Two Informative FDA Guidance documents

FDA has issued a Guidance for Industry document, ANDA Submissions ― Refuse-to-Receive Standards, which contains helpful hints on the Agency’s thinking and practices. Much of the contents may not be applicable to members of our industry, because homeopathic drug products are, by and large, not subject to the ANDA process, but hidden within the Guidance are clues on possible areas of focus during inspections.

For instance, FDA is putting an emphasis on sterility assurance data for sterile APIs. Likewise, batch size and stability study recommendations will likely be assessed as well, and the Agency has expected worst-case scenario (i.e. horizontal or inverted container) accelerated stability data certain dosage forms, such as liquids, solutions, semi-solids, and suspensions.

This guidance document reinforces FDA’s concerns regarding method validation and / or verification. This is an important section of the document to carefully review, as the Agency makes comments about their expectations of manufacturers regarding the use of compendial methods. The guidance document can be downloaded from

Another Guidance for Industry document, ANDA Submissions — Refuse to Receive for Lack of Proper Justification of Impurity Limits, can also provide helpful hints on the Agency’s practices. This document highlights the areas of identified and unidentified impurities in drug products. The homeopathic attenuation process, in its’ simplest form, is unlikely to lead to impurity issues. On the other hand, the introduction of a homeopathic attenuation into a dosage vehicle (e.g. cream or ointment base, syrup) does create scenarios in which impurities might be an issue. The discussion on justifications for limits can be especially rewarding for anticipating questions and issues that might be raised during meetings with Agency personnel. The guidance document can be downloaded from

If either of the above documents are of interest, you may also want to follow up on FDA’s free Small Business and Industry Assistance (CDER SBIA) Webinar that covers both of the Guidance documents. In either case, the hints that can be gleaned from a review of these documents will need some creative thinking to see the application of the points raised to homeopathic drug products. But one can be sure that Agency personnel will approach an inspection of all facilities the same, whether producing homeopathic drug products or not. The following link provides more information on the webinar, as well as the free software necessary to view the webinar content: