Mike Auerbach
In the dark days of December 1940, almost six months to the day after the Battle of Dunkirk and the fall of France, President Franklin D. Roosevelt gave a very important speech.
Ahmad Almaya, PhD, Joshua Hanson, PE
Conventional pharmaceutical manufacturing is based on batch manufacturing processes which are robust and have been producing high quality materials for decades. However, batch manufacturing processes contain numerous, disconnected steps; exhibit significant scale changes throughout development and commercialization; and typically involve product testing after manufacturing is finished.
Tim Sandle, PhD
It has been estimated that around half of the fungi found in the environment could cause infections in people (mycosis). For this reason, mycoremediation remains an essential part of any pharmaceutical manufacturer’s environmental control program. A sometimes-overlooked area in the fungal control strategy is raw materials (used as active ingredients, adjuvants, and excipients).
Tony Cundell, Ph.D., Edward C. Tidswell, Christine Massaro
The effects of different stress factors, i.e., heat, starvation, extreme pH, osmotic stress, antimicrobial agents, etc. on microorganisms recovered from manufacturing environments will be discussed. These factors common to manufacturing processes and drug product attributes have been argued as candidates for inclusion in study protocols to simulate stresses and will be discussed.
Michelle Neumeyer
Water quality is a common thread among pharmaceutical manufacturers striving to meet minimum standards for different applications. Whether used as a raw material or for processing, formulation, reagents, intermediates, and/or cleaning, water is fundamental to GMP processes and must be monitored as such.
Most applications for monitoring microbial contamination are based on general-purpose, nonselective culture media, such as Tryptic Soy Agar. However, aseptic processing environments require the routine use of disinfectants, so during surface sampling the swab or contact plate is likely to take up disinfectant residues alongside the contaminants, which could suppress microbial growth and lead to false negative results. This is why the culture media for such purposes must be supplemented with substances known as neutralizers that inactivate the disinfectants being used. USP <1116>, the FDA Aseptic Guide (2004) and ISO 14698-1 specify this requirement.
Sarah Pope Miksinski, PhD, Ciby J. Abraham, PhD
Continuous manufacturing is currently a hot topic in the pharmaceutical landscape despite the concept having been around for decades. One reason is that the majority of pharmaceutical manufacturing is, at present, accomplished by traditional batch processes. The use of batch processes has several limitations, including the lack of flexibility in batch size to meet potential fluctuations in patient supply and demand. Additionally, if a batch does not meet release specifications and if reprocessing is not an
option, the batch may have to be discarded. This can be very costly to the manufacturer and potentially create a drug shortage.
Mahwish Natalia, MA, PhD
Research in cell therapies has grown in the past few years with the FDA approval of Yescarta (axicabtagene ciloleucel) in 2017 for relapsed or refractory large B-cell lymphoma and Kymriah (tisagenlecleucel), also in 2017 for relapsed or refractory acute lymphoblastic leukemia, both of which are autologous Chimeric Antigen Receptor (CAR) T therapies. Currently research is underway for allogeneic ‘off-the-shelf’ CAR-T cells with the cell source being the major difference between the two therapies.
Andy Holt
Adeno-Associated Virus (AAV) gene therapy remains remarkably close to its roots in academia despite burgeoning commercial success and prolific investment. That combination of scientific curiosity and capital enables innovation to continue to accelerate, generating potential therapeutics addressing both larger patient populations and ultra-rare diseases previously considered off-limits due to either technological or commercial considerations. As these areas appear more feasible, we are forced as an industry to resolve challenges in manufacturing that have been in some ways left behind by the revolutionary aspect of the results of AAV gene therapy’s first successes.
Eric Henry
“Software,” as a term in the regulated life sciences industry, has a wide variety of definitions and uses. For example, software can be a stand- alone medical device devoid of dedicated hardware, embedded in an electro-mechanical medical device, embedded in manufacturing production equipment, used as an application for product design, or used to generate spreadsheets for making decisions regarding regulated Quality System processes. As compared to other software uses in the industry, software that is used to support manufacturing production or to automate work or decision-making within the Quality System is governed by a comparatively small library of regulatory literature and relatively inconsistent application of regulatory oversight globally.
Ken Shitamoto, Senthil Gurumoorthi
Computer Software Assurance (CSA) is a Case for Quality initiative that arose when computer systems validation was identified as a barrier to adopting technology for modernization and innovation. The FDA recognizes the value of using advanced technologies to enable the industry to make medicines of more reliable quality.
Christopher W. Lester, J. Timothy Ramsey, Jonathon S. Salsbury
Active pharmaceutical ingredients are often poorly soluble in water. The detection of bacterial endotoxins in such substances requires a homogeneous aqueous suspension, which presents difficulties in ensuring uniform dispersion of the sample through the mixture. We demonstrate a technique for sample preparation in which the drug substance is dissolved in dimethyl sulfoxide (DMSO), followed by dilution in water. This results in a more uniform suspension than can be achieved by direct addition of sample to water. This method allows testing for endotoxins via the chromogenic technique, which results in a 15-fold increase in method sensitivity compared to the gel-clot technique. The increased sensitivity allows for testing of higher sample dilutions, increasing the likelihood that sample interference can be overcome.
Naseem A. Charoo, Cyrus Funkhouser, Mathew A. Kuttolamadom, Mansoor Khan, Ph.D., Ziyaur Rahman
Three-dimensional printing (3DP) is a path breaking technology, which will undoubtedly open a new era in pharmaceutical manufacturing science. The International Standard Organization (ISO) defines 3DP as: “Fabrication of objects through the deposition of a material using a print head, nozzle, or another printer technology.” It is based on additive manufacturing technology in which three-dimensional objects are created by joining materials layer by layer from a digital computer aided design file. 3DP offers flexibility, versatility and agility for pharmaceutical manufacturing. Possibly, fewer manufacturing steps and lesser number of excipients are required than conventional manufacturing processes.
Neelam Sharma, M.S., Hemant N. Joshi, PhD, MBA
The purpose of this column is to highlight and summarize recent key patents in the pharmaceutical arena issued by the US Patent Office in November-December, 2020.