Pharmaceutical products routine testing

Ryle, P.R., Justification for routine screening of pharmaceutical products in immune function tests a review of the recommendations of Putman et al. (2003), Fundam. Clin. Pharmacol., 19, 317, 2005. 

The inclusion of the a routine microbial limit test in a marketed product stability protocol depends on the pharmaceutical dosage form. Typically, the test would be used only for nonsterile products, especially oral liquids, nasal sprays, and topical liquids, lotions, and creams that have sufficient water activity to support the growth of microorganisms. In contrast, tablets, powder- and liquid-filled capsules, topical ointments, vaginal and rectal suppositories, nonaqueous liquids and inhalation aerosols with a water activity too low to allow for the product to support the growth of microorganisms would not be routinely tested. 

Identifying pharmaceuticals, whether APIs or excipients used to manufacture products, and the end products themselves is among the routine tests needed to control pharmaceutical manufacturing processes. Pharmacopoeias have compiled a wide range of analytical methods for the identification of pharmaceutical APIs and usually several tests for a product are recommended. The process can be labor-intensive and time-consuming with these conventional methods. This has raised the need for alternative, faster methods also ensuring reliable identification. Of the seven spectroscopic techniques reviewed in this book, IR and Raman spectroscopy are suitable for the unequivocal identification of pharmaceuticals as their spectra are compound-specific no two compounds other than pairs of enantiomers or oligomers possess the same IR... 

Some of these government agencies and private companies, because of the nature of their business, will utilize the services of an analytical chemistry laboratory as part of their overall need to assure the required quality operation. For example, municipal governments will employ the use of an analytical chemistry laboratory to test their water supply on a regular basis to make sure it is free of toxic chemicals. The pharmaceutical company will house an analytical chemistry laboratory within its facility to routinely test the products it produces and the raw materials that go into these products to make certain that they meet the required specifications. A fertilizer plant will utilize an analytical chemistry laboratory to confirm that the composition of its product meets the specifications indicated on the individual bags of fertilizer. Companies that produce a food product, such as snack chips, cheese, cereal, or meat products, will have an analytical chemistry laboratory as part of their operation because they want to have the assurance that the... 

In general the quality control procedures for products obtained through biotechnology are very similar to those routinely used with traditional pharmaceutical products in areas such as raw material testing, documentation of process control, and aseptic processing. The fundamental difference is in the type of methods used, so as to determine the product s identity, uniformity, and purity. In the quality control of products obtained through recombinant DNA technology, it is necessary to employ validated tests for the final and intermediary products to ensure the elimination of undesirable impurities. 

The preparation of any pharmaceutical product requires controls over the production operations to assure the end result is a product that meets the required quality attributes. The methods utilized for this control are supported by formalized validation studies in which proof of consistency is demonstrated by appropriately designed experiments. The definition of appropriate operating parameters is the primary objective of the development activities and is further confirmed during scale-up to commercial operations. The validation supports that the routine controls applied to the process are appropriate to assure product quality [36], This is typically accomplished in formalized validation activities in which expanded sampling/testing of the product materials is performed to substantiate their uniformity and suitability for use [30],... 

Choosing between a robot plus peripherals and a workstation is a difficult task. From the beginning, automation held the promise of freeing analysts from cumbersome, time-consuming, repetitive tasks. This is especially true with the quality control (QC) laboratory, which must routinely test products such as pharmaceuticals or foods prior to release, often with a well-defined analytical procedure dictated by regulatory requirements. In these laboratories, workstations are typically the best solution as they are often more hardwired and are better in QC laboratories, where the analytical steps are well-understood and this equipment does save laboratories time and money. The best solution for implementing the complex treatments required by some solid samples is the sequential use of two workstations when this is impossible, a robotic station is the next-best choice in most instances. 

Specifications for the finished product Two specifications at release and end of shelf-life List general characteristics, specific standards tests and limits for results for the finished product must be provided Analytical test procedures described (physicochemical properties, identity of API) Quantitative determination of active, deviations, purity tests, pharmaceutical tests, colouring antimicrobial or chemical preservatives, results of validation studies, comments on the choice of routine tests and standards provided Copy of pharmacopoeia monograph and verification data Results of batch analysis (inc. date of manufacture, place of manufacture, batch size and use of batch tested) ... 

The multisource pharmaceutical product used in the bioequivalence studies for registration purposes should be identical to the projected commercial pharmaceutical product. Therefore, not only the composition and quality characteristics (including stability), but also the manufacturing methods (including equipment and procedures) should be the same as those to be used in the future routine production runs. Test products must be manufactured under GMP regulations. Batch-control results of the multisource product, and the lot numbers and expiry dates of both multisource and comparator products should be stated. 

Clinical analysis is one of the most important fields of analytical chemistry because of the importance to the health of the human body of the materials being analyzed. For example, because pharmaceutical products are meant to improve the health of the body, the analysis of pharmaceutical products in vitro as well as in vivo can be considered a branch of clinical analysis. Clinical analysis has two main branches research clinical analysis and routine clinical analysis. As always, it is very important to obtain the optimum conditions for the methods applied in clinical analysis. First, the methods are applied by the researcher for in vitro tests. Then, it is very important to obtain biocompatible materials for in vivo determinations. For clinical analysis, methods with high sensitivity, a low detection limit, and high selectivity are necessary. The rapidity of assurance is one of the most important characteristics of the method that is applied. 

Other physical tests may allow routine in-place evaluation of the microbiological integrity of vials. Headspace gas analysis is one such method. Many sterile products are held under nitrogen or some other gas in vials. The gas content of the headspace should, with a perfect seal, remain constant over time rather than becoming equilibrated with the atmosphere under a less than perfect seal. This type of analysis is amenable to chemical methodology and is likely done routinely in pharmaceutical production for reasons other than evaluation of microbiological integrity. 

Physical testing encompasses a wide range of techniques, from visual examination to spectroscopy. It is often the physical attributes which the patient or practitioner can evaluate prior to administration. For example, a particle found in a parenteral formulation can foretell the presence of a new chemical degradant found during stability studies. Many of the procedures in this chapter are performed routinely as part of release or stability testing of API or pharmaceutical products. 

The need for the determination of metallic constituents or impurities in pharmaceutical products has, historically, been addressed by ion chromatographic methods or various wet-bench methods (e.g. the USP heavy metals test). As the popularity of atomic spectroscopy has increased, and the equipment has become more affordable, spectroscopy-based techniques have been routinely employed to solve analytical problems in the pharmaceutical industry. Table 1 provides examples of metal determinations in pharmaceutical matrices, using spectroscopic techniques, and the reasons why these analyses are important. Flame atomic absorption spectrometry (FAAS), graphite furnace atomic absorption spectrometry... 

Thus, while a well-maintained instrument is important for any chemical/physical measurement, in NIR, without a concurrent standard for comparison, it is critical that the instrument be continuously calibrated and maintained. Since the major manufacturers of equipment have worked with the pharmaceutical industry, this has been formalized into what is called IQ/OQ/PQ, or Instrument Qualification, Operational Qualification, and Performance Qualification. The first is routinely performed (at first) by the manufacturer in the lab/process location, the second in situ by the user with help from the manufacturer, and the third is product/use dependent. These formal tests apply to all instruments in any industry. 

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