Pharmaceutical manufacturing unit process

Plasma fractionation is unusual in pharmaceutical manufacturing because it involves the processing of proteins and the preparation of multiple products from a single feedstock. A wide range of unit operations are utilized to accompHsh these tasks. They are Hsted in Table 3 some are common to a number of products and all must be closely integrated. The overall manufacturing operation can be represented as a set of individual product streams, each based on the processing of an intermediate product derived from a mainstream fractionation process (Fig. 1). 

Process validation is the procedure that allows one to establish the critical operating parameters of a manufacturing process. Hence, the constraints imposed by the FDA as part of process control and validation of an SMB process. The total industrial SMB system, as described, is a continuous closed-loop chromatographic process, from the chromatographic to recycling unit and, with the use of numerical simulation software allows the pharmaceutical manufacturer rapidly to design and develop worst-case studies. 

Once the cocaine has been legally produced from the coca leaf, it is exported to various countries for medicinal use, basically as a topical local anesthetic (applied to the surface, not injected, only treating a particular area). In the United States the crystalline powder is imported to pharmaceutical companies who process and package the cocaine for medical use. Merck Pharmaceutical Company and Mallinckrodt Chemical Works distribute cocaine in crystalline form (Hydrochloride Salt) in dark colored glass bottles to pharmacies and hospitals throughout the United States. Cocaine, in the alkaloid form (base drug containing no additives such as hydrochloride in the crystalline form) is rarely used for medicinal purposes. Cocaine hydrochloride crystals or flakes come in Vs, A and 1 ounce bottles from the manufacturer and has a wholesale price of approximately 20 to 25 per ounce (100% pure). 

Another special feature of biologies is that facilities are usually designed for a specific product in mind, with little room for flexibility to match the process developed for alternative products in the pipeline. This is the opposite case from that found in the manufacture of small drug pharmaceuticals where unit operations, lay out, and equipment can be used for multiple products. This makes the decision even more challenging to build a manufacturing facility for biologies. 

Raman spectroscopy has developed rapidly in the past few years and there are very interesting prospects for future process applications. By building on the fact that Raman spectroscopy is fast, selective, informative and can be remotely coupled to process vessels, it is very likely that we will see Raman spectrometers much more widely used in pharmaceutical manufacturing. Several challenges are still hampering future success in some areas as discussed above. In particular, more efforts on interfacing the Raman spectrometer to different secondary process unit operations are needed before we will see the robust use of the technique. 

According to 21CFR 211.110(a), pharmaceutical manufacturers are legally required to demonstrate the adequacy of mixing to ensure uniformity of in-process powder blends and finished dosage units. The uniformity of dose unit is usually a product specification for oral solid dosage forms and is tested to ensure it meets the compendial acceptance criteria. 

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