The Importance of Equivalence in the Execution and Maintenance of Validation Activities

The author explains the idea of equivalence and describes how it can facilitate equipment validation.
Dec 02, 2010
Volume 34, Issue 12

It is common in the global healthcare industry to have multiple pieces of identical equipment available for the purposes of added capacity and redundancy. These circumstances provide opportunities to streamline qualification and validation activities. When several pieces of equipment are identical in all respects, the qualification effort should seek to demonstrate their basic interchangeability for all uses to reduce the needless repetition of activities. The qualification protocols should identify essential performance criteria for the equipment that each unit must meet to demonstrate its equivalence. The criteria used for this evaluation should be formal, quantitative, reasonably tight, and realistic (the performance of a single piece of equipment will vary over time).* Once equivalence has been demonstrated during the qualification effort, subsequent performance-qualification efforts should be divided between the pieces of equipment to reduce the number of studies that would otherwise be required.

The principles of equivalence can be adapted to several other instances in processing and analysis (e.g., containers, materials, formulations, analytical instruments, and personnel) where basic similarities in performance can be exploited to simplify the overall effort. The principle of equivalence is relevant to even singular instances. The fundamental precept of the US Food and Drug Administration's draft process-validation guidance requires that firms demonstrate the consistency of the process at various scales from development, through scale-up, and continuing into commercial manufacturing (1). At the core of that guidance is an expectation for process equivalence during the course of the initial effort and recommendations for controls that will ensure consistent production over the product's life cycle. The guidance implies the expectation for equivalent performance over scale and time; however it is unfortunately not explicit.

Other citations in the regulatory arena refer to equivalence in the execution of validation. These citations also are somewhat more implicit. In a 1994 Warning Letter, FDA indicated the basic requirements for equivalence:

It is FDA's position, however, that while it is possible to rely on validation data from one chamber to represent that of another, it is only possible to do so for chambers at the same location which are identical in all respects. That means the chambers are of identical construction and installation (i.e., identical plumbing, characteristics, steam supplies, operating environments, etc.) and the product(s) to be sterilized are equivalent in all respects (2).

This letter serves as perhaps the clearest statement with respect to equivalence ever made by FDA. As the letter applies to a sterilization process, one of the more crucial processes requiring validation, industry has every reason to believe that the agency would take a similar view with respect to less crucial process equipment.

FDA's guidance document on revisions to new drug applications (NDAs) and abbreviated new drug applications (ANDAs) come close to touching on the subject of equivalence as it relates to equipment, but focus on the performance of the drug (3). This document and the individual scale-up and postapproval changes guidance documents clearly imply that when individual machines are identical, the implications for process equivalence are clearer and more certain (4).

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