Pharmacopoeial requirements

Deionized water often meets the pharmacopoeial criteria laid down for purified water . Sometimes, however, further purification may be necessary to attain this standard. This often entails a distillation or reverse-osmosis step. Deionized water will, however, not meet the pharmacopoeial requirements for WFI. WFI is best generated by distillation of deionized water. Distillation entails converting water to vapour by heat, followed by passing over a condenser, which results in condensation of pure water. Dissolved minerals and most organics are not volatile at 100°C. 

Specifications are normally written by QC personnel. They detail the exact qualitative and quantitative requirements to which individual raw materials or product must conform. For example, specifications for chemical raw materials will set strict criteria relating to the percentage active ingredients present, permitted levels of named contaminants, etc. Specifications for packing materials will, for example, lay down exact dimensions of product packaging cartons specifications for product labels will detail label dimensions and exact details of label text, etc. Specifications for all raw materials are sent to raw material suppliers and, upon their delivery, QC personnel will ensure that these raw materials meet their specifications before being released to production (the raw materials are held in quarantine prior to their approval). Final product specifications will also be prepared. As most products are manufactured to conform with pharmacopoeial requirements, many of the specifications set for raw materials/finished product are simply transcribed from the appropriate pharmacopoeia. 

Dooms-Goossens A, Dooms M. Contact allergy to petrolatums. (III). Allergenicity prediction and pharmacopoeial requirements. Contact Dermatitis 1983 9(5) 352-9. 

Table 3 contains the current pharmacopoeial requirements. The testing and guarantee of a particular microbial status and absence of pyrogens or endotoxins are not required by the pharmacopoeias in the povidone monographs. 

Permanent records, written or electronic, should exist for each stored product indicating recommended storage conditions, any precautions to be observed and retest dates. Pharmacopoeial requirements and current national regulations concerning labels and containers should be respected at all times. 

Dooms-Goossens A and Dooms M. Contact Allergy to Petrolatums. 3. Allergenicity Prediction and Pharmacopoeial Requirements, Contact Dermatitis 1983a 9 352-359. 

It is a pharmacopoeial requirement that suspensions should be redispersible if they settle on storage. However, the pharmacopoeias do not offer a suitable test that can be used to characterize this aspect of the formulation. In an attempt to remedy this situation, Deicke and Stiverkrtip (1999) have devised a mechanical redispersibility tester, which closely simulates the action of human shaking. The crystal habit may also affect the physical stability of the formulation Tiwary and Panpalia (1999) showed that trimethoprim crystals with the largest aspect ratio showed the best sedimentation volume and redispersibility. 

Removal of endotoxin from manufacturing equipment or materials can be done by appropriate washing and rinsing procedures. Pyrogen-free water can be obtained by several means. The oldest and most effective method is distillation —the heavyweight lipopolysaccharide molecules (MW of around 10 ) are left behind when water is rapidly boiled in a still. Reverse osmosis can remove 99.5 to 99.9% of water s endotoxin load in a single pass. For these reasons, distillation and reverse osmosis are the only two methods of preparing Water for injection allowed in the pharmacopoeias. The pharmacopoeial requirement for Wtuer for injection is that there should be no more than 0.25 EU (endotoxin units)/mL. 

Pharmacopoeias are texts providing specifications, standards, and test methods used in evaluating the purity and quality of both raw materials and finished pharmaceutical products. To claim a product is of pharmacopoea grade requires that the product be tested by a pharmacopoeial test method, or by a methods proven to be equivalent, and that the tested material meets the pharmacopoeial requirements in all its specifications. 

Specifications may be subject to change as the development of the product progresses. Changes should, however, be made in accordance with a written procedure authorized by a responsible person and clearly recorded. Specifications should be based on all available scientific data, current state-of-the-art technology, and the regulatory and pharmacopoeial requirements. 

In addition, other tests specific to the drug substance and formulation may apply, such as sterility, microbial limits, bacterial endotoxin, and pH. These types of tests would also be called for in order to comply with local pharmacopoeial requirements. Tests for subvisible particles beyond what is required in the pharmacopoeia may also be necessary due to immunogenicity concerns [29]. 

A number of physical and chemical techniques to eliminate or to destroy micro-organisms may be employed in order to assure that the microbiological quality of the product complies with pharmacopoeial requirements, immediately after production and throughout its shelf life. Since these techniques are discussed in detail in other chapters, they are mentioned only briefly. 

For industrial production, in addition to product control, process control was introduced. This occurred mainly with the introduction of Good Manufacturing Practices (GMP) regulation but also with pharmacopoeial requirements. 

It has a secondan- odour i-ecalling that of cumin. It contains from 50 to 70 per cent, of eucalyptol and a small quantity of aiomadendral and a sesquiterpene. This oil is much valued as a medicinal oil, and usually conforms admirably to pharmacopoeial requirements. 

It will be noticed that the specific gravity is abnormally low, and does not correspond with pharmacopoeial requirements, while the melting, and congealing-points are also very low. The refractive index is lower than has ever been found for pure aniseed oil, which has a value between 1-5530 and 1-5565, or thereabouts. The slight deztro-rotation indicatea nothing, as some samples of pure star-anise oil are faintly dextro-rotatory. 

Table 2 Summary of pharmacopoeial requirements for the calibration of IR and NIR spectrometers...

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