As we bid farewell to 2016 to face the opportunities and challenges of 2017, the global life sciences industry can be best described as being on the cusp of great change. For the last ten years, U.S. market growth has been transitory, with M&A activity defining the primary defensive strategy to stifle global competition and pricing pressures. Yet, continued growth in the virtual biotech sector elevates the importance of a cohesive outsourcing strategy for the successful development of a commercial product. The FDA’s new fast-track and breakthrough drug regulatory programs have been embraced by both industry and FDA as a conduit for novel drugs to get to market faster. However, the combination of faster review and approval cycles and outsourcing as the primary development framework has put greater emphasis on CDMOs and CROs to support the CMC and quality elements of the development program that were historically reserved for the drug developer.
Better Diagnostics Drive Insight
Change is driven by several factors. First is the unprecedented evolution of better tools, i.e. the trend to new therapies that rely on new sources of data made available as technology advances. Genetic engineering is a case in point. CRISPR - Clustered Regularly Interspaced Short Palindromic Repeats - a genome-editing tool, gives researchers the ability to quickly and easily target and study particular DNA sequences in the vast expanse of a genome, even providing the potential for treating disease by editing the genes of human embryos. Scientists have been able to edit genomes for nearly a decade but early techniques were expensive, costing $5000 or more per test. CRISPR costs as little as $30 per test and is a big reason for the breakneck pace we see in the field of genome research. With gains in speed and ease of use, editing DNA is but one trick that the CRISPR tools can be used for. Scientists are hacking the tools so that they can send proteins to precise DNA targets to toggle genes on or off, and even engineer entire biological circuits with the long-term goal of understanding cellular systems and disease.
New data brings new diagnostic capability and is the catalyst for the escalating interest in Companion Diagnostics. A companion diagnostic can be an in-vitro diagnostic device or an imaging tool that provides essential information for the safe and effective use of a corresponding therapeutic product. The use of companion diagnostics will allow physicians to identify patients who have specific disease states derived from specific root causes such as a specific genetic anomaly.
Personalized medicine, sometimes called precision medicine, seeks to stimulate the body’s own immune system to attack cancer cells. Combined with a companion diagnostic the potential for precisely tailoring of a drug therapy is unprecedented and represents the potential for a huge change in disease therapy. CAR-T cells (Chimeric Antigen Response-T cells) are engineered proteins composed of two distinct functional components. The first consists of an antibody fragment or target-binding domain that allows CARs to recognize targets that are present on the surface of cancer cells. The second provides signals that rapidly and powerfully activate the T-cell to attack and kill cancer cells. The personalized element is that the treatment uses the patient’s own white blood cells to modify the T-cells.. The challenge industry and FDA regulators face is how to modify the current definition of fit for use. The quality definition for conventional drug products and processes is based upon demonstrating process reproducibility and an effective control strategy. That paradigm goes out the window when you are only making one lot, along with autologous white cells to build a single lot with targeted functionality and critical quality attributes. Stage 2 process validation no longer applies in the conventional sense. How industry and FDA define the quality requirements will influence how quickly personalized medicine programs gains traction.
Outsourcing’s Responsibilities Escalate
Outsourcing has long been a component of the drug development lifecycle but the last decade has shown decided growth in the breadth and depth of responsibilities assumed by Contract Service Providers (CSPs). The move to a global supply chain has caused industry to rely upon CSPs for everything from early molecule identification to clinical and commercial manufacturing. This evolution creates challenges for organizations that were historically built and operated on vertical development and manufacturing models, particularly as they relate to the Quality Management System. Accommodating collaboration models between multiple developers confounds the roles and responsibilities that are typically solely the domain of the development organization. Within the U.S., virtual biotech continues to be a growing presence and the sector is utilizing CSPs for everything from method development to process design and regulatory filings. The challenge with each of these market evolutions is to align quality and development systems with the capabilities and constraints of each CSP. To embrace outsourcing as the core development model means having to modify the quality structure and formalize how and where all operational and quality systems interact.
Another driving factor behind the growth of biotech and virtual biotech has been the evolution of combination products as a vehicle for broadening the potential patient population for many disease therapies. By moving away from IV infusion as the route of delivery for many biologic drug therapies, auto-injectors and prefilled syringes make it possible to treat disease without a hospital or clinical visit. However, there is complexity associated with merging drug and device quality systems. The FDA has made major strides toward clarifying their minimum expectations by issuing 21 CFR Part 4 which articulates, at a minimum, what parts of CFR 210/211 and 820 are applicable. However, the practical challenges of aligning both quality paradigms remain.
