Leonor S. Castro, MSc, Patrícia Pereira, Mara G. Freire, Augusto Q. Pedro
The advent of biopharmaceuticals in modern medicine has brought enormous benefits to treat chronic and life-threatening diseases while improving the well-being of humans. Proteins (including antibodies) represent a large fraction of the biopharmaceuticals market, but are still amongst the costliest options due to the lack of cost-effective purification techniques. The most relevant strategies in the downstream processing of protein-based biopharmaceuticals are the highly selective nature of chromatographic techniques, which however, present some drawbacks including the difficulty to apply in large scale due to batch processing, large scale pressure drops, low chemical and proteolytic stability, and high cost.
Ajay Babu Pazhayattil, Marzena Ingram, Amanda Bishop McFarland, Naheed Sayeed
The ICH Q7 good manufacturing practice (GMP) guidance for active pharmaceutical ingredients (API) stipulates the basic GMP requirements involved in drug substance manufacturing from introduction of starting materials to processing and packaging. The guidance cover personnel, facility, equipment, material, manufacturing, laboratory, storage, laboratory, validation, change and quality management controls sections. ICH Q7 excludes vaccines, blood, plasma derivatives, radiopharmaceuticals and gene therapy pharmaceutical ingredients. API manufacturing utilizes designated starting materials (RSM), intermediates and raw materials at various steps, where some of the building block raw materials are commercially available. The API manufacturing segment differs from drug product GMP operations. API manufacturing has early stages of manufacturing building blocks for key steps and developing case by case rationale to determine the correct starting point of API manufacturing. ICH Q7 has attempted to clearly break down the requirements, for example, for a chemical synthesis.
Kara Stockett Quinn
If I wanted to talk to you about raw materials, would your ears perk up? No? You’re not alone. In fact, I’m surprised that you’ve read this far.
Robert F. Meyer, Yash Kapoor
What do the Lockheed Martin F-35 Lightning II fighter jet and an Oral Solid Dose (OSD) continuous manufacturing module like GEA’s CDC-50 have in common? Flexibility.
Sulaf Assi, Ph.D., Basel Arafat, Kieran Evans, Ian Robertson
Malaria is a widespread infectious disease that contributes to 435,000 deaths globally.1 Despite its major prevalence in developing countries, it also affects developed countries. Thus, it has been anticipated that 3.4 billion people worldwide are at risk of having malaria.2 The wide spread of malaria stimulates the urgent need of antimalarial medicines that increases the chance of counterfeit spread alongside limited resources, lack of effective drug regulations, and gaps in the supply chain. Hence, counterfeit antimalarial medicines were frequently reported on several incidents.
Hibreniguss Terefe, PhD, Isaac Ghebre-Sellassie
Amorphous solid dispersions of poorly soluble drug substances were prepared using a variety of technologies, the most popular of which are spray drying and hot melt extrusion. As a result, a majority of the oral dosage forms of poorly soluble drug substances in the market consist of amorphous solid dispersions manufactured by spray drying or melt extrusion. In this and subsequent articles, an attempt will be made to compare and contrast the two technologies, including their pros and cons, in five parts, i.e., (1) Historical Perspective, (2) Manufacturing Processing Conditions, (3) Scale up and Equipment Considerations, (4) Quality, Cost and Regulatory Implications, and (5) Downstream Process Interfacing.
Charlotte De Bleye, Johan Cailletaud, E. Dumont, Pierre-Yves Sacré, Yoann Gut, Yves-Michel Ginot, Philippe Hubert, Eric Ziemons
Since its discovery, the application of Surface-Enhanced Raman Spectroscopy (SERS) has extended to various areas, including the pharmaceutical field, facing up challenges in the SERS substrate and sample preparation. This paper will present how beneficially SERS can be applied to the quantification of low-dose compounds in pharmaceutical tablets, focusing on the determination of 4-aminophenol, a toxic impurity, in acetaminophen tablets.
Susan Schniepp
There are three topics in today’s pharmaceutical landscape com-manding the attention of both the industry and the regulators: drug shortages, quality metrics and aging facilities. It is increasingly difficult to discuss one of these topics without discussing the others. Maintaining facilities that are capable of manufacturing quality products and being able to provide these products consistently and without delay has become a high priority for the industry and FDA.
Tim Sandle, PhD
Following the death of one patient and another falling seriously ill (reported in June 2019), the U.S. Food and Drug Administration (FDA) has called for greater controls over fecal transplants and the introduction of microbial pathogen screening. The patients became infected with a multi-drug resistant bacterial infection.
During his time in academia, Andrew originally studied biological sciences in Cardiff, specializing in respiratory physics. In 1991, Andrew joined Glaxo Group Research, formulating and analyzing inhaled medicines.
From products to formulation to scale-up Ashland offers a complete drug development portfolio
Process Analytical Technology (PAT) guidance is a nonbinding FDA document that aims to encourage innovation in cGMP manufacturing.
The drug development process involves rigorous in vitro and in vivo studies to understand pharmacodynamics and pharmacokinetic properties of lead compounds.
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.
Luis Jimenez
An analysis of FDA enforcement reports from 2012 to 2019 showed that Gram-negative bacteria were the most common microbial contaminants of non-sterile drugs in the United States. Burkholderia cepacia was the number one reason for non-sterile drug recalls with 102 citations followed by Ralstonia pickettii (45 recalls) and the USP indicator, Salmonella spp. (28 recalls). Unidentified microbial contamination accounted for 77% of non-sterile and 87% of sterile drug recalls indicating extremely poor microbiology practices. The presence of yeast and mold was the reason for 52 recalls of sterile and non-sterile drugs with only 12% providing any information at the genus or species level. Gram-negative bacteria were the most common cause of microbial contamination for sterility failures with no species showing a predominant presence. However, out of specification results (34 recalls) were the most cited violation for non-sterility recalls. Most sterile drugs (1056) were recalled by the lack of sterility assurance. Undetermined cGMP issues (184 recalls) was the number one reason for lack of sterility assurance followed by compounded drugs with deficient cGMP procedures (121 recalls).
Shaukat Ali, Karl Kolter, Matthias Karl
Innovative 3DP technologies to design personalized medicines have become a new paradigm in the pharmaceutical industry.1 The recent launch of antiepileptic drug Spritam® by Aprecia in 2015, has created immense interest in the rapidly growing 3DP segment to cater to patients requiring special personalized medications for long term care or life cycle management.