The US Food and Drug Administration (FDA) on Tuesday issued draft guidance laying out quality considerations for continuous manufacturing (CM) for new and generic drugs.
The 27-page draft guidance is part of FDA’s effort to encourage the adoption of continuous manufacturing and covers quality considerations for solid oral small molecule drugs and builds on feedback from a public consultation
launched in 2017.
According to FDA Commissioner Scott Gottlieb and Center for Drug Evaluation and Research (CDER) Director Janet Woodcock, continuous manufacturing “transforms the traditional, step-wise manufacturing process into a single system that’s based on modern process monitoring and controls. It enables a steady output of finished drug products as raw materials are continuously added to the closed system.”
Gottlieb and Woodcock add that continuous manufacturing can reduce the risk of drug shortages as there are fewer starts and stops during production and operations can be scaled up more easily than with traditional manufacturing methods.
Other potential benefits of continuous manufacturing include a smaller manufacturing footprint, more efficient operations and a higher degree of consistency that Gottlieb and Woodcock say could lower manufacturing costs long-term.
While continuous manufacturing is still an emerging field, Gottlieb and Woodcock said that more and more drugmakers are working to implement the technology.
“Less than four years ago, there was only one approved product manufactured using CM processes. Today, there are four companies manufacturing five approved products using CM, treating diseases like cystic fibrosis, HIV-1 infections
, breast cancer and leukemia. About 20 additional companies – both brand and generic – have engaged the FDA in their efforts to develop and implement CM processes,” Gottlieb and Woodcock said.
They also said that international harmonization around continuous manufacturing will help encourage implementation, noting that FDA recently proposed the development of an International Council for Harmonization (ICH) guideline on the topic. In November, the ICH Management Committee endorsed
the concept paper and business plans for its newly established working group on continuous manufacturing.
Specifically, FDA says the draft guidance provides input on quality considerations for continuous manufacturing of small molecule, solid oral drugs submitted via a new drug application (NDA), supplementary new drug application (sNDA) or abbreviated new drug application (ANDA).
FDA also says it “supports the development and implementation of continuous manufacturing for drug substances of all finished dosage forms where appropriate, including those submitted in NDAs, ANDAs, drug master files (DMFs), biologics license applications (BLAs), and nonapplication over-the-counter (OTC) products.” However, while some of the recommendations made in the guidance may apply to other types of pharmaceuticals, FDA says the guidance does not provide recommendations for biological products.
The guidance itself discusses how key manufacturing concepts apply to continuous manufacturing, such as defining batches. For instance, FDA says that traditional definitions of batch and lot are applicable to continuous manufacturing.
“A batch can be defined based on the production period, quantity of material processed, quantity of material produced or production variation (e.g. different lots of incoming raw material),” FDA writes.
The guidance also covers manufacturing control strategies, process validation and quality systems considerations for continuous manufacturing and provides recommendations for scaling up production and demonstrating stability for finished drug products produced via continuous manufacturing.
Additionally, the guidance provides a list of sections within the electronic common technical document (eCTD) where information related to continuous manufacturing processes should be presented.
, Federal Register Notice