Troubleshooting

We have developed an in-house broth to neutralize a preservative for traditional microbiological testing following USP <61> Microbiological Examination of Non-Sterile Products: Microbial Enumeration Tests. We would like to use a rapid method to release product faster, but is there a broth that will be effective on our products?

Experts share how to choose analytical tools and techniques when scaling up a lyophilization process.

My application uses a peristaltic pump with silicone tubing running through it and a different, heat-sealable tubing material before and after the pump section. Recently, an operator installed the wrong section of tubing in a pump, resulting in lost API, equipment replacement, and hours of extra work. How can we avoid this kind of mix-up in the future?

New coating technologies achieve high uniformity and reduce waste through mixing system advances and pan and airflow configuration.

We are using a vacuum oven to dry our wet-cake intermediate. At 120 °C, it takes 26 hours on average to dry the material from 80% to 10% moisture. Can we shorten our drying time, possibly by agitating the product to improve heat transfer?

Equipment design and cleaning procedures both play a role in thorough sterilization and cleaning.

My network failed and I had to scrap my batch because my historian did not collect the required data. How do I upgrade the reliability of my network to maintain data continuity if my network fails again?

Critical issues that should be considered when scaling up a hot-melt extrusion process.

In our tablet coating process, we are losing up to 15% of our coating solution in each processing run. What can we do to prevent this problem in order to reduce waste and increase our cost efficiency?

We need to measure the particle size of a moisture-sensitive powder. We would like to use dry analysis on our laser-diffraction system, but the particles are fragile and we're struggling to get robust results. Is wet measurement with a nonaqueous solvent the only option?

I work in a quality control laboratory and use a pH meter with a single-junction reference probe to test samples taken from various pharmaceutical (drug) production lines. The probe I use has a six-month warranty. It slowly stops working after just a couple weeks. I am replacing it once a month. We make sure to store it correctly according to the manufacturer's specifications and even use probe cleaner at the end of each shift to ensure that it stays clean. What can I do to increase the lifespan to at least cover the warranty period?

We have several tablet formulations that are dwell-sensitive-they require more time under compression than other formulations. Given increasing demand, we do not have the luxury of slowing the tablet presses down in an effort to increase that dwell time. How can we maximize dwell time and maintain or increase output in our tablet presses?

We have changed the brand of our stoppers for a product that we freeze-dry in vials. Since the change, we have observed a significant increase in rejects for collapsed cakes. Why are the cakes collapsing? What can we do to prevent this problem?

When I run a small production batch of a particular formulation with the same tablet press used to develop it, I get compressibility and disintegration issues. What am I doing wrong?

In our manufacturing process, we are running into issues with our vial stoppers clumping in the feeder bowl. How can we ensure that the stoppers go through smoothly without clumping up?

We try to use previous experience to develop the optimal granulation process for each new ingredient, but we sometimes get it wrong. Many times, we?ve taken materials from the granulator only to find that they exhibit poor flow and insufficient density. How can we easily determine the end point of a given granulation process?

We?re attempting to validate a clean-in-place process using total organic carbon (TOC) as the analytical method. Our swab-sample recovery tests are giving us inconsistent results. Recovery values range from 95% to 205%, and there seems to be no correlation with the amount of drug product deposited on the coupon. What could be the problem?

Our company is getting low and unpredictable cycle life out of our diaphragm valves. This problem has caused us to implement standard operating procedures for frequent replacement of the diaphragms, which is costly and time consuming. What could be happening, and what are our options?

How do you assign a minimum sample weight for a US Pharmacopeia <41> balance application when the tested repeatability gives a standard deviation of zero?

We want to fill one of our oxygen-sensitive products inside an isolator system. Can we run an isolator with pure nitrogen and defined humidity?

We are making an emulsion using a high-shear in-line mixer. It?s a 60-gal batch, and it?s taking nearly an hour to get the results we?re looking for. We have tried changing the in-line mixer?s workheads to a two-stage configuration, but it doesn?t affect the mixing time. Where are we going wrong?

My drug failed a light-obscuration test, but after I filtered the drug for microscopic particle counting, I couldn?t see any significant particulate on the filter. What might have caused the failure, and why is it not visible?

An industry expert answers a reader's question about using a volumetric dry-material feeder and jet mill to create a finished product.