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FLEXIBLE FACILITIES

Manufacturing trends offering benefits

Sean Riley, Senior Director Media and Industry Communications PMMI the Association for Packaging and Processing Technologies

Modular facility design is a potential gamechanger for biopharmaceutical manufacturers It allows those companies seeking a more efficient sustainable building method the ability to grow or change locations This design option which implements standardised pieces that can be used as simple building blocks for factory setup allows for flexibility and easy expansion

In the early 21st century, one of, if not the primary goal of a pharmaceutical facility was to maintain large production lines and attain exceptional productivity and product throughput. Today’s pharmaceutical industry embraces smaller, more modular and flexible lines, with shorter lead times. The primary industry driver away from the big factory model is the growth of personalised medicines, the need for smaller batches and regionalised manufacturing.

An excellent example of regional manufacturing is vaccine manufacturing, particularly in underdeveloped markets. (As the pharmaceutical marketplace continues to globalise, the expanding middle class in “pharmerging” countries. China, Brazil, Russia, India, Algeria, Argentina, Colombia, Bangladesh, Indonesia, Mexico, Nigeria, Pakistan, Poland, Saudi Arabia, South Africa, Philippines, Turkey, Romania, Chile, Kazakhstan and Vietnam—now have access to supply chains and more importantly, money, for healthcare and vaccines1.)

Some years ago, there was a disruption in the global flu vaccine supply due to equipment cleaning issues. This led to more localised vaccine manufacturing and greater use of single-use components. The industry has come to view regional vaccine manufacturing as more cost-effective and ultimately safer. It eliminates some of the logistical headaches associated with getting vaccines to other countries with limited infrastructures and, in turn, has led to the growth of more modular production facilities.

In short, the industry is moving away from the big factory model. We see today more off-the-shelf performance modules that enable drug manufacturers to select components with shorter lead times. This also aligns with the growth of personalised medicines in which batches are smaller. Along with modularity is the trend of equipment with toolless changeover. Being able to pull out components and replace them quickly is partly the result of the rise of single-use modules and helps reduce downtime significantly2.

Single Use

Every pharmaceutical company looking to turn a profit understands the value in reducing manufacturing costs while maintaining a supply of drugs to treat patients. Yet the biopharmaceutical industry per its reluctance to change has been slow in transitioning to modern technologies for achieving these goals.

Currently, a paradigm shift in biopharmaceutical production is underway with the convergence of two complementary modern technologies, single-use systems and continuous production methods. Single-use pre-sterilised and disposable polymer-based components eliminate cleaning, sterilisation and associated validation steps. They also diminish contamination risks in product change-over, reduce manufacturing and energy costs, minimise plant footprints, and save time and labor. The environmental impact is favourable when compared to reusable steel equipment.

Years ago when the U.S. Food and Drug Administration (FDA) first allowed biotech manufacturers to go from producing biological products in dedicated facilities to providing multiple products in the same facility under the condition that the equipment met certain cleanliness thresholds, manufacturers began investigating single-use technology as high classification clean-room facilities are costly. With no standard definition of “clean,” defining cleanliness and proving clean equipment to an adequate level proved very difficult. Switching to single-use machinery removes the question of cleaning validation and speeds product time to market.

Single-use equipment—per its name—is used only once in a pharmaceutical manufacturing facility. Each new batch of pharmaceuticals (or in some cases, each campaign) requires new pieces. This eliminates the need for equipment cleaning and re-sterilisation throughout the manufacturing process, saving time and costs. Manufacturers do not need to halt production or allocate extra time to prepare the various components for the subsequent batch. They also no longer must purchase cleaning supplies for that purpose, dispose of used cleaning fluids, or use excessive amounts of water for cleaning, rinsing, and steam generation. Reducing cleaning materials, eliminating downtime, and keeping production in motion lead to overall improvements to the bottom line.

More significant benefits of the single-use design lie in alleviating concerns of facility equipment being unclean or compromised. Replacing pieces with systems that are virgin, pre-assembled, and pre-sterilised eliminates the worry about sterilisation, cleanliness, or exposure. Using fresh materials means the drug has a lower risk of contamination during production. Ultimately this benefits consumers and helps protect brand reputation.

Despite reducing bottom line costs for manufacturers, at first glance, single-use facility design seems to run counter to the pharmaceutical industry’s commitment to sustainability. Typically, the terms “recyclable” and “reusable” go hand-in-hand with sustainability. Manufacturing components are usually required to have these characteristics to qualify as environmentally friendly; however, in the case of single-use components, the matter is not so simple.

Made from a combination of plastics that are not themselves recyclable, incinerating or melting down single-use systems and converting them into reusable energy makes the systems infinitely recyclable. Eliminating the cleaning and sterilisation processes for the materials save significant water and energy. For manufacturers considering switching to this type of facility design, a big picture perspective is critical. Although single-use pieces do not appear to be eco-conscious at the outset, they do offer pharmaceutical companies a long-term investment in sustainability3.

Even with all the benefits, there are still challenges in implementing single-use systems. Currently, the biggest issue is to qualify the safety of extractables and process-derived leachables from fluid-contact plastics. While analytical methods exist, Good Manufacturing Practices (GMP) regulations require a demonstration of safety. The FDA does not prescribe the extent of studies and allowable limits, challenging suppliers and users with anticipating what and how much data is expected by regulatory authorities. Recently, several industry organisations published a standardised consensus recommendation, and USP is developing a standard. However, since regulatory authorities consider safety and quality aspects of extractables and leachables on a product-specific basis, there will always be some user and regulator judgment required and extractables and leachables data will never be standardised for all drug products.

When looking for a single-use solution, there are some critical issues to consider. It is important to ensure that the suppliers’ manufacturing processes are validated. Be sure suppliers have sufficient data to demonstrate the reliability and safety of their products, and that they have adequate quality systems in place. Another consideration is useful data on the consistent supply of raw materials. A robust change management and change notification system need to be in place to ensure minimal change along with clear change notifications. There is a concern when a supplier makes changes to the raw materials that affect the extractables and leachables profile. Look into security, continuity, adequacy of supply.

Qualifying must go further than just documentation. It’s essential to audit all suppliers consistently.

More Modular, More Flexibility

Modular facility design may also be a game-changer for pharmaceutical manufacturers seeking a more efficient building method and the ability to grow or change locations. This design option, which implements standardised structures as simple building blocks for the factory setup, allows for flexibility and natural expansion. With these modular components, manufacturers can assemble a facility in a fraction of the time needed for traditional installation, saving costs and building time. These pieces also do not require the expense of stainless-steel tanks and piping for the transport of rinsing materials, cleaning solutions, and steam seen with traditional stainless-steel design facilities, so they are not as difficult to assemble and cost less4.

No pharmaceutical company predicts their drug failing in the marketplace, but the modular design allows for quick dismantling or conversion if a drug isn’t successful and production must cease. The parts can be rearranged with relative ease to fit the model for a new drug. The standardised nature of the modular pieces also means a manufacturer has flexibility in factory size. A facility can shape-shift relatively quickly to accommodate the size and setup required for a different drug. A manufacturer can even build vertically if they need less square-footage.

Standardising manufacturing materials and equipment may also help speed up global pharmaceutical expansion. If each piece of equipment in a facility is similar or standard, companies can mix and match the pieces as necessary depending on product and location. Also, if they all fit together in the same way, adding or subtracting from a facility can be attached or detached with ease. Often pre-fabricated and shipped in containers, modular pieces are suitable for manufacturers looking to open new facilities around the world. If they use components that reflect this standardisation and familiarity, sophisticated facilities can be replicated in markets where construction might otherwise be difficult or, in some cases, impossible.

Additional global facilities are key for pharmaceutical manufacturers looking to meet international demand for vaccines and other drugs already maximised in North American or European markets. Standardised modular facilities with single-use equipment can be assembled anywhere in the world and are not dependent on sophisticated local engineering, capital, and resources. By using a modular facility design in developing countries, pharmaceutical companies can build facilities more cost-effectively, allowing them to set local drug or vaccine prices to meet emerging market needs5.

Single + Modular=Lower Cost

The result of this increased control is the ability to quickly change the flow or size of production as necessary, suggesting less labor, lead time, downtime and new equipment costs. Manufacturers can match their facility set up to reflect changes in their sales or to adapt to market trends and needs. It is this open-ended flexibility and decreased risk of capital loss that makes a modular facility design highly appealing.

Although each type of facility design offers its own benefits if a manufacturer implements both single-use and modular facility design in one system, options for flexibility and cutting costs may be unmatched. Modular pieces of equipment can be designed as single-use materials, which can result in smaller or low-level cleanrooms and standardised steps of purification. Marrying these methods can also cut down on resources and assembly time, reducing costs on a pharmaceutical manufacturer’s entire operation. Combining these facility designs may also allow for a speedier entry into the market6.

References:

1 https://www.packexpointernational.com/big-changes-big-pharma
2 https://www.pharmaceuticalonline.com/doc/major-trends-in-pharmaceutical-packaging-0001
3 https://www.pharmaceuticalonline.com/doc/modular-facility-design-single-use-equipment-considerations-for-pharma-manufacturing-0001
4 https://www.pharmaceuticalonline.com/doc/modular-facility-design-single-use-equipment-considerations-for-pharma-manufacturing-0001
5 https://www.pharmaceuticalonline.com/doc/modular-facility-design-single-use-equipment-considerations-for-pharma-manufacturing-0001
6 https://www.pharmaceuticalonline.com/doc/modular-facility-design-single-use-equipment-considerations-for-pharma-manufacturing-0001

--Issue 36--

Author Bio

Sean Riley

Sean Riley is currently PMMI’s Senior Director, Media and Industry Communications. He was Editor-in-Chief for PMMI’s Packaging Machinery Technology Magazine for nearly a decade and has over 20 years of experience working with and as a member of the packaging and processing media.

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