Compendial cycles

Table 3 lists the sterilization cycle specifications currently recognized by the three major pharmacopoeias ( compendial cycles ). A body of knowledge exists to support the view that products that are properly exposed to any one of these compendial cycles will be free from all viable microorganisms. The origins of the compendial cycles are lost in history except to say that they were probably based on available technology (121 C is achieved by saturated steam held at a pressure of 15 lbs per inch, which is equivalent to 1 bar or one atmosphere). 

The classic pharmacopoeial approach to steam sterilization has been the compendial cycle. Compendial cycles are described in terms of process specifications, for instance IS min at 121 C (USP/EP/BP) and 134 C for 3 min (BP compendial cycle for dressings). The specified temperatures and times are for... 

The move away from compendial cycles to overkill and SAL cycles w-ent hand in hand with an increasing interest in the concept of equivalent lethalities being obtainable from different temperature/time combinations—the Fq concept. 

Sterilization lemperature/time combinations for dry heal are directly analogous to those for sterilization by saturated steam. The options are compendial cycles, overkill, or a validated lO sieriliiy assurance level (SAL). The USP is curiously ambiguous about SALs for dry heat processes although accepting 10 as a standard it stresses that the approach is often to achieve SALs of 10. This is because so many dry heat sterilization treatments arc also intended lo inactivate bacterial endotoxins (see below). 

Compendia] cycles are only applicable to ovens because there are too many variables in tunnels (bell speeds, stoppages, preceding materials, etc.) lo be encompassed in simple generalized process specifications. Compendial cycles in the British Pharmacopoeia require 160 C for 2 hs, 170 C for I h, or I80 C for 30 min. The USP refers rather obliquely to temperatures in excess of 2S0 C. 

There are no compendial cycles recommended for endotoxin reduction. The standard quoted in the USP and being enforced by the FDA is that a claim to depyrogenation should be supported by evidence that endotoxin present on the product prior to tFeaimenl has been inactivated to no mote than 1/1000 of the... 

As mentioned in the historical synopsis (Section 5.1), Levine121 perfected the compendial partition column procedure in which aspirin in chloroform is first trapped in an immobile phase of sodium bicarbonate on a column of siliceous earth (celite) then eluted with a solution of acetic acid in chloroform and measured spectrophotometrically. This has been also used for separation in combination products.80 For the determination of salicylic acid in presence of aspirin by this method, see Section 5.61. Ion exchange columns filled with strongly or weakly basic anion exchange resin in the acetate or chloride cycle have also been used for separation of aspirin in combination products. 122 123/l2lf This has also been adapted for a student experiment.125 A Sepha-dex-G25 column has been used for the separation of aspirin from salicylic acid.126... 

Analytical method validation should track closely to the stages of development of the method itself However, it is not realistic to expect complete and thorough validation of the method until its development cycle is complete. An exception to this would be a situation where an accepted compendial method is applied to clinical material (such as a dissolution test or release testing of a compendial component). In these cases, companies must be prepared to demonstrate that consistent acceptable results can be obtained when using the compendial method in the company s laboratory (also known as methods verification). The obvious... 

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