Mike Auerbach
If you haven’t seen the series Stranger Things on Netflix – I urge you to give it a try.
Dr. Daniel Joseph Price, Dr. Finn Bauer
Poor drug solubility has become an increasingly important consideration in the development of orally delivered drugs. For example, although it is reported that 60% of approved APIs are poorly soluble, it is hypothesized that up to 90% of candidates in the development pipeline will fall under this category.
Robert Dream
Advanced therapy medicinal products (ATMPs) are medicines for human use that are based on genes, tissues or cells. They offer groundbreaking new opportunities for the treatment of diseases and injuries.
Stuart Levy
The transition of a drug from optimized medicinal chemistry lead to candidate nomination and development through clinical proof of concept has been referred to as the “Valley of Death.”1-3 It is the most consequential, high-risk period in a drug’s development. A relatively recent assessment indicates that the average success rate of development candidates in this portion of the drug development cycle is ~30%.4 During this interval, basic science knowledge needs to be translated into practical application in a clinical setting.
In single-use design and implementation, integrity and robustness of the system are critically important in assessing risk, especially where no sterile filtration is possible as part of the processing step. This case study describes the design and implementation of a custom AdvantaPure® molded filling assembly used in final fill.
Viral vaccines were the first pharmaceuticals manufactured using living cells, revolutionizing the industry at a time when regulatory compliance was controlled by the local pharmacopoeias (United States, European or Japanese).
Tim Sandle, PhD
In the manufacture of certain pharmaceuticals, viral removal or destruction is a key part of manufacturing (such as products produced from cell lines or from blood or plasma, as per ICH Q5A). This requires a combination of viral secure areas and viral removal steps. In a previous American Pharmaceutical Review article, this author examined the ways by which viruses can be removed or inactivated from pharmaceutical products (including solvent-detergent; low pH inactivation; heat; chromatographic separation; and nanofiltration). In terms of detection, nucleic acid-based assays such as Polymerase Chain Reaction (PCR) and Next Generation Sequencing (NGS) provide rapid and sensitive detection of adventitious and endogenous viruses in constituent materials and finished products.
Paula Peacos, Marc Glogovsky, MS, S.M. (NRCM)
Holistic, risk-based microbiological contamination control programs are being implemented throughout the industry as a means of increasing patient safety and improving the levels of overall process control and product quality. These multi-faceted programs integrate individual contamination control components such as cleaning and disinfection, environmental monitoring, gowning, facility design and maintenance etc. into a single comprehensive program that is tailored to the specific processes and products being manufactured. They also represent a change in the thought processes regarding how best to achieve and maintain an effective contamination control strategy. This paradigm shift in thought processes directly impacts microbiologists responsible for overseeing the efficacy of the facility’s contamination control program.
Michelle Neumeyer
In 2020 thus far, numerous warning letters have been issued from the FDA citing data integrity violations. Common findings violate principles of ALCOA+, 21 CFR Part 11, and the FDA’s data integrity guidance document.
When assessing the impact of extractables or leachables from a safety perspective, there are two important pieces of information that will allow completing an in-depth toxicological assessment: the compound’s identity and its concentration or dose to the patient.
Jeanne Moldenhauer
In recent months, the world has been dealing with an outbreak of a novel coronavirus, designated COVID-19. Requirements have been established for facial masks, social distancing, gloves, and 20 second handwashing, and the like as a part of everyday life. As our everyday life has a new standard for protection from contamination, we also need to consider the effects of this pandemic upon the production of pharmaceutical products and the personnel who produce them. Viruses are not new to many biotech and vaccine products. We have seen requirements for viral clearance studies for many years, however; it is not clear whether traditional contamination control programs are appropriate for today. This article discusses some concerns with contamination control in the COVID-19 era.
Jim Polarine, Thomas Walker
A clinical supply manufacturer was adding a new integrated filling operation to its aseptic filling capabilities. The new area provides a Grade C background environment with adjacent Grade D transition airlocks for material and personnel. The traditional sanitization/disinfection used by the facility included the routine use of hydrogen peroxide/peracetic acid RTU, 70% isopropyl alcohol (IPA), and hot Water for Injection (WFI). The site explored cleaning agents currently available and utilized at the adjacent affiliated commercial sites after realizing the limited cleaning effectiveness of the established regimen. As the site strategized to determine the revised regimen, the need for a global approach was considered to synergize all related activities.
Sulaf Assi, David Osselton, Hisham Al-Obaidi, Jordan Thomas
Rapid identification of cosmetics is important particularly in warehouses that witness the large inflow of products every day. Attenuated total reflectance Fourier transform infrared ATR-FTIR spectroscopy offers the advantage of measuring low amounts of samples (few milligrams or milliliters) in minimal time. Therefore, this work evaluated the accuracy of ATR-FTIR spectroscopy for identification of cosmetic products.
The Eclipse platform uses highly innovative technology and automation to make endotoxin testing easier and more efficient without changing the biochemistry or reagents used in the assay.
Going “Green” in today’s business climate where maximizing shareholder equity and conserving capital is a top priority can be difficult, especially if the project increases the overall cost of doing business.
I think there are many great technologies in existence that address complex controlled release challenges, but there is a general trend in industry of slowly eliminating barriers to addressing specific patient populations.
Camille Dumont, PhD
This article provides an overview of the processing techniques and the methods of characterization for evaluating Solid Lipid Nanocarriers (SLN) designed to improve the bioavailability of active pharmaceutical ingredients (API). It presents the commonly used formulation techniques for developing lipid-based solid nanocarriers and details the analytical approaches to assess these systems for size, morphology and zeta potential. Also discussed are the measures for encapsulation efficiency, drug release profile, intestinal permeability of the encapsulated API across cell models, and assessment of particle internalization.
USP <85>, “Bacterial Endotoxins Test” (BET) is a harmonized compendial analytical procedure that describes the use of lysates (extracts) prepared from the blood cells (amebocytes) of horseshoe crabs to detect and quantify endotoxins activity in parenteral products (USP 2019a). All of the methods currently described in <85> use reagents that are sourced from the hemolymph of living horseshoe crabs (HSC), Limulus polyphemus (LAL) and Tachypleus tridentatus, (TAL). BET assays are critical safety tests for parenteral drugs, biologicals, and medical devices, as results obtained using these procedures may be predictive of a febrile response in patients (Greisman and Hornick, 1969; Hochstein et al, 1994).
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 March 2020.