Behind the Scenes: Unveiling the essential role of finished product testing
Pharmaceutical innovation is one of the main driving forces behind healthcare advances. Piloting new and enhanced treatments has accelerated public health to never-before-seen heights.
From drug discovery and development to clinical research trials, each pharmaceutical product will undergo a substantial journey, with safety, efficacy and quality closely monitored throughout the process to confirm its continuation.
As the last line of defense before a pharmaceutical can hit the shelf is finished product testing. This valuable stage ensures compliance with regulatory standards, performing the final safety and quality evaluations prior to determining whether a product can be released to the market.
In this article, we explore the significance of finished product testing, including the testing methods employed to confirm the component safety of each drug product.
The essential role of finished product testing
Imagine that your doctor prescribed a brand-new medication that you’ve never taken before. In the world we live in today, we trust that this drug is not only safe for human consumption but will actively improve our health in one way or another.
Nevertheless, the only way that a medicinal drug can be administered by consumers, is once it has been quality checked. Thanks to the stringent and rigorous controls within the pharmaceutical field, drug innovators can confidently produce quality medications that perform exactly as intended.
Of course, that’s not to say that it’s always been that way. With pharmaceutical advancements speeding up dramatically throughout the past century, safety measures were somewhat of an afterthought up until 50 years ago. This left the public vulnerable to dangerous side effects and sometimes life-threatening repercussions.
Through the development of strict regulatory frameworks and rigorous safety monitoring, 21st century safety measures are far more advanced than those from 50 years ago. However, that doesn’t mean we’ve been completely immune to serious cases of product recall.
Take the Heparin drug crisis in 2008, for example; a medication designed to treat and prevent blood clots which involved contamination of the finished product by a counterfeit ingredient. This situation led to a worldwide product recall due to a mass of life-threatening allergic reactions and fatalities.
A scenario which undoubtedly raised concerns around the existing and seemingly outdated quality control measures. This case highlights exactly why pharmaceutical innovation must have rigorous safeguarding measures in place. Regulating medication with rigid and robust, routine assessments would ensure the safety of all consumers. This is where finished product testing comes into play:
What is finished product testing?
Finished product testing focuses solely on evaluating the physical and chemical components of pharmaceutical products prior to and after batch release. These tests provide a comprehensive and final assessment to ensure the product is safe, reliable, and meets its intended purpose.
The analytical tests conducted assess all essential parameters, including identity, potency, purity, microbiological content and more. A range of testing methods validated in accordance with ICH guidelines are employed. These quality control testing methods are designed to ensure that each product is in conformance with the approved specifications and performs exactly as it should.
Below, we delve into the common finished product analysis techniques and the specific parameters they assess:
Identity, purity and potency assessments
Critical to the effectiveness and safety of all medicines is a comprehensive assessment of the identity, potency and purity of the manufactured finished product. Included in the catalogue of analytical techniques used, are Liquid Chromatography (HPLC and UHPLC), Gas Chromatography (GC), Infrared and UV Spectrophotometry.
Through the preparation and analysis of samples in the liquid phase, HPLC and UHPLC techniques can be used to separate out the complex mixtures that arise within finished drug products.
Analysts can then detect and quantify each constituent individually; the active pharmaceutical ingredients (APIs) and excipients, other ingredients such as preservatives or flavourings, as well as the unwanted impurities and degradation products.
The testing methods used to determine the potency or active content of a finished drug product may also be applied to individual tablets, capsules or any other pre-metered dosage form. This will confirm the content uniformity across a manufactured batch, ensuring that each and every dose of an active substance administered to patients is within accepted limits.
In a similar way to the LC techniques, GC can be deployed for the analysis of drug product components in the gaseous phase. The determination of ethanol content is an important factor in assessing the formulation of a variety of medicinal products, such as cough syrups or some metered dose inhalers.
GC analysis is particularly useful in determining whether potentially harmful volatile or semi-volatile leachables may be present within a drug product at levels either above the AET (analytical evaluation threshold) or SCT (safety concern threshold) after being in contact with the drug product primary packaging or container/closure system.
