Quality control (QC) testing is one of the most vital components in the pharmaceutical lab, ensuring that drugs are free of harmful impurities and safe to use for the patients who rely on them for medical treatment. QC testing encompasses a variety of pharmaceutical testing methods and processes to detect contaminants and keep products compliant with government regulations and other safety standards. As you navigate this rigorous and critically important field of laboratory science, keep these tips in mind to optimize your productivity.
Tip 1: Know your impurities
Impurities testing is necessary to ensure the safety and efficacy of a drug by making sure it does not contain anything that would counteract the therapeutic effects of the active pharmaceutical ingredients (APIs) or have adverse effects on the human body. Anything present above the standard threshold of 0.1% should be identified and quantified for risk assessment. The three main types of impurities include: organic, inorganic or elemental and residual solvents.
- Organic impurities may be volatile, semi-volatile or non-volatile and arise from the manufacturing process or storage of drug substances, with possible sources including starting materials, by-products, intermediates, degradation products and regents, ligands and catalysts. Organic impurities are the most common impurity found in APIs and may be unidentified and of unknown toxicity, requiring more extensive investigation.
- Inorganic and elemental impurities, on the other hand, are typically identified and have a known toxicity, and can be quantified through pharmacopoeial procedures. They can arise in the manufacturing process from heavy metals, inorganic salts, regents, ligands, catalysts or materials, such as filter aids and charcoal. Elemental impurities are divided into classes based on their toxicity, with the “big 4” being the most toxic: arsenic, cadmium, mercury and lead.
- Residual solvents are used in the synthesis of a new drug substance that have not been completely removed, and are almost always readily identified. Residual solvents are also classified by toxicity, with the United States Pharmacopeia (USP) specifying concentration limits for each solvent of concern.
- Extractables and leachables are specific types of impurities in packaging, containers and delivery devices that could contaminate a drug product in accelerated or exaggerated laboratory conditions, or in normal storage and use conditions, respectively. Analyzing these impurities involves testing both the potential contamination source (ex. a drug package or inhalation device) and the drug after exposure to the container or device over periods of time.
Tip 2: Select the best equipment for your tests
Once you know your samples and what you’re testing for, selecting the best equipment for the task will be crucial in getting a full picture of the quality and compliance of your drug or drug components. Every testing method must be properly validated and equipment must be calibrated to ensure consistency and accuracy in every test.
Your method of impurity detection will depend on a range of factors such as molecular weight, volatility and the sensitivity and resolution you require. You can find guidance for analytical procedures from the USP, European Pharmacopoeia (Ph. Eur.), ICH and peer-reviewed scientific literature. Below are some common industry-standard methods for specific types of impurities:
- Residual solvents and volatile organic impurities: Headspace gas chromatography (HS-GC) with flame ionization detection (FID) or mass spectrometry (MS)
- Non-volatile organic impurities: High performance liquid chromatography (HPLC) with MS or nuclear magnetic resonance spectroscopy (NMR)
- Inorganic and elemental impurities: Inductively coupled plasma-optical emission spectrometry (ICP-OES) or ICP-MS
When it comes to purchasing analytical instruments for your lab, you will want to consider the features of both the samples you will be testing and the facility itself. Cost and desired throughput will factor into decisions, such as whether acquiring an accelerated solvent extraction system is a better option for your lab than using soxhlet or reflux extraction techniques. If you need more sensitive elemental impurities testing, lean toward ICP-MS over ICP-OES. Also, consider whether your lab would benefit from a more customizable instrument with various module options, which could allow for more flexibility in times of fluctuating demand, and accommodate additions as your laboratory grows.
Tip 3: Embrace automation
Automation is one of the biggest time-savers for laboratories and the number of processes that can be automated has only increased over the past decades. Automated technology has also been improving, with better consistency at every step of the analytical process, more controlled resource consumption to reduce waste and stronger safeguards against sample contamination and other potential problems. Automated equipment that can run unattended and continuously for repetitive processes will free up analyst time, reduce human error and greatly improve throughput. For example, headspace autosamplers provide an efficient means of extracting volatile compounds with little-to-no carryover, minimize time spent on sample preparation and improve repeatability with built-in temperature controls and precise injection. Automated equipment that syncs to computerized recording systems save further time and ensure data integrity.
Tip 4: Leverage computer technology for documentation
Extensive documentation of tests, movements, measurements, analytical data and everything in between preserves traceability, which is especially crucial for quality control labs. Synchronized computer systems have greatly streamlined this recording process by removing the potential for human error that comes with handwritten logs and manual data entry. Equipment that can automatically transmit test data to your lab’s computer systems will free up time, preserve data integrity and more easily link results back to a specific instrument and timestamp, and software systems developed specifically for quality control will include the tools and reference materials you need to analyze and visualize data. Automated vial labeling is another way to efficiently trace results to a specific sample with barcodes that link back to data stored in the computer. Computer technology can be integrated into daily workflows and standard operating procedures (SOPs), automating many tasks while maintaining or improving compliance.