Pharmaceutical Technology Is Now PharmTech: A Sharper Name for a Smarter Industry

Navigating FDA Shakeups and Obesity Drug Wars

Behind the Headlines Episode 28

Ask the Expert

Closing the Gap in Modern Process Control and Automation for QC/QA

Drug Digest December 2025

How It Helps Avoid Facility and Equipment Problems

A “Plan, Prevent, Prove” Approach

The pharmaceutical industry experienced a complicated 2025, with challenges arising in a variety of areas including supply chain security and market demand. 

 imposed by the Trump administration in the United States, geopolitical unrest, and 

 created a web of complexity that required the right talent, investments in technology, and embracing innovation.

, takes a look back at the past year and gives his opinion on which trends will carry over from 2025 into 2026.

PharmTech: Which trends did you see or experience in 2025 that you believe impacted the pharmaceutical industry the most?

 In 2025, we witnessed a fundamental shift: pharma finally began treating clinical operations as a strategic advantage rather than a necessary evil. AI emerged as a true differentiator in accelerating development timelines by streamlining administrative workflows, enhancing protocol design, improving site selection, and enabling precision patient matching at scale.

At the same time, the convergence of decentralized trial infrastructure and real-world data unlocked entirely new operational models. Sponsors can recruit patients nationwide through telemedicine, capture continuous data via connected devices, and integrate EHR [electronic health records] insights directly into trial databases with unprecedented ease.

In an environment where competitors often pursue similar therapeutic targets, success is no longer defined solely by marginal differences in the science. It hinges on who can execute faster while maintaining rigorous scientific and operational integrity.

What strategies are most effective in attracting and retaining top talent, especially as technological advancements shift frontline and technical roles?

It goes beyond compensation. It starts by creating an environment where people can do meaningful work with a tangible impact. When teams understand how their work contributes to better research or improved patient outcomes, engagement and retention naturally improve. Talented individuals also crave autonomy in the workplace. Small, empowered teams and room to experiment help people feel trusted and motivated.

How does the industry plan to maintain competitive advantage as patent cliffs, rising generic-drug competition, and pricing reforms intensify margin pressures?

Maintaining competitive advantage requires shifting from a model driven primarily by commercial exclusivity to one grounded in operational excellence and innovation throughout the development lifecycle. As patent cliffs and pricing reforms reduce the buffer that once protected returns, companies are increasingly focusing on improving the efficiency and predictability of R&D. This includes adopting technologies that shorten development timelines, redesigning trial processes to reduce operational waste, and making earlier, clearer decisions about which programs deserve continued investment.

Competitive advantage is also retained through obtaining real-world evidence, developing patient-centric delivery models like direct-to-consumer programs and companion apps that present a drug product as part of a holistic experience or treatment for a patient. Companies are also looking upstream by strengthening pipelines through strategic partnerships. The companies that adapt to these pressures will be those that prioritize efficiency, evidence generation, and patient relevance.

Which trends do you see driving innovation and drug development in 2026?

Looking ahead to next year, AI will continue to move from experimentation to practical integration, particularly in protocol generation and design, patient stratification, and decision support. We’ve already seen transformational improvements across the industry with advanced technologies. I believe there will also be increasing pressure for evidence that reflects real clinical use, especially as payers and regulators become more value focused. This is driving innovation in continuous data collection, long-term follow-up, and integrated evidence strategies that span from early clinical development through post-market evaluation.

, an end-to-end, full-service contract research organization running radically faster, more reliable clinical trials for life science pioneers. Beckwith was previously a venture capital investor and partner to biotech and digital health companies. He took part in the COVID-19 vaccine trial as a volunteer where he saw how trial outcomes could be improved by focusing on patient experience, ultimately leading to the formation of Lindus Health.

Articles

The pharmaceutical industry faced a challenging 2025, marked by supply chain issues, geopolitical tensions, and rapid technological advancements. A significant shift occurred as clinical operations were recognized as strategic assets, with AI playing a crucial role in streamlining processes. Decentralized trials and real-world data integration emerged as new operational models. To maintain competitive advantage amid patent cliffs and pricing pressures, companies focused on operational excellence and innovation. Looking to 2026, AI's integration and evidence-based strategies will drive innovation and drug development.

Meri Beckwith, Co-CEO of Lindus Health, provides a look at how trends that developed in 2025 will impact the pharmaceutical industry in 2026. 