To ensure complete discrimination of the identity of an active substance within a finished product, secondary orthogonal procedures are employed, these often include Infrared (IR) or Ultraviolet-Visible (UV-Vis) spectrophotometric tests which examine the precise absorption characteristics of the compound under test.
Taken together, the identification tests ensure that the manufactured product contains only the exact active pharmaceutical ingredient as is described on the label.
HMR labs offer a comprehensive range of validated testing services for the confirmed identity, purity and potency testing of your pharmaceutical products, APIs and excipients. Qualifying each sample before batch release is second nature to our dedicated team of experts, who have extensive experience in pharmaceutical testing.
When does finished product testing occur?
Finished product testing continues even after a pharmaceutical has been given the all clear for batch release. Ongoing analytical testing must be performed to monitor various batches of drugs in the market and ensure the component make up remains consistent even after it has hit the shelves.
This process involves finished product testing that accounts for:
Performance testing
The effectiveness of a pharmaceutical drug product is not always simply based on its ingredients. Often the in-vivo performance of a medicine will also depend on additional factors.
For example, the controlled release of an active ingredient from a tablet or capsule once ingested, the aerosolisation of an inhaled formulation for delivery to the nasal mucosa or the lungs, or the transdermal delivery of a drug from a patch or injector pen. Each of these drug product characteristics are assessed using in-vitro performance tests.
Dissolution testing is a critical indicator of drug quality, assessing solubility and the intended therapeutic effects of the API. Several methods are employed to simulate drug release within the human body for a particular drug, and the choice of method depends on its ability to best replicate the physiological conditions of the intended site of drug release.
Similarly for nasal and orally inhaled drug products, the amount of active pharmaceutical ingredient that reaches the site of absorption will depend on both the formulation as well as the design and operation of the chosen delivery device.
Any variation in these can have a significant effect on both the emitted dose and aerodynamic particle size distribution of the aerosol when released from the inhalation device. Assessing both of these parameters is critical in ensuring that an inhaled product conforms to the established pharmacopeial specifications.
HMR’s state-of-the-art facilities include a full range of qualified test equipment, with teams of analytical scientists dedicated to the performance testing of a wide range of pharmaceutical dosage forms. Interested in finding out more about our dissolution testing? Check out our previous article, you can find this here.
Microbiological testing
Microbiological testing is fundamental for the identification and detection of harmful bacteria and other microorganisms. It includes testing for microbial limits, preservative efficacy, bacterial endotoxins and more.
Microbial limit testing aims to ensure that samples are free from unwanted bacteria, yeasts, and molds through assessment metrics such as the Total Viable Count (TVC) or Total Yeast and Mold Count (TYMC). Specific pathogen testing methods can also be employed, along with antimicrobial effectiveness and preservative efficacy testing to evaluate the ability of preservatives to inhibit microbial growth.
Bioburden experiments are conducted to measure microbial contamination levels on or in a product. This is achieved using methods such as plate count or membrane filtration, which promote colony growth and help determine the initial number of microbes in a sample.
Bacterial endotoxin testing is used to detect and quantify endotoxins. This is often achieved through Limulus Amoebocyte Lysate (LAL) which can detect both viable and non-viable Gram-negative bacteria.
With 4 custom-built microbiology laboratories, our labs can provide confirmation and peace of mind surrounding microbial evaluation of all finished pharmaceutical dosage forms.
Partner with HMR on your journey to batch release
Finished product testing must be conducted with absolute precision, accuracy, and reliability. Given the complexity and stringent nature of the validated methods and their active role in safeguarding both pharmaceutical innovation and public health, choosing a testing provider is pivotal in drug development journeys.
With over 35 years of analytical experience, HMR Labs have assisted countless innovators on their journey to the shelf. Our extensive experience in finished product testing, full range of instrumentation and custom-built facilities are designed to accommodate the diverse needs and requirements of finished product analysis.
Looking to accelerate and maintain your batch release journey? Get in touch with our team today.