FDA Issues Draft Guidance on OSD Continuous Manufacturing

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FDA guidance on quality considerations for continuous manufacturing should help advance implementation by providing clarity and giving companies more confidence to make investments in the new technology.

FDA announced the availability of a draft guidance for industry, Quality Considerations for Continuous Manufacturing, which provides information regarding FDA’s current thinking on the quality considerations for continuous manufacturing of small-molecule, solid oral drug products that are regulated by the Center for Drug Evaluation and Research (CDER), the agency announced in a Feb. 26, 2019 press release. The guidance 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 continuous manufacturing process.  

FDA invites general comments to the docket on the quality considerations described in the draft guidance, including comments on control strategy, facility, and process validation considerations for continuous manufacturing of small-molecule, solid oral drug products.  In addition to comments on the guidance generally, FDA is requesting comments and related supporting information on the following topics:

  • Data storage and handling from process analytical technology systems

  • Potential approaches for situations where direct attribute measurement is not possible (e.g., low dose compounds)

  • Contract manufacturers employing continuous manufacturing

  • Risk-based reporting of routine model maintenance and updates 

  • Statistical approaches using large samples (e.g., Large N).  

FDA is seeking public comment on topics for potential inclusion in the final guidance or additional guidance and any other alternative approaches.  In addition to this guidance, pharmaceutical manufacturers with product-specific continuous manufacturing questions may submit a proposal to the Emerging Technology Program.  

In a Feb. 26, 2019 statement, FDA Commissioner Scott Gottlieb, MD, and Janet Woodcock, MD, director of CDER, described continuous manufacturing (CM) as “a key step towards promoting drug quality and improving the efficiency of pharmaceutical manufacturing.” They noted that the draft guidance “will clarify the FDA’s current thinking regarding innovative CM approaches and can help resolve potential issues some companies have as they consider implementation, such as concerns that use of new CM technology might impact the time FDA takes to assess applications for new products and switching from a batch to CM process for existing products.” The guidance should advance implementation of CM by explaining “what process and control strategy designs (including equipment) are 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. This can provide sponsors with more assurance about the costs of adopting these new methods and the payoffs they can anticipate from making these investments,” said Gottlieb and Woodcock in the statement.

They also pointed out that FDA proposed development of a guidance on CM to the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH). The ICH assembly accepted the FDA’s proposal and set a goal of finalizing the guidance by 2021. 

Source: FDA