CMC plays a critical role in the development of a biological product. While it may not be possible for early stage and mid-size biotech companies to have all the necessary CMC resources to steer through the maze and tangle of drug development challenges, there are steps you can take to ensure success.
So far, we have covered three essential steps to take:
- Have a Clear CMC Strategy
- Have a Clear Quality Target Product Profile (QTPP)
- Employ Simple, Practical, Scalable, Rugged, and Reproducible Technology
Today we will consider Step Four – Select the Right Contract Development and Manufacturing Organization (CDMO) Partner
Select the Right CDMO Partner
Outsourcing of CMC development activities is the most common approach followed by small and medium-size and stage biotech companies. Among other advantages, outsourcing of CMC development activities facilitates the small biotech companies to focus on their core strength as well as minimize capital outlays. Hence, the selection of the right CDMO is extremely important. Taking the time to do a detailed evaluation and due diligence is critical. The selection must be as objective as possible with a clear and agreed-upon selection criteria, appropriate weighting, and scoring methodology.
Choice of a good CDMO is dependent on several factors, not the least of which are:
- Strength of scientific and technical teams and their experience and expertise
- Available technologies and unit operations for scale-up and manufacturing
- Available scale of operation and capacity
- Capability and capacity to manufacture clinical trial material (CTM) as well as a commercial product
- Normal lead times for production, packaging, analytical testing and release of the product to supply clinical trials
- Depth of analytical development, quality control, quality systems, and regulatory compliance and track record
- Regulatory agency inspection history and outcomes
- Strength of project management and client interface
- Competitive quotation, flexibility, and negotiability – economic and practicality of doing business
- Ability to manage multiple clients and projects and eagerness to work with small biotech companies
- Strength and stability of management and finances
Equal importance must also be given to the intangibles.
- Do people look happy at their facility?
- What’s their working style and culture?
- Does the facility look well-staffed and well-equipped?
- Do people appear knowledgeable, well-trained, quality-conscious, and competent?
- Is the CDMO eager to work with small and medium-size and stage biotech companies? What’s their track record on this?
- What’s the CDMO’s normal response time and communication pattern?
- Is the CDMO accommodative, flexible, and amicable to do business with?
References from existing clients, consultants, and other colleagues must be obtained to gain insight on the width of gaps between what a CDMO promised and what was delivered. Oftentimes, CDMO’s working style and potential issues will come to be known from speaking to clients, consultants, and colleagues.
A challenging aspect of biologics development is that manufacturing facilities as well as the manufactured products must meet specifications approved by regulatory agencies. Prior to obtaining a license, the manufacturing facility must undergo pre-approval inspection (PAI) by the regulators while being fully operational and manufacturing the complete product for which a biologics license is sought. So, choosing a strong and experienced CDMO that can take the product all the way to market is important.
Biotech companies must obtain as much information as possible on the potential CDMOs and pay attention to the inconsistencies amongst them. At the minimum, three CDMOs must be shortlisted and proposals obtained to the same request for proposal (RFP) so that they can be compared directly. The extent and integrity of a CDMO’s quality system should be determined through an audit performed by the quality group of the company. Weak quality systems can significantly delay getting finished product to the clinic on time. Knowing up front where the strengths and weaknesses of a CDMO’s quality system lie will assist in selecting the best outsourcing partner. Post selection, supply and quality agreements must be established with all the vendors and suppliers including CDMOs and CROs (contract research organizations).
Independent of choice, biotech companies must give a very high priority to managing their interactions with the CDMO. With competing timelines and resources, it is understandable and not uncommon to find that timelines within a CDMO can and do slide. Without a proper CMC strategy and vigilant oversight during the execution of CMC-related tasks, such delays at the CDMO will severely impact the timely supply of clinical materials. Biotech companies must realize that unless a CDMO is selected and managed properly, the CMC work performed could be on the critical path of the clinical start date as well as all subsequent clinical trials.
In assessing the interconnecting relationships between CDMOs, sponsor biotech companies, and regulatory agencies, quite often the sponsor biotech companies are relatively inexperienced compared to regulatory agencies and CDMOs that have worked with multitude of sponsor companies. So, selecting a CDMO that is willing and eager to work with and educate without intimidating the sponsor companies, to be transparent in order to generate high level of trust and confidence, and to communicate clearly and precisely their strategy and cost structure is crucial.
Two types of risk in the development of biotechnology products are: the project risk, which should be borne by the sponsor biotech company, and the technical risk, which should be shared between the sponsor biotech company and the CDMO because the CDMO has the most intimate knowledge and control to mitigate technical risk if needed. Despite this, most CDMOs prefer not to assume the technical risk due to quality and regulatory compliance concerns, and this can lead to problems in contract negotiation. The value of data collected, and the associated metrics should help to ease these frictions and facilitate mediation.
CDMO selection should be based upon the strategy and needs of the project. Strategic selection process is usually a capacity-driven long-term plan. The tactical one is usually project-driven with a limited budget. For the success of the project, one needs to plan for the lifetime of a project before seeking a CDMO. Therefore, building relationship with CDMOs must be more about building strategic partnerships and less about tactical and operational outsourcing.