Quick Execution with Operational Integrity

Feliza Mirasol is the science editor for 

China’s National Medical Products Administration has approved the 

 (mAb) mepolizumab (brand name Nucala) as an add-on maintenance therapy for adults with inadequately controlled chronic obstructive pulmonary disease (COPD) characterized by elevated blood eosinophils, GSK announced on Jan. 5, 2026 (1). The approval marks a regulatory milestone for 

 in respiratory disease management in the country and reflects growing 

 of targeted immunologic approaches for a condition historically managed with inhaled therapies alone (1,2).

The approval was supported by data from two Phase III trials (MATINEE and METREX), which evaluated the mAb in patients with COPD who continue to experience exacerbations despite optimal inhaled triple therapy. According to GSK, these studies demonstrated statistically significant reductions in moderate and severe exacerbations compared with placebo, with a safety profile comparable between treatment groups.

“Given the high incidence of COPD in China and a mortality rate that is above the global average, there is a clear need for novel options to address COPD,” said Kaivan Khavandi, senior vice-president and global head, Respiratory, Immunology & Inflammation R&D, GSK, in a company press release (1). “The approval of Nucala offers patients in China a monthly add-on maintenance treatment to reduce exacerbations, including those leading to emergency department visits and/or hospitalizations, which account for a large proportion of annual direct medical costs.”

What does China’s approval mean for biologics in COPD treatment?

With this approval, mepolizumab becomes the first monthly biologic approved in China for COPD and the first evaluated across a broad patient population with blood eosinophil counts starting at 150 cells/µL, GSK stated in its release (1). The company noted that this threshold is clinically relevant because a substantial proportion of patients with persistent exacerbations fall into this category, despite receiving 

COPD affects an estimated 100 million people in China, where the disease accounts for more than 30% of global mortality attributed to the disease (3). Recurrent exacerbations are associated with accelerated lung function decline, increased hospitalization and readmission rates, and higher healthcare costs, creating both clinical and economic pressures on health systems (4,5).

How did the Phase III trials shape regulatory confidence?

In both pivotal trials, mepolizumab met primary endpoints by reducing the annualized rate of moderate or severe exacerbations when added to inhaled triple therapy. In the MATINEE study, the rate ratio was 0.79, while the METREX study demonstrated a rate ratio of 0.82, indicating consistent benefit across study populations with an eosinophilic phenotype (1).

Importantly for regulators and payers, the MATINEE study also showed reductions in exacerbations requiring hospitalization or emergency department visits, outcomes that drive a disproportionate share of COPD–related costs. The incidence of adverse events was similar between treatment and placebo groups, reinforcing the therapy’s safety profile in long-term use (1).

 heterogeneity, enrolling patients with chronic bronchitis, emphysema, or overlapping presentations, according to GSK. This breadth may have contributed to confidence in generalizability, particularly in a healthcare environment managing large, diverse patient populations (1).

Why does eosinophil stratification matter to the industry?

This approval underscores the increasing role of biomarker-driven stratification in respiratory drug development. Approximately 67% of patients with COPD who remain uncontrolled on triple inhaled therapy have blood eosinophil counts above 150 cells/µL, identifying a sizable subgroup that may benefit from targeted biologic intervention, according to GSK (1).

In addition, this decision highlights a shift toward precision medicine in chronic respiratory diseases and may influence development strategies, trial design, and regulatory engagement for future biologics. It also signals a growing willingness by regulators to expand biologic use beyond traditional indications such as asthma, potentially reshaping treatment paradigms for COPD globally (1,2).

Nucala (mepolizumab) Approved in China for Use in Adults with Chronic Obstructive Pulmonary Disease (COPD)

The Management of Type 2 Inflammatory Respiratory Diseases: A Chinese Expert Consensus [2024]

Wang, C.; Xu, J.; Yang, L.; et al. Prevalence and Risk Factors of Chronic Obstructive Pulmonary Disease in China (the China Pulmonary Health [CPH] Study): A National Cross-Sectional Study. 

Yin, P.; Wang, H.; Vos, T.; et al. A Subnational Analysis of Mortality and Prevalence of COPD in China From 1990 to 2013: Findings from the Global Burden of Disease Study 2013. 

