The ongoing battle against cancer has seen a paradigm shift with the advent of CAR-T cell therapy, a revolutionary approach that utilizes the patient’s own immune system to fight cancer. This innovative treatment, coupled with gene therapy, is transforming the landscape of cancer care. 

Unveiling CAR-T Cell Therapy

Chimeric Antigen Receptor T-cell (CAR-T) technique was designed to augment the body’s natural defenses by equipping T cells, the soldiers of the immune system, with engineered receptors known as CARs. These receptors enable the T cells to recognize and attack specific cancer cells, thereby providing a targeted approach to cancer treatment. 

CAR-T cell therapy has proven to be a game-changer in treating certain types of blood cancers, such as B-cell acute lymphoblastic leukemia and diffuse large B-cell lymphoma, that had previously shown resistance to conventional treatments¹. 

Manufacturing Process of CAR-T Cell Therapy 

The production of CAR-T cells involves several intricate steps, each requiring meticulous precision to ensure the utmost safety and efficacy of the final product. The process commences with the collection of T cells from the patient’s blood through a procedure called leukapheresis, where a specialized machine separates the desired cells.  

These collected cells, which play a crucial role in the immune system, are then transported to a laboratory, where they undergo a series of genetic modifications to express Chimeric Antigen Receptors (CARs) on their surface. This genetic engineering process involves precisely inserting the CAR gene into the T cells, allowing them to recognize and target specific cancer cells. Subsequently, the modified cells are cultured and expanded in the lab, undergoing rigorous quality control checks to ensure their purity, potency, and safety.  

Once these quality standards are met, the final product, consisting of the genetically modified CAR-T cells, is prepared for infusion back into the patient, where they can potentially combat the cancer cells with enhanced specificity and effectiveness. 

Contamination Risks in Cell Therapy Manufacturing: Safeguarding Patients and Preserving Quality 

Contamination can occur at various stages of cell therapy manufacturing, such as during genetic modification, cell expansion, or product formulation. Even a small presence of external contaminants, such as microorganisms or particles, can undermine the therapeutic value of the treatment and pose significant risks to patients. 

Complications arising from contamination may evade standard quality control measures, leading to the release of a contaminated batch. If administered to patients, this could result in adverse effects, reduced treatment effectiveness, or even serious harm. Moreover, such incidents could have far-reaching consequences for the manufacturer, including financial burdens, legal challenges, damage to reputation, and ethical concerns. 

Role of Closed System Devices 

CSTDs play an important role in the manufacturing and quality control processes of CAR-T cell therapy, improving sterility, decreasing batch failure rates and improving overall process efficiency. These devices prevent the introduction of contaminants into the system and restrict the escape of hazardous drugs or vapors, ensuring a safe and controlled working environment². 

Throughout the therapy manufacturing process, from transportation to quality control, air removal, and sampling, Closed System Transfer Devices (CSTDs) play a role in reducing contamination risks. Let’s take a closer look at how these devices effectively safeguard the integrity of the therapy. CSTDs offer a controlled environment for testing and analysis. By maintaining a closed system, these devices minimize the chances of external contaminants infiltrating the samples, thereby ensuring accurate and reliable results. This is particularly crucial as even the slightest contamination can skew test outcomes and lead to erroneous conclusions. 

By incorporating Closed System Transfer Devices (CSTDs), CAR-T companies can significantly reduce the potential for contamination throughout the manufacturing process of CAR-T cell therapy. These devices serve as a reliable defense mechanism, contributing to the safety, effectiveness, and integrity of the end product. 

Q: How does USP <800> refer to closed system transfer devices (CSTDs)?

A: CSTDs are referred to as a containment supplemental engineering control that provide adjunct controls to offer an additional level of protection during compounding or administration. Supplemental engineering controls may also facilitate enhanced occupational protection, especially when handling HDs outside of primary and secondary engineering controls.

Q: Does USP <800> acknowledge that all CSTDs will perform adequately?

A: No, USP <800> reveals that there is no certainty that all CSTDs will perform adequately. Therefore, users should carefully evaluate the performance claims associated with available CSTDs based on independent, peer-reviewed studies and demonstrated contamination reduction.

Q: Can hazardous drugs (HDs) vaporize at room temperature increasing risk of occupational exposure?

A: Yes, the Oncology Nursing Society (ONS) Toolkit for Safe Handling of Hazardous Drugs for Nurses in Oncology identifies 8 HDs with the potential to vaporize at room temperature including Carmustine, Cisplatin, Cyclophosphamide, Etoposide, 5-Florouracil, Ifosfamide, Nitrogen mustard and Thiptepa.

