It all started with the ancient Greeks

According to Greek mythology, scientific pharmaceutical compounding was first practiced in Greece around the seventh century BC. Pioneering the field was the goddess Hygieia, revered for her powers over health, cleanliness and sanitation, who also happened to be the granddaughter of the god, Apollo.

As the story goes, her physician father, Asklepios (Asclepius) Giver of Health, enlisted Hygieia’s aid to compound his medicines and various remedies. Hygieia also was credited with advancing early healthcare and medical hygiene; in fact, the term “hygiene” evolved directly from her name. The serpent often depicted in images of her is represented in the Rod of Asclepius, now a symbol of the American Medical Association and many other healing organizations, worldwide.

Of course, early pharmaceutical formulators didn’t have to reckon with global competition and economics, regulatory compliance and other issues we face today. They simply pressed their leaves, herbs or other raw materials into a solution, administered it, and hoped the patient survived.

But in the market-driven twenty first century, things are far more complex. To succeed, biotech innovators must address commercial as well as scientific elements of their business. As a result they must continually strive to reduce capital costs, manufacturing and operating expenses, and regulatory risks associated with bringing new products to market. Going forward, they also need to position themselves to quickly respond to the ever-changing future capacity and technology requirements of their industry.

With all of these strategic and technical considerations, it’s easy to see how the scientific side of pharmaceutical innovation has become just one facet of what began centuries ago in Hygieia’s primitive mortar and pestle.

A few thoughts on how bioprocessors can achieve their 21st century profitability and production goals:

• Single-use disposable technology; this emerging alternative enables processors to replace stainless steel vessels and piping with pre-sterilized, disposable plastic bags. These eliminate vessel cleaning and cleaning validation, along with the time and utility costs associated with these functions. Disposable technology also minimizes risk of product cross-contamination, improves process flexibility, reduces manufacturing space requirements and helps expedite product delivery to market.



• Optimizing gray space; many processors are reducing overhead through more flexible usage of costly clean room spaces. Repositioning closed equipment to less expensive unclassified spaces where it can be linked to clean areas for sampling, cuts down on the amount of clean room space needed, and helps reduce capital and operating expenditures.



• Modular fabrication; biotech manufacturers are discovering more ways to save time and capital by having critical process components and systems fabricated off-site for re-assembly in the plant. This has been used cost-effectively in assembling bioreactors, cell culture, buffer prep and hold, and clean-in-place systems, and can be easily implemented by coordinating system engineering details early-on in the fabrication process.



• Computer modeling; many drug producers are turning to early computer modeling of processes to isolate operating error at the source, improve product throughput and reduce cost of quality. This approach involves designing process configurations and operating parameters to meet commercial manufacturing and quality requirements, rather than strictly adhering to lab-based science and technology considerations. As an example, selecting buffers for compatibility with in-line dilution systems can virtually eliminate the need for large, fixed buffer vessels. In addition to enhancing product speed-to-market, this improves plant flexibility and cuts operating costs. In addition, Building Information Modeling, or BIM, is an innovative technique that facilitates seamless communications within architecture, engineering and construction. It represents a new way of working on projects that allows coordinated, consistent information for faster decision-making; provides better documentation at all levels, from concept to construction documentation; and enables modeled simulations that make it possible to predict performance before the project is constructed.



• Risk-based commissioning and validation; this concept makes validation members an integral part of the facility’s design team from the outset. In addition to facilitating regulatory compliance, the risk-based approach helps eliminate counter-productive duplication of effort while reducing validation time and expense.



• Sterile Finishing / Filling; Isolators increasingly make sense in biotech filling and finishing suites because the value of biologics per unit weight/ volume is so high.

Looking to the future, biotech processors need to recognize that successful design, construction and qualification of a facility are driven not so much by science, but by many implementation issues like the ones outlined here. This underscores the importance of building strategic partnerships with vendors and consultants who fully understand a processor’s economic, technical and scientific objectives, share in their corporate values, and have the tools and expertise to turn their visions into reality.

Do plastic bags hold a key to the future of pharmaceutical processing?

Apparently so. Or at least many drug producers seem to think so as they search out ways to create a safer, leaner, more flexible process chain; and one capable of operating with fewer resources, less plant infrastructure and within a smaller building footprint.

As a result, a growing number are doing what was once considered unthinkable. They are replacing their robust, fixed stainless steel reactors, vessels and piping systems with single-use components based on variations of the humble--and often defiled-- plastic bag!

Bioprocessors who have made the switch are claiming significant reductions in plant startup costs and construction time, up to 6-12 months faster than a conventional facility. Moreover, these measures directly impact the Holy Grail of pharmaceutical processing: enhanced product speed-to-market due to shorter product development, manufacturing, quality control and validation times.

These claims are also supported by economic comparisons of bags versus vessels that reflect a 15-25 percent reduction in capital cost requirements for disposables, with an added overall savings of 10 percent in cost-of-goods, depending upon size and applications.

Single-use technology offers many advantages, including:

• Simplified design and installation; by eliminating stainless steel vessel and piping fabrication, disposable technology reduces labor and time required to get a facility up and running. Simplified system design also minimizes validation time and complexity. Processors see a quicker return on their investment and faster product delivery-to-market.
• Savings in cleaning and validation; disposables arrive pre-sterilized and ready for use, eliminating the need for cleaning before and between batches. This results in savings on clean steam (SIP), clean air, clean-in-place (CIP) solutions, water-for-injection (WFI) costing up to $5.00 per gallon, and other clean utilities needed to flush contaminants and residual materials from piping and vessels.
• Enhanced product quality and safety; disposable components virtually eliminate cross contamination because contact surfaces are exposed to only one product, one time. Disposable packaging also reduces the risk of mishandling and misidentification of product during processing and storage.
• Improved efficiency and flexibility; disposables optimize plant efficiency by requiring less space than fixed vessels and piping. In addition, they offer greater speed and flexibility when manufacturers must reconfigure operations for a new process.

On the other hand, single-use disposable containers do have limitations, and may not be suitable for some applications, especially for larger scale batches and processes involving high heat ranges and caustic solutions. Other considerations include:

• Supplier reliability; processors must depend on vendors for cleanliness, compatibility and consistency of materials, as well as for reliable delivery.
• Environmental issues; depending on the process, some discarded disposable containers may be classified as hazardous waste and could present environmental concerns leading to added disposal costs.
• Limited capacities; disposable bag technology is currently limited to applications ranging from 500L up to 2000L. And filled bags can be bulky and require special storage and handling to prevent damage, especially when product solutions are processed in single use bags.

We have endeavored to present both the pros and cons of implementing disposable single-use systems as a means of optimizing bioprocessing operations. In considering such a transition, processors need to conduct, or secure the services of qualified specialists to perform, a thorough evaluation of their process, physical plant and future capital requirements in order to determine which approach will work best for their application.