Deciding to engage a contract manufacturing organization (CMO) for your non-sterile fill finish needs can bring a number of rewards, including manufacturing flexibility, reduced capital expenditures, speed to market, and scalability. Importantly, your team can also leverage the CMO’s expertise, rather than building it yourself. Finally, the complex burden of building, managing and following a Quality Management System (QMS) can be avoided by relying upon your CMO.
Fill and finish of non-sterile drugs (NSD) is closely related to aseptic fill finish, and they share many common regulatory requirements including cGMP regulations outlined in 21 CFR 210 and 21 CFR 211. However, the NSD manufacturing regulatory environment is being updated and based on a recent review of FDA Adverse Event Reports, the FDA has recently expressed concerns with high levels of microbial content in NSD’s and provided draft guidance noting:
“While a NSD is not required to be sterile, there is a threshold of microbiological content above which safety and efficacy of a given NSD may be adversely impacted.”
Therefore, it is increasingly important for CMOs to establish appropriate specifications and follow effective manufacturing controls in order to prevent contamination and ensure the safety, quality, identity, purity, and efficacy of the NSD, regardless of whether it will be terminally sterilized.
Below are some essential criteria to consider when evaluating a CMO for non-sterile fill finish services.
Quality and compliance are important: It is imperative to adhere to Good Manufacturing Practices (GMP) for non-sterile fill finish manufacturing. Document control, training, change control and corrective and preventive action (CAPA), should all be part of these systems. This lowers the risk of possible compliance issues that could delay your product launch.
Compliance with current regulatory guidance: As stated in the introduction, regulatory bodies are clarifying their expectations in non-sterile drug manufacturing. It is critical that the CMO you choose is compliant with current FDA guidelines and practices.
Modern equipment: Look for CMOs with state-of-the-art equipment tailored for your non-sterile application. Newer equipment means the CMO is investing in this field and that you are likely to reap the benefits of increased efficiency and product integrity.
Possess strong technical skills: Teams with high technical skills should be able to demonstrate proficiency in handling a range of formulations, filling, and lyophilization if required, and have the ability to customize your offering.
Evaluate the CMO’s track record: Review their past projects, dosage forms, and expertise in non-sterile products, including terminal sterilization if required. While some details may be confidential, they may still be able to provide references.
Review personnel credentials: Understand the staffs’ background and qualifications that relates specifically to non-sterile fill finish. Have the CMO present resumes of the team that will be working with your product.
Meeting evolving needs: Assess the CMO’s capacity to meet your changing needs, from small engineering batches to full-scale commercialization.
Flexibility in response: Your market is likely dynamic and you will need to be able to respond quickly- by scaling up, or by scaling back your manufacturing needs. A strong CMO should have the operational flexibility to change production volumes or timelines.
Responsiveness: As you draw near the end of your evaluation, note how communication flowed. Your questions should have been promptly answered with openness and approached with a problem-solving mindset. Emphasize the need for clear, pro-active communication.
Partnership: Your CMO should be an extension of your team and you should expect transparency, regular updates, and a dedicated project team. Consistency in the relationship is essential so you will want experienced teams with low personnel turn-over.
Evaluating a CMO for non-sterile fill finish services requires diligence to get the best fit with your organization. While some critical CMO characteristics can be determined by audit or technical site visits (such as equipment status, training efforts, and documentation processes), other vitals will need deeper review (including sourcing and contamination control strategies). The more difficult analyses can occur in grading communication and flexibility as you will have limited interactions with a new CMO. In summary, a good non-sterile fill finish CMO will act as your operations and manufacturing arm, with the relationship becoming stronger over time.
Full-service contract manufacturing
Bulk and custom formulations
Terminal sterilization options
Analytical and microbiological testing
Complete supply chain management for all suppliers and vendors
Argonaut is FDA inspected and we support a wide range of products under 21 CFR 820, 21 CFR 210, and 21 CFR 211.
cGMP, ISO 13485:2016, FDA Registered, CA FDB inspected.
We offer scaleable solutions to match your requirements and product phase.
Dedicated project teams with deep fill finish knowledge
Argonaut is a partner and will strive to suggest efficiencies and alternative approaches as applicable.
Argonaut is a recognized leader in lyophilization with a wide service selection including cakes, powders, beads, and dots.
