Industry inspector team working, QC staff work checking machine operation for safety and hygiene in drink factory

Contamination in pharmaceutical manufacturing remains a persistent threat to both product safety and regulatory compliance. Drug products are vulnerable to a wide range of potential contaminants, ranging from trace solvents or chemical degradation products to process-related impurities (PRIs), equipment residues and raw material variations. Even a trace-level impurity can derail a batch, triggering costly investigations or compromising patient safety. As regulatory scrutiny intensifies and development timelines tighten, pharmaceutical teams can no longer afford late-stage surprises.

For R&D teams and QC managers, the central challenge is twofold: detecting contaminants early to prevent downstream quality issues, and ensuring that manufacturing methods are robust to regulatory requirements. Authorities now advocate for science- and risk-based approaches across the full pharmaceutical life cycle,1 so analytical techniques that can offer fast, reliable insights into material quality have become indispensable.

In particular, Chemistry, Manufacturing and Controls (CMC) compliance is key to regulatory success2 yet demands a deep, demonstrable understanding of both product and process. Foundational international guidelines for CMC practice, including ICH Q8 (Pharmaceutical Development), Q9 (Quality Risk Management) and Q10 (Pharmaceutical Quality System), emphasise the importance of proactive control strategies and continuous monitoring of critical quality attributes (CQAs).1,3

Under this framework, spectroscopy is a frontline tool to rapidly detect contaminants, and Fourier transform infrared (FTIR) spectroscopy is gaining ground as a powerful and practical solution for pharmaceutical contamination detection. It supports drug product quality control and process monitoring needs, including real-time implementation as a process analytical technology (PAT), and is equally applicable to multiple sample types. This versatility makes it suitable across the development life cycle, from early R&D and formulation studies to commercial batch release.

This article explores how FTIR fits into CMC-aligned workflows, supporting R&D leads, QC managers and researchers to address impurity control challenges quickly and efficiently.

Understanding FTIR: a fast, sensitive tool for impurity detection

Fundamentally, FTIR spectroscopy measures how samples absorb infrared light across the mid-IR (and sometimes near-IR) wavelength range. The resulting spectrum is highly sensitive to the chemical characteristics of the sample, serving as a detailed ‘molecular fingerprint’.4,5 This means FTIR can distinguish subtle changes in chemical composition and environment, including the presence of contaminants. In the CMC context, it offers rapid insights throughout method development, process validation, routine QC testing and batch release, without the need for extensive sample preparation.

To extract actionable insights, many laboratories apply chemometric techniques to FTIR data, including partial least squares (PLS) regression and principal component analysis (PCA). These statistical methods help resolve overlapping signals and identify subtle spectral shifts, to enhance detection of low-level contaminants. Chemometrics may support trend monitoring, root cause analysis and classification tasks such as distinguishing between supplier batches or formulation variants. For R&D teams, this data-rich output can also streamline polymorph screening and stability profiling, while QC labs benefit from more confident impurity detection and trends over time.

Modes of FTIR sampling: which to use and when

Two common FTIR sampling modes used in pharmaceutical settings are summarised below. Each one caters to specific material types and matrices, so choosing the right option is essential to maximise detection sensitivity, reproducibility and operational simplicity.

Transmission

  • Ideal for: liquids, solutions, films.
  • Advantages: high-resolution spectra, path length control, quantitative capabilities.
  • Relevant tools: the Specac Pearl™ Accessory offers a liquid transmission cell with precisely engineered fixed path length options, supporting quick and accurate contaminant analysis.

Attenuated total reflectance (ATR)

  • Ideal for: solids, semi-solids, tablets, pastes, gels.
  • Advantages: minimal sample preparation, rapid results, high reproducibility.
  • Relevant tools: Specac’s Quest™ ATR Accessory sets the benchmark in performance and value for ATR-FTIR spectroscopy, while the Harrick ConcentratIR2™ Multiple Reflection Accessory incorporates a multi-bounce crystal to significantly enhance sensitivity, enabling trace impurity detection in liquid samples.

By selecting the appropriate sampling mode and accessory, analysts can extract maximum information from each sample. The next section explains how these methods are applied in real-world settings.

Monitoring contaminants across the pharmaceutical life cycle

From R&D to scale-up: where FTIR adds value

Impurity and contamination risks can emerge during early-stage R&D, intensify during scale-up and technology transfer, or persist into commercial manufacturing. During every phase, the capability to detect and characterise contaminants quickly and confidently is crucial to demonstrate the rigour required in regulatory CMC submissions, and of course, to ensure product safety.

The rapid, non-destructive and flexible nature of FTIR spectroscopy positions it to support these needs. It offers practical analytical insights across the continuum, from rapid proactive screening, to real-time analysis via PAT implementations, to reactive investigation of manufacturing incidents.

This responsiveness is especially valuable when building control strategies under ICH Q8 and Q11 (Development and Manufacture of Drug Substances), which require a sound scientific understanding of CQAs, sources of variability and potential impurity risks.1 With appropriate analytical workflows, FTIR spectroscopy can support every stage from raw material qualification to final batch release. The following case studies highlight how FTIR methods have been successfully applied at various stages of pharmaceutical development.

Real-world case studies: FTIR in contaminant detection

Each case below illustrates FTIR spectroscopy’s relevance to either R&D scientists looking to characterise complex systems or QC managers aiming for efficient, compliant operations.

