In today’s healthcare landscape, patient safety is becoming even more important. Finding the best and safest solutions for patients has become a key driver of business within the pharmaceutical industry as a whole. As equipment, component, drug dosage and medical device manufacturers gain a greater understanding of patient needs, they have each begun to offer more patient-centric solutions.
In addition to offering different types of products with novel delivery systems, companies are changing the way they implement manufacturing processes — again, based around patient safety. New digital technologies are being used to help manage manufacturing operations and, perhaps more importantly, track patient behaviors to enable enhanced product development. Many companies are increasingly focusing on how they can help patients through better communication and the offering of comprehensive services rather than just drug compounds.
One of the biggest changes in the pharmaceutical industry underlying these overall trends is the move away from the development of new medicines that meet the needs of large patient populations and toward the development of personalized medicines. The former typically carry a lower cost per dose, but often do not work optimally on the level of individual patients.
The leading personalized medicines include gene therapies, cellular therapies, oligonucleotide therapies and chimeric antigen receptor (CAR) T cell therapies, but many new immunotherapies also could be classified in this manner. These highly targeted medicines are designed to treat patient populations with specific genetic or other disease characteristics.
From a manufacturing standpoint, this means a batch no longer consists of 70,000 doses, but perhaps eight to ten doses, or even just one. The consequences are enormous; the entire approach to manufacturing, as well as the way patient information is managed, is very different for these therapies.
Significant changes are occurring even in traditional, lower-cost dosage forms. The delivery of many next-generation medicines requires new technology. Conventional biologics are typically administered from an intravenous (IV) bag in the hospital or as an injection from a prefilled syringe or a syringe filled from a vial. Those approaches often are not applicable for cell and gene therapies, for which extensive cryogenic operations may be involved. As a result, dosage forms and processes are changing rapidly, and innovation is being driven into all aspects of the pharmaceutical supply chain.
Facilities for the production of lower-cost drug infusion solutions are changing to enable the production of different types of IV bags and delivery systems designed specifically to meet the needs of cell and gene therapies. This change is new for this market. Unlike the high-cost next-generation drug market, the IV bag market is an extremely low-cost-per-patient market that has focused largely on achieving cost competitiveness.
Today, however, the need to address specific patient needs and patient safety — and operator safety — is impacting even this aspect of the pharmaceutical industry. These facilities are implementing more computerized and mechanized methods of manufacturing with reduced human interactions and potential for operator error to increase quality and patient safety. Platforms based on data acquisition and tracking are also impacting the input methodology associated with manufacturing equipment to enable trending for better decision making and cost control. As a result, low-cost-per-dose configurations that in the past ignored innovation are becoming highly innovative.
To date, these initial forays into digitalization and the move toward Industry 4.0 have been limited to a few early adopters. In general, equipment manufacturers do not yet fully understand the level of data involved, nor are they positioned to provide equipment that can process and leverage these large quantities of data. It is difficult to drive new standards into pharmaceutical equipment, particularly equipment with communication capabilities, which involves rethinking individual components (e.g., sensors).
In addition, most analysts and scientists do not yet know how to utilize the data that is currently available. The question of whether an issue should be considered a single point problem or a trending problem, which depends on the criticality of the data, has in many cases not been answered.
The use of artificial intelligence (AI) in systems that learn and refine process faces other roadblocks. The principal barrier is the fact that, in the pharmaceutical industry, manufacturing processes are expected to be highly consistent and repeatable to ensure quality and patient safety. Good Manufacturing Practices (GMPs) have been established to ensure that drugs are produced using well-understood and well-defined processes. Change management is a key component — driving AI into equipment so that it can decide to make changes based on trends or function goes against this core principle.
When it comes to Big Data and digitalization, it is also uncertain whether management executives understand the impact that the move to Industry 4.0 is having on hiring and staffing decisions. A recent CRB survey of clients revealed that one of the biggest pain points in the industry today is the inability to find qualified job candidates.
As the pharma industry transitions into the Industry 4.0 paradigm, the skill sets needed for new hires are changing dramatically. Instead of simply recruiting operators with college degrees, it is important to find individuals with computer science degrees that can serve as control or automation engineers. Unfortunately, the college education system is not keeping up with these needs. As a consequence, in some cases, location decisions for new facilities are primarily driven by the ability to access a sufficient base of qualified employees.
These issues are compounded by the rapid pace of change in the pharmaceutical industry, particularly in the cell and gene therapy space. In five years, the manufacturing technology and supply chain for these next-generation medicines will likely look nothing like it does today.
This rate of change can be exciting for experienced companies like CRB, because with each job, new technologies are available for consideration. It also increases the need to build flexibility into every facility to allow future modifications to be made to accommodate forthcoming innovations — while also ensuring that projects are easier, safer and as cost-effective as possible.
The move to modularity has expanded beyond modular construction approaches and modular facilities (e.g., pods) to include modular equipment (e.g., single-use technologies) and modular production (e.g., bulk manufacturing and packaging at different locations). Modular designs are also often needed. These solutions allow pharma companies to invest in new multi- product facilities where it is required initially, as well as to ensure accommodation of future changes; such designs take significant thoughtfulness.
At CRB, we recognize that our staff needs to be more informed, more innovative and more thoughtful than ever before. With the increased focus on patient safety, the rapid pace of change in the pharmaceutical industry and ever-shortening project timelines, our clients are looking to CRB for turnkey solutions. In addition to engineering and construction support, they seek assistance with verification, qualification and training. In essence, they want CRB to help them go from the design stage, including the performance of risk assessments, to an operational state.
We have responded to this need and now offer a whole range of services. For each project, we sit down with the client and discuss the right method and approach for achieving that operational state. We work diligently to first observe each project from the client perspective. The goal is to identify what assistance is required from CRB to get the client to where they need to be when they need to be there, and at a reasonable cost.
CRB has invested in the development of a lean approach to project delivery, from document development and management to design and construction efforts. We have investigated the various human behaviors associated with effective teamwork and implemented approaches that enable our teams to work better together and achieve results more quickly. As a result, our clients benefit from shorter times to project completion and better cost control. Improving and saving patient lives is what matters; our lean approach to executing, engineering, construction, verification and all other activities required to achieve a successful startup is designed to increase efficiencies and help get novel drugs to market as rapidly as possible.
At the same time, we are excited that the pharmaceutical industry is just beginning to cross the boundaries into truly novel areas of innovation, including processes, tools and functions that have the potential to dramatically improve drug product manufacturing.
Christa has been in the pharmaceutical industry for over 25 years and is a leader and Subject Matter Expert. Christa is a well-recognized speaker at conferences and is frequently on-stage teaching others about regulatory requirements, operational issues, and what to expect in the future of the industry. Christa champions approaches that integrate strong project execution and technical solutions. Christa is on the Steering Committee for the ISPE Community of Practice for Sterile Products Processing, a certified ISPE Instructor of the Sterile Product Processing Baseline guide, the Chair of ISPE’s Women in Pharma group, as well as an author of the most recent ISPE Sterile Processing Baseline Guide. Christa provides guidance and leadership to clients on how and when to utilize common or innovative solutions and continuously promotes the technical growth of people willing to learn more to advance the industry. She was recently awarded an honor as a 2019 Influential Woman in Manufacturing.