Mike Auerbach
Recently, with the advent of softgel vitamins and supplements, I’ve actually taken a liking to them. Soft, chewy, with a nice taste- they are almost like candy – the gummy bears of the supplement world.
Brian J. Hawkins, PhD
A cell therapy is defined as the administration of intact living cells to patients for the treatment of disease. The first successful cell therapy was performed in 1956 by Dr. E. Donnall Thomas, who treated leukemia by transplanting bone marrow between identical twin siblings, for which he was awarded the Nobel Prize in Physiology or Medicine in 1990. Cell therapy has since progressed from basic bone marrow transplantation to the use of genetically modified and ex vivo manufactured chimeric antigen receptor (CAR) T-cell therapies for the treatment of advanced blood cancers (Locke et al., 2017).
Tony Cundell, Ph.D.
In calendar year 2018, the FDA approved a record 62 novel drugs, with the Center for Drug Evaluation and Research (CDER) approving 59 and Center for Biologics Evaluation and Research (CBER) approving three cell therapies. The CDER classification breakdown was 40 chemical drugs and 22 biological drugs. It is notable that greater than 50% of the new drugs approved were biologics with many classified as immunotherapies. Industry surveys suggest this trend towards biologics in the pharmaceutical industry will continue with the percentage of biologics in the R&D pipeline between 25 to 50%. Associated with this change is the rapid growth in the field of gene and cell therapy products. Citing the 800 active INDs for cell therapy and gene therapy candidates and the expectation that it will be receiving more than 200 INDs each year by 2020, FDA Commissioner Scott Gottlieb, MD, in January 2019 outlined the FDA initiatives to support timely review and to enable the approval of 10 - 20 such therapies per year by 2025. Gottlieb announced that 50 new clinical reviewers would be added to the CBER staff to address this demand.
Approvals of antibody and nanobody therapeutics are increasing rapidly.1 The Antibody Society has estimated that 2020 will see fifteen to twenty new therapies approved for use in the US or EU, up from a 2014-2018 four-year average of ten. This success has been built on the continual optimization of in vivo and in vitro methods of therapeutic discovery. For example, transgenic mice generate more human-like antibodies against injected antigens2 and high-throughput binding and developability assays have allowed researchers to scan more antibodies than ever before for their suitability.3 However, these methods are often time- and resource-intensive, sampling many ineffective antibodies en route to identifying a feasible candidate. Such inefficiency is likely to be unsustainable in the coming era of personalized medicine.
Kirti Vatsa
The high potency drug market is one of the key revenue-generating segments in the pharmaceutical industry and the market holds enormous potential. There is high demand for oncology and other high potency drugs such as ADCs and IV fluids. On the demand side, buyers are looking for high capacity suppliers who can meet their API OEL limits, have lyophilization capability in injectable dosage forms and ample experience in handling high potency drugs. However, on the supply side, there are a limited number of CMOs who meet the exact needs of buyers as provided above.
Wayne K. Way, PhD
Over the past several years, biologics have continued to make up an increasing proportion of biopharmaceutical sales and pipeline candidates. Biologics now account for more than half of the top selling drugs by revenue. In fact, 2018 saw a record 17 biologics license application (BLA) approvals and the 5-year annual average has more than doubled over the last decade (Figure 1). This trend is expected to continue for the foreseeable future with many different modalities of biologics in preclinical and clinical development. Currently, most global pharmaceutical companies’ pipelines consist of 20-40% biologics; the tipping point to a majority biologics pipeline is expected this decade.
Ratul Saha, PhD
Microorganisms are ubiquitous and their numbers as well as their diversity is beyond comprehension. According to the review article by Gibbons and Gilbert (2015), the largest global survey of microbial diversity to date, carried out by the Earth Microbiome Project (http:// www.earthmicrobiome.org/), revealed the existence of 5.6 million Operational Taxonomic Units (OTUs) (97% similarity at the V4 region of the 16S gene; not including singleton OTUs) in the first 15,000 samples, which set a new lower-bound on the number of bacterial and archaeal phylotypes on Earth.
Jennifer Gygi
There are many options available for Container Closure Integrity (CCI) testing of glass vials and syringes. From traditional probabilistic methods like Dye Immersion (tracer dye) or Bacterial or Microbial Challenge testing, to a variety of deterministic methods like Vacuum Leak, Headspace Analysis, Mass Extraction, Voltage Leak, and Tracer Gas there should be an option for any need. Each method has pros and cons that should be considered when choosing an appropriate test method for a particular container type. Not all options are suitable for all sample configurations and some methods particularly shine in certain applications, but fall short in others. With the newest edition of USP 1207, the pharmaceutical industry is moving away from traditional dye and bacterial immersion test methods and moving toward deterministic methods for CCI testing.
