Proper planning prevents poor performance

A growing number of biotech processors are finding wisdom in this axiom taken from an old British Army training manual. They’re recognizing the many benefits of developing third-party engineering partnerships, and integrating them early-on in the master planning process; ideally, at a project’s inception stage.

Pharmaceutical processors operate in a unique environment influenced by many variables, including: capital availability, diverse market demands, complex regulatory standards, global competition, and critical compliance and commissioning requirements. As a result, they must focus assets to best achieve a competitive advantage through innovation coupled with effective cost control and speed-to-market strategies. Accomplishing that requires the highest degree of process/facility design integration driven by comprehensive master planning.

In the traditional process design model, in-house engineers and planners develop a strategic plan and define a project’s parameters. Then, independent engineering and construction specialists are called in to formalize the design and help execute the plan. But there are flaws in that approach which might seriously impact a project’s potential for successful execution.

For starters, internal, organizational dynamics can inhibit objectivity essential to developing plans and processes that support corporate-wide initiatives. To address this, master planners must rise above territorial boundaries and stay focused on key goals. In some corporate cultures, that could present political challenges for internal managers.

In addition, corporate management runs the risk of limiting creative resources at a point where innovation is most critical, during a project’s formative stage. Experience shows that incorrect assumptions made in early planning often lead to costly revisions and construction delays later in a project’s timeline.

Commercial processors who integrate design/build partnerships early in the master planning process report significant, measurable payback for their efforts. In addition to minimizing risks, alliances can help reduce capital outlay and project delays, and cut validation and commissioning costs. These advantages go a long way toward improving a processor’s ability to compete in the fast-paced, changing pharmaceutical marketplace.

For optimum results, a master plan must be aligned with a company’s strategic business goals; and the planning process should involve high level decision-makers within the organization. Management participation is essential to ensure that a master plan supports the new product pipeline, planned acquisitions, cash flow considerations and other strategic issues.

Of course, the real value of planning partnerships ultimately depends on a vendor’s knowledge and understanding of the unique character of the pharmaceutical industry. This means having the expertise and resources for dealing with virtually any facet of the business, from product development and production through quality assurance, packaging and delivery.

When evaluating a design/build partner for master planning, clients should look for comprehensive pharmaceutical experience, preferably on the corporate side. Qualified candidates should demonstrate global vision, along with a track record of providing services to technically complex, compliance-driven industries. Longevity of client relationships is another indicator of a vendor’s stability and capacity to successfully handle challenges, and deliver sound planning solutions to satisfy the needs of all stakeholders within an organization.

Taking the human factor out of aseptic processing

On average, we humans shed up to 10 million particles of dead skin and other microbial contaminants each day, making us the greatest threat to most high-purity manufacturing operations.

Since the 1970’s, clean rooms have served as a first line of defense in the pharmaceutical industry’s war against microbial contamination. To meet aseptic processing standards, clean rooms rely on specialized HVAC air handling systems, sophisticated HEPA and other filtration devices, and rigorous decontamination practices. Protecting operators from the product (and vice-versa) requires sterile clothing and time-consuming gowning procedures whenever personnel enter or leave a classified area. In addition to increasing operating costs, these factors can disrupt productivity and adversely affect a drug’s speed-to-market.

Moreover, FDA mandates that a Class 100 (ISO 5) clean room be housed in Class 1000 (ISO 7) surrounding support spaces. This increases capital outlay, along with plant footprint and operating costs. As a result, many are exploring more effective options to ensure product purity by minimizing human intervention.

Remote Access Barrier Systems (RABS); these protect operators and product by placing an aseptic filler inside a rigid-walled ISO 5 enclosure. HEPA-filtered unidirectional airflow provides an aerodynamic barrier to shield the critical process zone inside the RABS. While glove ports are employed to facilitate operator access, a RABS enclosure can also be opened for operations that cannot be performed through the glove port. Typically, RABS can be located in an ISO 7 or lower environment.

Though lower in cost than other options, like isolators, RABS are not airtight so they present some risk of contamination due to operator contact and open-door access. In addition, RABS systems need to be disinfected manually, which requires environmental monitoring of the cleaning process, placement and reassembly of sterile components. RABS are used in pharmaceutical processing, and even more widely in food and beverage applications.

Isolator systems; an isolator as defined by FDA is a decontaminated unit, supplied with Class 100 (ISO 5) or higher air quality that provides uncompromised, continuous isolation of its interior from the external environment (surrounding clean room air and personnel).

Isolators completely remove operators from the sterile area and incorporate a physical barrier along with HEPA-filtered positive airflow to seal out particulate contamination. These systems have already been proven effective in many bio-processing applications in the United States, Japan, China, India and Europe.

Initially, isolators had a reputation for high capital cost and long decontamination times. But with today’s pharmaceuticals costing as much as $1000 or more per dose, the economic picture has changed. Improvements in product throughput and speed-to-market easily offset isolator upfront costs, enhancing ROI. Consistently high sterility and safety help minimize product waste due to contamination, and reduce the risk of product recalls.

Vaporized hydrogen peroxide (VHP) cleaning/sterilization in-place (CIP/SIP) eliminates the need to dismantle, sterilize and reassemble components, and minimizes environmental monitoring requirements. As a result, decontamination cycle times can be cut to about three hours. Moreover, validated VHP sterilization is recognized by the FDA as more effective and reproducible than manual sanitation.

Since isolator systems fit into a small footprint, users are finding greater flexibility in designing critical process lines to accommodate their product development and manufacturing needs. Each module contains an interlock port for connecting to other components, so isolators may be added, deleted or combined as a user’s process evolves.

Looking to the future, as experience builds greater confidence in isolator systems, pharmaceutical and biotech manufacturers will see even more technological advancements. Currently, innovators are exploring ways to expand the use of automation and robotics for enhanced product safety, productivity and reliability. Some even envision a future in which human operators could be completely eliminated from the aseptic process.