Lori Stansberry is marketing manager, Pharma & BioPharma, Thermo Fisher Scientific.

Lori Stansberry

The biopharmaceutical industry is always under pressure to deliver cost-effective therapies to market in the shortest time frame possible, while adhering to the regulations that govern manufacturing practices. In recent years, however, biopharmaceutical organizations have experienced additional analytical challenges, with the trend towards increasingly complex and strict regulations that drive deeper product understanding. Vendors have responded with innovative analytical technologies that better support advanced bioprocesses and the rigorous analyses required for quality control. While new advances promise to accelerate biotherapeutics research and manufacturing, the adoption of new technology brings its own challenges—both tangible and perceived.

Faster progress can be achieved when biopharmaceutical companies, vendors, and regulatory bodies understand each other’s priorities and challenges. By better understanding the specific needs of biopharmaceutical companies, vendors, and regulatory bodies can be better positioned to deliver innovative technologies and appropriate guidelines that efficiently integrate into existing workflows. Biopharmaceutical leaders, however, must not only be receptive to change to achieve productivity gains from new technology, but they must also be able to demonstrate the potential benefits to others within their company if the changes are to be implemented. In this complex and changing landscape, how can parties work together to achieve joint goals of safety, quality, low-cost, and speed? 

Over the last decade, there has been an unprecedented explosion of knowledge and technological advances, enabling deeper biological insights and new possibilities for the development of novel therapies. New classes of biotherapeutics have emerged, such as antibody-drug conjugates and gene therapies, creating a need for new regulations to guide manufacturing. Regulatory agencies support the manufacture of new modalities by developing guidelines in line with the principles of Quality by Design (QbD)—a systematic, process-focused approach to development. For manufacturers, navigating this dynamic regulatory landscape can be difficult, as they must keep up with the constant changes and find ways to remain compliant.

Often, more sensitive technologies are needed to enable the detection of impurities at low concentrations. Therefore, biomanufacturing companies constantly have an array of cutting-edge technologies presented to them, and they must decipher whether the potential value of adoption is sufficient to warrant the change within their manufacturing processes. While these technologies often have desirable qualities, such as process simplification and more detailed analytics, the thought of change and its associated hurdles can make it less tempting to make the leap. Resistance to embracing new technology may occur for a number of possible reasons:

It can be difficult and time-consuming to identify which technologies truly offer the most value and are likely to help solve a company’s challenges without creating new ones.

When introducing a new instrument, companies must develop and validate a new workflow to remain compliant, which often requires a significant time investment.

There may be a reluctance to accept the financial cost required to invest in the new technology, which not only includes the capital cost but also the cost of potential short-term downtime and delays, plus the training of staff.

While manufacturers would want to be aware of impurities posing a potential safety risk, there may be concerns that the new powerful analytical technology may bring an awareness of previously unknown impurities. In other words, some may believe that it is easier not to risk adopting technology with a higher level of sensitivity in case the new analyses create a need for additional work.

Resistance to change is a natural component of human psychology that doesn’t always serve us when we are presented with new, better ways of working. Consequently, committing to new technology and workflows, individually and as a team, can be challenging—even when innovative, streamlined approaches may lead to productivity gains and increased operator confidence. Such resistance is compounded when there is less opportunity to engage in detailed communication between the parties. This is often also seen between biopharmaceutical companies and regulatory bodies. When this is the case, regulatory bodies may be viewed as barriers to development, and the potential for mutually beneficial discussions and developments is further limited.

Shifting perception to see knowledge as a competitive edge

Regardless of the challenges involved in their adoption, the reality is that analytical instruments are key tools that facilitate the manufacture of life-changing therapies. In the competitive biopharmaceutical space, with the increasing regulatory guidelines, compliance-friendly and streamlined instruments are needed more than ever. Sensitive, specific, reliable, and robust instruments can have a huge bearing on the cost-effectiveness and success at each stage of drug development and manufacture, including process development, improving ongoing quality control, and batch release testing.

Increased efficiency is amplified most successfully when an instrument not only has built-in compliance features, but also delivers multiple data types. Such capabilities are desirable in today’s environment, where the QbD concept is encouraged. QbD principles drive efforts to design and develop manufacturing processes during product development to consistently ensure a predefined quality at the end of the manufacturing process (ICH Guidance, 2009 [1]). The multi-attribute method (MAM) is one approach suited to QbD and has gained popularity in recent years, adding a more high-throughput dimension to molecular analyses (2). MAM has been developed with mass spectrometry-based techniques and, as the name implies, enables multiple critical quality attributes to be assessed. Originally developed to monitor and quantify multiple post-translational modifications in biotherapeutic molecules, MAM enables more information to be extracted from the results of a single analytical method—and has the potential to improve efficiency by replacing other conventional quality control methods (2).

