In this webinar, Declan O’Shea, Product Manager for Isolators and Containment Systems at ILC Dover, discusses the challenges and solutions related to handling potent products within sterile environments. The presentation covers trends in sterile manufacturing, the importance of containment, risk assessments, and the development of specialized equipment and SOPs (Standard Operating Procedures).
Watch the video or explore the transcript below to learn more.
Transcript
[Declan O’Shea] 00:00
Hello, good morning or afternoon, everyone, depending on where you’re joining us from around the world. Thank you for attending this ILC Dover webinar. We host these webinars monthly, typically around the middle of the month, and cover various topics related to the biopharma and pharmaceutical industries.
Today, we will focus on handling potent products in sterile environments. As some of you may know, we have recently developed a sterile manufacturing isolator. Over the past 18 months to two years, we have seen a significant increase in requests to handle alternative products in sterile manufacturing processes. Historically, as a containment company, we have managed products like these over time and developed solutions. Now, we are combining our containment expertise with our sterile manufacturing capabilities to create a unified environment for various processes.
We’ll wait another minute for any last-minute attendees before starting with an overview of today’s agenda.
[Declan O’Shea] 02:49
Let’s begin the presentation. If you have any questions, please post them in the chat. I’ll address them during the session if they are relevant to the current topic; otherwise, I’ll answer them at the end. If time runs out, I’ll follow up with you individually after the webinar.
Agenda
- Brief background on ILC Dover
- Review of trends in sterile manufacturing over the past few years
- Discussion on the potency of molecules in the pharmaceutical space
- Our role as containment specialists in the industry
- An overview of environments created for containment
- Handling potent molecules in sterile environments
About ILC Dover
[Declan O’Shea] 05:35
ILC Dover is primarily a film manufacturing company. We produce various products from flexible film, including powder bags for powder transfer and containment, containment isolators for the pharmaceutical and biopharmaceutical industries, and PAPRs (Powered Air-Purifying Respirators) for operator protection. We are also known for making spacesuits for NASA, a project that helped establish our reputation.
Our headquarters is in Delaware, USA, but we have facilities in Texas, Mexico, Ireland, Switzerland, the UK, Singapore, and a new facility in New Delhi, India. This global presence allows us to serve a wide range of industries and clients worldwide.
Sterile Manufacturing Trends
[Declan O’Shea] 06:40
In terms of trends, the frequency of certain practices in sterile manufacturing has increased. Notably, cell and gene therapy, patient-specific products, and antibody-drug conjugates (ADCs) have seen significant growth. ADCs represent a bridge between the pharmaceutical and biopharmaceutical sectors, linking a potent small molecule to a monoclonal antibody for targeted oncology treatments.
We’ve also seen a rise in the need for handling potent sterile powders that cannot be further sterilized. Additionally, there’s been a notable increase in contract manufacturing, with more companies outsourcing development work and early-stage commercial manufacturing to specialized firms. These trends highlight the evolving needs of the industry and the importance of flexible, adaptable solutions.
Involvement as Containment Specialists
[Declan O’Shea] 12:02
As containment specialists, we’re often the first point of contact for establishing suitable environments for specific processes. Our involvement usually begins two to three years before a project’s realization, where we assess the feasibility of handling potent substances in sterile environments.
Our experience spans various industries, including pharmaceuticals, nuclear, medical, and military sectors. This cross-industry experience helps us develop comprehensive containment solutions, applying best practices from one field to another to enhance safety and efficiency.
Creating an Environment
[Declan O’Shea] 15:04
Creating environments for containment has evolved beyond just constructing a box with positive or negative pressure. Today’s isolated technology offers advanced features, whether in hard-wall systems or flexible film isolators. For example, in cell banking, we create anaerobic environments with low oxygen content. In ADC compounding, we create high containment environments with negative pressure and double HEPA filtration to ensure operator safety and product integrity.
Each environment is specifically tailored to the needs of the product and process, ensuring compliance with regulatory standards and maintaining safety.
Risk Assessment
[Declan O’Shea] 25:14
Risk assessment is critical in these processes. We evaluate both operator protection and product protection. It’s not about choosing one over the other but ensuring that both are adequately addressed. We assess the environment inside and outside the isolator, considering cleanroom conditions, gowning procedures, and PPE. We also evaluate worst-case scenarios, such as breaches in containment, and develop measures to mitigate these risks.
We assess both operator protection and product protection, ensuring that both aspects are adequately addressed. This involves evaluating the environment inside and outside the isolator, including cleanroom conditions, gowning procedures, and personal protective equipment (PPE). We also consider worst-case scenarios, such as breaches in containment, and develop measures to mitigate these risks.