Advancing COPD Care in China Through a Comprehensive Approach

China's approval of mepolizumab as an add-on therapy for COPD marks a significant advancement in respiratory disease management, emphasizing the shift towards targeted biologics. Supported by Phase III trials, this approval highlights the efficacy of mepolizumab in reducing exacerbations in patients with elevated eosinophil levels. The decision reflects a growing acceptance of precision medicine in chronic respiratory diseases, potentially influencing future biologic development and regulatory strategies. This milestone underscores the importance of biomarker-driven stratification in addressing unmet needs in COPD treatment.

China clears GSK’s Nucala (mepolizumab) for COPD, highlighting growing acceptance in the country for biomarker-driven therapies.


China Clears Mepolizumab for COPD

Saharsh Part 2

 recently spoke with Saharsh Davuluri, Vice Chairman and Managing Director, Neuland Labs, to get his perspective on trends that shaped pharmaceutical development and manufacturing in 2025 and where things are headed in 2026. In this part 2 of our three-part interview, Davuluri explores a digital transformation within the API manufacturing sector. He observes that while the API industry has historically been slower to automate than other chemical sectors, a new paradigm is emerging through the adoption of AI-based tools and digital workflows. He notes Merck’s Synthia tool for route synthesis and equipping a new R&D campus with advanced parallel synthesis equipment to better mimic plant-scale production.

Davuluri’s ultimate vision is a fully paperless manufacturing environment driven by electronic batch records and a manufacturing execution system, which ensures complete traceability and product quality. Davuluri highlights the practical impact of these advancements for the workforce, stating: "This is real, and this is something that's going to make life a lot easier for process chemists who are looking at making scalable processes when it comes to manufacturing."

Central to this transformation is a shift attracting and retaining scientific talent through fostering a "knowledge hub" in which scientists collaborate on innovative processes for new chemical entities. Unlike traditional roles that may feel academic, scientists in such an atmosphere are encouraged to go into the plants to oversee scale-ups, allowing them to see their designs evolve into actual medicine for patients. This focus on high-level expertise marks a significant departure from traditional industry models. Davuluri explains, "We are living in a world where it's no longer about labor arbitrage; it's about knowledge arbitrage."

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Editor's note: This transcript is a lightly edited rendering of the original audio/video content. It may contain errors, informal language, or omissions as spoken in the original recording.

We are starting to see that there is a clear trend in using digital tools and AI for process development and scale up, but especially when it comes to API process development, scale up and manufacturing. What we are seeing is adaptation of AI-based tools. I think there's a Merck tool called Synthia that Neuland’s been using now; helps us, you know, identify the most appropriate route of synthesis for making an API.

That's a tool that we've been using now for quite some time and, right now, Neuland's in the process of building a new R&D campus in Hyderabad. As part of our plan, we intend to equip all our labs with these parallel synthesis equipment called Mya 4 by this company called Radleys.

The idea would be to use Synthia as an AI tool for coming up with the right process and then use these automated synthesizers at lab scale, which actually do a fantastic job of mimicking plant scale manufacturing, and then use eLab notebooks to capture all the data from these modern lab equipments and essentially give us a fully prepared recipe with no human intervention, which is kind of locked and loaded to plug into a manufacturing execution system, or an MES, at plant scale. This is real, and this is something that's going to make life a lot easier for process chemists who are looking at making scalable processes. 

When it comes to manufacturing, I think there's a lot of interesting developments. You know, the API manufacturing sector has not automated or modernized as much as the other industries like chemical manufacturing has. It's time to kind of make some moves over there. So we are starting to see a better adoption of DCS systems in our manufacturing environment.

You know, our vision for Neuland would be to eventually move into a paperless environment where we would have a manufacturing execution system coming out of our ERP telling us what's the recipe, and then, you know, actually plug it in and get the entire manufacturing done through electronic batch records so we don't have any paper and there's complete traceability and the ability to kind of assure the quality of the product for the patients. I think some of these will take time, but I think there is a clear crystallization of how these tools can really help us start embracing modernization for API manufacturing.

There's always dearth of talent. And I think in light of these technological advancements, it's very important to figure out ways in which you can not only attract, but retain top talent, especially on the scientific side… try to create an ecosystem that nurtures scientific talent, try to create a knowledge hub where, you know, there's a lot of scientific learning other than just kind of, you know, the grind of delivering projects and getting stuff done. There's a lot of community-based scientific discussions, and we have a very interesting mix of scientists. Most of them are Indian, because we are based in India, but a lot of them are trained in different parts of the world, and therefore they approach science from a different perspective.

