Enhancing Biomanufacturing Efficiency: The Role of Aseptic Fill and Finish - Dr. Reddy's - Krishna Venkatesh - Speaker Spotlight

In this Speaker Spotlight, Krishna Venkatesh delves into Dr. Reddy's approach to maintaining stringent quality standards and enhancing efficiency, highlighting the crucial need for innovation in the pharmaceutical & biomanufacturing industry.

This article provides insight into Krishna Venkatesh's upcoming panel discussion, "Enhancing Biomanufacturing Efficiency: The Role of Aseptic Fill and Finish," which will be featured at the European Biomanufacturing Summit. Additionally, this article will showcase Dr. Reddy's quality standards and strategies they have in place to increase efficiency without compromising on quality.

Krishna Venkatesh is a distinguished professional currently serving as the Head of Global Quality and Pharmacovigilance for Dr. Reddy’s. In this leadership role, he oversees all of the company's quality and pharmacovigilance processes on a global scale, ensuring the highest standards are consistently met. Krishna is also a member of the Management Council, the apex body responsible for organizational strategy and management oversight. With over 14 years of service at Dr. Reddy’s, Krishna has been instrumental in driving excellence and innovation within the company's operations.

I am a pharmacist by education. I got my undergraduate degree from India and my postgraduate degree from the US. I worked with a US company, Barr Laboratories, just outside of New York. I worked there for about 13 years. During the last two years, I was with Teva Pharmaceuticals, one of the largest companies in the world, as Barr was acquired by Teva. Subsequently, I returned to India and have been with Dr. Reddy’s for 14 years.

In terms of my career trajectory, I'm a techie and have always worked in technical areas. The early part of my career was in R&D product development, followed by some work in tech transfer. When I returned to India, I worked in process engineering, went back into product development, then tech transfer again, and managed injectable operations for about five years. Now, I have taken on the role of Head of Quality. I have spent my entire career spanning the life cycle of a product, except for marketing.

Ensuring the highest standards in pharmaceutical manufacturing is a complex and demanding task, particularly when it comes to maintaining accurate dosing and consistent quality in final product formulations. What innovative technologies or methodologies have you adopted to ensure accurate dosing and consistent quality in final product formulations?

I'll speak specifically about injectables because that's the topic of my presentation. The first thing to understand about injectable manufacturing is that protecting the product from microbiological contamination is crucial. This is the most important aspect of injectable manufacturing. All regulators and companies continuously seek advanced technologies to prevent microbiological contamination because the product is injected directly into the human body, where there is no defense mechanism once it enters the bloodstream. Preventing microbiological contamination is extremely important.

My entire career experience in injectable manufacturing operations has been with isolator technology, which is the best technology available because it prevents direct human contact with the product. Humans, by far, are the single biggest source of microbial contamination to products. By design, there is a rigid positive pressure barrier that can only be accessed through gloves, preventing any human intervention or human flora from impacting the product. From a technology standpoint, this is the best technology out there. This is what I have experience with and what I will be discussing.

Within barrier technology, it's also important to prevent unplanned interventions and eventually planned interventions as well. The more humans touch equipment, machines, or products, the higher the risk for microbial contamination. We continuously work towards achieving a zero-intervention process. The goal is to make all interventions zero except for the setup of the machine, after which you want to call it "lights out" and let the machine run. Achieving zero intervention involves a lot of background work, understanding, and capability. These are the areas we have focused on.

Advanced aseptic processing techniques are essential for maintaining product integrity and patient safety in pharmaceutical manufacturing. Can you share examples of specific aseptic processing techniques that have significantly improved your production outcomes?

Even with isolator technologies, we encountered several issues, such as products falling from the transportation mechanism and pumps not working properly. These problems resulted in frequent interventions in our system. It's crucial to have a fundamental, component-level understanding of how the equipment works. Without this knowledge, it becomes difficult to comprehend why machines behave a certain way when different components are integrated.

In modern manufacturing, especially for injectable products, equipment is highly advanced and sensor-based. It's more important to understand how the machine operates rather than how the product is manufactured because the machine handles everything. You don’t need a pharmacist to run the machine to ensure accuracy. The machine is interlocked, so if an issue arises, it will stop, give an alarm, and indicate the necessary action. Preventing such breakdowns and ensuring proper preventative maintenance processes are in place is crucial.

We have implemented many techniques to address these challenges. For example, when loading a freeze dryer, we initially used even rows of 28 and 26, leaving gaps between vials. We then changed this to an alternating pattern of 27 and 28, creating a holding mechanism that helped prevent the vials from falling. The pushing mechanism now holds the vials in place. These small adjustments, which combine hardware and software with a fundamental understanding, effectively resolve operational issues.

Pharmaceutical companies must adhere to stringent regulatory standards to ensure the safety and efficacy of their products. What rigorous quality control measures have you implemented to ensure compliance with regulatory standards, and how do you continuously improve these measures?

I believe that current regulatory compliance standards are ok, but technology can help better them significantly. Compliance should be seen as an entry ticket, not the boundary within which you need to operate. Thinking about quality and thinking about compliance are two different things. Quality involves continuous improvement and addressing any issues that arise, whether they are classified as failures or not.

If you operate in a quality-focused domain, which is a much stricter space than the broader compliance domain, you will naturally exceed compliance requirements. Our goal is to continuously tighten our operating space to produce better outcomes. We believe that quality is the primary driver for speed and productivity. Reducing quality standards to meet compliance and then trying to increase output is counterproductive. While it might yield short-term gains, it is not sustainable in the long run. Therefore, we view quality as the fundamental building block for productivity. Compliance is not the focus; quality is.

"If you operate in a quality-focused domain, which is a much stricter space than the broader compliance domain, you will naturally exceed compliance requirements."

In the highly regulated pharmaceutical industry, selecting the right equipment is critical to maintaining high standards of quality and efficiency. What criteria do you consider when selecting filling equipment to ensure it meets your quality and efficiency requirements?

I think it is fundamental that the equipment manufacturer understands and works with pharmaceutical manufacturers on the type of technology we need. Different equipment manufacturing companies have different capabilities, and we want capabilities that align with our way of thinking and our manufacturing processes.

For example, rather than emphasizing speed, I believe that while having a 400 vials-per-minute line is impressive, it's more practical to run the machine continuously and without intervention or stoppage at 250 vials per minute. Running the machine continuously without stoppages yields greater output and better quality outcomes compared to a machine that can run at 400 vials per minute but needs to stop frequently.

Thus, the actual performance and consistency of the machine are more important than its rated speed. This is something we constantly work on with our vendors. It's not just about the machines but also the packing materials we use. The rubber stoppers and vials must be compatible with the machine's technology, ensuring everything operates as one coherent system.

Can you discuss any innovative packaging solutions you've adopted that have enhanced the safety and stability of your products during transport and storage?

No, not from a packaging perspective, and not from an injectable manufacturing perspective either. We have our standard packaging solutions, and we send out products in cartons, blisters, or bottles. We have standard storage and transportation solutions in place, so there’s nothing major to consider in terms of packaging solutions.

However, the quality of our primary packaging materials for vials, barrels, and stoppers is crucial for our equipment and how they operate. Therefore, transportation viability and reliability become very important. Our machines need to run with standard packaging materials, and if they do, we don't face any issues.

From a packaging innovation perspective, we have transformed our packaging systems to achieve what we call "zero touch." This means that from the point where the vial is manufactured on the line all the way through to its packaging into individual or multi-cartons and into secondary packaging, everything runs in one continuous line. All our visual inspections, defect detection, labeling, and other processes occur online. This is something very few companies do, especially in a multi-product facility, because it is difficult to accomplish due to high changeover times, which can reduce output. However, we have worked with our vendors to significantly reduce our changeover times, and we’ve achieved several innovations in this area.

We want to express our gratitude to Krishna Venkatesh for his insightful contributions to this blog post. His expertise and perspectives will greatly enhance our discussion at the European Biomanufacturing Summit and provide our readers with valuable insights. We appreciate Krishna's collaboration and look forward to his session "Enhancing Biomanufacturing Efficiency: The Role of Fill and Finish" at the European Biomanufacturing Summit held on 10-11 September 2024 in Berlin, Germany.