminate parts, remove secondary action from tools, and convert assembly techniques to simpler methods.