Christopher Weikart, Robert Langer
A Leader for COVID-19 Vaccines by Operation Warp Speed The global hunt for a COVID-19 vaccine has been underway at breakneck speed by the best academic and industrial minds. This pursuit involves the development of both traditional and novel vaccine technologies aimed at undermining the SARS-CoV-2 virus. The Food and Drug Administration (FDA) has provided guidance for fast-tracking vaccine development and ultimately market approval of a safe and effective COVID-19 vaccine. At last count, four candidate vaccines are already in late stage clinical trials in the US and many more in the pipeline.
If you count the four years I was an editor on my college’s newspaper and my two years as an Associate Editor for a commercial construction news bidding paper BEFORE I got my first job covering the pharmaceutical industry, I’ve been an editor for, well, a very long time.
Early packaging of pharmaceuticals was based on the availability of mass-produced containers of the day. Glass was the best choice at that time for many non-parenteral drugs. Borosilicate glass became a better option over ordinary soda-lime glass due to its higher hydrolytic resistance and thermal shock resistance. These unique properties enabled parenteral and freeze-dried drug products to be packaged in borosilicate glass.
Michael Levitt
As we sit at home on our computers attending meetings on Teams or Zoom, each of us is dealing with this crisis in our own way. Our world is being fundamentally changed by a virus we don’t fully understand and can’t control. We are wondering how this will impact our careers, our income, our families or our plans for the future. It is also a time when we should reflect upon how we have done things and how we can do them more effectively.
Huiquan Wu, PhD
Since the publication of the FDA’s PAT Guidance in September 2004, significant progress has been made in many aspects which boosted innovation in pharmaceutical development, manufacturing, and quality assurance.
John Paul Tomtishen III
Cell therapies are living drug products that continue to provide hope and promise to patients around the world. They are transformative biological medicinal products that can address unmet clinical need for a variety of indications, including oncology and infectious diseases.
Many pharmaceutical QC tests such as dissolution testing, content uniformity, assay, and blend uniformity require sample filtration prior to HPLC or UHPLC analysis. Since quantifying analytes is critical for these tests, method validation should include filter validation studies to evaluate analyte loss to the membrane. Different membrane filters can bind analyte to varying degrees depending on membrane type, the nature of the analyte and analyte concentration.
Ronald A. Rader, Eric S. Langer, Dr. Kamna Jhamb
The trends affecting the biopharma industry that we’ve evaluated over the past decade have remained relatively stable. In this highly regulated healthcare industry segment, decision-makers often consider adoption of novel technologies, or solutions to be riskier than tried-and-true processes, approved methods or generally accepted practices. Thus, change can come slower than many would prefer. And sometimes it takes a crisis to stir the pot and accelerate change.
Paula Peacos, Marc Glogovsky, MS, S.M. (NRCM)
Environmental monitoring (EM) trending programs are an integral tool for use in making sound, scientifically justified cGMP decisions. Moreover, the usefulness of this tool is directly proportional to its quality, and that quality is likewise proportional to the trending program design and implementation. There are a number of considerations to be made when designing and implementing meaningful, applicable and effective trending programs.
Johannes Delp, Marcus Gutman, Johannes Reich
Bacterial Endotoxin Testing (BET) is mandatory for detection of Endotoxin/Lipopolysaccharides (LPS) in parenteral drug products. This is important as LPS is one of the most potent stimulants of the human innate immune system. Over the last decades the Limulus Amebocyte Lysate (LAL) test has been established as the gold standard for the detection of LPS. In order to qualify a test sample, the endotoxin activity is determined based on a standard curve using reference or control standard endotoxins. BET is described in international pharmacopoeias (e.g., Ph.Eur, JP, USP). Thus, the test does not need to be validated per se, however product specific verification with tests for interfering factors is required.
William Peterson
Pre-Use/Post-Sterilization Integrity Testing (PUPSIT) continues to be a much-discussed topic in the manufacture of sterile pharmaceutical and biopharmaceutical products. This article summarizes the outputs of a multi-year consortium between BioPhorum and the Parenteral Drug Association (PDA) on the topic.
Jürgen Müllberg
Contamination of a biological product with viruses, potentially harmful for humans, is of concern for therapeutics derived from human and animal sources, i.e. plasma, and for protein therapeutics and vaccines produced in mammalian cells. More recent “Advanced Therapeutic Medicinal Products (ATMPs)”, such as gene and cell therapies, share the same concern. Tests for viral contaminants are performed at several stages of manufacturing. Current tests for detection of viruses are lengthy; cell culture-based assays and animal experiments are required. Alternative molecular tests, such as “next generation sequencing (NGS)”, provide faster results, and can eventually replace in vivo animal studies. It is noteworthy that identification of a viral contaminant that evaded detection in classical tests, by NGS, has been demonstrated. Since NGS-based virus tests yield results significantly faster than current assays, additional applications for in-process testing and viral contamination control can be envisioned.
The global API market is estimated to reach USD 245.2 billion by 2024 from USD 182.2 billion in 2019. Chinese and Indian manufacturers account for more than 50% of all APIs used worldwide, which could
grow as the market grows. During the spring of 2020, as COVID lockdowns first started happening, we saw fractures in the supply chain based on shipping and trade challenges. This glimpse into the “what if” of losing access to certain APIs made the large reliance on Asia a deep concern because the adequate supply of APIs is the backbone for developing drug delivery systems.
