Manufacturing quality control test methods

Analytical methods used to determine purity and potency of an experimental API that is very early in development will need a less rigorous method validation exercise than would be required for a quality control laboratory method at the manufacturing site. An early phase project may have only a limited number of lots to be tested and the testing may be performed in only one laboratory by a limited number of analysts. The ability of the laboratory to control the method and its use is relatively high, particularly if laboratory leadership is clear in its expectations for the performance of the work. 

The quality assurance program for manufacture of butter oil, or anhydrous milkfat (AMF), also focuses on the quality of the raw materials. Naturally, many of the same considerations apply to handling raw cream for AMF manufacmre that apply to butter, except that vacreation is not used. As it is stored under ambient conditions, care against oxidation is essential. Oxidation is perhaps the most important mechanism by which milkfat deteriorates in quality. As the oxidation reaction is autocatalytic (i.e., the products of the reaction act as catalysts to promote further reaction), the normal quality-control tests, peroxide value and free fat acidity, could give misleading results when applied to stored butter. Methods of deaeration have been developed that could reduce potential oxidation (74). 

In the manufacture of sterile products, it is not sufficient that the finished product should meet the requirements of the quality control. The method of manufacture is of particular importance. Low bioburden of starting materials should be assured, and during the manufacture, the manufacturing area, personnel equipment and intermediate products should be controlled by microbiological tests. 

End-product testing (quality control) is toe reliance only on appropriate analytical tests to demonstrate toe quality of a medicinal material. End-product testing alone is considered as testing quality into the product. You only accept those materials that pass specification. This is not adequate to ensure that toe medicine is free from all manufacturing faults, that test methods employed are adequate to establish its purity and that a small proportion of defective materials would be detected. I will give several examples to iUustrate this point. 

The quality control testing of fluorescent colorants by the manufacturers has been based upon attempted simulation of the compounders testing. The colorants are dispersed by either an injection molder, extruder, or a Banbury mixer into HOPE for observation in both mass tone and tint forms. In addition, a common method of display is a side-by-side pressout as performed on a hydraulic press. Carefully trained technicians perform visual observations while those in the fluorescent industry await the development of technology which will allow for adequate computerized color measurement. 

Table 3 Quality control tests required for radiopharmaceuticals manufactured by different methods...

In the eontext of quality assuranee in the production of a product or a structure, independent test laboratories or inspection bodies supervise the manufacturing or construction procedure, perform controls and inspections and examine the manufactured produets using test methods, which are described in standards or guidelines. Table A1.7 of Appendix 1 describes the test procedures and frequencies for third-party control of resin, carbon black batch and geomembranes as part of the in-house QMS of the manufacturers of BAM certified HDPE geomembranes. 

Sulfur can be a catalyst poison in the aromatic chemical manufacturing process. This test method can be used to monitor the amount of sulfur in aromatic hydrocarbons. This test method may also be used as a quality control tool and in setting specifications for sulfur determination in finished products. 

In passing we remark that there are well-known statistical methods of hypothesis testing and parameter estimation used in decisionmaking. Sequential analysis is a method of sampling used to decide whether to accept or reject a lot with defective items, or whether to continue sampling. Also, there are various statistical methods used in quality control of a manufacturing process, to decide on how much the quality should be improved to be acceptable. 

Solvent absorption measurement has been shown to be a sensitive and useful test method in the manufacture of epoxy powder coatings. A test method was defined and the effects of time and temperature of immersion described. It was shown that solvent absorption is a measure of raw material properties (EEW of the epoxy resin, and CTBN elastomer type and concentration), the homogeneity of the extrudate, as well as the state of cure. The information obtained from solvent absorption measurements has proven to be extremely important not only in quality control analysis but also in providing an insight into the structure function relationships in epoxy resin chemistry. 

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