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When will the new draft FDA Bioanalytical Method Validation Guidance document be published?

The new draft FDA Bioanalytical Method Validation Guidance document was published for comment in September 2013.  Electronic comments regarding the draft document can be submitted to http://www.regulations.gov through 12-Dec-2013.  Depending on the extent of necessary revisions, the final document may be issued as early as 2014.  

What are pre-qualification / due diligence audits and why are they important?

These two terms are used to describe the same type of audit.  The purpose of this type of audit is to proactively demonstrate that the processes and procedures currently in place at a proposed laboratory partner are sufficient to produce timely precise, accurate and reproducible data that meet GLP and/or other applicable regulatory requirements.  It is most beneficial to perform the audit prior to placing work at the laboratory, since the severity of the risks associated with any potential issues can be evaluated and suitably resolved or an alternative laboratory can be located prior to placing the work.  If not performed in advance, these evaluations may also be conducted during a post study data audit.  Any issues identified at this stage may be more difficult and costly to address, but in any event, it is strongly recommended that any potential bioanalytical issues be identified and addressed well in advance of regulatory submission.

How frequently should pre-qualification / due diligence audits be performed?

If studies have been placed consistently with the same, pre-qualified bioanalytical CRO partner, and no significant site or laboratory management changes have been made, nor any FDA Form 483 has been received, then additional qualification audits should not be necessary.  It is, however, advisable to carefully review all SOP and process updates or changes when made, to ensure continued consistency with standard industry practices and compliance with applicable global regulatory and guidance recommendations.  If plans are to place work at a new, non-qualified CRO, or if significant site and laboratory management changes have occurred at your current CRO provider, a qualification audit should be considered. 

What factors should be considered when choosing a bioanalytical CRO partner?

The main factors we consider in selecting a qualified CRO include:  Scientific expertise, capabilities, regulatory expertise, capacity, size, responsiveness, project management, data and report quality, on-time delivery and cost.  The relative importance of some these factors will depend on the stage of development of your particular compound.  For example, scientific expertise and capabilities will more be important in pre-clinical / early stages of development since method development / validation and an overall assay strategy will play a greater role than when a validated method is transferred in for sample analysis.  SOPs and processes should be clearly defined and should meet GLP and global regulatory requirements, and comments and responses from all regulatory audits performed at the site during the last several years should be examined.  The CRO must have sufficient instrumentation and capabilities to not only complete your planned projects in a timely manner, but also to have sufficient backup resources available if necessary.  Some smaller companies have expressed concerns that the larger CROs may not be as responsive as to larger clients, but a dedicated bioanalytical Project Manager may help to alleviate this concern.  A measure of a CRO’s on-time delivery metrics can be beneficial to evaluate the likelihood of receiving data as promised, which may be a critical aspect if short study timelines are required.  Cost, although obviously an important factor, should not be the most important factor in CRO selection.  Risks and any non-financial costs related to any potential project delays and submission issues should also be considered.  Placing work at a qualified CRO with known high data quality and reliability and an excellent on-time delivery record may be the most preferable option in the long run, even at a higher per sample cost.

Why is a bioanalytical Project Manager important?

A bioanalytical Project Manager (PM) is an essential resource to plan an overall bioanalytical strategy and to plan and track bioanalytical activities such as method development and validation, stability studies, and sample analysis projects throughout a drug development program.   The goals of the Project Manager are to ensure that the proper bioanalytical methods are available and fit for use for the given study, to ensure that individual study timelines are closely tracked and met, to ensure sufficient communication with stakeholders, and to ensure that all bioanalytical data generated will be reliable, accurate and precise, and that all applicable global regulatory requirements will be met.  An internal bioanalytical PM (Company employee or consultant) is preferable, since Company timelines and interests will be emphasized throughout the development process.  Companies without internal bioanalytical PM resources often use the PM resources supplied by the CRO partner.  When working with a qualified CRO with excellent on time delivery metrics, this approach may be sufficient when no issues arise during the conduct of the study.  However, when scientific or internal CRO capacity issues arise, significant project delays commonly occur prior to Sponsor notification.  By closely monitoring project timelines, an internal PM should be able to quickly identify the problem and leverage the necessary additional resources to resolve the problem in a timely manner.