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“Blow fill & seal Technology” for more rapid container closure processing, elimination of aseptic critical-area personnel interventions, increased system uptime over traditional processing, pyrogen-free molding of containers and ampoules, more flexibility with container design, and an increased capability to capitalize on short runs. And for the consumer, increased safety and confidence in their drug products are strong additional benefits.
Assignment PHR-415 Blow Fill & Seal Technology Prepared by: A T M Omar Farooq ID# 062 155 046 Dept. of Pharmacy North south University Blow Fill & Seal Technology Introduction Traditional aseptic filling & sealing involves handling and manipulation of the material, containers, and sterilization filling processes with human intervention, and therefore has a higher potential for contamination during processing. the design of equipment used in aseptic processing should limit the number and complexity of aseptic interventions by personnel. Both personnel and material flow should be optimized to prevent unnecessary activities that could increase the potential for introducing contaminants to exposed product, container-closures or the surrounding environment. Airborne contamination is directly related to the number of people working in a cleanroom and the level of congregation by personnel in areas where critical aseptic manipulations are performed. Isolation of personnel from these critical areas would eliminate the major source of contamination in traditional aseptic processing. In traditional aseptic processing, changing or adjusting filling nozzles and heads necessitates the shutdown of the filling operation and requires re-sterilization of the entire equipment. This increases manual intervention in this critical area. Cleaning and sterilization which is carried out by personnel, opens the door to breaching of established procedures for microbial decontamination and potential introduction of other particulates like dirt, oil and chemicals. Mold is common flora found on floors, walls and ceilings of buildings. Contamination occurs due to the retention of water in cracks, edges and joints that are susceptible because of inadequate sealing. Brooms, mops and anything used for cleaning can become contaminated and increase atmospheric contamination because of raised dust or splashing water. In traditional aseptic processing, significant manual intervention is required in critical areas to maintain compliance with established sterile mandates. Advanced Technology An advanced technology is developed “Blow fill & seal Technology” for more rapid container closure processing, elimination of aseptic critical-area personnel interventions, increased system uptime over traditional processing, pyrogen-free molding of containers and ampoules, more flexibility with container design, and an increased capability to capitalize on short runs. And for the consumer, increased safety and confidence in their drug products are strong additional benefits. Blow Fill Seal Technology Blow-Fill-Seal technology refers to the manufacturing technique used to produce small, (0.1mL) and large volume, (500mL +) liquid filled containers. Blow-Fill-Seal technology was originally developed in Europe in the 1930s and was introduced in the United States in the 1960s, but over the last 20 years it has become more prevalent within the pharmaceutical industry, and it is now widely considered to be the superior form of aseptic processing by various medicine regulatory agencies including the U.S. Food and Drug Administration (FDA) in the packaging of pharmaceutical and healthcare products. The basic concept of blow fill seal (BFS) is that a container is formed, filled, and sealed in a continuous process without human intervention, in a sterile enclosed area inside a machine. Thus this technology can be used to Aseptically Manufacture sterile pharmaceutical liquid dosage forms. The process is multi-stepped, firstly pharmaceutical-grade plastic resin is vertically heat extruded through a circular throat, to form a hanging tube called the Parison. This extruded tube is then enclosed within a two-part mould, and the tube is cut above the mould. The mould is transferred to the filling zone, or sterile filling space where filling needles mandrels are lowered and used to inflate the plastic to form the container within the mould. Following the formation of the container, the mandrel is used to fill the container with liquid, following filling the mandrels are retracted and a secondary top mould seals the container. All actions take place inside a sterile shrouded chamber inside the machine. The product is then discharged to a non-sterile area for labeling, packaging and distribution. Blow fill seal technology reduces personnel intervention making it a more robust method for the aseptic preparation of sterile pharmaceuticals. BFS is used for the filling of vials for parenteral preparations and infusions, ophthalmic products and inhalation products for example Respules (TM). Generally the plastic containers are made up of polyethylene and polypropylene. Polypropylene is more commonly used to form containers which are further sterilized by autoclaving as Polypropylene has greater thermo stability. Blow-fill-seal technology has emerged as a preferred method for aseptic packaging of pharmaceutical and healthcare products due to unrivalled flexibility in container design, overall product quality, product output and low operational costs. The Weiler design is such a design and incorporates the multi-step process of blow moulding, aseptic filling and hermetic sealing of liquid products in one sequential operation on a compact, automated machine frame