Emphasizing quality and compliance through every step of the manufacturing process helps to ensure the safety and consistency of parenteral products.
Manufacturing parenteral products–from prefilled syringes and single-use vials to premixed IV bags and beyond–offers unique challenges, including growing pressure from competitors and patients and the stringent needs of regulatory oversight. Perhaps the greatest challenge facing the makers of parenteral products, however, is the need for an extremely high level of quality assurance in order to avoid potential contamination.
Contamination at any stage of the manufacturing process can have catastrophic results for the patients who are at the receiving end of the parenteral product. One of the key advantages of parenteral products such as premixed IV solutions is reduced risk of microbial contamination which may come with diluting concentrated drug vials. By eliminating a step of human interaction, premixed solutions eliminate the risk of gowning errors, unprotected environments, or simple operator error. Furthermore, premixed solutions have a shelf life of up to two years, giving hospitals greater control over their supply chain.
Today, drugs used for pain management, antibiotics, and other life-saving drugs make up the largest proportion of premixed IV solutions, but there are literally millions of parenteral products at hospitals all over the world that are used every single day.
Drugs that have to be diluted prior to injection carry the risk of everything from user error to contamination from outside sources, yet these dilutions are performed in hospitals all the time. The question for manufacturers of parenteral products becomes: How can we reduce the risks associated with our products while maintaining the standards that our customers have come to expect? While no system will ever be perfect, maintaining high standards throughout the parenteral manufacturing process helps to ensure safe and sterile products reach the doctors and patients who need them.
Quality control and regulatory compliance are vital at every stage of parenteral manufacturing to ensure sterility and safety.
The safety and efficacy of any product that is going to be used on a patient requires that exacting standards be maintained throughout the parenteral manufacturing process. Premixed solutions of the kind that are growing in demand across the healthcare industry should be manufactured in facilities that comply with current Good Manufacturing Practices (cGMP). They need to be sterile and free from contaminants, and the end user needs to be confident that they are correctly labeled.
This means that parenteral manufacturing requires careful quality assurance at every stage of production, from the acquisition of raw materials (such as the drug itself and any expients that are going to be used) to the sterile production of the finished product. Everything from packaging materials to labels needs to follow protocol, and each step in the chain must be carefully controlled and validated, so that the final product is safe to use.
Validation at every stage is vital in ensuring safety and traceability for the product. When dealing with potentially life-saving medical interventions, every component needs to be traceable to its original source, and every step of its manufacture needs to be carefully controlled so that any variables or contaminants are identified early and controlled for to prevent them from endangering the patient who is receiving the drug.
To this end, the entire workflow of a parenteral manufacturing operation should be designed and engineered to incorporate cGMP standards and ensure regulatory compliance at every stage. Ideally, parenteral products will be delivered directly from the manufacturer to the hospital, and labeled in ways that are consistent and intuitive.
Hospitals that switch over from vials that have to be diluted on-site to more stable products such as pre-mixed IV bags can also improve their own quality assurance efforts and cut down on time spent diluting or compounding concentrated, dried, and lyophilized substances.
Automation and other advances in parenteral manufacturing technology help to reduce the risk of contamination.
The sterility and safety of the end product relies on following cGMP standards throughout, as well as continual improvement of the parenteral manufacturing process. One major innovation of the past few decades has been increased reliance on automation, both to reduce instances of human error and to eliminate possible points of contamination. Because robotic systems never need to leave the cleanroom, the odds of microbial contaminants or pyrogenic contamination are severely reduced.
Advances in cleanroom technology have also helped the industry to reduce the risks associated with parenteral manufacturing, improving the efficiency of their processes while also increasing the safety of their parenteral products. Most facilities use restricted access barrier systems (RABS) or isolators. Each have their uses, depending on the needs of the facility, and the challenges of the product being handled.
Fundamentally, any cleanroom faces many of the same challenges, including the risk of contamination from the air system, the operators, and any incoming materials. Isolators and RABS technology both help to protect against these in different ways. Isolators are sometimes seen as the “more intense” aseptic process, with work taking place in a fully sealed unit that is often sanitized with vaporized hydrogen peroxide, or VHP. Isolators can provide safety for both the product and the human operator, but they also come with limitations, including difficulties in moving materials into and out of the cleanroom.
RABS technology can help facilities to create more dynamic cleanrooms that still provide the aseptic requirements needed for parenteral manufacturing. Depending on the needs of the facility, both open and closed RABS systems are available, with open systems offering passive and active options. Active RABS has a dedicated air supply, while passive RABS recycles air from the surrounding environment.
Regardless of what sort of cleanroom system is used in parenteral manufacturing, proper training in aseptic techniques as well as correct gowning procedures and other practices are essential to maintaining a chain of quality that runs from procurement of materials through the packaging and shipping of finished parenteral products.
A growing demand for new medical interventions offers challenges–and opportunities–for parenteral manufacturing.
As the demand for more and safer parenteral and other medical devices and technologies continues, companies are working on new aseptic options to make cleanrooms both safer and more efficient, including an advanced version of the RABS technology from Vetter called Vetter CleanRoom Technology (V-CRT), which combines the advantages of the RABS system with fully-automated decontamination applied via hydrogen peroxide.
Many within the parenteral manufacturing industry believe that the future will see fully automated production lines that can handle almost every step of the manufacturing process in a sterile environment, without the risks that come with humans having to enter and leave cleanrooms, such as gowning errors and so on.
As an aging population increasingly requires drug-delivery systems that can keep up with changing medical needs, the demand for parenteral manufacturing solutions that are quick, safe, and effective will only continue to grow. Premixed solutions and other parenteral interventions can help reduce the risks associated with dilution, dose calculation, and more–but in order for those interventions to be safe and effective, parenteral manufacturers face an increasing need to guarantee quality assurance at every step of the process.
Doctors and hospitals rely on parenteral products that they can trust; premixed IV solutions that are correctly labeled and free of contaminants, pre-filled syringes that are free from visible particles or other hazards. The future manufacturers of parenteral solutions will have to keep up with these growing and changing demands in a dynamic and competitive market without sacrificing the quality or safety of their end products.
