Mike Carroll, Quality Professional and Aseptic Processing Specialist, has an extensive history in microbiology and pharmaceuticals. One of his most recent commentaries is on Microbiological Quality Considerations in Non-Sterile Drug Manufacturing, a draft of guidance published in September of 2021.
This guidance is intended to assist manufacturers in assuring the control of the microbiological quality of their non-sterile drugs (NSDs). The recommendations herein apply to solid non-sterile dosage forms, as well as semi-solid, ande liquid non-sterile dosage forms (e.g., topically applied creams, lotions and swabs, and oral solutions and suspensions). NSDs can be prescription or nonprescription drugs, including those marketed under approved new drug applications (NDAs) or abbreviated new drug applications (ANDAs), and nonprescription drugs without approved new drug applications which are governed by the provisions of section 505G of the FD&C Act (often referred to as over-the-counter (OTC) monograph drugs). These recommendations, if followed, will also assist manufacturers in complying with the current good manufacturing practice (CGMP) requirements for finished pharmaceuticals and active pharmaceutical ingredients (APIs).
Center for Drug Evaluation and Research
For many years, drug products labeled as non-sterile needed not to worry about the bioburden and environmental factors that could produce microbial proliferation. However, with this new guidance, drug manufacturers must consider these prevalent issues. If a product is launched that contains spores or viable organisms, it must be up to quality standards, and there needs to be data produced on these microbial contaminants. The ability to defend your product and its standards are integral to the FDA approval process. These are referred to as microbial standards. Since it was never claimed to be sterile back in the day, many microbes were found in various products and caused quality and health issues. However, these quality issues caused many problems for the users of these drugs. This was seen as recently as the late 1980s and early 1990s with certain contraceptives. The FDA has researched this for several decades, and new guidance is coming to light to set a standard for drug corporations.
It was stated that corporations must effectively reverse engineer product quality by getting data on what they have and what it will support and backing it into contained limits. In extreme cases, this can even mean going back and sterilizing the filling machines of these products. The guidance is specific to individual products, as companies act as the expert on all aspects of a product. Corporations that produce non-sterile must know that the sponsor is responsible for this guidance. Products, such as topicals, are now under watch with this new guidance.
Some steps to take include having a full environmental assessment, and companies can produce a documented signed assessment to go over the things that fall into the guidance. The specific product may not be directly affected by this guidance, but it is important to keep it in mind. This assessment can help you defend your product when it goes in for submission and approval. The information about microbial factors should be found out as early as possible, even during initial phases. An environmental assessment of the entire program includes looking at excipients and reaching out to vendors with historical data and environmental factors to find all the information you can about the microbiology of your products and their ingredients. It is important to know this new guidance as it can significantly affect your submission process.
In conclusion, although it is only draft guidance, it does not mean it is not valid, it will be going through the official process, and it is still valid guidance that will be looked at and used by the FDA.
