Pharma groups say SUPAC guidelines should be updated, better aligned with ICH
Three major pharmaceutical industry groups—two in the US and one in India—have called for changes to the US Food and Drug Administration's (FDA) Scale-Up and Post-Approval Changes (SUPAC) guidelines. They believe these guidelines should be updated to reflect more modern manufacturing methods and better align with International Council for Harmonisation (ICH) standards.
The groups also suggested that the guidelines should be expanded to include a wider range of product types. Additionally, they recommended consolidating all SUPAC-related guidance into a single, structured framework.
In March 2026, FDA announced that it was seeking public feedback on whether its scale-up and post-approval changes (SUPAC) guidance documents for the pharmaceutical industry need to be updated and modernized; FDA published the first SUPAC guidance on IR dosage forms in November 1995; the guidance set out the framework for assessing post-approval changes for the other dosage forms. (RELATED: FDA seeks feedback on overhaul of its SUPAC guidelines, Regulatory Focus 2 March 2026)
The notice concerns five guidance documents: immediate-release dosage forms (IR), modified-release (MR) dosage forms, and non-sterile semi-solid dosage forms. It also covers a manufacturing equipment addendum (SUPAC-MEA) as well as a question-and-answer guidance on the IR guidance.
FDA requested public comment on several questions, including whether there are any sections of the SUPAC guidances that should be retained, and some of the challenges in interpreting or applying the recommendations in the SUPAC guidances.
AAM: SUPAC guidelines are a “confusing patchwork”
The Association for Accessible Medicines (AAM) wrote that the SUPAC guidelines have been beneficial in several ways: they have reduced the number of chemistry, manufacturing, and controls (CMC) changes that require FDA approval for supplemental applications. This has minimized delays in product distribution and enabled the FDA to focus its resources on changes that pose the greatest risks to product quality. As a result, these guidelines have improved efficiency and promoted timely, continuous improvement in accordance with current good manufacturing practices.
Yet AAM said that the time has come for these documents to be updated. The group wrote that “the SUPAC Guidance’s have evolved over two decades, and they are now a confusing patchwork of advice from FDA on post approval changes. The existence of multiple dosage form specific SUPAC guidance’s can contribute to inconsistent interpretations and overly conservative regulatory decisions. Furthermore, many classes of drugs (e.g., transdermal products, combination products, complex products, injectables, oral topical solutions) are not covered by the original SUPAC Guidances.”
AAM recommended that the guidances be expanded to classify changes for complex generics, combination products including changes resulting from a supplier change, and products with device components.
The group also mentioned that these guidelines are not in alignment with the ICH. The recent ICH guidelines “contains recommendations that may either supersede or potentially conflict with certain recommendations in the SUPAC Guidances.”
AAM recommended consolidating all SUPAC guidance into a single, structured framework. This framework should include clear definitions of reporting categories, detailed conditions for each type of change, required documentation and data for every type of change, as well as relevant examples and case studies.
PhRMA urges FDA to retain core of SUPAC
The Pharmaceutical Research and Manufacturers of America (PhRMA) provided more favorable reviews of SUPAC.
The group wrote that “the data expectations are generally clear and concrete, and the practical examples included in the guidances facilitate consistent interpretation of the guidance and minimize uncertainty. PhRMA members particularly value the insight the SUPAC guidances set forth as to FDA’s conception of risk and how these concepts map on to various reporting categories for postapproval changes.”
PhRMA also urged FDA to “retain several core principles” of the SUPAC guidances. “The SUPAC guidances are grounded in science and risk-based approaches and generally distinguish between programs with a significant body of knowledge to inform decisions and those without such prior knowledge. This core principle – a risk-based approach to postapproval changes – should be retained and must remain foundational in any revised, updated, or consolidated SUPAC guidances.”
However, the group also said it recognizes that “science, technology, and regulatory practice have evolved considerably in the last 30 years.” The group stated that, as acknowledged by the FDA in the notice, many aspects of the SUPAC guidances have been replaced by more recent guidances that better reflect current pharmaceutical manufacturing practices.
PhRMA recommended that FDA update the SUPAC guidances “to allow for greater reliance on prior knowledge (including commercial manufacturing experience), control strategy, design space, and product or process understanding, and to use such information to justify greater flexibility in reporting categories. We believe there is an opportunity to reduce unnecessary expectations for low-risk changes, including updating recommendations in revised guidance to streamline, as appropriate, the documentation expected to support low-risk changes.”
PhRMA also suggested that FDA consolidate the SUPAC guidances by combining multiple existing guidances. “Some information in the SUPAC-IR, -MR, and -SS guidances is redundant, and better clarity may be possible with a consolidated update. Dissolution and comparability expectations, for example, could be consolidated into a single, risk-based framework, as could expectations for stability data.”
The group said that the updated SUPAC guidance should be aligned with international principles. “The revision and consolidation of the SUPAC guidances is an opportunity to advance international regulatory harmonization and align with ICH guidelines.” For example, updated SUPAC guidances regarding formulation change should reflect updated biowaiver and bioequivalence frameworks under ICH guidelines M9 and M13.
Indian Pharmaceutical Alliance points out shortcomings
The Indian Pharmaceutical Alliance (IPA) highlighted some shortcomings in the guidelines. They noted that the scope is primarily limited to traditional immediate-release (IR), modified-release (MR), and semisolid dosage forms, and it does not sufficiently address complex products or combination products.
Other shortcomings include “limited alignment with modern manufacturing approaches such as continuous manufacturing, Process Analytical Technology (PAT), advanced analytics, and real-time release testing.”
The group noted that some equipment terminology and bioequivalence criteria are outdated or applied inconsistently. “Legacy terminology and incomplete treatment of emerging technologies create uncertainty in assigning reporting categories.”
IPA said that the FDA should “replace prescriptive and outdated equipment lists with process- and function-based equipment classifications” and provide more guidance on Quality by Design (QbD), lifecycle management, and pharmaceutical quality systems as specified in ICH Q8 and Q12.
The group also recommends developing a modernized two-part SUPAC framework that includes a unified core guidance comprising overarching principles, decision trees, risk assessment approaches, and mapping to 21 CFR and ICH Q12 concepts as well as annexes specific to dosage forms containing product-specific recommendations.
IPA also said that FDA should expand the scope of the updated guidances “to address several important areas that are currently either inadequately covered or not addressed at all.” These include complex products and emerging dosage forms, orally inhaled and nasal drug products (OINDPs), transdermal systems, combination products and device-containing products, continuous manufacturing, and co-processed and functional excipients.
