How do you ensure that your active pharmaceutical ingredients, their starting materials and intermediates, and the drug synthesis and manufacturing processes used to develop them are safe and efficacious?
Analytical testing.
The Importance of Analytical Testing
Analytical testing is a critical part of drug development and manufacturing – from route design and optimization through clinical trials and ultimately to a finished product. This testing ensures that the products used to make the drugs are safe – and that they remain safe across the drug’s lifecycle. Analytical testing unquestionably generates a wealth of data – but it is the interpretation of the data and the resultant process modifications that matters.
While analytical testing is broadly understood to involve ensuring the safety and efficacy of a drug, its impacts can be much more far-reaching. Analytical testing can accelerate R&D and smooth regulatory review processes for NDA or ANDA applications by demonstrating to regulators the Company has a thorough understanding of critical process parameters.
In some cases, analytical testing is the lynchpin to help ensure a drug process is properly optimized, which can spell the difference between a drug coming to market or washing out during development.
The challenge with analytical testing is that it can be extensive and complicated. Not all companies have the capacity to perform the necessary tests. That’s why many drug developers and manufacturers are turning to CDMOs (like LGM), or companies which offer standalone analytical testing services (also like LGM!) for help. When you hire an outsourcing company to perform your analytical testing, you can focus on your core competencies and rely on a team with proven expertise.
Types of Analytical Testing
So, what types of analytical testing are there, and what do they do? Some of the more common tests include:
- Identification: A test that verifies the identity of the active pharmaceutical ingredient. This test ensures the API is distinguishable from similar compounds. ICH Q6A guidance indicates that the test should be specific for the drug substance. For salt form of a drug, the ID tests should be specific to the individual ions.
Appearance: A qualitative test in which we describe the drug’s color, shape, and size. These tests are important because if the appearance changes throughout manufacturing or storage, the quality of the drug may be compromised.- Solubility: These tests measure the ability of a drug substance to dissolve in a solvent, typically a liquid. This test is crucial because a drug’s effectiveness is contingent upon its concentration in the bloodstream. If a drug is insoluble, it can negatively impact bioavailability and not produce the desired therapeutic outcome. Drug insolubility has become a critical issue in the small molecule drug space, with as many as 70% of New Chemical Entities thought to suffer from low solubility.
- Qualitative Assays & Quantitative Assays: An analytic procedure that assesses and measures a substance to determine the potency. An assay is critical because it identifies the presence, amount, and functional activity of an API or drug substance. Qualitative assays typically yield a pass/fail or positive/negative result (e.g., whether a protein present in the sample), while quantitative assays provide a precise numeric quantification of the trait being measured (e.g., how much of the protein is present in the sample).
- Water content and moisture analysis: These tests provide data on the effects of hydration or moisture absorption in the drug substance. The FDA labels these tests as crucial for drug substances that tend to absorb moisture from the air or are known to have a well-defined water content at a certain relative humidity (RH).
The above tests are critical to the characterization of a pharmaceutical product, so you’ll often find that many analytical testing labs provide these tests.
Microbiological Testing and Capillary Electrophoresis
With more than 60 QA/QC/Analytical specialists and three strategically located cGMP-compliant facilities, our analytical services team offers a wider range of services that you may not find elsewhere. For example, when a drug company with a peptide project needed a microbiological analysis in addition to numerous standard tests, we were able to help.
Microbiological testing can include everything from microbial limits to sterility and bioburden determination. These tests are vital because a contaminated drug can severely affect a patient – especially patients that are immunocompromised or susceptible to infections. The FDA identifies topical drug products, nasal solutions, and inhalation products as particularly susceptible to microbiological contaminates.
Capillary electrophoresis is another important test LGM Pharma performs in-house that you won’t find at many other labs. CE is a high-resolution separation technique that can detect analytes HPLC testing cannot. We use this test right now for dietary supplements at low claims.
Stability Studies
As part of our broader analytical testing capabilities, LGM conducts stability studies on Phase 1, Phase 2 and Phase 3 clinical batches, as well as finished drug products in the final marketed container/closure system to help determine the shelf life of a drug substance or drug product.
Typical stability testing conditions include 2-8° Celsius, 25° Celsius at 60% RH, 30° Celsius at 65% RH and 40° Celsius at 75% RH. There are a range of stability studies you may need, including:
- cGMP registration stability
- real-time or accelerated stability testing
- freeze/thaw cycle studies
- forced degradation studies.
Forced degradation testing – also known as stress testing – is one of the primary stability tests used to ensure a product is stable and can be used over time. These studies capture degradation over time under conditions such as oxidation, humidity, light and heat.
We also identify impurities through elemental analysis testing. These highly sensitive and specific tests identify impurities that could contaminate and impact a pharmaceutical product. They involve residual solvent analysis, elemental impurities, and residual solvents tests. The FDA is looking at these test results more now that the U.S. Pharmacopeia has updated the requirements for elemental impurity analyses. In fact, the FDA continues to investigate more types of analytical testing, making it even more important for drug companies to find a provider who offers comprehensive services.
Analytical Testing is the Cornerstone of Drug Development & Manufacturing
The goal of any drugmaker is to produce a drug that does exactly what it is intended to do. At LGM, we have the expertise, the cGMP facilities, and the equipment to provide high-quality contract analytical services that meet your budget and timelines.
Analytical Testing Services
Since we handle everything from API purchasing to formulation development and product manufacturing, we are uniquely positioned to handle all types of analytical testing. Contact us to discuss your drug project or your standalone analytical testing needs.
