The Importance of Equivalence in the Execution and Maintenance of Validation Activities - Pharmaceutical Technology

Latest Issue
PharmTech

Latest Issue
PharmTech Europe

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.


Pharmaceutical Technology
Volume 34, Issue 12, pp. 43-46

The keys to equivalence

Central to the use of equivalence is the establishment of criteria for the evaluation of the equipment's operational performance. This evaluation demonstrates that individual units perform identically. Criteria must be chosen with some restraint; adding too many criteria or nonessential criteria is unlikely to add meaningful value and more likely to result in the conclusion that the equipment is not equivalent. Common sense indicates that the criteria should focus on the crucial aspects of the equipment's performance. For sterilization processes, that most important criterion would customarily be F 0.* Other criteria in this determination for a sterilization process would add no meaningful value because these processes are intended to achieve lethal conditions. Criteria for other processes could be defined by their key performance measures (e.g., content uniformity, potency, fill weight, and residue level). Another possibility is to use a defined and calibrated test set as a standard for assessment. Test sets are ideally suited for attribute, foreign-particle, and label-inspection equipment and systems.

Regardless of what criteria are chosen, it is appropriate to establish in advance an acceptable range for equipment performance. In setting this range, one should consider the following factors:

  • The inherent analytical variability or measurement sensitivity used to assess the results
  • The normal variation in the underlying process
  • The limitations of sampling.

These factors should be first evaluated on a single piece of equipment in replicate studies in which these and other factors are assessed for their influence on the results. A single piece of equipment tested in replicate studies during a brief interval must be considered equivalent to itself. The actual variations between multiple items should be somewhat, but not dramatically, larger. In the absence of an independent assessment, the author suggests a range of not more than 10% of the target value, which itself is an average of multiple preliminary runs.

Should the firm set overly restrictive criteria or the equipment prove not to be equivalent, nothing is lost. The accumulated data must be augmented with whatever added studies are necessary to complete the overall exercise without relying on the simplifying effect that equivalence can afford.

Time equivalence

An aspect of equivalence that has largely been ignored is that of time. It is essential that any process provide consistent results over time, whether the process is performed with a set of equivalent equipment or in a single piece of process equipment. This principle might seem obvious, but FDA codified that expectation in the draft revision of the Guideline on General Principles of Process Validation (1). The expectation that a firm can establish equivalence across multiple items at a single point in time is wholly appropriate for the same firm using a comparable approach to demonstrate the equivalence of the same piece of equipment over several points in time. This is a core expectation of the revised guidance and should raise awareness of equivalence as a regulatory expectation when FDA finalizes that document.


ADVERTISEMENT

blog comments powered by Disqus
LCGC E-mail Newsletters

Subscribe: Click to learn more about the newsletter
| Weekly
| Monthly
|Monthly
| Weekly

Survey
FDASIA was signed into law two years ago. Where has the most progress been made in implementation?
Reducing drug shortages
Breakthrough designations
Protecting the supply chain
Expedited reviews of drug submissions
More stakeholder involvement
Reducing drug shortages
70%
Breakthrough designations
4%
Protecting the supply chain
17%
Expedited reviews of drug submissions
2%
More stakeholder involvement
7%
View Results
Eric Langerr Outsourcing Outlook Eric LangerTargeting Different Off-Shore Destinations
Cynthia Challener, PhD Ingredients Insider Cynthia ChallenerAsymmetric Synthesis Continues to Advance
Jill Wechsler Regulatory Watch Jill Wechsler Data Integrity Key to GMP Compliance
Sean Milmo European Regulatory WatchSean MilmoExtending the Scope of Pharmacovigilance Comes at a Price
New FDA Team to Spur Modern Drug Manufacturing
From Generics to Supergenerics
CMOs and the Track-and-Trace Race: Are You Engaged Yet?
Ebola Outbreak Raises Ethical Issues
Better Comms Means a Fitter Future for Pharma, Part 2: Realizing the Benefits of Unified Communications
Source: Pharmaceutical Technology,
Click here