Given these new concerns, the QC micro labs now also have the additional problem of trying to decide what on-market RMM technologies can help them adapt and improve their quality release processes in the new age.
Anvit Vasavada, M.S, 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 July- August, 2019.
In general, what are some of the current critical issues/trends facing pharmaceutical manufacturers in regards to microbiology testing and remediation?
Michaël Reynier, VP Healthcare Business Industrial Microbiology Unit, Health & Personal Care Business, bioMérieux SA: Microbiology testing still relies heavily on culture media and manual interpretation.
Therefore, it remains a slow and sometimes subjective process - especially when compared to analytical methods used in chemistry. Consequently, pharmaceutical manufacturers suff er from recurring
data integrity weaknesses and sub-optimization of their workforce due to limited automation.
Mo Heidaran, PhD
The development of cell and gene therapy products to address serious and life-threatening conditions that affect the pediatric population is growing exponentially. Although much is known about the Chemistry and Manufacturing Control (CMC) considerations for the adult population, the challenges of manufacturing complex products for younger populations are not yet fully understood.
Dr. Norbert Maurer, Dr. Jay Kulkarni
All cells function by an intricate mechanism that converts information stored as nucleic acid sequences (DNA) into messages (messenger RNA) for translation into functional products (protein). Endogenous checks and balances exist within this information flow, which can be leveraged as therapies to treat diseases closer to their genetic origin. The significant health opportunities of gene therapies are evident in the growing number of synthetic drugs, as well as modified viral delivery systems, which have recently been approved or entered clinical development.
Ronald D. Snee, PhD
The pharmaceutical industry is experiencing a growing need to improve performance driven by global competition and the increasing impact of information technology. Central to this need are good data, a characteristic of good science. Quality data are arguably more important today than ever before. It is becoming widely accepted that data are a corporate asset. The industry is also focusing on risk assessment and reduction as evidenced by FDA’s focus on data integrity. Methods and tools widely used in test method development are discussed with emphasis on how these tools reduce risk in method development, validation and use. Methods discussed include experimentation strategy, method repeatability and reproducibility, method robustness and test method performance verification.
Pieter-Jan Van Bockstal, Jos Corver, Thomas De Beer, Ph.D
Following the current trends in drug development, the focus of pharmaceutical companies is shifting from small molecule compounds towards biological drug products such as therapeutic proteins and vaccines. However, the stability of biopharmaceuticals formulated as an aqueous drug solution is often restricted due to water driven degradation pathways. Freeze-drying is a low-temperature drying process commonly applied to extend the shelf life of these biopharmaceuticals. About half of the group of biopharmaceutical therapeutics approved by the regulatory authorities (> 300) consists of freeze-dried formulations, despite the long processing time and high costs associated with this production process.
Luis Jimenez, Arianna Pinto, Adelajda Turku, Stephanie Perez, Vanesa Molina
Escherichia coli is one of the specific bacterial indicators required by the United States Pharmacopeia which can be considered hazardous to consumers if found in non-sterile pharmaceutical products. Standard microbiological testing requires four to five days to be completed to show the absence of E. coli from raw materials and finished products. A Real-Time (RT) PCR assay was developed to detect E. coli in pharmaceutical products contaminated with low levels of bacterial contamination. Different pharmaceutical suspensions were artificially contaminated with Burkholderia cepacia, Escherichia coli, Staphylococcus aureus, and Bacillus megaterium. After a 24-hour incubation in TSB with Tween 20, bacterial DNA was extracted from each sample by using a Tris-EDTA, proteinase K, Tween 20 buffer.
Dr. Syed Kaschif Ahmed, Dr. Rob Guenard, Saly Romero-Torres, Ph.D., Chris Antoniou
Classic automation control strategies use regulatory controls to maintain process variables at predefined set-points (Al-Rubeai 2015). Regulatory loops such as proportional, proportional-integral, and proportional-integral-derivative, are used to enable feedback control strategies. These control strategies aim to control the process outcome by controlling the process set-points to predefined values and within pre-defined ranges. The pre-defined set-points are locked down under the assumption that they are a global optimal or very close to a global optimal (within equipment constraints). Nevertheless, other sources of variability (such as human intervention, equipment drift, environmental fluctuations and raw material variability) could disturb the manufacturing process leading to deviations from optimal state/conditions. In these cases, it is desirable to re-calculate, in real-time, new optimal conditions to increase, or decrease, a particular process output based on the new disturbed process state. Based on the new conditions, new set-points can be directed to the controller to ensure output optimality within the new state. Control strategies that recalculate new optimal set points based on the process condition use process models at their core and are part of the Advanced Process Control (APC) toolbox.