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Home < Quality Assurance < FDA 483
Re: General cGMP Inspection by FDA conducted August 22-26, 2002 To Whom It May Concern: We are pleased to announce the results of the recent FDA cGMP inspection of our laboratory. Two inspectors, Sue Lee-Chan from the Pacific Regional Laboratory Northwest and Yumi J. Hirameine from Los Angeles District, spent three days performing a general cGMP compliance inspection. The inspection got off to a rocky start with a dispute over which records FDA could and could not review. Because of the confidential nature of our work, WCAS notified most of our pharmaceutical and nutraceutical clients to obtain prior approval from our clients so that FDA could review data and results during the inspection. FDA did not like this idea and stopped the inspection after about 3 hours on Monday. We received a phone call Tuesday afternoon from three FDA officials from the LA District: Tom Sawyer, Mark Tucker, and John Stampf. We reached an understanding that the FDA inspectors have the right to review records of anything associated with OTC or prescription drugs, but not data for R&D, foods, supplements, etc.. With this understanding, the inspectors returned Wednesday and continued the inspection. The inspectors started reviewing files associated with our complaint log and scheduled drug file. The inspectors reviewed SOPs, training files, analytical standards, data management, method validation, retest/OOS, notebooks, 21 CFR Part 11 compliance, metrology, as well as data from 47 jobs and approximately 28 raw data packages for more than 20 clients, They inspected laboratory data for metals analysis (mostly ICPMS), organic analysis (GC, GCMS, HPLC, and FTIR), and many USP tests. All clients whose data was reviewed have been notified. Click here for a pdf copy of the Form 483 (Page 1, Page 2) and our full response. Our response to the observations is as follows: 1. First, we distinguish clients who produce USP materials from those that use them. Those who produce USP chemicals must strictly follow USP methods to determine conformance with the USP specifications, or validate alternative methods. Those who use USP materials and who want to QC these raw materials may, at the companies discretion, use any scientifically valid approach to do so. Such is the case with large majority of our clients. Second, in our terms and conditions, we reserve the right to modify methods based upon our experience and current scientific literature. Such was the case with this client. Our policy is to alert such clients to any significant change in a published method. In this particular case, the deviation from the method was documented, but the client was not informed of the deviation until he asked because we did not consider this column change as a significant deviation. That point is no doubt arguable, but based on our experience changing the column from packed to capillary as in this case provides much superior separation. The column that we use provides a much larger number of theoretical plates as well as higher resolution. The column far exceeded the system suitability requirements of the method. In work previous to that in question the RSD of the relative response factors for the standard was also documented to be <1%. This was taken as sufficient validation for this particular case. The column change was proposed by an experienced analytical chemist and approved by the QA Officer (also an experienced analytical chemist) based upon the validation data. 2. We use Lotus 123 spreadsheets in a large number of applications to take raw data to a finished report. Where possible, in most simple spreadsheets, cells are locked and password protected to prevent tampering with calculations. In some more complex spreadsheets, we have not found a way to protect areas of the spreadsheet without preventing the spreadsheet from working properly. However, each spreadsheet has a version, each version is validated against separate hand or independent spreadsheet calculations, and any time the spreadsheet is used, known standards and reference materials are processed along with unknown samples for further validation of the spreadsheet at the time of use. 3. Any time that we routinely perform a method, we write an SOP. We have SOPs for some of the USP methods such as <467> OVIs, <231> Heavy Metals, <281> Residue on Ignition, and several others. In the observation, the sample was not a USP material. Instead it was a rather expensive peptide for which the client could only supply 20-100 mg quantities for testing. With the clients documented permission, the sulfated ash procedure in USP was modified to produce better results with this size sample. This modified procedure was used on a hand full of samples for a one time project. The method and results were documented in our internal bench sheets and in the client report. 4. The inspectors were given copies of our SOPs dealing with current practices on computing systems, software, network, and archiving. We also provided them with a draft document on the assessment of 21 CFR Part 11 compliance and implementation plan. When the inspectors were asked about this observation, they cited specifically from Part 11. When we have data systems that are Part 11 compliant, we will need to update our practices in our SOPs. But as of right now, we document our current practice. So I don’t know why this observation was put on the 483. 5. This is another observation pertaining to Part 11 compliance. As stated above, our plans for Part 11 compliance were given to the inspectors. At this point in time, instrument data systems that can be made to comply with Part 11 do not exist for all the equipment. Those systems that are available require both software and hardware updates at a cost that may not be warranted until the equipment is replaced with newer models. 6. In our opinion this is another observation that should not be on a 483. The documents provided to the inspectors clearly showed that the samples never exceeded our storage temperature requirements according to our SOP. When a freezer failed, the samples were moved to new freezers that had not been previously used or intended for use for sample storage. They were monitored from that point while samples were stored in them until the original freezer was repaired. The repaired freezer was monitored before moving them back. This was an atypical situation. The main point of the observation may be that we had freezers in the lab that were not monitored according to our SOP. However, these freezers were not (prior to this) and are not currently being used for storage. We will however start monitoring them even though we have no intention of using them in the near future. Please email your comments or questions regarding this inspection to jack.northington@bodycote.com. Also click here for the 2006 Inspection, the 2004 Inspection, or 1999 Inspection. |
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