Kayla Hager, Product Manager for Pharm/Bio at ILC Dover, addresses the challenges in the chemical synthesis of active pharmaceutical ingredients (APIs). She explains the complex multi-step process of API synthesis and highlights the importance of proper containment to ensure operator safety and maximize throughput, particularly as the potency of the powders increases.
Kayla also highlights the benefits of single-use technologies over traditional stainless steel solutions, noting their improved process versatility, better environmental control, and reduced cleaning requirements. These technologies effectively address key challenges in API manufacturing, including powder containment, operational efficiency, sustainability, and handling poorly flowing powders.
Watch the video or explore the transcript below to learn more.
Transcript
0:09
Hello everyone and welcome to our next monthly installment of the ILC Dover webinar series.
0:18
My name is Kayla Hager and I’m the Product Manager for PharmaBio here at ILC Dover. Today, we’ll be talking about the chemical synthesis of active pharmaceutical ingredients, the challenges associated with this process, and how flexible containment solutions can help solve these issues.
0:38
Here’s a brief overview of today’s points. We’ll start by going over the chemical synthesis workflow, mention some common challenges API manufacturers face, and then discuss single-use technologies and how they compare to stainless steel alternatives. Finally, we’ll touch on specific ways ILC Dover can help solve these challenges.
1:13
The synthesis of APIs is a complicated, multi-step process involving numerous chemical transformations on various raw materials with different properties. There are many operational challenges for API manufacturers, including ensuring operator safety by properly containing the process to eliminate accidental exposure to hazardous substances, and maximizing campaign throughput. Starting with the arrival of materials in the warehouse, where they often need to be reprocessed before charging the reactor, the process goes through a series of chemical reactions before finally reaching a dryer and mill for the oral solid dosage process. As these series of chemistries progress, the potency of the powder increases, presenting an increased hazard for the operator.
2:17
Many challenges can be categorized into four main areas: powder containment and dust mitigation, operational efficiency, sustainability, and handling difficult-to-contain powders. To address these issues, let’s start with the basics of containing at the source.
3:13
Single-use technology enables process area versatility, being portable and easy to move and attach where needed. This allows better control of the environment, reduces airborne particulates by keeping the system closed, protects operators from exposure to hazardous materials, reduces cleaning requirements and cross-contamination risks, and addresses ergonomics and containing individual equipment.
3:55
In the chemical synthesis process, consider the repackaging of raw materials prior to dispensing into a reactor, typically in bags, drums, or FIBCs. These can be safely transferred using flexible containment systems like PST injectors, jet mixers, or powder conveyor systems. For reactor charging, non-potential standard FIBCs or Type C FIBCs can be used. During centrifuge and chemistry steps, flexible solutions like basket centrifuges or continuous liners can be employed. For the drying step, various flexible isolator solutions offer ergonomic handling and operator protection.
5:15
Utilizing single-use solutions ensures a closed process, meeting company policies and FDA inspector preferences. They enable easier handling and transfer of powders between centrifuges and reactors, especially wet cakes that are difficult to discharge. Flexible intermediate bulk containment solutions allow for better manipulation and discharge visibility compared to traditional stainless steel IBCs.
7:33
A sustainability study shows significant utility savings with single-use technology versus stainless steel. Single-use technology eliminates lengthy cleaning processes, holds time, and cleaning validation, minimizing cross-contamination risks from material retention.
8:35
The upfront cost of ownership is also lower with flexible FIBCs. Implementing an IBC system costs around $650,000, including the IBC itself, containment valves, precision lifts, washing systems, and additional space requirements. In contrast, FIBCs require only a high containment docking system, a simple hoist system, and the FIBCs themselves, totaling about $120,000. This significant cost difference makes FIBCs more economical.
11:32
Setting up an IBC project is more complex than FIBC projects. IBCs require selecting sizes and numbers, containment valves, precision lifts, cleaning processes, floor space management, electrical controls, FAT, SAT, operator training, and validation documents. FIBCs, on the other hand, involve selecting sizes, simple hoist systems, minimal floor space, and straightforward training and validation.
13:19
Even the hardest-to-contain parts of the process can be safely contained using flexible solutions. Relying solely on PPE is risky, as it puts the burden of protection on facility controls. Flexible isolators or single-use flexible isolators provide safer containment.
14:08
For tray dryers, single-use solutions can contain the equipment, reducing cross-contamination risks and reliance on PPE.
15:01
ILC Dover addresses chemical synthesis challenges with a variety of containment solutions. Our products ensure closed charging, minimizing contamination risks, especially in shared facilities. The DoverPac and D100 systems maintain closed processes, protecting both operators and the environment from contamination.
15:34
Containment transfer FIBCs enable charging or discharging of vessels in a closed process. The DoverPac is suitable for highly potent powders, the D100 for lower to mid-potency powders, and the GuardianPac for inert or non-hazardous powders. ILC Dover also offers continuous liners and flexible enclosures customized to your equipment.
16:36
As we move through the chemical synthesis process, the powder becomes more potent. Flexible solutions like the GuardianPac, D100, and DoverPac handle various potency levels, along with continuous liners and flexible enclosures. ILC Dover’s products are developed specifically for pharmaceutical powders, ensuring safe handling during the synthesis process.
17:30
The DoverPac and D100 systems feature shower caps and bag out sleeves, maintaining closed charging and minimizing contamination risks. They also allow fully contained sampling with integrated sample sleeves, ensuring no exposure to the powder inside.
20:24
ILC Dover provides documentation for all products, including certificates of performance, sealed packaging for protection, traceable labels, drawings, and assembly/use documentation. Our ArmorFlex films meet various regulatory standards, are reach compliant, and have a drug master file on record. They are designed for high strength and solvent resistance, crucial for handling wet cakes in chemical synthesis.
21:27
ILC Dover’s motto of “contain at the source” ensures maximum operator safety, operational efficiency, and sustainability. Our single-use solutions reduce water and energy consumption, handle poorly flowing powders, and take up less floor space than stainless steel alternatives.
23:50
Thank you for your attention. If you have any questions, please reach out through our website, ilcdover.com. You will also receive a questionnaire and a copy of this recording after the webinar.
