Lean Changeover in Biopharmaceutical Facilities: Developing A Risk-Based Approach

Ten years ago, it was not unusual for an entire biopharmaceutical manufacturing facility to be dedicated to producing large volumes of a single blockbuster product. Today, the industry landscape looks vastly different.

Increasing approvals of biologics as well as the rise of orphan drugs and personalized medicines for smaller patient populations have driven the need for the creation of multiproduct manufacturing facilities. Large, single-product facilities are being superseded by smaller-scale, flexible, modular multiproduct facilities. Single-use technologies, the use of controlled nonclassified (CNC) spaces with closed systems, modularization, and continuous processing are often taking the place of fixed stainless-steel installations. These nimbly designed modular manufacturing facilities may even be moved to different locations should the need ever arise (1).

From almost every vantage point, the increase in multiproduct manufacturing facilities heralds good tidings for the industry. More products equate more benefits from facilities and, ultimately, increased availability of needed medicines to individual patients. However, as those who have already embarked upon the journey can attest, the shift to multiproduct facilities does not come without its challenges. 

Traditionally, product changeover has been a multi-tiered, multi-step process designed to eliminate any risk of cross-contamination. Stringent control measures are, of course, vital to protect the quality, potency, and purity of products and to ensure the safety of the patients who will receive those products. The traditional method of completely stripping down all equipment and installing dedicated materials and components for each product, however, has proven to be a cumbersome and costly process for multiproduct facilities. It is not unusual for changeover to require weeks to complete when traditional methods are followed. With the changing industry tide favoring multiproduct manufacturing facilities, methods to enhance efficiency without sacrificing quality or safety are needed. A scientific approach that uses a robust data set and that meets quality risk management principles can be adopted to significantly streamline changeover, enabling manufacturers to change from one product to another in a matter of days versus weeks.

Establishing Best Practices for Lean Changeover: The Case of Elastomers

Representatives from manufacturers across the industry shared their experiences with and approaches to changeover through a team assembled by the BioPhorum Operations Group (BPOG). Culled from its collective expertise, the team then developed guidelines for a data-driven, risk-based approach to changeover that aligns with regulatory guidance. The guidelines point to bench-scale studies, cycle validation, and lifecycle management as the key elements of a lean changeover model that provides manufacturers with the robust data needed to confidently identify and eliminate waste and redundancies and to enhance efficiencies without increased risk.

 One example of how a data-driven, risk-based approach can be used to enhance efficiency can be seen in the case of elastomers. Elastomers, or soft parts, are essential for the smooth operation of a biopharmaceutical manufacturing facility. These seals, filters, gaskets, and O-rings are designed to prevent leakage and to preclude certain fluids from coming into contact with one another.  Traditionally, prior to changeover, all elastomers are stripped and removed. Once the manufacturing equipment has been cleaned and rebuilt, dedicated elastomers for the new product are installed. This is a timely and costly process, particularly given the high volume of elastomers that are likely to be present in any given facility.

Some manufacturers have begun to transition away from this traditional approach; instead, data from benchmark clean-in-place (CIP) studies are used to perform a risk assessment. Oftentimes, these data show that elastomers can be properly cleaned during the cleaning process, thereby eliminating the need to remove and replace them, except during specified maintenance intervals. Thus, this scientific, risk-based practice results in reduced consumption, reduced waste, and offers significant savings of time and personnel resources as well.

BPOG estimates that 50% of biopharmaceutical manufacturing facilities have already adopted this streamlined approach. Given the pressures facing the industry as a whole-namely, to produce more products in less time, to meet regulatory requirements, and to do so without increasing risk-it is likely that other manufacturers will soon follow suit in a collective bid to enhance efficiency while delivering much-needed quality products to patients.

Reference

1.     J. Markarian, “Tracking Biopharmaceutical manufacturing facility trends: new facility designs enable flexible, multiproduct production,” PharmTech.com, Nov. 20, 2013, http://www.pharmtech.com/tracking-biopharmaceutical-manufacturing-facility-trends, accessed June 13, 2016.