FDA Recommended Resources for Water Treatment Systems


The following six links to resources were provided directly from FDA to AAHP to be shared with the homeopathic manufacturing industry following the association’s June 12, 2024 half-day seminar on water treatment systems. William Yang, Ph.D., a consumer safety officer in the Office of Manufacturing Quality, Office of Compliance within the Center for Drug Evaluation and Research at FDA, presented the keynote talk on trends in cGMP deviations and violations pertaining to pharmaceutical water purification systems noted in recent FDA drug warning letters. Microbial contamination in non-sterile drug products is one of the most common reasons for an FDA warning letter regarding homeopathic products. If you missed AAHP’s seminar, the links below provided by Dr. Yang will aid in improving product quality and preparing for FDA inspections.

  • FDA Draft Guidance: Microbiological Quality Considerations in Non-Sterile Drug Manufacturing: This 2021 guidance assist manufacturers to control the microbiological quality of non-sterile drugs (NSDs). The recommendations apply to both prescription and over-the-counter solid non-sterile dosage forms, as well as semi-solid, and liquid non-sterile dosage forms (e.g., topically applied creams, lotions and swabs, and oral solutions and suspensions). The guidance discusses product development considerations and certain cGMPs that are particularly relevant to microbiological control in a manufacturing operation for an NSD. It provides recommendations to help manufacturers assess the risk of contamination of their NSDs with objectionable microorganisms to establish appropriate specifications and manufacturing controls that prevent such contaminations and assure the safety, quality, identity, purity, and efficacy of the NSD.


  • FDA Advises Drug Manufacturers that Burkholderia cepacia Complex Poses a Contamination Risk in Non-sterile, Water-based Drug Products: In this 2023 article, FDA informs manufacturers of non-sterile, water-based drug products about Burkholderia cepacian complex (BCC) contamination due to deviations from cGMP requirements. This bacteria is linked to multiple instances of opportunistic infections. Over-the-counter (OTC) and prescription drug recalls due to BCC contamination date back to at least the 1980s and early 1990s. This article provides background, checklists, and other resources to avoid deficient manufacturing practices, particularly in the design, control, and maintenance of water systems.


  • FDA Guide to Inspections of High Purity Water Systems: This is 10-page guide from 2016 for FDA investigators review and evaluation of high purity water systems used in the manufacturing of drug products and drug substances. It includes a review of the design of the various types of systems and some of the problems that have been associated with these systems. Readers will learn about system validation, microbial limits, water for injection systems, stills, heat exchangers, holding tanks, pumps, piping, reverse osmosis, purified water systems, process water, and the agency’s inspection strategy.


Additionally, for those with a subscription to the United States Pharmacopeial Convention, Dr. Yang also recommends the following resources: