Risk-Based Approach to Method Transfer

Jeffrey Staecker, PhD (jstaecker@biohpia.com)      BioPhia Consulting, Inc., November 1, 2018

An article summarizing the CMC Forum “Methods on the Move: Addressing Method Transfer Challenges for the Biopharmaceutical Industry” was recently published in BioProcess International and can be found at https://bioprocessintl.com/business/cmc-forums/methods-on-the-move-addressing-method-transfer-challenges-for-the-biopharmaceutical-industry/.   The article summarizes various ideas and approaches to test method transfer.

I was fortunate to both co-chair and present at this Forum where I focused on using a “Risk-Based Approach to Method Transfer”.  My presentation can be found on the BioPhia website (BioPhia website link inserted here).  Some key principles from my presentation include:

• Method transfers can introduce changes in bias and/or precision.
• The commonly employed risk tool of FMEA (Fault Mode Effect Analysis) can be utilized in evaluating the risk of method transfer.
• The risks associated with method transfers are impacted by how “close to the edge” the process as measured by current testing is running. That is, a centered process with results far away from specifications is less at risk than a process being measured as running near a specification extreme.
• Many companies use Cpk to monitor processes which can be leveraged to predict probability of errant results from introduction of bias and/or imprecision.
• A statistical approach can be devised to ensure that only an acceptable level of bias/imprecision is introduced during method transfer.
• After transfer, appropriate SPC (statistical process control) monitoring can ensure that method at receiving site continues to operate within pre-defined limits.

An alternative to method transfer is to use the identical statistical approach for all method transfers regardless of process/method performance.  The danger of this approach is to introduce a small amount of bias or imprecisions that passes method transfer criteria but results in inappropriately passing or failing material.  I personally experienced this when a method was transferred for a process running at the high end of the specification range.  The method transfer introduced a small bias (less than 2%) that resulted in inappropriately failing drug product.