And we have a very open culture where we not only look at protecting IP, but within the framework of IP sensitivity, we also encourage this talent pool to exchange ideas on what might be an interesting way to crack a problem. A big part of what we do as a CDMO business, we spend a lot of time working with innovators, hand in hand, trying to develop novel, innovative processes for new chemical entities. And a big outcome of doing creative work over there is that our scientists get to put their names on patents, although these patents are attributable and owned by our customers, which is the, the pharmaceutical companies, the names of the authors are very frequently the scientists working at Neuland who have contributed to that IP. And that creates a very high level of attraction, especially in an industry, in an area, like India. There's a lot of generics business and, therefore, it creates an additional motivation.

The other thing I would say is, you know, there's a lot of emphasis on successful scale up and delivering product to the patient because Neuland is… you know, 90% of the work we do is commercial manufacturing, and therefore when a scientist wants to come and work for Neuland, they recognize that they are actually coming and working for a company that is likely to put a pill in the hands of a patient and not necessarily just doing work in the lab, which might seem academic at times.

So the ability for a scientist to go stand in the plant and oversee a scale up, that's something that does not happen in a lot of organizations. But we have started to encourage our scientists to go into the plants, oversee campaigns, learn from the engineering groups, learn from the manufacturing groups on how their process that they have designed is performing in the plant scale.

That is a unique exposure, which also stimulates a lot of scientists, and that's also something that helps us attract the right kind of talent. We are living in a world where it's no longer about labor arbitrage. it's about knowledge arbitrage. And we cannot operate in the old paradigm where… Neuland is located in India, which is a developing economy and therefore there are these labor arbitrage opportunities. I think that does not work anymore and therefore, you know, trying to get to a paradigm of knowledge arbitrage.

Videos

Saharsh Davuluri, Neuland Labs, discusses the move from labor to knowledge arbitrage for API manufacturers, using AI tools to empower scientists in process development.

Advancing Pharmaceutical Quality through Integrated Digital Systems and Collaborative Scientific Innovation

J. Mark Wiggins is owner and compendial consultant with Global Pharmacopoeia Solutions LLC.

Joseph A. Albanese, director of Analytical Strategy and Compliance at Janssen Research and Development, LLC

Gail Reed is senior scientist with Johnson & Johnson.

Yelena Ionova is senior manager, Data Strategy and Analytics with Redica Systems.

silicon dioxide, also known as silica, is silicon oxide. Anti-caking agent, antifoam, viscosity controller, desiccant, beverage clarifier and medicine or vitamin excipient | Image Credit: ©RHJ -stock.adobe.com

 detailed a practical approach to establish specification equivalence for in-house harmonization to ensure multi-compendial compliance for excipients. Application of this approach allows a manufacturer to minimize testing for the material while remaining compliant with regulatory requirements in different regions of the world. This paper provides a technical assessment of compendial tests commonly found in the

United States Pharmacopeia–National Formulary (USP–NF)

, detailing differences between the methods and acceptance criteria, and the potential impact of these differences on multi-compendial compliance. Recommendations are also provided to facilitate a paper-based determination of specification equivalency. The assessments may be applied for in-house harmonization of drug substances and drug products, in addition to excipients.

Establishing Excipient Specifications–Considerations for Specific Tests

The following is a detailed assessment for many of the compendial tests typically used for excipients with a recommendation of which method may be most appropriate to select in an evaluation of specification equivalence. In general, minor differences between compendial methods are not expected to impact the fundamental pass/fail decision for a particular test and are not expected to necessitate the use of multiple compendial methods to assess multi-compendial compliance. Detailed considerations for the appropriate selection of specific test methods and acceptance criteria are provided below. The selection recommendations generally apply to a paper-based assessment of the methods, but may also include an evaluation of existing data, or a laboratory study. A monograph for a particular excipient may include tests in addition to these, and similar principles should be applied in evaluating any other compendial tests.The authors caution the readers that the conclusions suggested below are applicable to general tests/monographs as of June 2025, and users should confirm that there have been no subsequent updates to the pharmacopoeias.

Section 1. Tests/information included in monographs

Assessment: as stipulated in the General Notices of the 

, the appearance, characters, and/or description provided in a monograph for an excipient are not considered compendial requirements but are provided for information. These tests typically employ a simple visual assessment.

