5 March 2019
FDA Issues Draft Guidance on Pharmaceutical Continuous Manufacturing
The Food and Drug Administration’s Center for Drug Evaluation and Research on 26 February issued draft guidance for public comment on pharmaceutical continuous manufacturing. According to the FDA, the process of continuous manufacturing is one of the most important tools for modernising the pharmaceutical industry because it transforms the traditional, step-wise manufacturing processes into a single system based on modern process monitoring and controls.
The agency states that the closed and continuous nature of CM systems means that the process is easier to control than traditional batch manufacturing. Under the traditional approach, the finished drug product is made using a long series of discrete steps that involve many stops and starts, with each step introducing a degree of complexity and uncertainty. CM helps to ensure consistently-made products, allows manufacturers to more easily scale their manufacturing operations to meet demand, and can help reduce drug shortages by minimising operational stops and starts. The high-tech and small footprint attributes of these systems promote localised manufacturing, helping to shorten the drug supply chain.
The draft guidance provides information on the FDA's current thinking on quality considerations for continuous manufacturing of small molecule, solid oral drug products that are regulated by CDER. It describes several key quality considerations and provides recommendations for how applicants should address these considerations in new drug applications (NDAs), abbreviated new drug applications (ANDAs), and supplemental NDAs and ANDAs for small molecule, solid oral drug products that are produced via a CM process. This guidance can apply to the production of brand, generic and over-the-counter drugs.
The FDA also discusses in its guidance the process and control strategy designs (including equipment) needed to meet regulatory considerations and how a CM platform technology can be used to manufacture multiple products, so that product developers can have more certainty about the capital investments they need to make. Since processes and facilities for CM differ from traditional operations, some companies have asked questions about the impact of this new technology on the way the FDA and other regulators assess new drug applications when the products are being made using these methods and how regulators will approach facility inspections. Early adopters have developed innovative solutions such as modular and miniature CM equipment in their facilities. This design allows a company to run its CM operations in a smaller physical footprint and transfer identical units to different sites, thereby facilitating a faster launch of CM operations in different locations.
More broadly, the draft guidance supports a global effort with other regulatory authorities to encourage the implementation of CM. The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use has accepted an FDA proposal to develop guidance on CM and is hoping to finalise such guidance by 2021. This harmonised guidance will help advance the brand and generic drug industries’ ability to obtain approvals for products manufactured using CM processes in multiple regions.