1) Big Data Evolves the Pharmaceutical Industry
As the global market increases, pharmaceutical manufacturing will adjust and conform to what is coming in the pipeline. The rapid new and changing global markets increase data sets in research and development, and the United States encounters new competition. Traditional paper tracking investigations in CAPA processing will accelerate with software solutions in analyzing data with lower costs and better results.
38% of pharmaceutical global industrial respondents expect the greatest technology impact will come from Big Data.
China’s biopharmaceutical sales grew almost 25% annually from $9.4 billion USD from 2012 to 2016. If it continues to grow at the expected rate, the sales volume will be $48.8 billion USD by 2021.
2) AI Partners with Big Data Combining Human Reasoning with Machine Functionality
Humans can reason and innovate, but machines can analyze big data quickly without bias. Human reasoning alone could not solve the mystery of which biochemical pathways of an anti-fungal drug caused liver toxicity. A student at Washington University solved the mystery by using artificial intelligence.
Pharmaceutical manufacturing is more progressive with new technologies than other areas of the pharmaceutical industry. Robotic technology and artificial intelligence are reducing manufacturing floor downtime and product waste. Single-use disposable solutions are replacing open transfer manufacturing techniques for safer storage and drug transport.
AI can identify even the slightest change in air quality or temperature changes on the shop floor 24 hours a day and respond immediately for sterile manufacturing requirements. It is critical to catch any potential problem before it damages a product which may cause a costly shutdown, a massive product recall, or require equipment replacement.
Through the PhD programs, the Novartis-MIT Center is piloting new continuous manufacturing research with Industry 4.0 artificial intelligence. Using Novartis pharmaceutical products, they have pledged a ten-year $65 million to the Center.
3) Expanding Biosimilar Markets Due to Biologic Patent Expirations
As the pharmaceutical regulatory agencies grapple with legal safety and procedural standards for biosimilars, and the public clamors for lower drug costs and more access to pharmaceuticals, manufacturing must adapt to new markets. They expect biosimilar drug markets to increase around the world. Latin American countries is an area to watch as these countries have their own research and development for producing and commercializing patent expired biologic drugs.
The FDA expects to review more biosimilar applications in 2019 because 66 biologic U.S. patents are expiring between 2020 and 2025.
4) Contract Developments, Collaborations, Mergers and Acquisitions
IQVIA predicts that the $1.2 trillion 2018 value of the pharmaceutical industry will increase by 2023 to $1.5 trillion. Contract development and manufacturing organizations, needing to improve speed, increase efficiencies and expand globally are consolidating. Mergers and acquisitions are also being driven by an aging population with a greater demand for generic drugs combined with drug patent expirations. Older companies are teaming up with visionary newer investment growth companies. Boehringer Ingelheim’s acquisition of a biotechnology Swiss company will target immune responses in cancer research. Global research collaboration of Gilead and Galapagos promise new innovative drug discoveries. AbbVie acquires Allergan and will expand its therapeutic focus of inflammatory diseases.
5) Advanced Compressed Air Technology
Due to the confusion surrounding specific regulations, reliable monitoring and quality standards have slipped under the radar in manufacturing risk management. Pharmaceutical manufacturers continue to navigate the ISO 8573-1 internationally approved guidelines to assure maximum air quality for the particular process and product they are manufacturing. Air quality classes identified by the ISO 8573:2010 directives show compressed air creates the purest air. The compressed air is free from particles, microorganisms, and all forms of water and oil including liquids, vapors, and aerosols. Regular testing is required to monitor these contaminants in certain sensitive areas and manufacturing processes. Some parts of the pharmaceutical manufacturing process are not required to have that level of air purity. Manufacturers wrestle with identifying which aspects require compressed air purification, how to separate the areas, and monitoring and testing the areas using compressed air.
Gases are used in some manufacturing processes, and cleanroom specifications established by the FDA Industry Sterile Drug Products says after filtration, air quality should be the same or better than the air into which the gas is introduced.
A cubic meter of untreated air may contain up to 200 million dirt particles and other substances according to Nexflow in 2018.
6) Product Manufacturing and Labeling for Cannabis and Other Non-Prescription Formulas
CBC product labeling debates keep manufacturing at bay as they provide additional information and are forced to delay submitting their applications. Manufacturers have been guided to provide further information than the approved drug facts labeling. They remain on hold as the regulatory agencies resolve the complex legal implications before they can claim the authenticity of a new dietary ingredient.