Selection: the specification may include a requirement for appearance that is appropriate for the material used, but the appearance is not considered a compendial requirement.

Appearance of solution (color and clarity/degree of opalescence)

are usually limit tests using standard solutions of color and opalescence for comparison to the sample (or sample solution) to evaluate conformance. Method differences may include sample preparation and solvent. The comparison is usually visual, although instrumental methods are also possible. By contrast, the tests in the 

are generally more qualitative, employing a simple visual assessment of color and clarity without comparison to specific reference solutions.

. method, with associated acceptance criteria, is considered superior due to the comparison to standards, and therefore is the method of choice to ensure compliance with similar tests in the 

Assessment: differences between compendial titration methods may include the use of visual or potentiometric endpoints, different titrants and indicators, and different concentrations of the sample, titrant, or indicator. In comparing compendial titration methods, these differences are not expected to have a significant impact on the analytical results or the pass/fail decision.

Selection: if the outcome of the method comparison is conclusive, standardizing to the 

 titration method will generally ensure compliance with 

 titration methods. The tightest acceptance criteria will be applied to ensure multi-compendial compliance.

Assessment: differences between chromatographic assay methods in the various compendia may include column packing, column dimensions, system temperatures, mobile phase, gradient or isocratic systems, injection volume, flow rate, detector type, detector wavelength, sample and standard concentrations and preparations, and system suitability requirements. Allowable variations for several of the chromatographic parameters are detailed in the corresponding 

 General Chapters. In considering chromatographic methods, many of these potential differences are not significant since the compendial methods have been validated for linearity, accuracy, repeatability, etc. and the results are expected to yield the same pass/fail decision.

Selection: if the outcome of the method comparison is conclusive, standardizing on a chromatographic assay method from the 

 chromatographic requirements. The tightest acceptance criteria will be selected to ensure multi-compendial compliance, with consideration given to whether the method has sufficient precision to allow application of the tighter limits.

Assessment: it is difficult to compare different assays where one test is performed by titration and another by chromatography. Titration procedures are generally more precise, but chromatographic methods are generally more selective. The acceptance criteria may also be different to reflect the precision of the particular method.

Selection: in many cases, it may be necessary to carry out analysis using both the chromatographic and titration assay method to ensure multi-compendial compliance for the excipient. There may be cases where the 

 titration assay method and acceptance criteria may provide assurance of conformance to the chromatographic assay methods in the 

. To help address potential issues with selectivity, the 

. titration method must be coupled with a chromatographic method for determination of impurities. There may also be cases where the 

 chromatographic assay method and acceptance criteria may provide assurance of conformance to the titration assay methods in the 

. Any such determination must be documented as part of the assessment carried out for the specific excipient.

Assessment: differences in compendial specifications for boiling point/distillation range may include the apparatus, rate of heating, and the acceptance criteria.

Selection: because there is minimal potential for the apparatus and heating to impact the result, the use of the 

method to determine the boiling point or distillation range will be used, with the tightest acceptance criteria applied.

Assessment: current good manufacturing practices (CGMPs) require that at least one specific identity test must be performed for all excipients. The underlying goal of identity testing is the confirmation, with an acceptable degree of assurance, of the material’s identity. Compendial monographs may include several different identity tests for the same material. Some of these tests are intended to identify the entire chemical or molecule (e.g., IR) while others are intended to identify a particular moiety (e.g., a selective chemical test for a specific counter ion). Specific identity tests are preferred to non-specific chemical tests. The 

. monographs may provide subdivisions entitled “First identification” and “Second identification”. The test or tests that constitute the “First identification” may be used for identification in all circumstances, as stated in the 

. General Notices. If the “First identification” tests are performed, the “Second identification” tests do not need to be performed.

“First identification” tests will be selected to establish the identity of the excipient. If the 

. monograph does not include divisions for “First identification” and “Second identification” tests, then all of the 

. identity tests will be included in the compendial release requirements, with the expectation that an excipient so identified would pass any other compendial identity tests. In the event that the 

 monograph includes an identity test for a specific characteristic of the excipient (e.g., a test for a particular counter ion or physical characteristic), which is not otherwise addressed by a comparable 

 test should also be performed to ensure compliance with the appropriate compendia. If there is no 

. monograph for the excipient, appropriate 

identity tests will be included, based on a similar principle.