Data Management Will Become Strategic
There are several major initiatives within the industry that will be disruptive in terms of business strategy and execution. One is the next step in the Drug Quality Security Act- H.R. 3204, legislation that requires all manufacturers to have serialization in place by November 2017. Serialization equipment and control procedures are not inexpensive and can easily cost $500,000 in hardware and software solutions per packaging line. The control and reporting elements will require the creation of infrastructure that must manage a practical framework across legacy and new customers. Beyond the normal system integration challenges when engaging a CMO focused on quality and the supply chain, the need for transparency as part of the serialization process will impact the IT architectures of both the CSP and the customer. Currently there is no formal mechanism in either the Supply Agreement or Quality Agreement structure for handling this shared responsibility.
One innovation that is already having a huge impact on not only the industry but society in the broadest sense is the integration of smart technology. The “Internet of Things” (IoT) deployed in the industrial sector and making inroads in the consumer sector is providing unprecedented access to behavioral and decision making data. Lifestyle technologies measure everything from diet and exercise to how much sleep you get. The Industrial Internet of Things (IIoT) is a network of sensors that collects data in real time and transmits the data to other machines or people using the cloud or other systems. This data can build upon existing data acquisition systems such as Supervisory Control and Acquisition Systems (SCADA) or Distributed Control Systems (DCS) although they typically can measure other types of data. The IIoT has the potential for real time data access and analysis and there are myriad hardware and software solutions from major manufacturers to build this capability within our industry. These systems are being used in many innovative ways on the factory floor, including modular intelligent facilities and equipment designed to measure and report their operations on a continuous basis. This information is being used by the industry to generate predictive analytics that can be used to inform operational and clinical design. One area of significant concern is the security of data generated by IIoT devices. These systems typically communicate via Bluetooth or Ethernet with IIoT devices typically connected an IP network to the global Internet. Although these architectures are by design, simple they can be vulnerable to Man in the Middle (MIM) cyberattacks where an attacker secretly relays and possibly alters the communication between two parties who believe they are directly communicating with each other.
Clinical trial management has seen significant transformation over the last five years thanks to the ubiquity of smartphones and the maturity of mobile patient interfaces. New software applications are designed to meet GCP requirements as well as CDISC/CDASH elements of good clinical data management and have dramatically reduced the cost of data input. Any patient data being captured and transmitted must meet HIPAA privacy requirements for data security. Today these security and privacy requirements are relegated to the project level however, the consequences of non-compliance will be greatly elevated because of regulations associated with the Good Data Protection Regulation slated to go into law in Europe in 2018. This new regulation will expand the definition of privacy and comes with potential punitive damages up to 2 percent of an organization’s global revenue! These issues, compounded by Clinical Data Transparency requirements which have been required by law across all EU member states since 2013 will move data management to the forefront of any business strategy for drug developers.
Issues surrounding data privacy and cyber security are intimately linked. Cyber security breaches consistently make the headlines as the instances of ransomware increases and the depth and extent of data breaches continue to escalate. Complicating any countermeasures are the varying levels of cybersecurity requirements across the global supply chain. Some governments that do not embrace the same privacy requirements complicate both the architecture and reporting solutions for data security and privacy.
What's Next
Historically the pharmaceutical industry has lagged behind other markets in terms of its integration of technology, often citing the limitations created by regulation as a main justification for not innovating. However, this is changing. Technology as a framework to provide new and better tools for drugs development will dominate the regulated life sciences, and will have to meet the impending demands of data regulation. Just as 2016 has been a year of extensive activity, the responsibility for commercial product development scale-up and regulatory and compliance guidance fell to CSPs, spurred by the growth of combination products and drug delivery projects and the rise of virtual biotech. The evolution of each of these areas will escalate the role information security and privacy play in an organization's business strategy and are likely to be the basis for long term and lasting change in our industry.
Mr. Chatterjee, President and Chief Scientific Officer for Pharmatech Associates, has been in the bio-pharmaceutical, pharmaceutical, medical device and diagnostics industry for over 30 years. He has guided the successful approval of over a dozen products across U.S. and Europe and is a frequent speaker at industry and regulatory events.