Issue link: http://www.e-digitaleditions.com/i/845331
Tablets & Capsules July 2017 32C covalent bonds of any substance in the original material." The Guidance cites several processes that chemically alter an ingredient, including hydrolysis, chromatography, distil- lation, and filtration. If enforced, that standard would require NDINs for many ingredients already on the market, including botanical extracts used in conventional foods. The draft Guidance also says a combination of ingredi- ents—including combinations of pre-DSHEA ingredients, combinations of a pre-DSHEA ingredient and an approved NDI, or combinations of NDIs—need separate notifica- tions. The idea here is that although an individual pre- DSHEA ingredient may be considered safe, the combined ingredients may interact, posing new health risks. One example cited in the 2016 Guidance is combining huperzine A, an NDI the FDA has reviewed with no comment, with yohimbe bark, a pre-DSHEA ingredient. Together those ingredients can cause low blood pressure, low heart rate, gastrointestinal distress, and irregular heartbeat. Techniques that improve product effectiveness by increasing bioavailability and purity or that use different solvents would also require a notification. Without an NDIN, those changes put manufacturers at risk. Cara Welch, a senior advisor in the FDA's Office of Dietary Supplements, said that the Agency "intends to take into account the magnitude of change in a composition or structure and whether it would affect the ingredient's safety" when evaluating manufacturing changes [3]. "If it is a chemical change, it is self-explanatory [that the ingredient would need an NDIN]," Couch said. "But if there is no chemical change, [some may argue] that it is not really a new ingredient." Yet, she also said that new delivery methods, such as extended-release tablets and softgels, are considered manufacturing changes and should be reported to the FDA. "Even if it is the same vitamin pro- file, these different dosage forms would require an NDIN." Own-label distribution and contract manufacturing In some cases, companies that outsource production aren't familiar with the FDA's manufacturing requirements. But as anyone who has read an FDA warning letter pertain- ing to GMP can attest, contracting out manufacturing does- n't release a company of responsibility for product safety. The same is true for an own-label distributor (OLD), a company that markets and distributes turnkey products manufactured by another entity. "OLDs may not even be aware that they have to submit," Couch said. No matter who actually manufactures a product, the OLD is responsi- ble for ensuring legal marketing and compliant production. The same is true of ingredient selection: It's the responsibil- ity of the OLD, not the contract manufacturer. Pre-DSHEA ingredients made using different techniques or delivered in different dosage forms may require an NDIN. Dr. Schleuniger ® Pharmatron is a brand of Our new generation of tablet hardness and disintegration testers allow you to save time & money by maximizing the efficiency of your quality control process. Innovative technology paired with proven mechanics makes operation simple, reduces processing time, and provides precision results you can rely on. www.pharmatron.com Quality matters. How efficient is your quality control?