Q: Why does USP <800> indicate that it is important to contain HDs vapors?

A: USP <800> states that a potential opportunity of exposure during administration includes generating aerosols of HDs by various routes (Ex. Injection, irrigation, oral, inhalation or topical administration).

Q: Does USP <800> indicate that a CSTD can help contain HDs vapors when utilized?

A: Yes, USP <800> states that some CSTDs have been shown to limit the potential of generating aerosols during compounding.

Q: Does USP <800> still allow for the use of two tiers of containment (Ex. CSTD within a BSC) that is in a non-negative pressure room for facilities that prepare a low volume of HDs?

A: No, USP <800> states that a CSTD must not be used as a substitute for a containment primary engineering control (C-PEC) which must be in a room with negative pressure between 0.01 and 0.03 inches of water column relative to all adjacent areas.

Q: When does USP <800> indicate that a CSTD should be utilized?

A: USP <800> states that a CSTD should be used when compounding HDS when the dosage form allows. Furthermore, USP <800> states that a CSTD must be used when administering antineoplastic HDs when the dosage form allows.

Q: Do USP standards indicate how affixing a CSTD to a vial impact beyond use dating (BUD)?

A: No, USP <797> revisions and USP <800> do not state that attachment of a CSTD to a medication vial either reduces or prolongs the beyond use date (BUD) of a medication vial (single or multiple dose). Therefore, for medication vials with an attached CSTD, BUD remains unchanged from USP standards. USP, Joint Commission and other regulatory bodies also do not currently endorse the utilization of a CSTD for prolonging the BUD of single dose vials, which is also known as dose vial optimization (DVO) due to patient safety concerns.

Current State of Pharmacy Compounding Automation

In the rapidly evolving landscape of healthcare, the realm of pharmacy is undergoing a transformative shift with the advent of compounding automation. This paradigm shift is revolutionizing the way pharmacies function in the United States, leading to enhanced efficiency, improved accuracy, and increased safety. Pharmacy compounding, once a labor-intensive process requiring meticulous manual effort, is now becoming an automated operation, harnessing cutting-edge technology to streamline workflows and mitigate potential errors. This article delves into the current state of pharmacy compounding automation in the U.S., exploring its benefits, challenges, and the potential it holds for the future of pharmaceutical care. From reducing the risk of cross-contamination to ensuring precise dosage and formulation, automation is poised to redefine the standards of pharmacy compounding, making it a compelling topic of discussion in contemporary pharmaceutical discourse.

What are the main challenges?

Pharmacy compounding automation, while offering numerous benefits, does present its own set of challenges. The initial cost of adopting automated systems can be substantial and may deter some pharmacies, particularly smaller operations. Additionally, implementing these systems requires a significant amount of training and adaptation for the staff, potentially disrupting workflow during the transition period. Interoperability issues, where different systems fail to communicate effectively with each other, can also pose a challenge. However, the market is evolving rapidly to meet these challenges head-on. Numerous companies are developing more user-friendly interfaces, comprehensive training programs, and better integration capabilities to ensure smooth operation. Meanwhile, the long-term savings in terms of time, reduced wastage, and improved accuracy often outweigh the initial investment, making automation an increasingly viable option for pharmacies of all sizes.

Pharmacies play a critical role in providing safe and effective medications to patients. However, a study suggests that approximately 9 percent, or nearly 1 in 10, of IV preparations may contain errors, with the most common problem being incorrect ingredients and/or volumes. These errors have the potential to cause harm or even result in patient fatalities¹. One area where advancements in technology can significantly improve safety and efficiency is the pharmacy compounding process. By leveraging artificial intelligence (AI), pharmacies can streamline their operations while minimizing the risk of errors. This blog post will discuss how AI can help reduce human error and enhance accuracy and consistency in pharmacy compounding, as well as the essential role of Closed System Transfer Devices (CSTDs) in maintaining a contamination-free environment. 

Harnessing AI to Reduce Human Error in Pharmacy Compounding

The integration of AI technology into pharmacy compounding processes offers several benefits, including:

1. Precision and Consistency: AI algorithms can precisely measure and dispense drug components, ensuring consistency and accuracy in the final product. This reduces the likelihood of dosage errors reaching the patient2.
2. Real-time Monitoring: AI-driven systems can continuously monitor the compounding process, detecting and correcting errors before they become a threat to patient safety.
3. Data Analysis and Learning: AI can analyze historical data to identify trends and patterns, enabling continuous improvement in the compounding process and reducing the risk of future errors.

