Guidance For Industry - Food And Drug Administration: Fill & Download for Free

There are few links from FDA I think will be helpful:1. Investigator responsibilities:- Regulation and Clinical trails:Page on Fda2. Information Sheet Guidance For IRBs, Clinical Investigators, and Sponsors FDA Inspections of Clinical Investigators:Page on Fda3. Guidance for Industry Investigator Responsibilities — Protecting the Rights, Safety, and Welfare of Study Subjects :Page on Fda

This is a great question, Michael Schrader. U.S. US Food and Drug Administration defines excipients as “inactive ingredients that are intentionally added to therapeutic and diagnostic products, but that: (1) [FDA believes] are not intended to exert therapeutic effects at the intended dosage, although they may act to improve product delivery (e.g., enhance absorption or control release of the drug substance); and (2) are not fully qualified by existing safety data with respect to the currently proposed level of exposure, duration of exposure, or route of administration.”Excipients do not undergo approval outside of the New Drug Application (NDA) or Abbreviated New Drug Application (ANDA) approval process, unless the excipient is a color additive. In this case, the color additive would have to be approved for use in accordance with section 721(a)(1)(A) of the Food Drug and Cosmetic Act. As a part of the NDA/ANDA approval process, the applicant must provide information demonstrating that the inactive ingredients “do not affect the safety or efficacy of the proposed drug product,” (21 CFR 314.94(a)(9)(ii)).FDA does recommend strategies to test new drug excipients for safety in its Guidance Document entitled, “Guidance for Industry: Non Clinical Studies for the Safety Evaluation of Pharmaceutical Excipients (May, 2005).” The strategies discussed in this Guidance address the various potential uses of the excipient (e.g., in products intended for long-term use, intermediate use, short-term use, etc.) and provide a description of the types of studies that will be useful to demonstrate safety.It is important to note that these strategies, though important, do notconstitute an approval process. Rather they provide a means for the excipient manufacturer to demonstrate that the excipient is safe for inclusion in a drug product.U.S. FDA Drug regulations can be complex and nuanced. If you would like more information about U.S. FDA Drug Regulations, our team of regulatory advisors is available 24/7 via Live Help (http://www.registrarcorp.com/LiveHelp) or call Registrar Corp’s U.S. Office at: +1-757-224-0177.

Though it varies depending on roast and type (e.g., instant vs. brewed), the average amount of acrylamide in a cup of brewed coffee is about 0.45 micrograms (μg). Instant coffee is higher, and grain-based coffee substitutes are the highest (at an average of 3.21 micrograms per cup). Not surprisingly, since the acrylamide is generated in the roasting process, dark roast coffees generally have higher levels than light roast, but the coffee species, Arabica vs. Robusta (the latter is widely used in some instant coffees), didn’t make much of a difference. You may wish to consult this abstract: https://www.ncbi.nlm.nih.gov/pubmed/24325083 (the full paper is also available at no charge).The same researchers also examined the levels of acrylamide in cigarette smoke and found them to range from 455.0 to 822.5 nanograms per cigarette for an average of 679 ng/cigarette. In the population studied, smokers were calculated to be exposed to more than 50% more acrylamide than non-smokers: https://www.ncbi.nlm.nih.gov/pubmed/27660868.For comparison, that 0.45 micrograms in the cup of brewed coffee is equal to 450 nanograms, so a cup of brewed coffee is at the low end of the dose from a cigarette.The authors concluded that the main source of acrylamide in human diet are potato products (especially fried), cereal products and coffee, along with cigarettes. Acrylamide is also produced industrially for use in products such as plastics, grouts, water treatment products, and cosmetics.Health Canada has published an extensive list of the measured acrylamide content from common foods and food products (https://www.canada.ca/en/health-canada/services/food-nutrition/food-safety/chemical-contaminants/food-processing-induced-chemicals/acrylamide/revised-exposure-assessment-acrylamide.html).Though the U.S. Food and Drug Administration has not determined an acceptable level for acrylamide in food, they have issued a guidance document (https://www.fda.gov/downloads/Food/GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/ChemicalContaminantsMetalsNaturalToxinsPesticides/UCM374534.pdf) and a consumer Q&A (https://www.fda.gov/Food/FoodborneIllnessContaminants/ChemicalContaminants/ucm053569.htm).Other researchers have estimated the Tolerable Daily Intake (TDI) for neurotoxicity to be 40 μg/kg-day (that’s kg of body weight); for cancer to be 2.6 μg/kg-day. These levels significantly exceed the estimated exposure to acrylamide from foods, which organizations in Canada, Sweden, and the U.S. estimate to be between 0.3 and 0.5 μg /kg-day.Thus for a 70 kg person (154 lb.) the TDI for cancer would be about 182 μg/day or over 400 cups of coffee or 267 cigarettes. I drink a lot of coffee, but not that much.(Of course, these studies were done in rats, not humans. You will be happy to know that no Starbucks patrons were harmed in this research.)I might also add that current epidemiological research suggests that coffee drinkers have a lower all-cause mortality (that means they live longer) than non-coffee drinkers. That definitely can’t be said for cigarette smokers.