Recent trends facing the pharmaceutical industry pose numerous challenges to manufacturers. Large and small companies focused on both small molecule and biological therapies must conduct operations in accordance with cGMPs and protect their employees and the environment from exposure to the increasing number of highly potent actives being developed today. At the same time, cost control has now more than ever before become a primary issue for all players in the industry.
Equipment manufacturers have responded to the changing conditions with the introduction of technologies that require lower capital investment, provide improved efficiencies and the enhanced containment levels necessary for potent substances. Isolated systems and the availability of a wide range of disposables with applicability from lab to commercial scale, and throughout the entire production process from reaction to final filling and packaging, are helping to dramatically improve operating efficiencies (and thus reducing costs) while increasing employee protection.A recent conference organised by the International Society for Pharmaceutical Engineering (ISPE) at Bosch Packaging Technology in Waiblingen (Germany) focused on these issues. Speakers from both pharmaceutical and CMOs exchanged information on technical approaches to containment design. They also discussed key trends in high containment, including protection of employees, avoiding crosscontamination, cleaning processes and new equipment options for filling operations.
The containment conundrum
The need for a better understanding of high containment is driven by the rapid growth of the pharmaceutical market. Just 10 to 15 years ago, only a small fraction of drugs were classified as highly potent compounds. Today, that percentage has been multiplied many times over and will continue to grow as highly potent compounds are developed to treat chronic heart disease, musculoskeletal problems, central nervous system disorders and other health problems, as well as cancer. With highly potent drugs, much less active ingredient is required in the final formulation, which leads to cost savings for manufacturers. A rising interest in personalised medicine is also leading to the development of targeted therapies, which often require highly potent actives.
Working with potent compounds presents a different set of manufacturing challenges, though. Although these drugs can be highly effective at fighting disease, they can pose a real threat to healthy people and thus present a heightened exposure risk, leading to the need for higher containment levels, which in turn require higher investment costs compared with non-potent drugs. Smaller market sizes for these specialised products means that most manufacturers need to produce multiple products in a given facility. GMP requirements for cleaning validation of systems can be time consuming and add significant cost too.
Isolating the problem
Approaches to containment of highly potent drugs are evolving — as attendees at the ISPE conference learned. At the conference, attendees recognised that over the past several years there has been an increase in attention paid to operator and environmental safety at the development and production stages within the pharma industry, with an emphasis on equipment engineering as the primary solution.
Early containment programmes focused on personal protection for the operators, according to Dr Bernd Mümmler, Director of Pharmaceutical Production for contract manufacturer Excella. "Now we have a three-step approach, and personal protective equipment is the third line of defence, serving as a back-up only to equipment design and use of specifically adapted procedures."