Not just the different analytical techniques, but the multiple data formats generated by MAM and other technology combinations can be difficult to manage and can cause issues when creating a robust audit trail. Whereas the use of multiple data formats creates more room for error and inefficiencies, a streamlined, built-for-purpose data software system decreases the burden on technicians and auditors alike. Central data systems are increasingly being designed to calibrate instruments, manage workflows, and provide real-time reporting across multiple technologies. Today, chromatography data services exist where combinations of gas, liquid and ion chromatography, and mass spectrometry can be managed through one system.

In order to continue the development of biotherapeutics alongside tightening regulations, there is a need to not only embrace innovative technologies, but also foster cross-industry collaborations. For biopharmaceutical companies, forming a long-term partnership with a trusted vendor who reliably delivers on their commitment can bring about wide-reaching benefits that extend beyond customer support. With the right cross-section of experts, vendors can offer a high level of technical and practical knowledge to complement the expertise found within biopharmaceutical companies.

As vendors are constantly designing systems to work within the highly regulated biopharmaceutical industry, they are well positioned to help companies develop workflows that ensure compliance and speed up the progression of the product to market. Therefore, leveraging a vendor’s comprehensive, up-to-date regulatory understanding can be invaluable for biopharmaceutical companies. Often, intricate knowledge is an indication of a well-connected vendor; when vendors help regulatory bodies understand the technology available to support compliance, in turn they also benefit from the partnership, which ultimately strengthens industry alignment.

Strengthening the industry through training initiatives

In recognition of the importance of experiential learning and shared perspectives, training laboratories have emerged to equip scientists and other industry professionals with the knowledge and skills required for the future, such as those related to document keeping, data integrity, and good manufacturing practices (GMP) inspection. At the Biopharmaceutical Analysis Training Laboratory (BATL) of Northeastern University, there are ongoing efforts to train regulators, students, and various decision-makers and industry leaders in the areas of biotherapeutic manufacturing, with special emphasis on surrounding regulatory issues. Providing professionals with the opportunity to obtain a deeper understanding of the analytical capabilities and realities of the laboratory helps give them the background knowledge they need to update guidelines and be open to new technology.

One of the key aims of BATL’s training courses, as well as providing access to skill-based credentials, is to reduce the fear around innovating in the analytical space. Such an approach is welcome for vendors who witness the hesitation around the adoption of new innovations first-hand—a frustrating experience when they believe the technology can help get a product to market faster and ensure better quality. Trainers at BATL have been encouraged to see increasing openness by regulatory authorities to industry conversations and innovation, as well as showing an eagerness to learn more about the changing biomanufacturing space.

When navigating the analytical and regulatory challenges within the biopharma space, it helps to remember that biopharmaceutical companies, vendors, and regulatory bodies are ultimately all working towards the same goal: to bring innovative, high-quality drugs to patients using the safest, fastest, and most economical approaches. Each party contributes to the space differently and can strengthen their own capabilities by forming strong partnerships.

Driving biotherapeutic development through open communication

By working closely with regulators, vendors can anticipate trends and stay one step ahead of biotherapeutic development. Bioprocesses can be optimized sooner when vendors clearly communicate the value, scope, and limitations of their technology, which is made easier when regulatory bodies are open to conversations around new technology and product innovations. In summary, open communication channels across all parties is critical to maintaining alignment across the sector and helps avoid unnecessary delays in implementing new ideas.

The biopharmaceutical industry of today is complex, dynamic, and increasingly driven by quality. It is an evolving landscape that holds exciting possibilities for the development of cutting-edge biotherapeutics and also prevents challenges for all parties involved. In order to move forward in this tightly controlled space, vendors, regulatory bodies, and biopharmaceutical companies need to communicate openly in order to anticipate opportunities and understand each other’s challenges. Collaborative and networking opportunities can be found in training initiatives, such as those provided by BATL, where each party can decipher how best to navigate obstacles and implement the innovations at hand.

Guidance for Industry, Q8(R2) Pharmaceutical Development

 (CDER, CBER, November 2009).
2. R.S. Rogers, et al., 

, j.auclair@northeastern.edu, is associate dean, Professional Programs and Graduate Affairs, and director, Biopharmaceutical Analysis Training Lab, Northeastern University, and Lori Stansberry is marketing manager, Pharma & BioPharma, Thermo Fisher Scientific.

To whom all correspondence should be addressed

Articles

Vendors are finding ways to address the increasingly complex analytical challenges in the biopharmaceutical industry to further biotherapeutic development.