Related Experiment Video
Updated: Jun 23, 2026
12:02
Automated Modular High Throughput Exopolysaccharide Screening Platform Coupled with Highly Sensitive Carbohydrate Fingerprint Analysis
Published on: April 11, 2016
In-line Raman spectroscopy real-time glucose prediction method for commercial pneumococcal vaccine drug substance
Griffin P Thomas1, Brian C Marks2, Barbara B Alvarado-Hernandez2
1Vaccines and Advanced Biotechnologies Process Research and Development, MRL, Merck & Co., Inc., Rahway, New Jersey, USA.
Biotechnology Progress
|June 21, 2026
Summary
Raman spectroscopy offers real-time glucose monitoring in drug fermentation, replacing slow, costly off-line methods. This in-line process analytical technology (PAT) improves control, reduces costs, and enhances safety in manufacturing.
Area of Science:
- Pharmaceutical manufacturing
- Analytical chemistry
- Process analytical technology (PAT)
Background:
- Traditional off-line methods for quantifying drug substance fermentation metabolites are time-consuming, expensive, and potentially hazardous.
- Existing assays require manual operations, posing risks when handling pathogenic biological organisms.
- There is a need for efficient, safe, and real-time analytical methods in pharmaceutical manufacturing.
Purpose of the Study:
- To develop and validate Raman spectroscopy as an in-line process analytical technology (PAT) for real-time glucose quantification.
- To replace conventional off-line assays with a more efficient and safer in-situ method.
- To demonstrate the feasibility of Raman spectroscopy for mitigating challenges in process development and commercial manufacturing.
Main Methods:
- Method development and validation of Raman spectroscopy for in-line glucose monitoring.
- Application of chemometric techniques and multivariate analysis on Raman spectral data.
- Development of a partial least squares (PLS) model for predicting glucose concentrations.
Main Results:
- A partial least squares (PLS) model accurately predicted real-time glucose concentrations with a root mean square error of prediction (RMSEP) of 1.2 g/L.
- The Raman PAT glucose quantification method was validated for making process decisions in a commercial manufacturing facility.
- The method accurately indicated glucose concentration within the target range of ±2 g/L for triggering process operations.
Conclusions:
- Raman spectroscopy serves as an effective in-situ PAT for real-time glucose quantification in drug substance fermentation.
- Implementation of this method led to advanced process control, reduced operating costs, and improved safety.
- This validated Raman spectroscopy method represents a significant advancement for pharmaceutical manufacturing processes.
Related Concept Videos
01:27Production of Alcohol
Continuous fermentation is a key strategy in industrial ethanol production, particularly when efficiency, scalability, and high yields are essential. This approach allows for uninterrupted operation and optimized resource utilization. The primary feedstock, corn starch, undergoes enzymatic hydrolysis facilitated by α-amylase and glucoamylase. These enzymes break down the starch into fermentable sugars such as glucose, which are readily assimilated by fermentative microorganisms.Fermentation...
01:25Rapid Identification of Pathogens
MALDI-TOF MS has transformed clinical microbiology by offering a rapid and reliable method for pathogen identification. The traditional approach to microbial identification typically involves time-consuming culture techniques and biochemical tests, which can delay the initiation of appropriate antimicrobial therapy. MALDI-TOF MS avoids these delays by using characteristic ribosomal protein mass patterns of microbial cells, enabling accurate species-level identification within minutes.Principle...