Issue link: http://www.e-digitaleditions.com/i/477622
recalls and implements the thickness parameters for dif- ferent tablet products. These parameters, however, are not independently verified, so be careful. In fact, the ref- erences may be dimensionless numbers that relate only to the machine, not to the tablet's actual thickness specifica- tion. And the computer can't detect or report part wear that can cause the settings to drift. Another potential source of variation is using tablets taken from a good batch to establish the roller settings for another batch. That's a bad idea because the tablets can wear and change thickness. They're also likely to become lost in the batch, and you'll spend all day trying to find them; when you can't, regulators will presume they never existed. Instead, use a caliper (photo) or standard tablets machined from brass or stainless steel. I prefer brass stan- dards because they remain precise and don't jump much on the rollers. Avoid using plastic or aluminum tablets, which tend to jump during sorting. Sorting and GMP compliance Sorting every batch of every product is not the solu- tion, as the FDA made clear in the warning letter cited above. Thus, if you have a sorter and plan to use it, estab- lish a standard operating procedure (SOP) that defines when to use it: • As part of the operational qualification of a tablet press • During initial product validation (three batches) • When there is cause to suspect that the tablet press' reject gate has failed • As part of an investigation when absolute product quality is in doubt • Occasionally to verify tablet press performance • Every X number of months on a random batch of each size and shape of each product • As a means to verify a process improvement to the tablet press [10]. Conclusion Off-weight tablets are a genuine problem, and dimen- sional tablet sorters can help when used correctly. While the FDA has not addressed dimensional sorting recently, that could change if the practice becomes standard, as I've observed in India. To avoid problems with the FDA, establish an SOP for tablet press startup and the handling of rejected tablets. And train your staff to challenge the tablet compression process. If you're sorting every tablet produced, inspectors can only conclude that your process is out of compliance with GMP. T&C References 1. Rowley, F.A. "Why overweight tablets are not going away." Presentation at ISPE Facilities Conference: Learning from 483s, Tampa, FL. February 2012. 2. "An upsurge of overweight tablets and a recent FDA Warning Letter Show Industries Process Understandinsg Shortcomings," International Pharmaceutical Quality, March 5, 2012. 3. Eglovitch, Joanne S. "Recalls of overweight tablets reflects knowledge gap in industry on tablet making; solutions offered." The Gold Sheet, 46(3) March 2012. 4. FDA Enforcement Reports. www.fda.gov/Safety/ Recalls/EnforcementReports/ 5. "Tablet pressing in focus." What's Next? Fette Com - pacting Customer Magazine 2/2014, pp. 16-17. 6. Yu, Lawrence. "Quality and bioequivalence stan- dards for narrow therapeutic index drugs." Presentation at GPhA Fall Technical Workshop, Bethesda, MD. October 2011. 7. FDA Warning Letter 12-NWJ-10, West-Ward Pharmaceuticals. February 3, 2012. 8. FDA Warning Letter 10-NWJ-11, CorePharma. June 21, 2010. 9. Donovan, Jon. "Bulk inspection of tablets: Assuring product quality at manufacturing and packaging." Pharma Times, 42(6) June 2010. 10. Rowley, F.A. "Understanding and preventing over- weight tablets." Presentation to FDA-CDER, Silver Spring, MD. May 2011. Fred A. Rowley is the owner and chief lecturer at Solid Dosage Training and Troubleshooting, 497 Phoenix Circle, Vallejo, CA. 94589. Tel. 925 352 5724. Website: www.soliddosageindia.com. He is also an editorial advisor to Tablets & Capsules. Tablets & Capsules March 2015 27 Use a caliper (shown) or tablets machined from brass or stainless steel to establish and verify the gap between rollers. www. tabletscapsules .com