Assessment: differences in IR identity methods typically involve sample preparation (Attenuated Total Reflectance [ATR], Potassium Bromide [KBr], mull, film, or solution) and are not considered significant when evaluating the fundamental properties of the chemical bonds through IR analysis. In most cases, the spectrum from a sample is compared to that of a reference spectrum or reference standard similarly prepared, which provides unequivocal information regarding the identity of the material. The specific wavelength ranges used for the test may also vary, but this is also not considered significant in making an appropriate identification determination.

Assessment: differences in UV identity methods may involve sample concentration, solvent, temperature, path length, and the particular wavelength used for the evaluation. Because most methods involve comparison to a reference spectrum or reference standard similarly prepared, these potential differences are not considered significant.

. UV method will generally ensure compliance with 

Assessment: different chromatographic identity procedures are capable of confirming the identity of the particular material. Differences between chromatographic method types (high-performance liquid chromatography [HPLC], gas chromatography [GC], or thin layer chromatography [TLC]) or differences between similar method types (see assay [chromatography] above) are not expected to have a significant impact on the ability of a particular method to establish the material's identity.

. chromatographic identity method will generally ensure compliance with 

Assessment: chemical identity methods may employ color change, precipitate formation, and/or solution formation based on a specific reaction of the excipient to provide assurance of the identity. Different tests may be necessary to ensure the identity for each moiety in a given excipient. Because an excipient may undergo a wide variety of reactions, there may be a large number of different chemical identity methods in compendial monographs for a material. These chemical methods are not typically specific to a particular excipient and therefore may not provide unequivocal identity. In addition to differences in the fundamental reactions utilized, these identification methods may also vary in the sample concentration and reagents used. Differences in chemical identity tests are not considered significant if the reactions are intended to evaluate the same chemical property of the material (such as presence of chloride). Multiple identification methods are usually unnecessary if one selective and specific method is available. Multiple tests may be necessary to demonstrate the identity of different moieties in the excipient.

chemical identity methods will be included in the compendial specification, if they are among the "First identification" tests. If the 

. chemical identity methods will be included in the compendial specification. No additional 

 chemical identity methods will typically be needed to ensure multi-compendial compliance.

Impurities–organic/related substances (chromatography)

Assessment: as with chromatographic assays, the differences between chromatographic impurities/related substances methods in the various compendia using HPLC may include column packing, column dimensions, system temperatures, mobile phase, gradient or isocratic systems, injection volume, flow rate, detector type, detector wavelength, sample and standard concentrations and preparations, and system suitability requirements. Another typical difference for impurities methods lies in the procedures used for calculating results (e.g., weight percent, volume percent, area percent, use of an internal standard, use of an external standard, or use of a diluted sample as standard). Allowable variations for several of the chromatographic parameters are detailed in the 

. General Chapter. In considering chromatographic methods, many of the potential differences are not significant because the individual methods are validated for linearity, accuracy, repeatability, etc. and the results should yield the same pass/fail decision. TLC may also be used as a suitable compendial method for control of impurities, although an HPLC method would generally be considered superior to TLC for quantitation, and this should be taken into account when selecting the test or tests required to ensure multi-compendial compliance for the excipient.

Selection: standardizing on a chromatographic method for impurities/related substances from the 

. will generally also ensure compliance with 

 requirements. The tightest acceptance criteria for each specified impurity should be selected to ensure multi-compendial compliance. The 

. General Monograph–Substances for Pharmaceutical Use and General Chapter 5.10 Control of Impurities in Substances for Pharmaceutical Use should also be considered when establishing the appropriate limits.

Assessment: there are a number of compendial tests which are intended to limit the amount of various inorganic impurities that may be present in excipients. These tests usually include wet chemical methods but may also employ instrumental methods. The test may be qualitative (i.e., pass/fail), semi-quantitative, or quantitative. These tests are not broadly applied to all excipients but are usually included in specific monographs as appropriate.

Examples of this type of test are aluminum, ammonium, arsenic, calcium, chlorides, iodides, iron, lead, magnesium, mercury, nickel, sodium, and sulfates. Wet chemical procedures generally rely on a chemical reaction to provide a visual change, such as color, turbidity, or formation of a precipitate, which enables a determination of the presence of the particular impurity at or below the acceptance criteria. Differences in compendial wet chemistry approaches for a specific inorganic impurity would typically involve different chemical reactions intended to detect the same impurity. Instrumental techniques may also be used for lower-level impurities or where greater sensitivity may be required. Instrumental methods are generally considered superior to wet chemical methods for determination and quantitation of inorganic impurities, as in the evaluation of an excipient for elemental impurities. Other than as listed in specific excipient monographs, a test for an inorganic impurity would only be included if the elemental impurities assessment determines there is a need to employ a control strategy for a specific inorganic impurity in the particular excipient.

