Why is the CEHT important for the control of a cleaning process?

  • Essentially the reason is that nothing stays clean forever.
  • It should be realized that recontamination of the equipment may be an event-related phenomenon; however, as a practical matter one sets an expiration period of a fixed time assuming certain storage conditions.
  • In dealing with possible ways the equipment could be recontaminated, one should consider both endogenous sources (such as growth of microorganisms already within the equipment) as well as exogenous sources (such as entry of external contaminants into the equipment).

Three important issues for the CEHT include:

  • The characteristics of the cleaned equipment,
  • The nature of possible recontaminants, and
  • The storage conditions of the equipment.

1.A major issue related to the Characteristics of the Cleaned Equipment is whether the equipment is stored wet or in a manner such, that microbial proliferation is a possibility.

  • If the equipment is stored wet for a sufficient time, there is a reasonable probability microbes will readily grow to an unacceptable level, and thereby render the equipment unsuitable for manufacturing use.
  • Another issue related to the characteristics of the equipment involves possible routes of entry for external contaminants. For small pieces of equipment (ex. scoops), this involves exposure of the item itself. For larger pieces of equipment (ex. tanks), this involves any opening in the equipment.

2. For Possible Re-contaminants, the two major sources are microbes that may already be in the cleaned equipment and external “dust” which is in the storage atmosphere.

  • Residues such as product residue and cleaning agent residue, which are in the equipment at trace levels, are generally not expected to change over time.
  • The only exception to this may involve an active, which is present in the cleaned equipment at an acceptable level at the end of the cleaning process, but which over times degrades to form a specie that (because of unusual toxicity/ safety concerns) would make the equipment unacceptable for use.

3. Storage conditions are probably a rare occurrence.

  • It includes any steps taken to protect the equipment, such as wrapping it in plastic film or nonwoven, or covering openings in the equipment with a bonnet of a plastic film or nonwoven.
  • It also includes the room the equipment is stored in; conditions of the room include temperature, humidity, air quality, and external access.

How does one establish a maximum CEHT?

  • It would be helpful to contact the manufacturing group to find out, under normal conditions, what the longest time interval might be that the equipment would be unused after cleaning.
  • The objective should be adequately protecting the equipment during that time period and then to provide adequate justification that the equipment remains safe to use throughout that time period.
  • One should analyze the storage situation (considering factors such as characteristics of the cleaned equipment, the nature of possible recontaminants, and the storage conditions), and see what can be done proactively to protect the equipment from recontamination.
  • There are two main options for justifying the CEHT.

a. One is professional judgment based on an analysis of the storage situation.

  1. For example, if the equipment is adequately cleaned and then stored dried, if all external ports or openings to the storage room atmosphere are closed or covered with a plastic film or nonwoven, and if the equipment is stored in a controlled room, one might document CEHT of several months. It should be noted that this approach has its limits.

b. A second method of justifying the CEHT is to develop data.

  1. This would involve holding the cleaned equipment for the maximum CEHT, and then sampling surfaces and analyzing those samples for possible recontaminating residues. To do this, one must decide what the possible recontaminating species might be.
  2. As a general rule, these are limited to bioburden and “dust”.
  3. Testing procedures for bioburden are relatively straightforward using accepted microbiological techniques. For “dust”, one might consider either a particle counter, TOC, or perhaps even an enhanced visual inspection (a white or black cloth wipe).
  • For sampling sites, one must consider which sites are most likely to be recontaminated during storage.
  • For example, for agitator blades, the bottom of the agitator blade (a worst-case cleaning location) may be the appropriate sampling point as part of the cleaning validation protocol; however, for determination of the CEHT, the top of the agitator blade may be the appropriate sampling point for “dust”.
  • Reasonable acceptance limits must also be set.   
  • This testing to determine a CEHT can be handled as part of the cleaning validation protocol, or as a separate test procedure.
  • If it is part of the cleaning validation protocol (either as part of the “normal” validation activities or a separate protocol), one should do three PQ runs.
  • However, particularly if one has a reasonable justification for supporting a CEHT without data, and one wants only to confirm that judgment, then one might only perform one evaluation to support that professional judgment.
  • If the potential recontaminating species is just “dust”, this may be readily removed by water pre-rinse. If the purpose of the pre-rinse is solely to reduce “dust” to an acceptable level, then that step essentially becomes part of the cleaning process and must be validated.
  • If a CEHT is specified for a cleaning process, and if that CEHT is critical for control, then it is important to record the time of the end of the cleaning procedure and the time of the beginning of manufacture.
  • The former should be defined based on one’s cleaning process & the latter is defined based on one’s manufacturing process.

What to do if the CEHT looks like it might be exceeded in an actual manufacturing situation ?

  • Option 1 is to allow the CEHT to be exceeded, and then quarantine the equipment. The equipment is then tested in much the same manner as any initial testing to establish the CEHT. If it passes, it is released and there is some justification for extending the DEHT. In such a case, the released equipment should be used immediately. If it fails, it is cleaned and tested again. In that case, there is no justification for extending the CEHT.
  • Option 2 is to clean the equipment (using the standard cleaning procedure) before the CEHT is exceeded. In this case one is merely cleaning (with a validated cleaning procedure), equipment that is already clean. In essence, one is “re-setting” the CEHT.

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