Failing Fast at the Forefront of Innovation for Pharma Companies
In one sense, “failure” can be devastating for a biopharmaceutical company, but by failing early enough, companies can learn lessons, avoid unnecessary expenditures and conserve resources for other, more successful projects which can lead to better outcomes in the future. While no one likes to talk about failing along the way, failure is quite common and almost necessary for a process to succeed.
Biopharma companies are used to failure, as roughly 90% of clinical trials fail each year. But by “failing fast,” companies can take a step back, examine the problem and make the necessary changes to ensure success. Failing fast improves speed to market, ensures patient safety and confirms the product will work.
Incorporations of fail-fast methods and approaches are being folded into all aspects of life science research, from manufacturing, to the way the experiments are being performed, all the way down to what instruments are on the lab bench. All facets of pharmaceutical development actually lean into a “fail-fast” approach.
Build or outsource?
All pharmaceutical innovations must conform to cGMP requirements, which can be a major hurdle for a primarily R&D organization to overcome for the first time. Choosing the right option for such manufacturing and testing activities is critical to the fail-fast mantra.
Pharmaceutical companies typically face two manufacturing options: building their own facility or using a contract manufacturing organization (CMO) to do the work. There are potential drawbacks to each.
In building a facility, companies have complete control of their process, but this option takes considerable time and money, which is not feasible for smaller-scale or start-up companies. Additional timeline delays can build up due to supply chain issues and the establishment of cGMP infrastructure, personnel training, quality management systems and facility qualification.
With a CMO, developers often give up some of their intellectual property, have limited flexibility and face significant wait times. Not having complete control with a CMO won’t allow companies to make necessary changes to their process if an issue arises, which adds more time to the path ahead and certainly doesn’t enable the “fail fast” model. Additionally, CMOs can waitlist companies anywhere between 16 to 24 months because most contract organizations are at capacity.
Further complicating contract manufacturing is the lack of specific training in the organization for certain laboratory conditions or a lack of particular types of laboratory equipment required for some processes.
A new alternative to building or contracting
Because neither of these options is ideal for fast-moving organizations, pharma companies of all sizes are turning to a new approach to manufacturing, in which companies can license and customize cleanrooms to fit their manufacturing needs. Many advantages come with cleanroom licensing: having full control over the process, space, quality control, scheduling and other activities.
Some licensing companies also provide GMP and compliance advisory solutions and other services, such as materials handling and storage, that many early-stage companies are unfamiliar with. With so much flexibility, companies can “fail fast” and make the necessary changes to their process to keep their molecule moving forward.
One company at the forefront of this relatively new manufacturing path is Azzur Group which has a “Cleanrooms on Demand” offering. They have facilities in Waltham, MA; Vista, CA; and Burlington, MA; and are opening three new facilities in the United States in the coming year to keep up with industry demand.
Ravi Samavedam, chief innovation officer at Azzur Group, explains that “licensing cleanrooms is the middle ground between the traditional options that enable companies to focus on the science while we focus on the compliance. Our clients who are building their own facility or have current facility restrictions will use our services, so the science never stops.”
Lab bench in the sky
An experiment is the starting point for any new idea, concept or hypothesis. It allows scientists to reach conclusions that generate more questions about their overall mission. As the increase in research and development continues to surge, so are the ways in which experiments are being performed.
With the exponential growth in technology, companies are integrating automation, artificial intelligence and fractional laboratory services in the cloud into their daily work. This ranges from high throughput instruments to electronic lab notebooks (ELNs) and laboratory information management systems (LIMS). Some companies are going the extra mile by removing the scientist entirely from the laborious operational aspects of running an experiment.
Typically, scientists spend roughly 80% of their time at the lab bench with operating procedures such as setting up experiments, maintaining/fixing lab instruments, and hiring/training lab technicians. Only 20% of the time is left for data analysis and designing new experiments. This creates a bottleneck in research and development with the amount of time and capacity a scientist can run experiments.
Emerald Cloud Lab (ECL) is one company at the forefront of solving this problem. Located in South San Francisco, ECL’s facility enables scientists to run experiments from anywhere in the world. “By removing the operational burden of labs for scientists, we are giving them the power to run multiple experiments in parallel 24/7/365,” says DJ Kleinbaum, co-founder and CEO of Emerald Cloud lab. “The cloud lab is changing how experiments are performed so that scientists can push their research at an accelerated pace that will enable them to know if they are successful or failing in their research.”
