The use of contract development manufacturing organisations (CDMOs) is now the established norm in the pharma/medtech supply chain. The CDMO model provides cost-effective, reliable and compliant solutions with speed to market for critical healthcare products. It takes advantage of core competencies/experience from the contract giver (eg, brand development, marketing, etc) and contract acceptor (eg, manufacturing excellence, quality operations, etc) to allow for targeted focus on key operational pillars to ensure overall programme success and synergies.

However, with a multitude of CDMO options available, all providing specialised expertise and solutions for diverse and complex activities, it can be difficult to know where to start with the selection process, having to juggle between the technical non-negotiables and setting the foundations to deliver on a common and cohesive product goal.

Here are some considerations prior to engaging with a potential CDMO:

• What exact capabilities are required from a CDMO (understanding the ‘essentials’ vs ‘nice to haves’)
• What phase is your project at and what are the current timelines?
• What are the known current risks, eg component supply, method validation, regulatory approval, etc
  – Have mitigation actions been identified and accessed?
• What is your commercial forecast and ‘go to market’ strategy?
• What funding is available and is funding available to accelerate the timeline if needed?

‘As part of the selection of the CDMO, it is important to review the skill set of the wider team and indirect roles’

Some factors to include on your criteria for the selection of a CDMO are outlined below.

Technical knowledge and experience

• How long has the CDMO been in operation? Does the CDMO have a proven track record in your niche technology? Review case studies, success stories and client reviews
• Will the CDMO deliver a quality product on time and within budget? You must strike a balance between cost, speed and quality and be prepared to make tough decisions. Sometimes speed incurs an additional upfront cost, but can pay significant dividends in the long term by gaining market share
• Can the CDMO support your forecast commercial ramp-up plans – what is its expertise in technology transfer and ability to scale up?
• Can the CDMO offer an end-to-end finished product solution – packaging and distribution?

• Does the CDMO have a proven track record of regulatory compliance?
• Does the CDMO demonstrate a clear awareness and understanding on the FDA’s definition of adulterated product, ie, ‘if it fails to conform to compendial standards of quality, strength or purity’ and the consequence of such a violation?
• What regulatory authorities have audited it? When and what was the outcome?
  – How robust are its responses to regulatory findings?
• Is its QMS suitable, adequate and effective for you? Thoroughly critique the CAPA system, change control, deviation management, self-inspection programmes
• How are internal issues identified and resolved in a sustainable and robust manner?
• How does the CDMO address issues that could impact product quality?

• Is the facility (warehousing, manufacturing, testing) clean and well-maintained, meeting all regulatory expectations?
• Is the facility equipped with the right technology and sufficient equipment capacity to handle your project needs?
• Is there an active contamination control strategy?

• Does the CDMO have a structured and documented approach to risk management?
• Does the CDMO develop defendable risk rationales and assess the risk scenarios from one client to a potential impact to your project?
• How does the CDMO adapt to change in a compliant way when things do not go as expected?

All too often, organisations focus on the primary technical manufacturing team.  However, as part of the selection of the CDMO, it is important to review the skill set of the wider team and indirect roles such as quality assurance, quality control, supply chain, facilities, project management, regulatory and others.

• Does the CDMO have strong quality culture in which those who have responsibility for oversight and control over manufacturing take ownership for quality – focusing decisions on patient safety?
• How does the CDMO’s senior leadership demonstrate its commitment to quality and continuous improvement at every level and actively pursue employee recognition programmes?
• Does the CDMO invest in training, mentorship programmes, professional development and set high standards for excellence?
• Is there an active succession planning programme in place and retention measures to retain key skill sets?
• Does the CDMO drive a continuous improvement mindset and invest in electronic systems that provide real-time metrics and analytics to both employees and clients?

‘Be prepared to manage the unexpected with proactive contingency planning to deal with the ‘what ifs’ of supply chain disruptions’

• Do the values and core operating principles of the CDMO align with your company values and is there is a symbiotic relationship between business and quality objectives? In simple terms, will the CDMO become an extension of your business and good to work with?
• Is QA perceived as the police or the mentor?

Be prepared to manage the unexpected with proactive contingency planning to deal with the ‘what ifs’ of supply chain disruptions.

• Be clear and realistic on your project’s specific goals, milestones and budget
• Develop targeted and customised scenario plans, eg:
– Best case scenario: assume no project delays
– Realistic plan: assume delays with regulatory approvals, repeat testing

• Use standardised templates to ensure consistency in documentation
• Identify potential risks early on and develop mitigation solutions in advance should the risk manifest itself. Risk mitigation solutions can include:
– Dual sourcing of critical components
– Targeted training programmes
– Regular audits
– Enhanced testing during the project phase, building a data repository and confidence targeted updates on project status with regulatory agencies

• Be cognisant of market needs and retaining market share during a project phase by having sufficient safety stocks in place.

Transparent, open and honest communication is an essential element in building a strong partnership that is anchored on mutual trust and respect.

• To avoid surprises and ensure the project stays on track agree a communication plan upfront, including the frequency of communication, format of communication and the audience/escalation path
• Ensure key decision-makers are identified from the client and CDMO – use a RACI (responsible, accountable, consulted, informed) as applicable as a mechanism of defining roles and responsibilities
• Schedule a regular cadence of two-way communications, regular steering meetings, planned stage-gate reviews at specific project milestones into the overall project plan. The strength of open and transparent communication at regular intervals is transformative to ‘product/process knowledge’ and establishes the roadmap for mutually enduring partnerships.

• Agree on the key performance indicators (KPIs) during a product transfer and into commercialisation. Technology transfer complete is not the same as commercial manufacture at the expected and required production forecasts. Be thoughtful on defining stabilisation metrics such as percentage yield, percentage defects, cost of poor quality, testing cycle times, etc, in order to allow scale up by the CDMO in a compliant, efficient and sustainable manner
• Think about the future and invest collaborative time in defining a joint supply chain reliability definition by fostering a culture of proactive continual improvement focusing on optimised process performance and product quality
• Be clear on the project boundaries, eg, is the CDMO responsible for post-approval product management?
• Celebrate shared project milestones, accomplishments and successes as one entity.

• Ensuring the quality technical agreement is developed and maintained as a ‘living’ document and not ‘gathering dust on the shelf’. Both parties need to be aligned on responsibilities, including the ‘who’ and the ‘what’ in the event of any ‘what if’ scenarios.

The CDMO operating model is a competitive and rapidly evolving landscape, with adaptability, agility and speed to market in a cost-effective, sustainable and compliant manner being the ultimate goal underpinned with the constant assurance of cGxP requirements, ie ‘minimum current good manufacturing practice for methods to be used in, and the facilities or controls to be used for, the manufacture, processing, packing or holding of a drug to assure that such drug meets the requirements of the act as to safety, and has the identity and strength and meets the quality and purity characteristics that it purports or is represented to possess’.

To achieve this, the contract giver and contract accepter must work collaboratively as a single entity to achieve common goals – sharing a commitment to patient safety, quality, regulatory compliance, continuous improvement and underpinning that commitment through constant collaboration and communication.

The FDA’s perspective on the use of contract manufacturers is very clear and documented in recent warning letters: ‘Drugs must be manufactured in conformance with CGMP. FDA is aware that many drug manufacturers use independent contractors such as production facilities, testing laboratories, packagers and labellers. FDA regards contractors as extensions of the manufacturer... You are responsible for the quality of your drugs regardless of agreements in place with your contract facilities. You are required to ensure that drugs you deliver into interstate commerce are not adulterated.’

Where the FDA states the products are considered ‘adulterated’ under the FD&C Act, both the partnership of the contract giver and contract accepter should always consider these words as an indication that a recall is warranted.

Similarly, the requirements of the European Medicines Agency are consistent in that ‘a direct written contract should also be in place between the manufacturing/importers authorisation holder responsible for qualified person certification of the product and sites involved in the various stages of manufacture, importation, testing and storage of a batch before it undergoes certification’.

This partnership is best realised when the CDMO is seamlessly embedded as an extension to your existing business rather than just being perceived as a third party. Such a partnerships enable a win-win scenario with alignment on the technical non-negotiables while in parallel seamlessly ensuring shared operating values.

References are available on request.