Overcoming Outsourcing Challenges With Creativity And Collaboration
By Life Science Connect Editorial Team
The demand for pharmaceutical manufacturing partners continues to grow exponentially. As drug sponsors look to identify the contract development and manufacturing organization (CDMO) best suited to manufacture their product to achieve regulatory approval and reach patients as efficiently as possible, CDMOs are simultaneously navigating a number of obstacles. As new modalities become increasingly common, CDMOs must update legacy facilities to better accommodate production of advanced therapies. Furthermore, as the ongoing ramifications of COVID-19 continue to affect the supply chain, manufacturers and sponsors must have reliable supply chain management teams to ensure accurate timelines and high-quality raw materials.
At a recent Outsourced Pharma Live event, Chief Editor Louis Garguilo interviewed industry experts: Christine Feaster, VP of Quality Executive Partners; Karla Knower, global head of regulatory affairs at Paradigm Biopharmaceuticals; Erin O’Brien, head of small molecule development at Biogen; and Bikash Chatterjee, chief science officer at Pharmatech Associates, a USP Company. They shared their insights on the critical relationship between quality and regulatory factions as well as the ideal qualities to look for in a manufacturing partner.
What Are We Up Against?
Securing a reliable manufacturing staff is essential and often difficult. According to Feaster, “To manage this better with your CDMO or even in your own facility, think outside of the box. Look for people who have agile learning, problem solving, and critical thinking skills.” She encourages sponsors and manufacturers to consider nontraditional candidates with transferable skills. At times, staffing difficulties are exacerbated by delays in manufacturing due to the need to update outdated manufacturing lines to better accommodate advanced cell and gene therapies. However, updating said lines is a crucial step toward preventing line failure and contamination of the product.
Many cell and gene therapies are granted accelerated approval pathways from health authorities. Though this designation may be exciting for stakeholders, it is challenging for sponsors and CDMOs who must rapidly define chemistry, manufacturing, and controls (CMC) protocols and set critical quality attributes. Per Chatterjee, “The context and scope of what a CMC development professional needs to do has changed dramatically. New and novel frameworks for process and product design have pushed the envelope in terms of classic regulatory expectations. There's a convergence between technical, quality, and regulatory where folks have to understand each other's worlds to make an argument that's compelling to a health authority.”
What Are The Critical Qualities Of An Outsourcing Partner?
For many reasons, the experts point to the benefits of forming a long-term partnership with a manufacturer to mold your program into something that works well for both teams. Consider that there may be no unicorn CDMO that checks all your boxes from the beginning. O’Brien encourages more of a slow burn: “You've got to find a good partner that meets your quality standards, and then build over time to get to that place. It's not something that may be there from the beginning.” That said, there are several reliable features to look for in a CDMO to ensure they have the chops to manufacture your product.
Communication, transparency, and a willingness to accommodate with creative solutions are essential. From the beginning, consider how a manufacturing team handles communication. Are they open and honest about the timelines they can deliver on? Are they carefully interrogating your target product profile and ensuring they are able to meet the standards of your quality agreement? Are their suppliers able to provide a reliable supply of high-quality raw material without delays? Do they have backup suppliers in the event of supply chain hiccups?
O’Brien describes the importance of transparency: “Certain countries are asking a lot of questions about the quality aspects of your regulatory starting material. They want to know that there are no impurities that are going to track through to the API. You need to know exactly what impurities are present and how they purge in the process. To do that, you need to have transparency into how they were made.” Thus, being able to establish reliable, direct communication with suppliers is critical. A CDMO must also implement cutting-edge technologies to successfully manufacture cell and gene therapies. It is critical to adapt platforms proactively rather than fixing something once it has already caused a financial setback or delay.
How Can We Achieve Better Collaboration?
Quality, technical, and regulatory must be aligned to make a partnership as seamless as possible. Per Knower, “Quality and regulatory departments have to work hand in hand to oversee suppliers across multiple time zones and determine how best to align a synchrony of events. A strong pharmaceutical quality system impacts how well you can manage your outsourcing needs.” With so many different modalities, there are different quality needs; as a result, your quality team may need to explain to manufacturers what is expected for a specific modality. Prior to meeting with suppliers and CDMOs, ensure that your regulatory, quality, and technical teams are internally aligned on goals.
Communication is a two-way street. From a sponsor’s perspective, build product needs and expectations into your quality agreement and target product profile. Your target product profile is used to establish minimum specifications, ingredients, and preferences. Use it to define your expectations from manufacturers and their suppliers from the outset. Consider scheduling in-person visits to their facilities as soon as possible. If you are working with a CDMO located elsewhere in the world and cannot readily travel, hire a qualified auditor to conduct an on-site audit on your behalf.
If you find a CDMO that checks almost all of your boxes but may be coming up short in one area, consider creative solutions to assist them to the finish line. Sometimes a partnership is easy and harmonious from the start. Other times, you have to take a few steps back to align on roles, responsibilities, and expectations. Troubleshooting is a natural part of the process.
Where To Start?
As you begin your outsourcing journey, set the critical priorities for your drug product and determine what you need from your manufacturer and suppliers. Once your team has a set of defined goals, consider the offerings of different CDMOs and their facilities. Each drug program has unique needs, and yet, outsourcing experts primarily stress the importance of straightforward communication, supply chain management, and overall reliability for a successful partnership.
Looking to learn more? To listen to the full Outsourced Pharma Live event, click here.