While AI is already making a significant impact, its potential in the field of pharmacy is far from fully realized. Future developments could see AI being used to automate more complex tasks, further reducing the burden on human pharmacists and minimizing the risk of errors. For instance, we could see AI systems that can interpret complex prescription orders or even dispense medications autonomously.

By adopting AI-driven automation, pharmacies can significantly reduce the occurrence of human errors, leading to safer and more efficient compounding processes.

The Role of Closed System Transfer Devices (CSTDs) in Ensuring Safety and Sterility

While AI can greatly improve the accuracy and consistency of pharmacy compounding, maintaining a sterile and contamination-free environment is equally important. Closed System Transfer Devices (CSTDs) serve as an additional layer of protection against contamination, particularly when handling hazardous drugs.

CSTDs are specially designed drug-transfer devices that create a physical barrier between the drug, the environment, and healthcare workers. They are used to prevent the escape of hazardous drug vapors, aerosols, and droplets during compounding and administration³. By incorporating CSTDs into the pharmacy compounding process, pharmacies can:

1. Minimize Exposure Risks: CSTDs reduce the risk of healthcare workers and patients being exposed to hazardous drug particles, ensuring a safer working environment.
2. Maintain Sterility: CSTDs help maintain the sterility of compounded medications by preventing contaminants from entering the drug preparation process.
3. Complement AI-driven Systems: The integration of CSTDs with AI-driven automation systems can provide comprehensive protection against both dosage errors and contamination risks.

Embracing AI and CSTDs for a Safer Future in Pharmacy Compounding 

By integrating artificial intelligence technology and Closed System Transfer Devices (CSTDs) into their compounding processes with products like the EQUASHIELD Pro, pharmacies can significantly enhance safety, efficiency, and accuracy. This powerful combination of cutting-edge technology and robust protective measures can help minimize the risk of medication errors, ensuring optimal patient care and public health outcomes. 

In the United States, it is estimated that there are over 100,000 veterinary healthcare workers, including veterinarians, veterinary technicians, and support staff, who play a crucial role in the care and treatment of animals¹. These professionals are often exposed to hazardous drugs, such as chemotherapy agents and immunosuppressive medications, which can pose significant occupational health risks. Long-term effects of such exposure can include skin and respiratory irritation, organ damage, and an increased risk of developing various cancers³ . Research on the demographic characteristics of veterinary healthcare workers indicates that most of these professionals are women and may be at a higher risk of reproductive toxicity due to hazardous drug exposure². It is essential for veterinary healthcare workers to be aware of these risks and implement safety measures to minimize exposure and protect their health. Safety measures include using personal protective equipment (PPE) and closed system transfer devices (CSTDs) when preparing and administering hazardous drugs. 

Cancer in Pets is on the Rise 

According to the American Veterinary Medical Association (AVMA), cancer is a leading cause of death in pets, accounting for almost 50% of all disease-related pet deaths annually5. The growing number of cases has been attributed to several factors, including increased life expectancy due to advancements in veterinary care, improved diagnostics, and greater awareness among pet owners. Among household pets, dogs have the highest incidence of cancer, with one in four dogs developing cancer at some point in their lives5. Cats also experience cancer, albeit at lower rates compared to dogs. This upward trend in cancer cases among pets highlights the need for continued research, early detection, and advanced treatment options to improve outcomes and enhance the quality of life for affected animals.

In this blog post, we will discuss the different types of hazardous drugs used in veterinary settings, detail the potential risks involved in handling these drugs, and provide a step-by-step guide for veterinarians to follow when handling hazardous drugs, focusing on the use of closed system transfer devices (CSTDs).

Hazardous Drugs in Veterinary Medicine 

Hazardous drugs are medications that pose a potential risk to humans through exposure due to their inherent toxic properties. In veterinary medicine, hazardous drugs can include: 

1. Chemotherapy agents used to treat various cancers in animals 

2. Hormones and hormone antagonists 

3. Immunosuppressive agents for managing autoimmune diseases and facilitating organ transplants 

4. Antiviral medications 

5. Certain antibiotics and antifungal agents 

Potential Risks and Precautions

Veterinary healthcare professionals often handle hazardous drugs to treat a variety of medical conditions in animals. These professionals must understand the potential risks associated with handling these drugs and take necessary precautions to ensure their safety, as well as the safety of the animals they treat. Handling hazardous drugs can pose risks to veterinary healthcare professionals, including skin irritation, respiratory issues, and reproductive toxicity. Often, vets are compounding hazardous drugs without engineering controls, such as biological safety cabinets or compounding aseptic containment isolators. These veterinary healthcare providers may be at a higher risk for exposure to hazardous drugs and vapors.

