FDA review details use of manufacturing process models in drug applications
Drug manufacturing process models represent a "growing area" of scientific development and have been utilized in new drug applications (NDAs), biologics license applications (BLAs), and supplements to these applications, according to a recent review by US Food and Drug Administration (FDA) officials.
The review, published in the International Journal of Pharmaceutics in July, found that between 2012 and 2025, drug manufacturing process models were successfully applied in at least 15 FDA-approved applications from eight companies. The paper was authored by Adam Fisher, director, enterprise project staff in the Office of Pharmaceutical Quality within FDA’s Center for Drug Evaluation and Research, and colleagues at FDA.
According to the review, 12 of these submissions were approved before their goal date by an average of 20.3 days early; the three submissions that were not approved by their target date faced issues unrelated to modeling. The authors also noted that prior research has shown that submissions that feature continuous manufacturing have been approved faster than those relying on traditional batch manufacturing.
Of the 15 applications in the review, 11 included continuous manufacturing models, while the remaining four were for batch manufacturing. The products included small molecule drugs, peptides, monoclonal antibodies, biosimilar monoclonal antibodies, and an inhalation product.
The models included residence time distribution models to measure variations in feeder flow for continuous manufacturing of a small-molecule tablet, as well as chemometric models for bioreactor (Raman) and feeding control in the batch manufacturing of a biosimilar monoclonal antibody.
The authors said the goal of the paper is to provide practical experience in reviewing process models to promote global regulatory alignment for their use.
They further noted that FDA modeling experts are often consulted when evaluating an applicant’s modeling and control strategy to support an application decision. At times, FDA has built in-house models calibrated using submitted experimental data.
“FDA intramural and extramural research has long supported the development of process models to enhance design and control of drug manufacturing processes,” the authors wrote.
Ajaz Hussain, an independent pharmaceutical regulatory science expert, told Focus that the paper descends from the work that began at FDA decades ago to promote greater process understanding, the use of design space, and process analytical technologies (PAT).
“The value of models is no longer theoretical; they have been used for material traceability, diversion logic, and in-process control in commercial files,” he said.
The review is significant because it marks the first time that FDA has shared their experiences in this area. Hussain said the research opens “a window into what is happening and the struggles and how many applications have progressed.”
Hussain is a former deputy director of the Office of Pharmaceutical Science in FDA’s Center for Drug Evaluation and Research (CDER), as well as the former Vice President and global head of biopharmaceutical development for Sandoz.
Despite FDA’s efforts to promote greater transparency in this area, Hussain pointed out that adoption of these process models remains low. He noted that “fifteen files from eight companies over thirteen years is progress but is still an outlier.”
Hussain emphasized the need for increased efforts to promote the adoption of advanced technologies in the generic drug sector. He highlighted that implementing process models using advanced manufacturing techniques could support the onshoring of domestic production and reduce reliance on foreign suppliers.
