Background
The term "Large Volume Parenteral" (LVP) solutions, is the technologically accepted nomenclature of the U.S. Food and Drug Administration (FDA) for intravenous (IV) solutions. LVPs or IV solutions consist of either sterile water or low concentrated solutions of saline, dextrose, carbohydrates, electrolytes, lipids, vitamins, proteins, etc. in pure sterile and pyrogene free water intended for intravenous administration to patients who require acute maintenance therapy and also total parenteral nutrition (TPN) because of inability to swallow or digest.
IV solutions are either administrated alone, or as a vehicle for delivering into the human body drugs and medications which are mixed in for a wide variety of therapies. Among such formulations are: antibiotics, anesthetics, antiinflammatory or chemotherapy for cancer treatment, etc.
Approximately 95% of IV solutions are packaged in aseptically-filled, terminally sterilized, pyrogen free medical grade plastic bags from 100ml to 1,000ml in volume. Glass bottles are still used for special purposes, such as an administration of nitroglycerine or certain lipids that can bleed into the rigid plastic or flexible bags.
All solutions are administered with aid of the so called "giving" sets consisting of various length and diameter of tubular plastic with the sharp plastic spike on one end and a stainless steel needle on another, and various nipples and valves in the middle. Some solutions in most cases are injected through the gravity drip system. However, lately more and more often the IV solution administration process requires aid of specifically designed electric pumps and electronically controlled timers. These sets and devices are produced seperately by the companies which are using special equipment and measuring devices.
Few countries today have the capability to make quality IV solutions, especially those for pump administration, so they are currently mass-produced in a few places throughout the world and shipped to the point of use. Transportation is a major cost factor, and first of all in international markets. The shipping also dictates that an additional capital be extended for stocking and keeping adequate inventory of IV solutions to satisfy local needs.
IVPC Facility™ Concept
The IVPC facility was especially created for international markets to provide medically developing countries with an indigenous capacity to produce the basic components for their own quality medical care (alleviating the costs associated with shipping and inventory maintenance), as well as high-valued pharmaceutical products for export.
Based on vast experience in international and developing country markets, EWMA committed itself to providing a comprehensive, turnkey program with 5 essential components:
• Complete external building (under seperate contract) and internal build-out for the state-of-the-art Blow-Fill-Seal (BFS) equipment and computer systems
• Complete facility engineering and equipment installation including water for injection (WFI) purification plant, mixing a formula module, lab and warehouse, power and utility support.
• Thorough training program for management and production personnel
• Marketing assistance and product promotion among local medical personnel training
In addition, EWMA is committed (under seperate contract) to providing on-going technical and operational assistance to ensure that the products continue to maintain GMP, US pharmacopoeia and US FDA quality standards, the highest standards in the world.
Design and Manufacturing
The IVPC Facility™ concept is the newest, most innovative entry in the field of advanced aseptic manufacturing. With it's dedicated Research & Development Department Weiler Engineering, Inc.- the main vendor of EWMA, is constantly enhancing BFS technology to create more effective and easier to validate methods of filling and packaging sterile pharmaceutical, biological and medical products. Engineers and designers with extensive knowledge, background, and direct, day-to-day experience with blow-fill-seal and conventional sterile manufacturing facilities provide customers with constant project support, from product development, protocol implementation and manufacturing through regulatory guidance and assistance including process validation.
At Weiler Engineering BFS equipment is produced in a 45,000 sq. ft. of manufacturing space facility near Chicago, Illinois. IVPC BFS machines are contained within complete HEPA ceiling Class 1,000 "clean rooms" supported by a series of Class 10,000 "service rooms". Ingredient preparation and solution compounding is performed in a Class 1,000 batching area. Processed water is WFI quality purified by a GMP multi-effect still feeding a recirculating storage loop maintained at 80° C water. All operations comply with current US FDA Good Manufacturing Practices (GMP).
Weiler Engineering, Inc. is staffed by engineers whose disciplines are vital to building state-of-the-art BFS machinery including mechanical design, mold design, PLC control system design and engineering, and pharmaceutical process engineering.
The immense requirement for IV solutions in all medically developing countries necessitates high-volume, highly reliable production. Current standards in the U.S. permit an undetected contamination variable of one-in-one million production units. In other words, the 1 billion plus IV units used in the U.S. annually permit the probability that 1,000 contaminated IV units may enter use undetected. The unique, state-of-the art technology of the IVPC facility improves upon this factor by 1,000 times. The chance of having undetected contamination in an IV unit produced by an IVPC facility is reduced to a probability of one-in-one billion.
Weiler/EWMA integrated technology provides a major improvement over the traditional manufacturing methodology and results in highest degree of product quality for IV solutions. Traditional factory environment permitting many airborne particles and contagion are replaced with a clean room facility achievable only in the small setting on the IVPC facility. De-ionization of the feed water occurs prior to distillation eliminating the possible contribution of particulate matter from the de-ionizing process itself.
Furthermore, distilling water that is relatively free of dissolved mineral content prevents superheating of the water and the resulting entrainment of solute particles in the downstream water stock. The downstream implication of minimizing particulants in the mixing tank and filter are essential to achieving a superior-quality product.
The air quality of the filling zone is critical for aseptic filling processes. The traditional rotary filling of containers is replaced by an innovative machine that blows a plastic container, fills it and seals it all in one operation. Bottles or bags produced separately from the filling operation must be examined for bacterial and particulate contaminants. The Weiler Engineering Blow-Fill-Seal machine, by producing a seamless container from plastic resin at temperatures in excess of 300 degrees centigrade and injecting water or other solutions into the sterile container before scaling, greatly reduces both the chance of contamination and the need for secondary inspection and testing. The HEPA nozzle air shroud in conjunction with a new partical removal system, consistently provides air quality at Class 100 conditions or better during actual production runs.
