Residue limits cleaning equipment process

It is important in any discussion of residue limits to understand that limits for a cleaning process may be expressed in different ways. This includes the limit of the residue in the subsequently manufactured product, the limit of the residue on the cleaned equipment surfaces, and the limit of the residue in the analyzed sample. These are all related, but they are usually different numbers. For an active ingredient in the cleaning of a finished drug product, the limit in the next product is usually calculated based on application of a safety factor (usually 0.001 or lower) to the minimum daily dose of that active in the maximum daily dose of the subsequently manufactured product. The active or level of active in the subsequently manufactured product is irrelevant unless there is information about unusual deleterious interactions. This calculation is also independent of manufacturing issues such as batch size and equipment surfaces areas, and can be calculated solely on information about the dosing of the two products as follows ... 

Organic solvents Remove adhesive and solder paste residues have a wide-process window can clean at room temperature do not oxidize or corrode metals Solvents and solvent vapors may he flammable high cost may be slow drying limits on VOCs and ozone-depleting solvents (ODSs) require explosion-proof equipment... 

Metal cleaning wastes result from cleaning compounds, rinse waters, or any other waterborne residues derived from cleaning any metal process equipment, including, but not limited to, boiler tube cleaning, boiler fireside cleaning, and air preheater cleaning. 

After the limits are calculated for all products that are to be processed and all equipment used, the limits are compared. The smallest limit calculated for a product using all of the calculations becomes the acceptance limit for the cleaning verification for that product. If product B, the lot to be manufactured next, is unknown at the time of manufacture of Product A, the worse case should be assumed in the calculation. For example, if the smallest lot that has ever been manufactured in the facility is 5000 dosage units, or alternatively 1 kg, those values should be used in the equation to generate a maximum allowable carryover of product A. To reiterate some of the initial points, the rationale for which equation is utilized should be documented, and the limits that are established should be practical, achievable, and verifiable based on the most deleterious residue. 

The hazardous nature of azide manufacture necessitates simple facilities, which are easy to keep clean and tree from grit and residues, provide protection to the operator through the use of barriers and remote control, yield only limited-size batches, and permit unimpeded access to reaction vessels. In general, because of the similarity between the processes utilized by different manufacturers, there is little difference between the facilities and equipment used at the various locations. 

Many excipients are produced using multipurpose equipment. Fermentation tanks, reactors, dryers, grinders, centrifuges and other pieces of equipment are readily used or adapted for a variety of products. With few exceptions such multiple usage is satisfactory provided the equipment can be adequately cleaned according to written procedures. Equipment that contains tarry or gummy residues that cannot be removed easily should be dedicated for use only with limited portions of a process. 

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