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    Home > Medical News > Latest Medical News > American Journal of Pharmaceutical Technology: Progress, Problems and Challenges in the Continuous Production of Solid Preparations.

    American Journal of Pharmaceutical Technology: Progress, Problems and Challenges in the Continuous Production of Solid Preparations.

    • Last Update: 2020-09-02
    • Source: Internet
    • Author: User
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    Pharmaceutical Technology, a professional journal in the U.S. pharmaceutical industry, conducted an exclusive interview on the application of continuous production in the pharmaceutical industry, with industry experts describing the progress made in the continuous process of oral solid preparations.
    interview background The continuous production of oral solid preparations has the following advantages: faster development, smaller equipment footprint, greater flexibility in production scale, stricter process control and the potential for real-time release.
    Vertex Pharmaceuticals, one of the few FDA-approved companies that can produce continuously, began working with Hovione in 2016.
    Hovione is a U.S. commissioned production company responsible for the production of Vertex products using continuous production equipment.
    Pharmaceutical Technology spoke with Hovione's continuous production team members: Alexandra Adao, head of continuous production QA; Sarang Oka, process development engineer; and Jose Luis Santos, head of continuous pharmaceutical production, described their experience in implementing CM.
    And Challenges Pharmaceutical Technology: What benefits have been realized with the commercialization of the CM process for solid drugs? What challenges have arisen? Santos: CM is a great opportunity to bring drugs to market compared to traditional mass production, and further improves product quality based on an understanding of the process and a richer data environment.
    1) The investment is significant, not only in terms of the equipment itself, but also in terms of integrated software, which should include a robust process analysis technology (PAT) framework, facilities for placing equipment, and all related public systems.
    2) Team formation may be very different from the standard team for solid preparation batch production.
    , teams should now include a strong background in process modeling, automation, and control, and PAT is a mandatory role in the team.
    quality team should adapt itself to the new model, or a new focused QA team should be formed.
    3) Development is more difficult and requires more complex process understanding, including process modeling.
    given the steep learning curve of most companies, development may not be as fast as batch production.
    but throughout the drug's development cycle, it shows significantly faster potential than batch production, as development is always carried out on the same equipment and scale.
    our experience is still limited, but in terms of equipment occupancy, we have shown clear advantages over batch production processes.
    , CM can make better sustainable use of assets than batch production methods.
    Pharmaceutical Technology: What are the challenges of bringing materials into the system and what are some of the best practices implemented? Oka (Process Development Engineer): The feed challenge that plagued CM technology in the early days has two cores: feed at very low flow rates and feed with poor fluidity powders with significant electrostatic adhesion.
    substantial progress has been made in addressing the challenges, there has been little change in powder feeding technology.
    weightlessness (LIW) spiral feed is still the main feeding technology.
    For example, a few years ago, an academic team prototyped the use of salt-shaker feeders, a technology that showed only limited success, so we continue to be limited by spiral feeders without any innovative improvements to the LIW spiral feed.
    as mentioned earlier, we have made some substantial progress in addressing the challenges when feeding poorly liquid powders or feeding them at low flow rates.
    challenge of poor powder fluidity is inconsistent pitch filling.
    suppliers have tried a variety of agitators and screw geometry to improve screw filling, which shows encouraging results.
    , some powders, such as certain grades of silicon dioxide, still pose a challenge because of their very low accumulation density and strong electrostatic adhesion trends.
    technique is to treat the poorly mobile powder with the booster and then introduce it into the feeder.
    , for example, the active ingredients with poor fluidity are premixed with silicon dioxide to improve their fluidity before they are fed through a spiral feeder.
    , we have designed and developed accessories that are ideal for continuous production and have not encountered the above challenges.
    in the case of low flow feed, we are largely constrained by physical limitations.
    has a physical lower limit, and even for the most complex load cells, the signal-to-noise ratio becomes too low for effective weight control, which prevents us from feeding at too low a flow rate.
    management strategy is to premix low-content ingredients in the formula with another ingredient.
    Technology Transfer and Expansion Pharmaceutical Technology: What are the best practices for technology transfer or expansion for CM processes? Oka (Process Development Engineer): These advantages are many when developing CM products.
    development is on a scale, eliminating the need for rigorous scale-up studies like batch production.
    technology transfer is usually between very similar (size and other characteristics) or the same units.
    when developing on non-commercial devices, challenges arise.
    we still have no correlation to help us transfer processes between different equipment or process columns.
    Process Modeling Pharmaceutical Technology: How to use process models/digital mapping in CM process development/process control? What will be done in the near future? Oka (Process Development Engineer): The development of digital mapping is being carefully carried out for continuous production process training and individual unit operations, with a basic modeling framework that includes discrete element-based methods (DEM), balancing models, or other experienced and semi-experienced methods.
    popular application for digital mapping is to experiment with in-computer dwell time allocation (RTD).
    experiments can be performed at the unit operating level or at the entire process series level.
    of RTD enables people to track the evolution of process disturbances, which is a key element of today's control solutions.
    if the model is well calibrated, it allows the operator to "step in" directly and verify the required RTD, all of which can be done on a comfortable desk.
    applications also include understanding the impact of material properties and process parameters on process performance and the quality of the final product.
    digital mapping and even predict product performance, i.e. the performance of the drug in the body.
    Real-Time Release of Pharmaceutical Technology: Is Real-Time Release Happening? What are the remaining obstacles? Adao (QA Owner): Hovione has introduced all the required elements in order to implement real-time release inspection in the quality system.
    companies have successfully implemented it, and we believe we have all the conditions for implementation.
    there are technologies that enable real-time release inspection, such as online and inline PAT functions, automated control system design (e.g., equipment monitoring, material tracking).
    the appropriate control strategy of these two functions is the key element of implementing real-time release in CM.
    in Hovione, these functions are already in place and system confirmation has been made, taking into account the requirements of real-time release inspection.
    of potential challenges in real-time release implementations is the solubility test.
    in order to achieve real-time release, based on process parameters and key quality attributes (CQA), the model's solubility prediction values need to be used, so appropriate model maintenance procedures are required.
    to maintain parallel inspection procedures in the model and to conduct a controlled study of the corresponding laboratory/regulatory test methods.
    , in addition to performing confirmation work, there are many important tasks related to the model life cycle.
    As a commissioned processing company, we have been preparing for this type of release, and we recognize the benefits of doing so because it improves quality assurance, reduces release time, and brings overall benefits to patients.
    Ref: GainIng Experience in Continuous Manufacturing. August 14, 2020. Jennifer Markarian. Pharmaceutical Technology.
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