Case study 1: isotopic impurities in raw materials

Deuterated drugs are a notable growth area, inspired by the recent FDA approvals of deutetrabenazine and deucravacitinib.6 To reduce its rate of metabolism, deucravacitinib incorporates a deuterated trimethylamide group which is synthesised using d3-methylamine hydrochloride in the commercial process.7,8

Without a precise method to quantify isotopic impurities, Bristol Myers Squibb researchers risked introducing these uncontrolled variants into the API, which would be a red flag for regulators. An FTIR method was developed using PLS chemometric analysis, capable of quantifying d0-, d1– and d2-methylamine impurities down to levels of ~0.3% and validated according to ICH Q2 guidelines.9

  • Why FTIR: Ideal to distinguish isotopic impurities, since C–H and C–D bonds absorb IR radiation at different wavelengths due to the mass difference between hydrogen isotopes.
  • Recommended tool: Given the high cost of isotopically labelled reagents, Harrick ConcentratIR2 is perfect for this type of trace-level analysis due to its low-volume sample requirements (~10 µL) and enhanced sensitivity.

For QC labs, this kind of trace-level quantification means more defensible batch records. For R&D teams, it ensures the upstream process doesn’t compromise final product safety.

Hand holding blue capsule pack at medicine pill production line, Industrial pharmaceutical concept.

Case Study 2: unknown materials encountered during manufacture

Unexpected materials discovered during manufacturing can halt production and trigger costly investigations. When Amgen scientists found unidentified fibres and residues in a fill/finish facility, product integrity and patient safety were at stake. They combined FTIR spectroscopy with spectral library matching and functional group analysis to quickly identify the foreign materials as nylon 66 and styrene–butadiene rubber,10,11 enabling preventive actions to be taken.

  • Why FTIR: The availability of large reference spectral databases aids identification of unknown samples.
  • Recommended tool: To optimise database matching, the Pearl liquid transmission and Quest ATR accessories enable high-quality FTIR spectra for liquid/solution and solid samples, respectively.

Here, FTIR supported manufacturing investigations and broader QC efforts to prevent recurrence, which are both extremely valuable for teams managing Corrective and Preventive Action (CAPA) systems under ICH Q10.

Case Study 3: process-related impurities in simvastatin drug products

When APIs are manufactured by multiple suppliers, consistency in impurity profiles is a major regulatory and therapeutic concern. Simvastatin, a widely prescribed generic statin drug,12,13 is prone to PRIs including lovastatin and other trace impurities, depending on the chemical synthesis pathway.

One study used transmission FTIR (KBr disc method) and chemometric modelling to determine lovastatin and total impurities in 20 commercial simvastatin formulations, demonstrating good agreement with HPLC results.14

  • Why FTIR: Faster and more resource-efficient than HPLC-based methods.
  • Recommended tool: The Quest ATR accessory offers convenient analysis of solid samples via ATR-FTIR, compared with more laborious transmission approaches.

For QC teams, this represents a faster, lower-resource alternative for impurity tracking in generic products, and a way to ensure consistency in complex supply chains.

Integrating FTIR into a robust CMC and quality strategy

Aligning spectroscopic tools with regulatory expectations

Under modern CMC frameworks such as the ICH Q8–Q12 guidelines, pharmaceutical manufacturers are encouraged to build robust quality systems and control strategies. Analytical methods must be thoroughly validated to support full life cycle management, risk mitigation and decision-making among R&D leads and QC managers. When integrated into control strategies, FTIR spectroscopy supports these expectations by contributing to:

  • Raw material characterisation and qualification.
  • Detection of PRIs and reaction by-products.
  • Root cause investigations during non-conformance or out-of-specification (OOS) events.
  • Routine QC for batch release and stability testing.
  • Real-time process monitoring within PAT environments.

Validated chemometric methods may further enhance the value of FTIR spectroscopy by defining reaction end points in real time, enabling rapid material classification and contaminant analysis, or significantly streamlining release testing and batch variability assessment.

FTIR and its analytical peers: complementary, not competing

While FTIR methods are flexible tools for process development, real-time verification and troubleshooting, they often prove most effective when used alongside complementary analytical techniques, including:

  • Raman spectroscopy: Provides complementary information to FTIR with much less interference from water;15 widely used to characterise polymorphs, salts, excipients and drug delivery systems.16,17
  • UV/Vis spectroscopy: Excels at detecting chromophoric PRIs or degradation products, but lacks structural specificity.
  • NMR and LC-MS: Offer detailed structural and molecular information but are resource-intensive and less practical for routine or rapid screening; generally confined to offline use.

Making FTIR a pillar of your contamination control plan

Contamination in pharmaceutical manufacturing is a regulatory liability that threatens drug product quality and patient well-being. However, with the right instrumentation and strategy, FTIR spectroscopy becomes a key asset to support contamination control in pharmaceutical labs at every stage of the product life cycle.

From raw material verification to final batch release, FTIR methods give essential insights into chemical identity and integrity. Compatibility with multiple sample formats, as well as alignment with CMC documentation requirements, make these techniques an invaluable addition across many impurity control applications, while also supporting proactive quality practices in line with ICH principles. Whether used for real-time contamination monitoring, routine QC or retrospective root cause analysis, FTIR spectroscopy enables pharmaceutical manufacturers to reduce risk, fulfil regulatory documentation requirements and support data-driven decision-making.

Next steps: equip your lab with the right tools

Specac offers a suite of FTIR accessories designed with the demands of pharmaceutical development and manufacturing in mind:

Whether you’re updating your CMC control strategy or building a new analytical QC platform, these accessories can help your lab operate with greater precision, speed and confidence.

To see how these accessories can transform your workflows and help de-risk your next product submission, watch our expert-led webinar for more information.

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