Personalized Medicine – How Will the Batch Size Change Our Lives?

Hardly a week goes by without the announcement of a new scientific break-through in science and medicine that promises safer, more efficacious and personalized medicine.  Where are all these developments coming from and how can they sound so certain that this medical wonder is so safe and made with me in mind?  Well, the outcomes of the Human Genome Project have resulted in a plethora of technology and knowledge leading to better bio-therapeutics.  Will these therapeutics be manufactured in disposable equipment to prevent cross contamination of individualized medicine? And how will the quality assurances and validation the possibly innumerable be conducted?

· The Genome Projects’ Contributions

Among the enormous amount of information that resulted from the Human Genome Project, pharmacogenomics has the greatest probability of impacting the biopharmaceutical industry.  The ability to understand how an individual’s genetic inheritance affects the body’s response to medicine offers tremendous safety and economic advantages.  The ability to precisely diagnose, accurately prescribe and monitor the efficacy of a drug product are all impacting to the biopharmaceutical industry’s business and ethical strategies as well as its manufacturing strategy.  It is logical to expect that more accurate and disease specific diagnoses will either expand a manufacturer’s market of potential patients or potentially show that their ‘one size fits all miracle drug’ is not actually medically indicated for a certain existing subset of patients.  The differentiation of their current patient pools will drive the need for better targeted medicines that are more efficacious and have less undesired-able side effects.  That fragmentation of the market will either cause the exclusion of potential revenue generating patients or it will drive manufacturers to a wider family of medicines made in smaller batch quantities.  Those smaller batch volumes will cause a shift in manufacturing facility and process design paradigms.

· Will Disposables Be The Wave Of The Future?

When bio-therapeutic firms invest in designing and building a bio-manufacturing facility, the return on that investment has to be calculated in the hundreds of millions if not billions of dollars in order to be attractive enough to proceed.  Therefore a firm has to either know that their product will be a blockbuster with many years of profitable returns and dedicate a plant to that end or a firm must have a flexible platform on which numerous multimillion dollar products can easily and interchangeably be manufactured.  Until very recently, the standard bio-manufacturing facility consisted of big and bulky equipment with materials of construction consisting of highly expensive, high grade, low carbon stainless steel.  These fixed assets must be cleaned and verified to be free of prior products before being changed over to manufacture another product.  The concerns with cleaning validation and cross-contamination of products is one that has existed in this industry for over a decade and one that is highly scrutinized by regulatory agencies.  How does a firm deal with or eliminate those concerns? Perhaps disposable equipment may provide a solution to smaller volume and high change-over rate facilities.  The state of the disposable art in bio-pharmaceuticals has come a long way and is certainly being employed at pilot scale manufacturing facilities.  Perhaps six smaller suites consisting of smaller disposable bioreactors will provide a longer term financial advantage than two suites with three behemoth bioreactors in each where product conversion can take several months to accomplish.

· Will Old Paradigms Prevail (In A Stripped Down Fashion)?

With the use of those smaller, disposable manufacturing suites, how will manufacturing firms assure quality and validated products? With the 2011 FDA Guidance on Process Validation, a firm is required to have a robust design, qualification and continued verification of their manufacturing process.  With personalized medicine, the old paradigm of some number of runs (typically three) to demonstrate control and consistency will no longer be immediately feasible.  Much more attention and care will need to be placed on identifying critical process parameters and quality attributes upfront by development scientists who are responsible for understanding those elements necessary to manufacture a safe and efficacious product.  Certainly, a process validation protocol per individualized medicine will not be realistic to conduct, but as regulatory agencies are more versed and comfortable with process analytical technologies (PAT) the opportunity exists for real time monitoring of each and every batch produced. The European Medicines Agency has put forth that continuous process verification may provide a practicable method of batch to batch consistency, quality assurance and control.

As technology and scientific knowledge continues to amass and change the face of medicine so must the bio-manufacturing medicines industry adapt to this new smaller and more personalized approach.  The need to understand a plethora of new clinical entities and how to rapidly and safely manufacture them will revolutionize the infrastructure of the bio-manufacturing industry as well as the paradigms to assure that valid, quality and safe medicines are readily available to those who need them.