Do you remember the 1990s? The Soviet Union fell, Friends was the most popular TV show, and for some inexplicable reason, hammer pants were a viable fashion option.
But while 90’s era political, entertainment, and fashion trends may have come and gone, many regulatory guidances from that time are still in effect. In my role as a regulatory writer, I find that many of my clients are confused by the SUPAC guidance documents and whether they apply to their drug program. In this blog, I will explain the history of these documents, and how they may be required for your organization.
In the pharmaceutical manufacturing environment, post approval changes (PACs) are a necessity (read this blog to learn more about change management). These are changes that need to be made to the drug product manufacturing process, manufacturing facilities, formulation, and/or testing sites after the product has been approved. Historically, the United States Food and Drug Administration (FDA) has had difficulty developing a regulatory policy for many PACs that both FDA reviewers and the regulated industry representatives could interpret. In 1990, the FDA accepted the American Association of Pharmaceutical Scientists (AAPS) offer to assist the FDA in compiling the information necessary to support scale-up/scale-down (i.e., the process of adjusting the scale of production for a drug substance or drug product to meet the demands of clinical trials or commercialization of the product) of solid oral dosage forms. In April 1990, the FDA, the United States Pharmacopeia Convention (USP), and AAPS sponsored a workshop on this topic. Work on this project was continued under a research contract with the University of Maryland, the University of Michigan, and Uppsala University (Sweden).
In April 1995, President Bill Clinton made a commitment in the National Performance report “Reinventing Drug and Medical Device Regulations” that the number of manufacturing changes requiring preapproval by the FDA would be reduced. It was estimated that this reduction, along with the other components in the report, would save the drug and medical device industries $500 million per year. Due to the work started in 1990, the FDA was better prepared to fulfill this commitment.
SUPAC Activities
In November 1995, the FDA introduced the first SUPAC guidance document for immediate release (IR) solid oral dosage forms (SUPAC-IR). This guidance was unique at the time as it listed various types of quality and manufacturing changes, such as components and composition changes, site changes, and batch size changes. The document also listed what supporting documentation was needed to make the change(s), what documentation needed to be submitted to provide for the change(s), and how this change(s) should be submitted to the FDA (e.g., annual report, changes being effected-30 days [CBE-30], or prior approval).
The SUPAC‑IR guidance was followed with the SUPAC Nonsterile Semisolid (SUPAC-SS) guidance in May 1997, the SUPAC Modified-Release (SUPAC-MR) guidance in September 1997, the Post Approval Changes-Analytical Testing Laboratory Sites (PAC-ATLS) guidance in April 1998, and the DRAFT SUPAC Manufacturing Equipment Addendum (SUPAC-MEA) in December 2014 (which superseded the DRAFT SUPAC Manufacturing Equipment Addendum dated December 1998).
Each of these guidance documents lists the following: standard changes that may be made to components and composition, manufacturing, batch size (such as scale-up and scale-down), and manufacturing site/facility changes. Following the recommendations in these guidance documents enables the Regulatory Affairs Professional to correctly identify what information and documentation will be needed for about 90% of the potential drug product chemistry, manufacturing, and controls (CMC) changes. The FDA has also introduced a provision that allows for more than one change to be made at a time if the following two provisions are met:
(1) the changes to be made are discussed with the FDA reviewing division before any changes are made, and
(2) the most onerous filing route is chosen (e.g., if one change requires an annual report filing and another change requires a prior approval filing, both may be filed as prior approval changes).
All documentation noted for all the changes being made should be included in the filing.
Active or Inactive?
Since these documents were predominantly issued in the late 1990s, drug developers frequently assume that they are no longer valid guidance documents. This is not the case. Each of the documents listed above are still available from the FDA website, and they are all still valid documents. The only SUPAC document that is no longer applicable for human drugs is the Bulk Actives Postapproval Changes (BACPAC) I: Intermediates in Drug Substance Synthesis. Although a 2006 BACPAC guidance document is still available on the FDA website, it is only applicable to animal drug products submitted to the Center for Veterinary Products.
If your company’s manufacturing and/or quality groups propose a change, and a comparability protocol is not in place that will cover the proposed change, then an investigation should be done to determine if the change will fit into one of the available SUPAC guidance documents.
Do you need help maintaining compliance with these regulations? Our regulatory writers have authored over 200 CMC documents for sponsors over the past 5 years. Learn more about our regulatory writing services here:
References:
PAC-ATLS. https://www.fda.gov/media/70885/download. Accessed 11Jul2023.
Skelly JP, Van Buskirk GA, Savello DR, AmidonGL, Arbit HM, Dighe S., et al. Scaleup of immediate release oral solid dosage forms. Pharm Res 10 (3), (1993).
SUPAC IR. https://www.fda.gov/media/70949/download. Accessed 11Jul2023.
SUPAC-MEA. https://www.fda.gov/media/85681/download. Accessed 11Jul2023.
SUPAC-MR. https://www.fda.gov/media/70956/download. Accessed 11Jul2023.
SUPAC-SS. https://www.fda.gov/media/71141/download. Accessed 11Jul2023.