Guidelines For Selecting A Strategic Partner For Your Combination Product

The pharmaceutical industry has experienced an unprecedented shift over the past five years with the growth of biologics outpacing that of small molecule drugs. Complex biologics have brought innovative new treatment options to patients with many chronic illnesses, including rheumatoid arthritis, Crohn's disease and certain cancers. This steady rise in biologics is also spurring innovation in combination devices and drug delivery systems. Today, the patient experience drives drug packaging and delivery trends. Additionally, pharma is looking for ways to reduce internal resources and expects more ownership of the supply chain. Select CDMOs are now able to provide additional services including drug handling, cold chain storage, sterilization, analytical testing and final packaging. Collaborating with the right CDMO early on, in the process can have many benefits, including risk mitigation, innovative strategies and a faster speed-to-market.

Selecting an experienced CDMO is an important decision that may impact a drug product’s ultimate success, so a methodical risk-based approach should be taken. Consider these guidelines when evaluating potential device contract manufacturers.

• Perform a comparative analysis: This analysis can be completed quickly with minimal expense, and will narrow the potential vendor list considerably. Subsequently, by following a risk analysis of each option, a cross-functional site audit is advisable to evaluate not just capability, but cultural fit. Quite often, medical device or combination product manufacturers are sought based on core technical competency or manufacturing capability, when in fact a company’s culture is just as important or more important to the success of the program. When performing comparative analysis and evaluating the CDMO’s manufacturing capability, consider the following to establish strategic fit:

Company / Experience

• Does the CDMO produce a product with similar features and characteristics? Or have they in the past?
• Does the CDMO have final packaging, drug handling and labelling capabilities?
• What is their history of performance during a build (tooling, equipment)?
• What is the total cost of ownership associated with working with this CDMO?

Engineering Capabilities

• Does the CDMO's technical staff possess the education, background, training and experience to be successful with this endeavor?
• Does the CDMO have the capability to perform manual, semi-automated and/or fully automated assembly?
• What type of final acceptance activities will be required?
• What support will be required for product serialization? Have they implemented for other products?
• What’s the CDMO’s technical solution and the risk associated with that solution?

Delivery / Support

• How successful is the CDMO in scale up and commercialization, and can they handle the projected volumes?
• What’s their ability to meet deadlines, post commissioning support and provide references?
• Does the CDMO have a robust equipment, qualification and validation process in place?

Financial Strength

• What is the financial stability of the proposed partner?

Quality Systems

• Does the facility and infrastructure align with the overall manufacturing environment and have the proper risk mitigation controls?
• Does the CDMO calibration preventive maintenance and statistical process control systems in place?
• Do they have ISO certification and what is it in?
• Is there a sense of quality control when you’re on the audit?
• Does this device require a core competency or specific innovative technology that the CDMO can support?

• Understand their product development and manufacturing capabilities: Manufacturing complex drug delivery devices and combination products such as autoinjectors, pen systems and respiratory devices requires the right people, advanced processes and equipment. Before selecting a partner, it is critical to understand if the device contract manufacturer has knowledgeable project teams that are capable of providing necessary support. During initial product development phase, the right CDMO partner will be able to provide valuable input on device design ensuring the design and manufacturability are robust for commercialization. They should be able to provide appropriate scale-up plans for the device including risks/delays associated with each phase of the product lifecycle. Additionally, they should propose a tooling and assembly strategy that meets your commercial plans. Some core capabilities to identify in a device partner include:
  • Tooling
  • Molding
  • Assembly expertise
  • Automation experience
  • Metrology
• Look for a proven quality management system: Before making your decision, assess the robustness, reliability and track record of the CDMO’s& quality management system (QMS). It is essential that they have a demonstrated record of compliance with processes for traceability and documentation on device history records, reports on calibration procedures and test data – all of which will help with FDA and ISO 13485 compliance. Requesting third-party certifications and regulatory inspection history (and if there were any findings) may provide a view into the overall compliance profile. Pharmaceutical companies should look for a CDMO whose QMS approach fulfills key elements of its own QMS. At the same time, the CDMO’s QMS should not merely be an extension or rely upon the sponsor’s QMS.
  • Does the CDMO follow FDA guidelines 21 CFR Part 11, Part 820 & Part 210 &211? what ISO standards are they certified to and ISO standards do they follow for testing?
• Understand how the CDMO manages risk: ​An evaluation of the CDMO's risk management program should be a part of the review process in both the due diligence and audit. If possible, review how Failure Mode and Effects Analysis (FMEA’s) are generated and managed. Are other tools utilized and are they applied appropriately and consistently? Application of an overall risk management process throughout the QMS may provide further assurance that the contract manufacturer will recognize and institute actions to prevent future issues of critical or major concern.

When reviewing the strength of a risk management program, evaluate how the CDMO is applying risk management into its QMS, including: internal audits, nonconforming products, complaints, corrective and preventive action (CAPA) and change management. Look for evidence of the practices described above as another early indicator of quality culture fit and future success.

• Visit the site: Pharmaceutical companies need CDMOs that embrace their values and are motivated to continuously improve and add value. Once you have narrowed the field down to a few potential candidates, it is in your best interest to conduct a site visit. It all starts with the agenda and what you want to accomplish. Do you need device design, industrialization and commercialization? Or is this a device transfer project? This will help frame the visit and ensure you meet with the right team.

Once at the site, look to see if the CDMO can demonstrate what was presented/proposed such as operational excellence, lean manufacturing and a robust quality system. What technologies are they using to ensure quality is met? Is there a continuous improvement mindset and a culture that is compatible? These factors should be included in the overall risk profile and potential impact to the total cost of entering into a partnership. Site due diligence and compliance audits can mitigate the risk of selecting a contract manufacturer that might result in the high costs associated with poor quality (including unanticipated increased oversight).

• Consider the supply chain: Material costs of medical device manufacturing can be a significant portion of the finished product. It is therefore imperative that the pharmaceutical company evaluate the methodologies and techniques utilized by the supplier to manage their vendor base. How are MRP systems and vendor quality control programs integrated? Understand the buying power that they may be able to offer in order to procure the required materials at lower prices without sacrificing quality or delivery timeframes.
• ​Evaluate using a multifunction team: Initial due diligence reviews of potential CDMOs should be conducted by a team inclusive of technical, business, operations and quality representatives. The due diligence visits should cover core aspects of the CDMO, such as:
  • Quality Management System
  • Risk management approach
  • Manufacturing capabilities
  • Design control system
  • Root cause analysis
  • KPI metrics
  • Financial stability
  • Cultural compatibility
  • Quality agreement

Collaborating with the right device contract manufacturer can improve the likelihood for success with your combination product or drug delivery device system. It is imperative to choose an experienced partner that can ensure the products provided are of the highest quality, minimize disruptions to the supply chain and bring safe, effective drug products to patients quickly and efficiently.