[Declan O’Shea] 29:04
When designing isolators, we consider both positive and negative pressure systems, depending on the specific needs of the process. Positive pressure systems are typically used in fill-finish operations to protect the product, ensuring that any breach in the containment system pushes air out, preventing contaminants from entering the critical zone. However, if handling potent powders, negative pressure might be necessary to protect the operator, containing any potential escape of hazardous substances.
Design elements such as safe product and waste removal, pressure cascades, and maintaining cleanroom standards are crucial components of effective isolation systems. These elements help ensure that both the product and operator are protected, even in the event of a containment breach.
Product Development
[Declan O’Shea] 33:18
Our product development process is guided by customer feedback and rigorous engineering standards. We’ve developed standard units and custom solutions tailored to specific processes, incorporating features like single-use options and VHP (Vaporized Hydrogen Peroxide) compatibility for sterilization. Our goal is to provide equipment that is efficient, reliable, and meets the stringent requirements of sterile and containment environments.
We also emphasize ease of assembly and installation, ensuring that our systems are user-friendly and compliant with all regulatory standards. This approach helps streamline operations and reduce downtime for our customers.
Summary
[Declan O’Shea] 41:54
In summary, our goal is to create efficient and productive equipment with a small footprint, automated control systems, and single-use options to eliminate cleaning validation. This approach helps streamline operations and reduce downtime for our customers. We aim to lower capital costs, reduce lead times, and mitigate risks while meeting all regulatory requirements.
By incorporating customer feedback and adhering to rigorous engineering standards, we ensure that our systems meet the highest standards of safety and performance. Our experience across various industries enables us to develop solutions that address the unique challenges of handling potent substances in sterile environments.
Questions
[Declan O’Shea] 44:05
Let’s move on to the questions.
[Question 1] 44:10
How do you identify a loss of containment problem with materials with OELs in the lower nanogram range where there may be no visible evidence?
[Declan O’Shea]
For materials with lower nanogram OELs, we use strict containment measures and single-use disposables to minimize risk. This approach reduces the chance of contamination and ensures the safety of both the operator and the product. If you need further clarification, I’ll follow up via email.
[Question] 45:20
Are your units listed in a nationally recognized testing?
[Declan O’Shea]
Yes, our units have been tested and validated. For example, our partnership with Disposable Lab in France has provided publicly available information on our isolators’ performance. We welcome discussions with potential partners to share our experiences and capabilities.
[Question] 46:05
Does ILC Dover provide guidance on cleaning and preventive maintenance?
[Declan O’Shea]
Yes, we provide comprehensive documentation, including operation and maintenance manuals that cover all necessary aspects of cleaning, maintenance, and validation. These manuals are detailed and designed to ensure that our systems are properly maintained and operate efficiently.
[Question] 47:10
What is the maximum containment level you can achieve?
[Declan O’Shea]
For sterile manufacturing units, we can achieve a one-microgram OEL. For pharmaceutical containment units, we’ve achieved a one-nanogram OEL, demonstrating our ability to handle highly potent substances safely. Our isolators are designed to meet the specific needs of our customers, including the most stringent containment requirements.
[Question] 48:15
Is the market share for VHP-compatible units bigger than single-use ones?
[Declan O’Shea]
Yes, currently, VHP units are more prevalent, but we provide both options depending on the customer’s needs. VHP units offer a versatile solution for many applications, while single-use systems are ideal for specific scenarios, such as handling highly potent or sensitive products.
[Question] 49:25
How do you handle positive and negative pressure systems for potent materials?
[Declan O’Shea]
The choice between positive and negative pressure systems depends on the risk assessment. In general, positive pressure is used to protect the product, while negative pressure is used to protect the operator. The decision is based on the specific requirements of the process and the materials involved.
[Question] 50:20
How do you protect the operator in case of a flexible isolator rupture?
[Declan O’Shea]
Protection can be achieved by using downflow booths or ensuring operators are in full PPE, with strict de-gowning procedures. These measures help contain any potential exposure and protect the operator’s health and safety.
[Question] 51:15
Does ILC Dover cover assembly and installation?
[Declan O’Shea]
Yes, we provide assembly and installation services, ensuring the unit is fully operational and compliant with all regulatory standards. Our team works closely with customers to ensure a smooth installation process and provide any necessary training or support.
Thank you, everyone, for attending. My name is Declan O’Shea, Product Manager for Isolators and Containment Systems at ILC Dover. If you have any further questions, please feel free to contact me via email.
This session has been recorded and will be available for those who attended or wish to share it with colleagues.