Shiksha Mantri
Lipids are gaining enhanced momentum due to their vital role in the field of ribonucleic acid (RNA) therapeutics and vaccine development for diseases such as cancer and COVID-19.
Moo Sun Hong, Weike Sun, Amos E. Lu, Richard D. Braatz
Biomanufacturing is moving toward digital manufacturing with increased application of Process Analytical Technology (PAT) and continuous manufacturing. This article discusses strategies and components of the digital biomanufacturing approach, including mechanistic models and their validation, automation of the construction of models by data analytics and machine learning to improve efficiency and improve model quality, and real-time feedback control of critical quality attributes (CQAs).
Aaron Stewart, Deanna Mudie
Drug development pipelines are inundated with candidates with poor aqueous solubility. To achieve target exposure and be efficacious, these compounds often require use of a bioavailability-enabling technology that enhances solubility and/or dissolution rate. Drug development scientists have many such technologies at their disposal, but selection of the optimal technology remains crucial to ensure success at reasonable cost and timeline. The ultimate goal in any drug development program is to propose the simplest, most cost-effective solution for developing the targeted drug product, and the choice hinges on applying an integrated approach where bioperformance, stability, and manufacturability are considered throughout the development cycle.
John Lunger
Cell Therapy, including engineered T-cells, is becoming a more familiar feature in the medical world, especially as a treatment option for patients with late-stage cancer. One of the challenges faced by companies is how to deliver these living therapies rapidly and safely to patients. The importance of manufacturing and supply chain to meet this challenge cannot be underestimated. With autologous cell therapies, in particular, traditional means of scaling manufacturing such as producing larger batches and building drug product inventory do not apply and new ways to meet patient needs must be developed.
Kevin Williams
Given the recent successes of recombinant Factor C, there has been an increase in commercial supplier comparison studies for recombinant Factor C (rFC). The results of such studies appear to have been wholly adopted at face value as reflected in recent articles1 and a new USP draft chapter <1085.1>.
Luis Jimenez, Brittany Cardona, Tae Min Kim, Hadassah Haricha, Anna Maclejewska, Yarah Abazah
Three human coronaviruses originating from zoonotic events are responsible for severe acute respiratory syndrome outbreaks around the world. The first two, SARS-CoV and MERS-CoV were disseminated by symptomatic individuals and controlled by rapid quarantine of people with illness, general use of personal protection equipment such as masks, rapid testing, and contact tracing. However, because of the asymptomatic transmission of SARS-CoV-2 and the different mutations related to virus attachment and entry to the host cell, transmissibility and infection rates were higher than SARS-CoV and MERS-CoV leading to the current pandemic of COVID-19. SARS-CoV-2 showed similar genomic organization related to other human coronaviruses with specific mutations in genes related to the spike glycoprotein and other accessory genes. Current mortality rates for SARS-CoV-2 are lower than those reported for SARS-CoV and MERS-CoV but the worldwide disruption has been more significant. Therapies such as vaccines and chemotherapeutic drugs are currently under development to either prevent infections or treat sick patients with agents that will inhibit viral entry, replication, or assembly.
Michelle Neumeyer
Total organic carbon (TOC) and conductivity data are used in various applications to demonstrate equipment cleanliness, purified water chemical purity, process understanding, and process control. Not only do these analyses offer numerous quality and efficiency gains within a process but monitoring CGMP equipment and pharmaceutical grade water systems is mandated by regulatory organizations around the world, including the FDA.
Yunyu (Linda) Yi, Yutong Jin, Rashmi Menon, Bernice Yeung
Polysorbate (PS) refers to a family of amphipathic, nonionic surfactants that is derived from ethoxylated sorbitan or isosorbide (a derivative of sorbitol) esterified with fatty acids. Polysorbates, specifically polysorbate 20 (PS20) and polysorbate 80 (PS80), are the most widely used surfactants in biopharmaceutical formulations to prevent proteins from denaturation, aggregation, surface adsorption and flocculant formulation during thaw.
Endotoxin from Gram Negative Bacteria (GNB) interacts with cellular receptors to trigger strong systemic inflammatory responses including fever, septic shock and death. The threat of endotoxin to the pharmaceutical and healthcare industries cannot be overstated. Unless GNB and endotoxin contamination in parenteral drugs and implantable devices are rapidly and reliably detected to enable their elimination, peril lurks. The quality control (QC) of biomedical products begun in 1942 with the slow, laborious and costly rabbit pyrogen test (RPT).
Kim Huynh-Ba
Method validation is a critical activity in the pharmaceutical industry. Validation data are used to confirm that the analytical procedure employed for a specific test is suitable for its intended purposes. These results demonstrate the performance, consistency, and reliability of the analytical method. This paper summarizes the requirements of method validation and data generation to document the evidence which demonstrates the suitability for its intended use. It also discusses the critical validation parameters required based on the ICH guidelines and various pharmacopeia as the procedure must be fully validated before being used for release or stability testing.
Even before the current pandemic laser-focused the pharmaceutical industry’s attention on achieving a coronavirus vaccine, the spotlight on injectable drugs was bright thanks to the accelerating innovation
in delivery devices and the rise of chronic diseases. According to ReportLinker’s report “Injectable Drug Delivery Devices Market - Growth, Trends, and Forecast”, the growing prevalence of conditions
like cardiovascular diseases, obesity, and diabetes drove significant growth in the injectable device market as of February 2020.
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 June-July, 2020.