Biopharmaceutical and pharmaceutical manufacturers must follow good manufacturing practices (GMP) and adhere to the FDA 21 CFR Part 11 requirements. These requirements “set forth the criteria under which the agency considers electronic records, electronic signatures, and handwritten signatures executed to electronic records to be trustworthy, reliable, and generally equivalent to paper records and handwritten signatures executed on paper.”
As part of their GMP and FDA requirements, biopharmaceutical and pharmaceutical manufacturers must identify and authenticate their raw materials. Compliance and efficiency are top concerns for raw materials managers, but thoroughly analyzing all incoming materials takes time and resources.
Ionic salts are common materials used in pharmaceuticals. According to an article on drugs.com, “over 50% of all drug molecules used in medicine exist as salts, most frequently as the hydrochloride, sodium, or sulfate salts. … drugs are often chemically made into their salt forms to enhance how the drug dissolves, boost its absorption into your bloodstream, and increase its effectiveness.”
The article goes on to say that additional advantages of drug salt formation include “development of controlled-release dosage forms, improved stability to extend shelf life, targeted drug delivery in the gastrointestinal tract (stomach or intestine), improved taste, improved drug effectiveness, reduced pain on injection, ease of processing, and extended patent life.”
Biopharmaceutical manufacturers use salts in buffers throughout production – in upstream or cell culture production phase to help maintain cell culture media pH, downstream or purification phase to support optimal purification conditions and prevent aggregation, and during formulation and storage to promote protein product stability.
The top five salts used include sodium chloride (NaCl), potassium chloride (KCl), magnesium chloride (MgCl2), calcium chloride (CaCl2) and sodium hydroxide (NaOH). These salts, of course, must be authenticated before being released into production. Pharmaceutical companies purchase these salts in large amounts and are required to test each container to meet the strict regulatory requirements. That’s a tedious and costly process when using standard wet chemistry lab or near-infrared (NIR) benchtop testing.
There is technology, however, that puts laboratory-grade capabilities directly into the hands of raw material and quality control managers anywhere in the manufacturing plant. Pharmaceutical and biopharmaceutical manufacturers can verify the identity of ionic salts in the warehouse in a matter of seconds with portable X-ray fluorescence (XRF) analyzers.
XRF (X-ray fluorescence) is a non-destructive analytical technique used to determine the elemental composition of materials. XRF analyzers determine the chemistry of a sample by measuring the fluorescent (or secondary) X-ray emitted from a sample when it is excited by a primary X-ray source. Each of the elements present in a sample produces a set of characteristic fluorescent X-rays (“a fingerprint”) that is unique for that specific element, which is why XRF spectroscopy is an excellent technology for qualitative and quantitative analysis of material composition.
During the X-ray fluorescence process, the ionic salt is irradiated with high energy X-rays from a controlled X-ray tube, and then the following actions happen:
- When an atom in the sample is struck with an X-ray of sufficient energy (greater than the atom’s K or L shell binding energy), an electron from one of the atom’s inner orbital shells is dislodged.
- The atom regains stability, filling the vacancy left in the inner orbital shell with an electron from one of the atom’s higher energy orbital shells.
- The electron drops to the lower energy state by releasing a fluorescent X-ray.
- The energy of this X-ray is equal to the specific difference in energy between two quantum states of the electron.
The measurement of this energy is the basis of XRF analysis.
Because it is non-destructive and needs minimal sample preparation, XRF analysis helps preserve production volume and ensure optimal throughput. The latest handheld XRF analyzers are easy-to-use and comply with 21 CFR Part 11, offering user access control, audit trails, electronic signatures, and full synchronization capabilities for proper storage of all electronic records. Thus, they can reduce the time and cost of pharmaceutical materials testing while helping to maintain regulatory compliance and rigorous quality standards.
- Free ebook: A Practical Guide to Improving Pharmaceutical and Biotech Manufacturing Processes and Production Methods
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