A public hearing was held on May 31, 2019, to help the FDA evaluate its standards in overseeing cannabis and cannabis compounds. Over 150 interested parties attended the hearing, and the FDA continues to evaluate the data and information obtained.
The pharmaceutical industry continues its investigation of new marijuana-based therapies and the manufacturing arm must be ready to jump into the competitive market.
The FDA wants to make sound decisions based on science. Recalls related to label issues alone may cost a pharmaceutical company $100 million or more a year.
7) Balancing Safety, Regulatory Requirements and Meeting Manufacturing Demands by Modernizing, Digitizing, and Streamlining Applications
The pharmaceutical manufacturing platform or the shop floor operations are finally breaking out of antiquated paper processing applications. The old operational systems are being modernized and replaced with new digitizing software that reduces human errors and accelerates manufacturing processing. They are able to make smarter decisions in real-time 24 hours a day. New mobile technologies and cloud solutions are enabling rapid communication from the front office to the workstation on the shop floor. Teams are able to access needed information immediately to maintain the required quality and compliance while improving speed and efficiency.
Pharmaceutical manufacturers are finding that the new advanced software is making it easier to ensure compliance with regulations. The old manual platforms may leave critical data open to human error manipulation and misinterpretation.
A violation found in a factory inspection brings a possible price tag of $10 million. A dreaded warning letter can cost approximately $200 million, and a settlement could cost upwards of $1 billion.
8) Continuous Processing and New Mixing Technology Features
In 2003 the FDA drafted a guide that led to changes favoring continuous processing to produce quality products where they can be measured and monitored continuously.
Mixing technology with improved data documenting quality, formula accuracy, and increased speed of the continuous processing are able to convert raw materials into the finished product within minutes, thus reducing the need for large storage tanks and batch mixers. Flexible specific controls meet the needs of multiple manufacturers. The mixers are designed for sanitation and easy cleaning to reduce contamination risks in pharmaceutical manufacturing plants.
GEA, a global equipment and process technology provider, collaborated with Merck & Co., Inc. to conduct a trial run of a continuous processing system. The 120-hour trial run created more than 15 million tablets. They said that running a typical batch process to produce the same number of tablets would require 10 separate events employing three operating teams working in three production areas for 5–7 days.
9) Solid Dose Pharmaceuticals Remain Strong
New technologies are not likely to replace the oral dose pharmaceutical products anytime soon. Solid doses that patients are familiar with maintain their high demand status and will continue to expand. New solid dose formats and improved efficiency are steering the expansion of solid dose pharmaceutical manufacturing.
According to an article published in Pharma Manufacturing the preferred solid dosage form will be tablets and an estimated sales of more than $500,000 by the end of 2027. Of the 59 new molecular entities approved in 2018, 24 were solid dose tablets and 7 were in capsule solid dose form. Catalent recently concluded a $1.2 billion gene therapy collaboration with Paragon Bioservices and are now investing $40 million to increase tablet and capsule controlled release capacity. In 2018 Metrics Contract Services invested $80 million in a new manufacturing facility in North Carolina to produce oral solid dose pharmaceuticals.
9) Instrument Verification Sensors and Calibration Procedures.
Pharmaceutical companies are getting a better understanding of the manufacturing processes. New manufacturing plants are replacing traditional manual step batch processing and implementing automatic processing with the real-time analysis that monitors quality control of all aspects of the manufacturing processes. Flow measurements, conductivity, temperature, pressure, calibration and verification sensors are saving time, money, and increasing safety of pharmaceutical products.
Recent temperature sensor technology makes it possible to eliminate unnecessary lab calibrations and document data. The sensor performs an automatic on-site calibration constantly of a referenced temperature range of 118 to 121 degrees centigrade and any problem prompts an electrical signal to a comparison calibrator. An alarm or error message is sent immediately.
10) Precision Medicine is Making Waves
How will pharmaceutical manufacturing adapt to meet the demands of precision medicine for a targeted smaller grouping of patients as opposed to the traditional volume demands of one-size-fits-all industrial methods? A new division of the FDA, Office of Drug Evaluation Science, will be setting the guidelines. The development of genetic-based precision formulas will impact the industry and could begin a major shift.
In the last twenty-five years, adverse reactions have resulted in the withdrawal of more than 450 medicines worldwide. Precision medicine could be a game changer.