Active manufacturing site

Full details of this work were pubHshed (6) and the processes, or variants of them, were introduced in a number of other countries. In the United States, the pharmaceutical industry continued to provide manufacturing sites, treating plasma fractionation as a normal commercial activity. In many other countries processing was undertaken by the Red Cross or blood transfusion services that emerged following Wodd War II. In these organisations plasma fractionation was part of a larger operation to provide whole blood, blood components, and speciaUst medical services on a national basis. These different approaches resulted in the development of two distinct sectors in the plasma fractionation industry ie, a commercial or for-profit sector based on paid donors and a noncommercial or not-for-profit sector based on unpaid donors. 

This relatively new trend in PCM manufacturing business amounts to creating a polymeric matrix out of the liquid or gaseous phase directly on the filler surface which has previously undergone special conditioning aimed at generating active polymerization sites on it. 

The Competent Authorities are obliged to appoint Inspectors for checking that all activities associated with clinical trials are conducted in compliance with the regulations. The inspectors can inspect any sites concerned with the clinical trial, particularly the trial site (GCP), the manufacturing site of the investigational medicinal product (GMP), any laboratory used for analyses in the clinical trial (GLP), and/or the sponsor s premises. 

The manufacturing process is sometimes discussed in terms of the characteristics of the active ingredient, e.g., the need for nonaqueous granulation processes, the need for controlled humidity in the manufacturing environment. The number of different manufacturing sites requested is mentioned in the assessment reports. Special manufacturing processes such as extrusion/ spheronization are mentioned in the EPARs. 

The Amb a 1 concentration of the final purified intermediate bulk is determined by an absorbance method chosen for its precision, accuracy, and simplicity. Because Amb a 1 bulk intermediate will now be conjugated to 1018 ISS (and the number of linked 1018 ISS affects the activity of the resulting AIC), it is essential to quantitate the Amb a 1 concentration accurately and precisely. A significant over- or underestimation of protein concentration will result in an over- or underestimation of the heterobifunctional linker required to activate the protein for coupling to 1018 ISS. The absorbance method, more dependent on well-calibrated instrumentation than lab technique, was chosen because it is an easy procedure to transfer to the production site. Dilution skills are the only requirement for robust performance of a well-developed and validated absorbance method. Hence a contract manufacturing site could readily quantitate Amb a 1 without the... 

Manufacturing sites within Australia must comply with the Australian Code of GMP for Medicinal Products - August 2002, which is based entirely on the international standard Guide to Good Manufacturing Practices for Medicinal Products, Version PHl/97 (Rev.3) 15 January 2002, published by the Pharmaceutical Inspection Cooperation Scheme (PIC/S). The ICH GMP Guide for Active Pharmaceutical Ingredients has also been adopted. 

Media fill failures are investigated in accordance with manufacturing site SOPs. The investigation may include, but is not limited to, a review of the aseptic fill data, review of the environmental monitoring data, review of the component sterilization results, review of all intervention activities, and identification of the contaminants found. Also, additional media fills may be performed to demonstrate that the area and processes are under aseptic control. If the system cannot be shown to be under control, product produced subsequent to the media fill failure on that fill line will be placed under management review for final disposition. 

Although it is the responsibility of an excipient user to qualify their excipient suppliers, that burden is shared with the distributor as well. A pharmaceutical distributor must provide the user with the assurance that the excipients supplied are unadulterated, have not been tampered with, and are free from contamination. To ensure this, a distributor must have warehouse and internal controls in place, comply with current regulatory standards, and should be an active NACD member. Trace-ability of ingredients is another critical need that must be met by pharmaceutical distributors. This can be achieved by providing the manufacturer s original packaging, documentation, and manufacturing site address, confirmed by the manufacturer. 

To plan and describe the validation activities for the deployment of the very useful system (VUS) at a particular manufacturing site. 

One approach to describe the kinetics of such systems involves the use of various resistances to reaction. If we consider an irreversible gas-phase reaction A — B that occurs in the presence of a solid catalyst pellet, we can postulate seven different steps required to accomplish the chemical transformation. First, we have to move the reactant A from the bulk gas to the surface of the catalyst particle. Solid catalyst particles are often manufactured out of aluminas or other similar materials that have large internal surface areas where the active metal sites (gold, platinum, palladium, etc.) are located. The porosity of the catalyst typically means that the interior of a pellet contains much more surface area for reaction than what is found only on the exterior of the pellet itself. Hence, the gaseous reactant A must diffuse from the surface through the pores of the catalyst pellet. At some point, the gaseous reactant reaches an active site, where it must be adsorbed onto the surface. The chemical transformation of reactant into product occurs on this active site. The product B must desorb from the active site back to the gas phase. The product B must diffuse from inside the catalyst pore back to the surface. Finally, the product molecule must be moved from the surface to the bulk gas fluid. 

Evidence of compliance with an acceptable standcird of GMP should be supplied for each finished product manufacturing site and packaging site specified in an application, except for related products used externally. This requirement includes manufacturers of intermediate products and sterilisers of the finished product. For bulk active pharmaceutical ingredients, evidence should be supplied to show that the material is manufactured consistently and produced with acceptable quality-... 

The activities of the MCA are by statute required to be self-funding, and the fees structure is based upon that remit. The broad principle is to levy fees in proportion to the duration of professional and administrative work involved in any peir-ticular case, be it for assessment of a new application, routine inspection of a manufacturing site, or in respect of ongoing post-marketing surveillance. 

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