May 7, 2019

Demands to rapidly advance drugs while minimizing cost as well as maintaining sterility assurance and high safety standards are accelerating the pace of change across the fill/finish industry.  As medicines shift from one-size-fits-all treatments to personalized and small-batch drugs for rare diseases, the sector is also having to modernize to meet changing manufacturing needs.

With the quantity and diversity of drugs in clinical development rising across all major markets including the US, Europe, and Asia Pacific, the industry is experiencing a need for highly flexible manufacturing equipment. Small-batch products are on the rise, requiring automated systems that can robustly handle frequent product shifts. In response to these pressures, single-use technologies, automated systems, robotics, and modular technologies are increasingly being adopted.

While there is no doubt that this is an exciting time for the industry, and modernizations that help reduce costs, speed development, and increase product safety will ultimately benefit patients – a goal shared by all. But making these changes is no easy task for the sector – by the time therapies reach fill/finish, pharmaceutical companies have already spent millions of dollars to advance their drug, so there is no room for error.

Shifting to single-use technologies

Stainless-steel systems have been used for decades in clinical fill/finish manufacturing, however, the equipment is expensive to install and qualify, and requires dedicated cleaning methods with associated time and expense. As a result, the industry has been investigating alternative manufacturing methods and although resistant to change, have accepted that it is simpler to use and dispose than develop and/or improve cleaning methods1-3. Step up single-use technologies…

Single-use technologies eliminate between-batch cleaning time, shortening turnover times, increasing capacity, and reducing costs1-3. In fact, it is estimated that the total time saved using disposables ranges from four months to more than a year4. What is more, in contrast to stainless-steel systems which are expensive to modify, manufacturing changes are much more cost efficient to implement with single-use technologies. This flexibility is particularly beneficial for customers at the early stages of development, when future adjustments are likely5.

AMRI, for example, has adopted multiple single-use disposables, including single-use glass, or ultralow-density polyethylene (uLDPE) formulation and filling vessels, pre-assembled, irradiated filters and filling lines, and single-use isolators for operator protection to minimize the potential for product contamination. These risk reductions have been viewed favorably by external auditors and regulatory agencies, allowing auditors to quickly move beyond a focus on fill/finish, which, prior to the development of single-use systems, was an area of significant regulatory scrutiny6.

It is important to flag that single-use systems are not foolproof – employee training is critical in order to successfully implement sterility assurance management.

Automation

Automation is successfully used across many industries to improve efficiencies and reduce cost, so it is no surprise that the FDA has cited it as key for improving operator safety, reducing human errors, and improving drug quality in the fill/finish sector6.

Introducing an automated filling with closed restricted access barrier system (cRABs) within an existing cleanroom facility allows one to focus on developing modular single-use systems, including isolator containment, to maximize product diversity and expedite process turnaround. This kind of system delivers the sterility assurance levels required by regulators while allowing for swift changeover from product to product.

Automated filling systems within barrier systems and format-free robotics also have the major advantage of removing humans from cleanroom sterile core, thereby eliminating the primary source of environmental contamination7. In addition, automation also provides safety benefits for workers, protecting operators from potential exposure to potent products.

That said, while automation and robotics inevitably reduce direct operator involvement and headcount, there will still be a need for human involvement to appropriately qualify processes and maintain and troubleshoot any equipment issues.

Mix-and-match modular systems

In seeking maximum flexibility to support diverse product scales and allow rapid turnaround in production batches, modular systems are highly attractive and work well with automated systems and robotics. Modular systems enable plug-and-play capabilities, including switching out filling lanes, bags, or filters with universal sterile connections.

This allows significant scalability, providing companies with the ability to smoothly execute fill/finish on batch sizes ranging from less than 500 mL up to more than 100 liters. These rapid access flexible systems reduce impact on operator safety, which is particularly important with today’s highly potent APIs.

Taking action

As the industry adjusts to meet the changing needs of drug development, fill/finish providers that can offer technologies to address these needs will be in demand. By working with a solutions-oriented, culturally aligned partner offering modern solutions for the fill/finish process, you will be well positioned to bring ultra-safe products to market as quickly and cost efficiently as possible.

AMRI has in-depth knowledge in this sector and offers comprehensive capabilities designed to meet any need through the entire life cycle of a sterile drug product, whether for simple solutions or the most complex challenges. We have a proven track record with simple and complex liquid, suspension and lyophilized products and are experts in formulation development. Operating from state-of-the-art facilities utilizing equipment with best-in-class containment procedures that enhance sterility assurance, regulatory compliance and operator safety, we offer a complete suite of development and manufacturing services which help bring safe medicines to patients faster and more efficiently.

To find out more, please contact us.

References:

  1. Markarian, BioPharm International29 (5) 2016.
  2. Tyson, “How Single Use Systems Could Revolutionize Fill Finish Changeover,” NNE.com, www.nne.com/techtalk/speed-up-fill-finishchange-over-with-single-use-systems/, accessed May 11, 2018.
  3. J. Smalley, “Single-Use For Fill-Finish: Is It Worth The Risk?,” Pharmaceuticalonline.com, Nov. 7, 2016.
  4. Roth, “Disposable Technology—Use of Disposable Technology in Clinical Fill & Finish Manufacturing: Benefits & Considerations,” Drug-dev.com, April 2014.
  5. Markarian, Pharmaceutical Technology10 (7) 2017.
  6. FDA, “Pharmaceutical cGMPs for the 21st Century—a Risk-Based Approach,” FDA.gov, September 2004.
  7. Fuchs and S. Mauri, “Why Change is Inevitable in Aseptic Manufacturing?” Fedegari.com, January 2016.

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