Finished products parenterals

For parenteral use, the antibiotic is packed in sterile vials as a powder (reconstituted before use) or suspension. For oral use it is prepared in any of the standard presentations, such as film-coated tablets. Searching tests are carried out on an appreciable number of random samples of the finished product to ensure that it satisfies the stringent quahty control requirements for potency, purity, freedom horn pyrogens and sterility. 

Process controls include daily testing of water for injection (USP), conformation of fill doses and yields, checking and approving intermediate production tickets, and checking label identity and count. Finished product control includes all the tests necessary to ensure the potency, purity, and identity of the product. Parenteral products require additional tests, which include those for sterility, pyrogens, clarity, and particulate analysis, and for glass-sealed ampoules, leaker testing. 

Finished-product biopharmaceuticals, along with other pharmaceuticals intended for parenteral administration, must be sterile (the one exception being live bacterial vaccines). The presence of microorganisms in the final product is unacceptable for a number of reasons ... 

In addition to chemical or biological assay and specific requirements for a finished product, such as those for parenteral administration, the condition of the dried cake also needs to be identified. These include the physical appearance of the dried cake and the ease with which the dried material goes back into solution. 

Whereas the compounding and administration of parenteral products and intravenous admixtures continues to be a vital and important component in the care of hospitalized and home health care patients, there is continued interest in easing the preparation, storage, and administration of these products with respect to controlling contamination of the finished product and protecting the health care providers from needlestick injuries. It is estimated that more than... 

All manufactured products are vulnerable to contamination by a myriad of aerosolized contaminants, including microorganisms, pyrogenic dust, ash, pollen, smoke, hydrocarbons, and other chemicals that are omnipresent in the environment (Pig. 1). Because of the potential dangers to the patient resulting from a parenteral product containing even minute quantities of these contaminants, exceptional measures are required to exclude them fromthe finished product. 

For parenteral use, solid sterile substances are distributed in their final packages. A clear solution nearly free of particles or a uniform one is obtained after shaking with the prescribed volume of an appropriate sterile liquid. Freeze-dried substances for parenteral use are also used. After dissolution or dispersion, preparations must comply with assay requirements for injectable preparations or injectable preparations for perfusion. Their preparation requires the same care as parenteral solutions, i.e. sterilization of raw material or finished product sterilization. ... 

To ensure that each of the aforementioned requirements for a parenteral product is properly met, the following chemical and microbiological tests are typically conducted for the finished products. 

The manufacture of parenteral products is focussed at all times on the requirement for sterility of the finished product. Despite the fact that the regulators are clear in their preference for products to be terminally sterilized, the vast majority of parenterals are filtered through sterilizing grade filters and filled aseptically, primarily because stability considerations preclude the use of moist heat sterilization. The statistical limitations of sterility testing a sample... 

This section specifically concerns itself with filters that must be used that do release fibers. It is noted that an additional filter with a maximum pore size of either 0.2 or 0.45 pm must also be used to finish the filtration. This is an absolute requirement with asbestos filters used because of the total concept of safety and effectiveness of the drug. This section simply sets the time limit for instituting good filtration procedures for parenteral products. 

Its major disadvantage is its selectivity it only detects endotoxin-based pyrogens. In practice, however, endotoxin represents the pyrogen that is by far the most likely to be present in pharmaceutical products. The LAL method is used extensively within the industry. It is used not only to detect endotoxin in finished parenteral preparations, but also in WFI and in biological fluids, such as serum or cerebrospinal fluid. 

Although bacterial endotoxins are of microbiological origin, they are not lost with loss of viability. Of the sterilization processes commonly used in the manufacture of sterile parenteral dosage forms (see above), only dry heat is capable of destroying bacterial endotoxins in a reasonable time frame. There is therefore no practical way of removing bacterial endotoxins from finished drug products thus, they must be controlled at source. 

The results of endotoxin tests for in-process solutions, bulk materials, and finished parenteral products should be reported in the same units as those assigned to the product. Two factors determine the sensitivity of a BET. For infusion solutions and device extracts, the gel-clot sensitivity or the lowest point on the standard curve (lambda for kinetic LAL) and the amount of dilution determine test sensitivity.For products that have an endotoxin limit in EU/mg, the choice of lambda and the concentration of the test material determine sensitivity. The formula for product-specific sensitivity (PSS) is a convenient way to calculate the sensitivity of a BET for this type of product, where ... 

Finished parenteral products prepared in the radiopharmacy department must be sterile. Based on a risk analysis one may conclude that the risk of non-sterility is very low for standard radiopharmaceutical kit preparations. The risk of contamination is somewhat higher for the eluate from radionuclide generators, especially when they are used for a long period. The injection bottle on top of a Tc generator (sterile sodium chloride solution for injection) is changed asepti-cally each day however, the inside of the generator system is not sterilised nor disinfected. For that reason it is recommended to control the microbiological quality of the... 

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