Life Sciences Industry Experts Weigh In on Challenges Facing CMOs

Recently, Contract Pharma assembled a panel of three seasoned manufacturing experts in a webinar to address the challenges contract manufacturing organizations (CMOs) have been facing in a pre- and post-COVID-19 pharma manufacturing environment. The Q&A-style program featured:

• Gil Roth – President of Pharma and Biopharma Outsourcing Association (PBOA).
• Win Thurlow – Executive Director of MedTech.
• Brian Curran – Senior Vice President of Manufacturing Excellence Success at MasterControl.

Each panelist had an opportunity to address and exchange ideas on various topics, including:

• The future of audits.
• Finding and retaining skilled employees.
• The drawbacks of functioning in a manual, paper-based operation.
• Addressing the current supply chain woes.

The valuable insights the panelists provided on these and other CMO compliance issues are presented below.

#1 What are some of the lessons learned from COVID-19 and how will the pandemic impact audits and inspections in the future?

Roth: [The pandemic] was challenging for inspectors worldwide — especially for the U.S. Food and Drug Administration (FDA) not being able to visit facilities for pre-approval inspections, surveillance inspections, and other inspection-related activities. However, prior to the pandemic we had a process called desk inspections. For example, we could waive a pre-approval inspection for companies such as a pharmaceutical contract manufacturer that had a good inspection record.

Another process is called a remote interactive evaluation where records are requested and reviewed remotely. The caveat behind this is it cannot be called an inspection unless there are inspectors at the facility. Everything else is an assessment, evaluation, etc. For compliance, CMOs have had to adjust their practices and compile documents with their customers to satisfy the FDA’s records requests.

These experiences, along with some of the reporting that Congress is putting into the upcoming User Fee Authorization (USFA), will be added to the FDA’s toolbox going forward. They’re not going to swing the pendulum all the way back and do only in-person inspections once we’re safely out of the pandemic.

Thurlow: One of the takeaways from this experience is how different the learning curve was for various-sized companies in pharmaceutical contract manufacturing. We talk about the virtues of being nimble, and none of us are as nimble as we would like to be until we’re forced to be. What we saw was that some of our smaller members who invested a lot of time and money into ensuring they were compliant with the established regulatory scheme, all of a sudden they had to learn a completely new way of doing business.

Curran: From a manufacturing software vendor’s side, we’ve been seeing this trend for some time. Historically, it was common for customers to want to do vendor audits with a team of people over the course of three or four days. This took a lot of time, so we built tools to allow the customers to do some homework before and after to shrink the amount of time. Today, we’ve had to switch to full virtual. Two years ago, we would have never considered this kind of format. Everything would have been in-person. We find it advantageous because being virtual we can reach out to a broader audience in a shorter amount of time.

#2 What are the challenges with staffing in terms of both finding new employees and retaining good employees?

Roth: Even before COVID hit, some of the CMOs working on vaccine production were involved in expansions. They were primed for infrastructure expansion, but they still faced the challenge of bringing aboard staff and making sure people were fully good manufacturing practice (GMP) trained and able to handle the rigors of a highly regulated contract manufacturing organization.

Thurlow: Workforce recruitment and retention issues were the biggest challenges CMOs faced pre-COVID. And, of course, COVID accelerated that trend. That was a challenging experience and will continue to be well into the post-COVID period, especially in an environment where we hope will have some increased flexibility for CMOs’ compliance endeavors.

#3 Do you think digitization plays a role in that aspect where modern facilities might be more appealing to employees?

Thurlow: Digitizing is a way to provide a flexible and remote working environment for employees. It’s amazing to me that we didn’t look at paper files as antiquated much earlier than just in the past few years. There seems to be no reason to justifiably maintain paper files anymore. I think if you were to bring young, potential employees into a file room and tell them this is what their work experience is going to be, you’re going to have a hard time convincing them to come work at your place.

Roth: We’re in an app society with younger employees and e-based systems such as contract manufacturing software. Also, we can’t ignore the cost savings of a digitized environment. It gives companies resources to spend in other places such as increased wages and other factors that are going to make employment more attractive.

Curran: It’s mind-blowing to me how we’re still trying to convert life sciences manufacturing to use digital batch records. In an app society, it’s hard to expect employees to embrace manual records processes and using pens to make edits.

There’s a lot that goes into employee retention and one of the important things is to give staff a more modern environment to work in.

#4 Does going digital open the door for more meaningful work?

Curran: Initially, I thought that adopting technology would be an age- or experience-related problem. Yet we all carry phones and we all have minicomputers. People of all ages are accustomed to using digital formats — using pens is not appealing.

It’s really challenging to know what to work on when all your data is being captured and stored on paper. Just being able to easily leverage data because it’s not locked away is where efficiency increases, allowing companies to scale more quickly. We’re finding that experienced contract manufacturers as well as start-up companies can scale as needed with up to 30% fewer full-time employees.

Roth: For CMOs, compliance is another advantage. You still see a lot of warning letters going out with a citation where an inspector saw a ripped-up logbook in the trash. And that’s where the wrong data was recorded. If you were doing all this digitally, it would be a lot easier for employees and your facility overall.

#5 Why do you think the life sciences industry is still stuck in manual processes and paper?

Roth: One issue is there are regulatory concerns, especially from a pharmaceutical contract manufacturer’s perspective where a number of the products you’re making for your customers might be older, legacy products. Those originated in paper. Transitioning everything around these products to digital while making sure they all remain compliant in each market might be perceived as a considerable hurdle.

