TIDS AND BITS

This newsletter is a little late because I was waiting to see if we had any news from the agency at this weeks meeting in Baltimore. I also attended the Bioanalytical Equipment Validation Symposium sponsored by SQA and wanted to relay any new ideas or information.

The Red Apple II document "A Quality Approach to Computerized Data Systems for Nonclinical Safety Assessment" is finished and was sent to the printers before the first of the year. It should be available for purchase any time now from DIA.

Dr. Viswanathan presented a brief update regarding FDA activities. They are still concerned about incurred sample reproducibility. Incurred samples are still creating quite a bit of discussion in the BA community and will be further discussed in February at the AAPS workshop entitled - AAPS Workshop on Current Topics in GLP Bioanalysis: Assay Reproducibility for Incurred Samples - Implications of Crystal City Recommendations.

There have been issues regarding the use of commercial assay kits and how much validation is necessary since the kit has been approved by FDA. Dr. Viswanathan stressed that the approval was through CDRH as a diagnostic tool, not necessarily as an accurate and precise quantitation tool. The kit instructions are a starting point, but these still must be validated by the end user.

FDA is concerned about animal welfare issues. The Study Director must be aware of all issues regarding animals and must work closely with veterinarians to make sure animal welfare issues are adequately addressed in GLP studies.

Audit trails must be in place for analytical equipment and must not be turned off by the user. The issues with audit trails further indicate why FDA is adamant about the electronic record being raw data for data captured electronically. Problems recently discovered by FDA include:

• Audit trails not enabled at installation
• Audit trails activated only after samples were integrated. QCs were set to establish integration parameters
• Audit trails disabled

If a TK/PK scientist is requesting repeats, they must have an SOP and valid criteria to do so. It cannot simply be because they do not like the value. FDA feels that the analyst should be responsible for sending valid data to the PK/TK scientist so there should not be a lot of reasons to request repeats. Of course, written procedures must also be available on how to handle repeats.

As most know, FDA is engaged in a modernization of GLPs initiative, and have solicited input from several organizations, including SQA. It appears that there may be major changes to the existing GLPs, which could include emphasizing requirements that the SD have accurate dose analysis and characterization data; establishing better ways to assess the quality systems; tightening up disqualification authority and modifying portions of the GLPS to accommodate current technologies, innovations and the complexity of certain types of studies. They are also under pressure to harmonize with the OECD multi-site guidance document and address test site issues. FDA is in the "information gathering" stage right now, but one major goal appears to be harmonization of GLP enforcement and requirements across all centers.

Robert Cypher from EPA also presented an EPA update with current metrics. The compliance rate of field sites was good in 2007, with 28 of 35 sites inspected having no findings. Product Chemistry facilities still have the worst compliance rates. In 2007, there were 5 studies rejected from one lab.

The EPA website listing facilities that have been inspected and the status of the inspection should be up and running in the next couple weeks. The address is not known now, but one should be able to access the site at www.EPA.gov and then searching for "GLP inspections". Information provided will include the name of the facility, date of inspection and whether the inspection is active or closed. Active status means that the inspection report has not yet been issued; that the inspection report is in peer review; or that the inspection has been referred for enforcement. Closed inspections indicate there were minor or no findings.