Don’t ignore the small peaks. Tackle impurities now.

The overall aim of the pharmaceutical industry is to produce drugs that give the maximum desired effect with minimum side effects. Impurities are inevitable in any chemical process, but pharmaceutical impurities, even in minute quantities, can significantly influence the behaviour of a drug, with implications for both safety and efficacy.

 The resulting product recalls can have far-reaching consequences for both patients and pharmaceutical companies. There are huge costs associated for manufacturers, both in lost revenue and regulatory fines, in addition to the negative impact on public perceptions of the pharma industry and the potential for drug shortages.

A prime example of the negative impact impurities can have on the industry can be seen in the case of impurities in angiotensin receptor blockers (ARBs), which are widely used to treat hypertension, heart failure and kidney disease.

In August 2018, the US Food and Drug Administration (FDA) announced that N-nitroso dimethylamine (NDMA) impurities had been detected in the ARB drug valsartan.The quantities of the probable carcinogenic impurity were above acceptable levels, leading to a chain of voluntary product recalls. Over the following months, two further impurities were identified in the ARB drugs irbesartan and losartan, as well as valsartan, resulting in further recalls. The timeline below highlights the scale of the crisis, with an estimated

2 million patients exposed to the impurities prior to the FDA’s findings

Similar recalls have since occurred for the diabetes drug, metformin, after NDMA impurities were found to be present. Since the FDA’s statement in December 2019, several pharmaceutical companies have recalled all lots of their metformin products. To prevent shortages, patients were advised to continue taking the potentially contaminated medication until a healthcare professional could prescribe an alternative.

As highlighted by the above examples, the presence of pharmaceutical impurities can have a catastrophic effect on the industry as a result of lost revenue and financial penalties. Impurity control is therefore vital to ensure only safe and effective drugs reach the market and prevent large-scale recalls. To this end, pharmaceutical drugs must be highly pure, and drug developers must also have a thorough understanding of the likely impurities for each product, as well as their formation mechanism. Impurity profiling and analysis is essential to inform our understanding of how and why impurities arise and facilitate their detection and prevention.

Hence Finding and addressing impurities earlier in R&D and process development can reduce the risk of unsafe impurity levels later in manufacturing processes, helping you stay on time and in compliance with regulatory expectations.

Assess and control for impurities throughout the entire drug lifecycle

• R&D
• method development
• manufacturing
• quality control
• stability testing
• post-market surveillance Strengthen analytical R&D and process development

Strengthen analytical R&D and process development

• conduct analytical tests during early formulation feasibility studies
• perform spiking studies during process R&D to demonstrate depletion upon recrystallization
• retention times and/or spectra
• determine relative response factors
• determine degradation impurities produced during stress studies
• identify unknown impurities that formed during ICH stability conditions
• identify impurities which are present in the Reference Listed Drug
• develop, validate and transfer analytical methods
• test for and profile impurities not listed in drug substance and drug product monographs

It is clear that an understanding of pharmaceutical impurities, including how and why they form, is imperative for the manufacture of safe and effective drugs. The presence of potentially harmful impurities can impact the pharmaceutical and healthcare industries through damaging product recalls and drug shortages, but most importantly, such impurities threaten patient health. Impurity formation can occur in a number of ways throughout the formulation process and is not always easy to detect and prevent.

Isha separation Sciences combines a  highly experienced team and superior problem-solving skills with state-of-the-art analytical instrumentation to support impurity analysis. Our custom synthesis service can provide complex or commercially unavailable impurities for analysis or internal standards, and our labelled isotopes can facilitate further studies into metabolites in biological systems.

While techniques and regulations for impurity control are continually updated, impurity screening and analysis will always have a place in safeguarding therapeutics for patients around the globe. Through our products and services, we can support research into impurities to help ensure that only safe medicines reach the marketplace.

ISP Standards: Partnering for Impurity Analysis and Control

At ISP Standards, we specialize in impurity detection, synthesis, and analysis, offering the tools and expertise needed to support pharmaceutical manufacturers:

• Custom Synthesis Services: Create complex or commercially unavailable impurities for analysis or internal standards.
• Labelled Isotopes: Facilitate studies of metabolites in biological systems.
• State-of-the-Art Instrumentation: Employ advanced techniques like LC-MS, GC-MS, and NMR for precise impurity profiling.
• Expert Team: Leverage decades of experience in analytical R&D and problem-solving to address even the most challenging impurities.

Safeguarding Patient Health

While impurity regulations and techniques evolve, impurity screening and control will remain indispensable for ensuring patient safety. By understanding impurities and addressing them proactively, manufacturers can protect patients, maintain compliance, and safeguard their reputation.

Remember: Don’t ignore small peaks—understanding your impurity profile early is essential to building quality into your process and preventing costly errors later. Through our comprehensive products and services, ISP Standards helps you bring safe, high-quality medicines to the marketplace with confidence.