Thurlow: I think another reason is we grew up in paper and understood how we needed to remain compliant with paper files. One example is people likely looked at companies like Eastman Kodak, thinking we would always need film; Bausch and Lomb and think we would always need ground glass lenses; and Xerox and think we would always need copies. The digital revolution came around and it turns out that we don’t need film, we don’t need ground glasses, and we don’t need copies. The sooner we adopt digitization, such as using contract manufacturing software, the greater the likelihood that we’re going to succeed.

Curran: One of the things we see with the traditional manufacturing execution system (MES) solutions that businesses deployed is they were implemented at a time when companies were willing to spend more on their highest volume lines. You visit these companies and there is a lot of equipment and automation. There is also paper moving from station to station. We’ve successfully deployed technology in the manufacturing process, but we have not deployed it sufficiently in some areas. And we need to finish out that adoption of technology.

One customer admitted to spending 150 days reviewing a batch record because they have to go line by line and page by page. They wanted a system that would get them to 28 days. With MasterControl software, they’re under one day. It’s mind boggling about the 150 days. The product is ready to go, but the paperwork is not yet done.

Another issue is the fear of adoption. The questions posed are about how to get the software or how to implement change control. Then there are companies that feel comfortable with their paper-based systems. It’s not broke, they have passed the audits, and they have completed everything necessary to remain compliant. In these cases, they lose sight of what efficiencies could be gained with digitization.

#6 What is your advice for managing the supply chain and its associated risks?

Thurlow: Going back to my earlier comment about how we all think we’re nimble until we discover we’re not. I realize we don’t want to spend all of our energy solving the last crisis. But I think that the last crisis being COVID is going to be replicated in whatever the next crisis is. I think we would be well advised to devote time, energy, and investment to the durability of our supply chain.

Roth: There are huge lessons to be learned from COVID. One of my industry peers in pharmaceutical contract manufacturing explained how his company got approval for a generic product. The company had active pharmaceutical ingredients (APIs) sourced out of India, but during that time there were problems getting materials out of India. The company’s risk mitigation plan was to use a second API supplier based in Italy, which was also shut down. Consequently, the company wasn’t able to launch its generic product in time.

Curran: I think COVID forced us to re-evaluate because we don’t often spend enough time thinking about our own systems. One of the concepts I enjoy about digitization is transparency on the shop floor. For example, when I order a $20 pizza, I have more visibility into the process of that product than I do with a million-dollar batch that’s using paper.

It’s important to understand your inputs and every aspect of manufacturing. For example, one customer mentioned that the company doing labels for them didn’t have the backing paper for the labels. They had the labels, but they didn’t source the paper you’re supposed to attach it to so you could run the labels out. This turned into a production bottleneck.

#7 What one piece of advice do you have for life sciences manufacturers about where to focus their efforts to remain competitive?

Roth: Basically, know your own company and your market. At a research event, one pharmaceutical manufacturing company gave a long, virtual tour of the company and talked about all the great work they were doing in high-potency oral solid dosage. The first question from an attendee was if they were going into cell and gene therapy. The pharma manufacturer knew what its strengths were and that it was important not to go chase something outside of their strengths.

Thurlow: Know your customers and what is driving them. If you’re not focusing on the large macro trends in the industry, you’re going to be swallowed up. Time is well spent looking at where the industry is going and where your product mix is headed. Also, where are your partners going? What are they saying to pay attention to?

Curran: We’re all focused on our day-to-day activities, but occasionally we need to step back and look at things strategically. It’s easy to say get rid of the paper, but it’s important to look at yourself and your environment and do a business case and ROI to determine areas where you can improve your business.

#8 What challenges and opportunities are you seeing in the field of cell and gene therapy?

Roth: From a pharmaceutical contract manufacturing perspective, we’re seeing tremendous investments in this area. On the other side, there are regulatory and pipeline-related issues where the FDA needs to be clearer or start developing more guidance in terms of how some of these products are going to be developed.

With the new Prescription Drug User Fee (PDUF) five-year reauthorization that’s coming up, the FDA is supposed to be hiring a lot more reviewers for the Center for Biological Evaluation and Research (CBER). That should start easing the application reviews logjam. Some of these products are in the category of personalized medicine, which will present more challenges as opposed to the mass-produced products we’re accustomed to seeing.

Thurlow: That’s one area where we’re going to see a huge acceleration. It’s important to look at the reimbursement landscape and follow where it’s going in terms of your risk tolerance and ability to move in those areas. There are some valuable opportunities as the reimbursement landscape has not caught up to where it needs to be. Realistically, a product that you’re not able to see a reimbursement on is a product you’re not going to be able to sell.

Curran: Switching to a vein-to-vein process is very different and requires different skills, techniques, tools, etc. We’re at the beginning stages of this transformation. For example, as an individual, if I need a knee replacement, I would like to have one grown from my cells because it’s likely going to work better. We have customers developing products that are more curative rather than just treating symptoms.

#9 What final statements do you have for the audience?

Thurlow: Going back to the discussion on impediments to full adoption of digitization, one of the concerns is around cybersecurity. We would be well advised to think beyond that the only solution to stay safe from a cyberattack is to keep everything on stone tablets in the office. That may give a sense of control, but it’s not an effective approach to protecting data.

Roth: Back on the supply chain discussion, it’s important to know all of your inputs, where everything is coming from, and how it’s all coming together to make a product for the patient. This is something we’ve really learned the value of and something we would like to see advanced further.

Curran: Cybersecurity is a valid concern. We’ve seen customers who were concerned about keeping their proprietary information with a third-party company due to the security issues. If you think about the ability of a company’s IT department to fend off cybersecurity threats as opposed to larger, cloud-based vendors such as Amazon who has thousands of customers, they’re leading in the technology to best combat those threats. The recommendation is to take a step back and look at the broader landscape and not just default to the way you’ve always done things.