From Compliance To Outsourcing — Advice From 4 Biopharma Manufacturing Execs

By Rob Wright, Chief Editor, Life Science Leader
Follow Me On Twitter @RfwrightLSL

Readying for this year’s annual outlook issue (published in December), Life Science Leader presented a variety of questions to various biopharmaceutical executives, including those responsible for manufacturing. The purpose of the exercise was to gain insight on what to expect for 2022 and beyond. We ended up with more advice than could be shoehorned into our annual outlook print edition, so we opted to share them here. Don’t miss out on all the other knowledge and wisdom provided by the more than 40 biopharmaceutical executives taking part in this year’s annual outlook by becoming a Life Science Leader subscriber today.

What Should Biopharma Be Doing To Improve Product Quality And Compliance In 2022?

Sadik Kassim, Ph.D., chief technology officer, Vor Biopharma: Drug developers have a responsibility to work with their network of suppliers and vendors, including contract manufacturing organizations (CMOs), to ensure both the overall compliance and quality of their drug product and the associated critical raw materials. As manufacturing leaders, we are the stewards of the life-saving therapies upon which millions of patients rely. Maintaining the highest possible standards is our most important responsibility to ensure patients are reliably receiving the highest quality and safest therapies.

The FDA has helpful guidance documents for drug developers regarding best practices for ensuring compliance when working with CMOs. For example, sponsors should make sure they have explicit quality agreements in place with the CMO. These agreements should also cover audits, inspections, and communication of findings.

Although these guidance documents and best practices have long served as a template for the industry, the traditional models of enforcing them, such as on-site audits and frequent in-person meetings with CMO partners, broke down during the COVID-19 pandemic. Moving forward, drug developers and CMOs need to develop new virtual and remote systems that enable continuous monitoring and enforcement of quality agreements that adhere to the spirit of the best practices and guidance documents developed by health authorities.

What Are Keys To Consider When Opting To Outsource Biopharma Manufacturing In 2022 And Beyond?

Charles (Chuck) Calderaro, global head of technical operations, Kite Pharma (a Gilead Company): When deciding to outsource biopharma manufacturing, one considers the pros and cons of a “make vs. buy” decision with a common set of criteria: cost, time, risk mitigation, intellectual property, quality, compliance, etc.

Some of the most significant pros of a “buy” decision are capital avoidance and time savings. One does not have to invest hundreds of millions of dollars over a three- to five-year period to design, build, and license a manufacturing site. Nor do you incur the associated depreciation, labor, operating, and maintenance costs. This is an attractive option for companies that may lack time or financial means, their product portfolio is not large enough to justify the investment, and/or the product/process technology is nascent and unproven.

By making a “buy” decision, one generally enters into a fee for service agreement with a contract manufacturing organization (CMO). Most of the cons are related to control, agility, speed, and responsiveness. Specifically, CMOs have their own internal operating procedures, quality standards and systems, and compliance expectations, which may or may not align with the customer’s. The CMO serves multiple customers and strives to schedule production months/quarters in advance. New production requests typically enter a queue that may be 12 to 18 months long. Avoiding the queue is sometimes possible if one pays a significant premium. If there is a need to change a previously negotiated production date, a financial penalty is typically incurred – assuming there is capacity available on the newly desired production date. Often, an intricate set of service, supply, and quality agreements are negotiated, and an elaborate governance structure is put in place to manage the flow of information and resolve disagreements. This contractual relationship is typically slower and more cumbersome compared to an internal manufacturing site.

What Should Biopharma Do In The Next 3 To 5 Years To Reduce The Vulnerabilities To The Global Biopharma Supply Chains Exposed During The Pandemic?

Daniel Leblanc, chief technology officer, Ensoma: The COVID-19 pandemic highlighted a critical flaw in the “just-in-time” approach in the supply chains the pharmaceutical industry was following. With a crushing uptick in needs for critical materials, such as vials and single-use reactors, along with a lack of capacity for manufacturing, there was a shortage of materials and infrastructure to produce vaccines when needed.

To combat this in the future, innovators will need to look to develop more standard approaches to manufacturing to allow a more rapid transition of their products from one facility to another. This will allow collaboration across the industry, as seen when companies such as Sanofi were able to ramp up production of the Pfizer-BioNTech vaccine utilizing spare capacity in their facilities. Additionally, suppliers will need to look to ways to better build capacity in the supply chain. This may involve manufacturers storing more base components, such as glass cane, to convert to vials depending on the market needs, or holding more capacity of filters.

This will not make significant impact without the help of worldwide regulatory agencies in creating standard compendia for raw materials, common approval processes for facilities, and increased guidance for industry on areas such as comparability and release of novel products.

What Advice Might You Offer Regarding Cell And Gene Therapy Companies Building Capacity?

Kee-Hong Kim, Ph.D., SVP manufacturing and technical operations, Tenaya Therapeutics: A competitive bidding process with construction vendors, unknown restrictions and regulations, and sensitive inflation on key raw materials, especially during a pandemic, make adhering to “original” timelines and costs a challenge. Appropriate risk assessment at each stage, with proactive and reactive risk mitigation and/or cautious processes, should be in place ahead of time to minimize the impact of the materialized risks on the timeline and costs. Additionally, proper site selection is essential. It is important to consider factors like co-location of the process, maintenance of company culture, exchangeable staff, and consistent quality oversight into that decision. Process/assay development and GMP MFG/QC/QA on the same site is also recommended for easy technology transfer and effective quality oversight. GMP-grade manufacturing equipment is often on an on-demand basis, so it’s important to initiate dialogue with key GMP equipment vendors ahead of time to allow for adequate lead-time for equipment and process flow design to meet cGMP compliance. Lastly, both the cell and gene therapy business boon, as well as the increasing number of companies internalizing GMP manufacturing, have created ferocious competition for talent. Recruiting and retaining GMP staff should be the highest priority, even before breaking ground.

What Innovation Have You Been Considering Implementing Over The Next 3 To 5 Years?

Thomas Lequertier, head of cell therapy manufacturing, Celyad Oncology: I’m always looking for ways to improve to achieve better patient outcomes. One part of my work that is important, though it might not seem particularly innovative, is maintaining our company’s relationships with our suppliers and continually building new relationships. Our suppliers are critical to our ability to produce great quality and consistent cell therapies that we can feel confident giving to patients. Additionally, we are interested in ways we can increase consistency, scalability, and efficiency through automation. There is constant innovation in the cell therapy space with machines that can perform important steps in the manufacturing process. This saves time and ensures a level of consistency that is hard to match, even with highly trained personnel. The more automated our production becomes, the easier it is to overcome external challenges to production that limit personnel, something we've been thinking about more as a result of the ongoing pandemic.