Emerald Cloud Lab is the first-ever highly automated, secure and centralized research laboratory, housing 200+ different types of instruments that allow scientists to run all of their daily experiments through a single digital interface. Once a researcher has a new idea for an experiment, they can have their experiment up and running within hours. The exact process can take days or even weeks in a traditional lab.
Lab equipment and quality control
As more complex therapeutics, drugs and treatments come to market, the fail-fast philosophy applies at every level—all the way down to the equipment at the lab bench. Companies are strategically looking at how precise, sensitive quality control techniques can produce deeper data without sub-par materials creating the need to repeat experiments to see if a process will work or not. Using these lab techniques will help detect contaminants and ensure potency, purity and correct dosage so that the end product is safe for the patient. Furthermore, if anything were to go wrong, it could be flagged early in the process.
DNA detection and quantification are especially important parts of the biopharmaceutical manufacturing process for cell and gene therapies. In the case of CAR T therapy and manufacturing, a type of immunotherapy used to battle cancer by altering the patient’s own immune cells, the CAR transgene is introduced into the patient’s T cells and infused back into the patient to fight cancer cells. The level of efficacy may vary depending on which location the transgene integrates into the cell’s DNA and whether gene expression reaches target levels. Additionally, cell cultures are prone to bacterial contamination at every stage of the development and manufacturing process. Testing the therapy at every step is critical to patient safety.
To promote patient safety, scientists are turning to technology to conduct DNA testing on each batch of cells to reveal whether bacteria or replication-competent viruses are present within their therapy. The proper technology to provide a robust set of data will be the deciding factor on whether or not a therapy will fail fast or slow.
Traditionally, pharma companies have turned to quantitative PCR (qPCR) to carry out DNA testing for quality control during drug manufacturing. Although it is a common technique, this method has drawbacks and doesn’t ensure a fail-fast approach. qPCR requires scientists to generate a standard curve before comparing and interpreting the results. These steps are subject to human error, limiting assay sensitivity and reliability when measuring faint nucleic acid signals.
Among a host of quality control techniques, Droplet Digital PCR (ddPCR) is emerging as the most comprehensive by providing absolute quantification of nucleic acid molecules. Bio-Rad’s technology enables pharma manufacturers to count individual copies of DNA at a time, which is below the limit of detection for qPCR. Liquid samples are partitioned into 20,000 droplets, each containing either zero, one or a few DNA strands. During PCR amplification, the target sequence multiplies, and the DNA concentration within the sample is determined.
“ddPCR technology takes quality control testing to a whole new level for testing new therapies and maintaining quality for ongoing production,” says Marwan Alsarraj, biopharma segment manager at Bio-Rad Laboratories. “Delivering absolute quantification with an ultrasensitive technology allows researchers to develop a robust data set without needing to run standard curves to be confident in their results and the quality of their product,” Alsarraj adds.
Highly sensitive techniques such as ddPCR technology will allow companies to fail fast for new complex drugs, therapies or treatments. Doing so promotes reliable drug manufacturing and reduces the chance of setbacks down the road.
Pharmaceutical testing and manufacturing is a fast-paced pursuit that cannot afford to be hamstrung by limited access to space, laboratories, or the equipment necessary to determine whether a particular substance will yield beneficial results. The ability to fail fast is a legitimate and important business concern for pharmaceutical companies of all sizes.
At every point in the process, new technologies and service offerings are emerging to allow companies to understand the viability of a particular course of experimentation more quickly. These new approaches will ensure that successful future treatments and therapies will make it from the lab to the clinic faster than ever before.
About the author:
Bill Brydges was one of the original leadership members of bioKinetics, the first bioengineering EPCmV, Turnkey Design/Build firm in the United States, which became a renowned biopharma project engineering firm. He remained as President of Foster-Wheeler Biokinetics after they merged with Foster-Wheeler. Bill has 40+ years of pharmaceutical engineering experience and is currently CEO of Phylloceuticals, a global company dedicated to making affordable medicine.