To minimize these risks, it is essential to follow proper handling procedures, including:

1. Wearing appropriate personal protective equipment (PPE) such as gloves, gowns, and eye protection.
2. Utilizing engineering controls like biological safety cabinets or compounding aseptic containment isolators when possible.
3. Implementing safe work practices, such as avoiding hand-to-mouth contact and washing hands thoroughly after handling hazardous drugs.
4. Regularly training staff on safe handling practices and staying updated on the latest guidelines and recommendations.

The Role of Closed System Transfer Devices in Veterinary Medicine

CSTDs, such as EQUASHIELD CSTDs, play a crucial role in mitigating the risk of exposure to hazardous drugs during the preparation and administration process. These devices create a sealed barrier between the drug and the environment, preventing the escape of hazardous drug or vapors.

Clinical studies⁴ have shown that by incorporating CSTDs into their practice, veterinarians can:

1. Reduce the risk of exposure to hazardous drugs for themselves and their staff.
2. Minimize the risk of contamination during drug preparation and administration.
3. Improve the overall safety of handling hazardous drugs in veterinary settings.

A Step-by-Step Guide for Handling Hazardous Drugs

To ensure safety when handling hazardous drugs in veterinary medicine, follow these recommended steps:

1. Storage: Store hazardous drugs separately from other medications, ideally in a designated area with proper ventilation and limited access.
2. Preparation: Prepare drugs in a designated area, using engineering controls like biological safety cabinets. Institute safety measures such as using CSTDs and wearing appropriate PPE during preparation.
3. Administration: Administer drugs following the recommended route and dosage, ensuring the use of proper PPE and equipment, including CSTDs.
4. Disposal: Dispose of hazardous drug waste including used vials, syringes, and contaminated PPE, according to local, state, and federal regulations.

In conclusion, handling hazardous drugs in veterinary medicine requires diligence and adherence to proper safety protocols. By implementing safe handling practices, utilizing closed system transfer devices, like EQUASHIELD CSTDs, and staying informed about the latest guidelines and recommendations, veterinary healthcare professionals can enhance their safety and the safety of the animals they treat. 

According to the National Institute for Occupational Safety and Health (NIOSH), a CSTD is a drug transfer device that mechanically prohibits the transfer of environmental contaminants into the system and the escape of hazardous drugs or vapors outside of the system1. These devices serve as a critical tool to prevent exposure to hazardous drugs, which can cause serious health effects in healthcare workers. The use of CSTDs has been mandated in several countries, including the United States, due to the high incidence of hazardous drug exposure among healthcare workers. In this article, we will explore the key features and regulatory requirements of CSTDs, and why they are essential in protecting healthcare workers from hazardous drug exposure.

Why are CSTDs so important?

Hazardous drugs, such as chemotherapy agents, antiviral medications, and immunosuppressive drugs pose significant health risks to medical personnel who handle them. These risks include skin irritation, allergic reactions, reproductive issues, and even the development of cancer². To minimize exposure to hazardous drugs and ensure the long-term health and safety of medical personnel, it is essential to implement best practices and safety measures. 

What is the regulation status in the USA? 

Specific requirements mandated by USP 800 guidelines include: 

USP 800 is a set of guidelines³ developed by the United States Pharmacopeia (USP) and mandated by the Occupational Safety and Health Administration (OSHA) to prevent occupational exposure to hazardous drugs for healthcare workers. USP 800 aims to protect healthcare personnel, patients, and the environment by outlining safety standards for the handling and disposal of hazardous drugs in healthcare settings. 

1. Proper use of personal protective equipment (PPE), such as gloves, gowns, masks, and eye protection. 

2. Establishment of designated areas for receiving, storing, compounding, and administering hazardous drugs. 

3. Implementation of engineering controls, including biological safety cabinets and compounding aseptic containment isolators. 

4. Proper handling, decontamination, and disposal procedures for hazardous drugs and contaminated materials. 

Specific requirements mandated by USP 797 guidelines include:   

USP 797⁴ is a comprehensive set of standards designed to ensure safe compounding practices for sterile preparations. These regulatory requirements address critical aspects, including personnel qualifications, training, and hygiene; environmental quality and control; facilities and equipment; standard operating procedures (SOPs); and quality assurance and documentation. Personnel involved in sterile compounding must undergo proper training and demonstrate competency through written and practical assessments while adhering to strict hygiene protocols.  

