Robots’ Role in Flexible Fill–Finish Lines

By Erik Greb

The pharmaceutical industry has a history of developing innovative medicines and

novel drug-delivery systems, but not all of its manufacturing processes use cutting-

edge technologies. Citing regulatory and technological reasons, drug companies

have been reluctant to adopt robotic automation for upstream applications, such as

isolated fill–finish, even though the automotive and semiconductor industries have

used robots extensively for years. But changes in the market, such as increased

generic competition and decreasing batch sizes, could make robots crucial to

drugmakers’ future success.

In terms of accuracy and speed, robots far exceed what the pharmaceutical industry

requires. But, for a long time, robots did not meet the industry’s requirements for

aseptic manufacturing. Operators could not decontaminate robots with hydrogen

peroxide in a way that could be validated. In addition, robots shed particles at

unacceptable levels and often were made of materials, such as aluminum, that were

not suitable for filling operations. But these problems have since been overcome,

and technological advances are no longer necessary for drugmakers to implement

robots. “They can do it today,” says Chris Procyshyn, CEO of VanRx Pharmasystems.

Many firms are trying to increase their flexibility to adapt to evolving patient needs

and new products. Robots’ key advantage is that they can provide this flexibility,

says Josh Russell, principal engineer in life sciencesat Automated Systems of

Tacoma. The vast majority of traditional filling machinery is dedicated to a specific

container format, such as syringes, vials, or cartridges, and this design limits its

capability. But robots integrated within an isolator–barrier system can fill–finish

various container formats aseptically on a single modular system, says Russell.

Robotic systems can minimize the operational and financial requirements for

expanding filling capabilities, and also enable facilities to be smaller and leaner than

before.

Robotic filling systems also can help maximize equipment uptime because

companies can change them over rapidly to another batch or product, regardless of

container format, says Russell. Reconfiguring robotic systems requires few change

parts, few process changes, and no manual adjustments, unlike the changeover

process for traditional filling lines. Robotic systems’ autoadjust functionality

manages production parameters and eliminates the need for operators to adjust the

system manually.

Although no scientific or engineering challenges are preventing the industry from

adopting robotic systems, the current emphasis on the strict control of change may

have a chilling effect on technological innovation, according to Jim Akers, president

of Akers Kennedy and Associates. It would be helpful for government–industry

partnerships to reconsider change control as a requirement, and re-examine

regulatory submission and review procedures for process improvements and

innovation. “We need to find ways to encourage innovation and ongoing

improvement without increasing concerns about changes affecting product quality,”

says Akers.

To other observers, regulators seem to understand the advantages that robots can

provide. “I don’t believe the regulators are standing in the way,” says Procyshyn. “If

you come back to the regulators and say, ‘I can achieve a six-log decontamination, I

operate at ISO 5 for particles, and I completed all of my validation media fills,’ the

response from the agency is going to be, ‘OK. Sounds good to us.’”

The introduction of new products could spur the development of new and

innovative robotic production lines. “I think many newer products and associated

delivery systems absolutely require both automation and isolator or restricted-

access barrier approaches either to mitigate contamination risk or to reduce

operator exposure risk,” says Akers. “The move to greater automation is a reality in

all manufacturing industries, including pharmaceuticals and biologicals.”

The future of aseptic manufacturing may come to rely heavily on robotic systems.

Drugmakers are slowly abandoning the idea of discovering blockbusters and filling

millions of units. Today’s clinical pipelines include many products that are highly

specific to particular patients or patient subpopulations. These products will call for

smaller batch sizes in production and more changeovers. Flexibility will become

paramount, and robots will help manufacturers achieve it, says Jörg Zimmermann,

director of process development and implementation at Vetter Pharma-Fertigung.

The regulatory atmosphere, current technology, and the characteristics of

developing pharmaceutical products seem to favor industry’s adoption of robots for

aseptic filling. “I don’t hear anyone saying that they don’t think robots are the future,”

says Procyshyn. “The questions are how, where, and who, but it’s coming, for sure.”