with fill volumes ranging from 0.1 millilitre (ml) to 1,000ml. A variety of polymers may be used in the process, low and high-density polyethylene and polypropylene being the most popular. The innate ability to form the container/closure during the actual aseptic packaging process allows for custom design of the container to meet the specific needs of the application. This flexibility not only improves container ease of use, but provides a means of interfacing with many of today’s emerging drug delivery technologies, most notably in the field of respiratory therapy. Recent advancements in machine design allow for insertion of pre-moulded, pre-sterilized components to be moulded into the container creating additional design options to create multi-use and inject able product containers. Furthermore, the blow-fill-seal process flow is normally impacted by only two raw materials, product and polymer, that are each processed inline, thereby making the process menable to large uninterrupted batch sizes, some in excess of 500,000 units, and fill durations of up to 120 hours. The net effect is routinely an increase in production efficiency and a subsequent decrease in operational costs for the user. Blow-fill-seal systems represent a niche market within the larger form-fill-seal marketplace for pharmaceutical packaging equipment. The blow-fill seal process is a robust, advanced aseptic processing technology, recognized by worldwide regulatory authorities for its inherent operational advantages over conventional aseptic production. Blow-fill-seal systems offer a unique combination of flexibility in packaging design, low operating cost and a high degree of sterility assurance. The machines require a minimum number of operating personnel and have a relatively small space requirement. Blow - Fill - Seal Process Container Moulding Thermoplastic is continuously extruded in a tubular shape When the tube reaches the correct length, the mould closes and the parison is cut. The bottom of the parison is pinched closed and the top is held in place with a set of holding jaws. The mould is then transferred to a position under the filling station. Container Filling The nozzle assembly lowers into the parison until the nozzles form a seal with the neck of the mould. Container formation is completed by applying a vacuum on the mould-side of the container and blowing sterile filtered air into the interior of the container. The patented electronic fill system delivers a precise dosage of product into the container. The nozzles then retract into their original position. Container Sealing Following completion of the filling process, the top of the container remains semi-molten. Separate seal moulds close to form the top and hermetically seal the container (see Figure 3d). The moulds open and the container is then conveyed out of the machine. Process Performance Increasing regulatory scrutiny in the area of product quality, most notably product sterility assurance, has challenged the pharmaceutical and healthcare industries to consider alternatives to traditional methods of aseptic packaging. Blow-fill-seal has been recognised by the US Pharmacopeia (USP XXIV) and the Parenteral Drug Association (PDA) (Technical Report 26) as an ‘Advanced Aseptic Process’, which may be defined as a technology that can dramatically reduce the potential of contamination from human presence during aseptic processing operations due to its design and functionality. The process reduces the amount of the amount of product-contacting components, there is limited operator intervention and the critical fill-zone is physically isolated under a continuous flow of filtered air. Since blow-fill-seal is a completely automated technology that allows for remote operation it is an ideal system for examining the relationship between the level of airborne micro-organisms in the environment and the product contamination rate. A series of published studies have been conducted to investigate and quantify this relationship and potentially provide a means for predicting sterility assurance levels.1–3 This experimental work was performed by producing controlled challenges of micro-organisms dispersed in air at concentrations extending over a 1,000-fold range in a containment room housing a blow-fill- seal machine producing containers filled with a medium that supports the growth of the challenge organisms. Results of the studies demonstrated a direct relationship between the fraction of product contaminated and the level of airborne micro-organisms. The linearity of the curve provided a reasonable basis for extrapolation. The resulting predictions imply that a sterility assurance level similar to that targeted for terminally sterilized product is achievable with a properly controlled blow-fill-seal process. These challenge studies also provide a means to rationalize machine design and conditions of operation. Product Application Blow-fill-seal technology has gained much market focus in recent years due to the increased focus on biologics, proteins and other complex solutions. These important products often cannot withstand exposure to high temperatures for extended periods of time without degradation of their active components. Conventional terminal sterilization, therefore, is not an acceptable method to produce a ‘sterile’ product. Bulk sterilization, sterilization by gamma irradiation or filter sterilization followed by direct packaging utilizing the blow-fill-seal process are often used successfully for these types of products. References: Recent Technical Advancements in Blow-Fill-Seal Technology, a report by Charles H Reed Sales Manager, Weiler Engineering, Inc. www.rommelag.com/en
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