1. Personnel Qualifications and Training: Ensure that all staff involved in sterile compounding have appropriate training, demonstrate competency through assessments, and follow strict hygiene protocols. 

2. Environmental Quality and Control: Maintain defined air quality standards using primary engineering controls, and regularly monitor the compounding environment to minimize contamination risks. 

3. Facilities and Equipment: Design compounding areas that are segregated from other activities, with proper equipment such as laminar airflow workbenches or biological safety cabinets, and adhere to controlled temperature and humidity conditions. 

4. Standard Operating Procedures (SOPs) and Quality Assurance: Develop and implement SOPs for all compounding activities, including preparation, labeling, storage, and disposal of compounded sterile preparations, and perform quality control measures such as sterility testing, endotoxin testing, and beyond-use dating. 

Closed System Transfer Devices (CSTDs), such as EQUASHIELD’s CSTD product line, play a crucial role in reducing the risk of exposure and contamination while complying with USP 800 and USP 797 guidelines. EQUASHIELD CSTDs provide a physical barrier between the clinician and the hazardous drug, preventing the escape of hazardous drugs or vapors into the environment during compounding and administration processes. 

When does exposure to hazardous drugs occur? 

Exposure to hazardous drugs and their vapors occurs throughout the whole chain of drug handling, from receiving at the hospital warehouse until disposal. Compounding and administration constitute the major portion of the drug handling chain as more people are exposed, thereby increasing the risk of exposure.

Contamination with hazardous drugs can occur via several routes: 

• Oral – through ingestion 
• Inhalation – breathing in vapors 
• Dermal – contact

Different roles in handling hazardous drugs require specific recommendations: 

Pharmacists and Pharmacy Technicians

1. Use closed-system transfer devices (CSTDs) during drug compounding to prevent the escape of hazardous drugs or vapors. 

2. Work in a designated area with proper ventilation, such as a biological safety cabinet or compounding aseptic containment isolator. 

3. Wear appropriate personal protective equipment (PPE), including gloves, gowns, masks, and eye protection. 

4. Dispose of contaminated materials properly, following the facility’s hazardous waste disposal guidelines.

Nurses and Healthcare Providers 

1. Utilize CSTDs during drug administration to minimize the risk of spills or leaks.  

2. Wear PPE, such as gloves and gowns, while administering hazardous drugs and handling contaminated equipment. 

3. Follow proper procedures for handling and disposing of hazardous drugs, including using puncture-resistant sharps containers for needles and syringes. 

4. Educate patients and their families about the safe handling of hazardous drugs at home, including proper storage, administration, and disposal. 

Environmental Services and Waste Management Staff

1. Wear appropriate PPE when cleaning areas where hazardous drugs are prepared or administered. 

2. Follow facility-specific protocols for decontamination and cleaning procedures. 

3. Dispose of hazardous drug waste according to local, state, and federal regulations. 

Medical facilities and employers play a critical role in supporting these safety measures by providing adequate resources, including: 

1. Regular training and education for all staff handling hazardous drugs, ensuring they are well-versed in safety protocols and procedures. 
2. Supplying the necessary PPE and CSTDs for all personnel who handle hazardous drugs. 
3. Implementing specialized ventilation systems and designated areas for drug preparation and administration. 
4. Establishing clear guidelines and procedures for decontamination, cleaning, and waste disposal. 

How can EQUASHIELD CSTDs help?  

Pharmacists can protect themselves from hazardous drug exposure by implementing various safety measures, including the use of EQUASHIELD® Closed System Transfer Devices (CSTD). These devices are designed to create a physical barrier between the clinician and the hazardous drug, minimizing the risk of exposure during the compounding and administration process. 

EQUASHIELD® CSTDs are unique in their ability to cover more routes of exposure than other solutions. Extensive clinical evaluation and studies⁴ have shown that standard syringes can become contaminated with hazardous drugs on surfaces exposed to the environment, potentially leading to vapor escape and plunger contamination. EQUASHIELD® addresses this issue with its closed-back syringe design, providing superior protection compared to alternative systems. 

In conclusion, minimizing exposure to hazardous drugs is crucial for the long-term health and safety of medical personnel. By implementing best practices, using CTDS, appropriate PPE and equipment, and providing ongoing training and support, medical facilities can create a safer work environment for all staff members involved in handling hazardous drugs.