An important question for many companies in the pharmaceutical industry is whether to use membrane filtration or direct inoculation of liquid culture when developing new sterility testing methods. USP <71> recommends membrane filtration as the preferred method for sterility applications whenever the nature of the product permits. Filtration methods have the advantage of allowing large sample volumes to be tested for meeting USP requirements and recommendations. Also, for products with antimicrobial activity, filtration allows rinsing and thus the removal of the inhibitory characteristics of the product.
Hrishikesh Kadam
The use of drugs across a vast demographic in the U.S. has surged rapidly in recent years. Whether it is marijuana, heroin, or prescription drugs, the need for drug abuse testing in the region has reached alarming levels. In fact, according to the Substance Abuse and Mental Health Services Administration (SAMHSA), a branch of the U.S. Health Department, in 2017 there were more than 30 million Americans aged 12 or more who used an illicit drug in the past month.
Dr. Clare Trippett
The human body is home to a huge and diverse community of microorganisms, consisting of bacteria, fungi, protozoa and viruses. Collectively these organisms are referred to as the microbiota, and the collection of genomes from these microorganisms is referred to as the microbiome, however the two terms are often used interchangeably. It is estimated that over 10,000 species of microorganisms occupy the human microbiota, and that there may be more than eight million unique genes associated with the various microbiomes in the human body.
Malcolm B. Berry, PhD
In recent decades, the pharmaceutical industry has witnessed a revolution in the regulatory requirements to obtain approval for the manufacturing processes of new medicines. The reliance on end-product testing, was replaced with a paradigm where the control of product quality was designed into the process. Accordingly, when the process variables are held within the designed and studied ranges, end-product testing is now just one of many controls that provide assurance in the supply of consistently high-quality medicines.
Paula Peacos
Data integrity is a topic of great importance in our industry. Robust data integrity is critical to ensuring patient safety by assuring that correct and appropriate decisions are made, and that all test results etc. accurately reflect the quality of products being manufactured. To this end, all firms must ensure that all generated records are complete, accurate and trustworthy. Ensuring and maintaining “data integrity” involves protecting original data from modification (either accidental or intentional), falsification and/or deletion.
Michelle Neumeyer
Total organic carbon (TOC) and conductivity testing are important quality control measures for ensuring water purity and equipment cleanliness and can be deployed to accommodate various sampling scenarios and efficiency needs. TOC and conductivity analysis help manufacturers achieve compliance to USP <643> and USP <645>, or with process control needs. While conductivity is traditionally measured with a meter and probe, advanced TOC technologies can also offer conductivity measurements simultaneously with TOC analysis. The three common deployments of TOC technology are laboratory, at-line, and online analysis. When choosing which strategy and deployment are best for a unique application, consider the following to ensure you get the most out of the technology.
Patrick Mayrhofer, Renate Kunert
Traditional bioprocesses of mammalian cell cultures are operated in batch- or fed-batch mode. To increase space-time-yields, reduce cost of goods, accelerate time-to-market and enhance flexibility at reduced lab-footprint, perfusion processes are envisaged for various bioprocess intensification tasks.
Tim Sandle, PhD
Microbial monitoring in cleanrooms is generally performed using standard, cultivation dependent approaches based on the usage of contact plates or swabs. It is well-established that environmental monitoring methods are limited in their ability to recover organisms from a surface due to inherent limitations with the methods; the selectivity of the culture media and incubation time; the complexities of microbial surface adhesion; and due to the presence of ‘active but non-culturable’ organisms. This places a greater emphasis upon environmental control. One control aspect is with cleanroom surface design.
Tony Cundell, Ph.D.
The U.S. Federal Good Manufacturing Practices (GMP) Regulations, i.e., 21 CFR 211.113 Control of Microbiological Contamination require pharmaceutical manufacturers to exclude objectionable microorganisms from their non-sterile pharmaceutical drug products. What microorganisms that may be considered objectionable can be determined from the clinical literature, microbial infection outbreak investigations especially associated with drugs and medical devices, and to a lesser degree U.S. drug product recalls. In the absence of regulatory guidance, this issue was the subject of the 2014 PDA Technical Report No. 67 Exclusion of Objectionable Microorganisms from Non-sterile Pharmaceutical and OTC Drug Products, Medical Devices and Cosmetics.
Carla V. Luciani, Martin D. Johnson, Ph.D.
While most of the published work on the impact of residence time distribution (RTD) to pharmaceutical continuous manufacturing (CM) processes focuses on drug product, drug substance process dynamics is vastly different. This work focused on investigating what could represent the major contributor to residence time distribution of a drug substance fully continuous process as it matures: surge vessels. Changes in size or type of surge vessels significantly affect the resulting RTD and this work presents several numerical examples of such an impact. Process development repercussions are also discussed.
Annabel Igonin Ph.D., Jenifer Mains
One of the main challenges faced by the small molecule industry today is the increasing number of poorly water-soluble molecules in the drug development pipeline. We estimate that more than 80% of the drug candidates currently under development are poorly water-soluble and experience bioavailability challenges, which leads to difficulties in formulating drug products. Indeed, the use of conventional dosage forms to deliver these molecules is not always sufficient to achieve the expected drug exposure.
Sunny Christian, MS, Neelam Sharma, M.S., Hemant N. Joshi, Ph.D., 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 January 2020.
Kristopher Garibay, Eric Olson, Jonathon S. Salsbury
Due to its simplicity and precision, laser diffraction is an analytical technique frequently used in the determination of particle size distribution profiles. For a commonly used laser diffraction instrument, the wide dynamic range is accomplished by using a sequential combination of measurements with red and blue light sources.