Selection: if the outcome of the method comparison is conclusive, standardizing on a wet chemical procedure from the 

. for these types of inorganic impurities will generally also ensure compliance with 

 wet chemistry requirements for the particular impurity. An instrumental compendial method is generally superior to a wet chemical method and this should be taken into account when selecting the test or tests required to ensure multi-compendial compliance for the excipient. Standardizing on an instrumental procedure from the 

. for inorganic impurities will generally also ensure compliance with 

 wet chemical or instrumental requirements. The tightest acceptance criteria for the particular impurity should be selected to ensure multi-compendial compliance. Consideration should also be given to the superior, International Council for Harmonisation (ICH)/ Pharmacopoeial Discussion Group (PDG) risk-based approach for control of elemental impurities (including appropriate test methods and acceptance criteria).

Assessment: differences in LOD methods typically involve sample size, temperature, time, vacuum, and desiccants in the procedure for drying. The differences may have an impact on the result obtained and should be considered in selecting the method to be used. If the method specifies that the test is performed until constant weight is achieved, the differences in the methods are not expected to impact the final result, and the identical pass/fail decision should be reached.

Selection: if the outcome of the method comparison is conclusive, standardizing on the 

. method for LOD will generally ensure compliance with 

requirements. The tightest acceptance criteria should be applied to ensure multi-compendial compliance. In establishing the acceptance criteria, the impact of time and temperature on the result should be considered (i.e., the longer the time and the higher the temperature, the higher the expected LOD result) to ensure the tightest acceptance criteria are applied.

Assessment: differences in compendial methods for these tests may include the apparatus, heating rate and the acceptance criteria.

. method to determine the melting point or range will be used, with the tightest criteria applied.

Microbiological tests (microbial limits, bacterial endotoxins, sterility)

Assessment: the microbiological tests in the 

 have been harmonized by PDG and assessed by ICH Q4B. Based on this assessment, the tests in the individual compendia are equivalent.

Selection: typically, the microbiological procedures from the 

 will be selected with appropriate consideration of sample qualification requirements.

Assessment: differences in pH methods typically include instrumentation, indicators, sample concentration, and measurement temperature. These differences may impact the result obtained and should be considered when selecting the method to use. The impact of sample concentration on the result may be considered in terms of the Henderson-Hasselbalch equation. Acidity or alkalinity of a sample is determined by assessing the occurrence or absence of a color change upon adding an acidic or basic reagent in the presence of an appropriate indicator. Differences in acidity or alkalinity tests may include sample concentration, solvent, titrant, and/or indicator.

Selection: tests for pH and acidity/alkalinity evaluate the same fundamental attribute for the material related to its inherent acidic or basic functional groups, or those of residual materials present along with the excipient itself. If the outcome of the method comparison is conclusive, standardizing on the 

 method for pH or acidity/ alkalinity will generally ensure compliance with the corresponding 

 methods. For pH, the tightest acceptance criteria may generally be applied to ensure multi-compendial compliance. For acidity/alkalinity, the acceptance criteria associated with the selected method should be applied.

Assessment: the primary difference in refractive index methods for liquid excipients is the measurement temperature. The expected trend for the effect of temperature on the result is difficult to predict. Despite temperature differences in methods, the refractive index result, as a fundamental physical property, is expected to comply with the corresponding, appropriately established acceptance criteria.

 method for refractive index will generally ensure compliance with 

 requirements. The specific acceptance criteria associated with the selected method should be used.

Assessment: differences in specific gravity/density methods typically involve sample preparation (neat liquid or solution), solvent, and the measurement temperature. The general trends expected are that the higher the sample concentration, the higher the result, while the higher the temperature for the test, the lower the specific gravity/density result. Despite differences in methods, the specific gravity/density result, as a fundamental physical property, is expected to comply with the corresponding, appropriately established acceptance criteria.

Selection: If the outcome of the method comparison is conclusive, standardizing on the 

method for specific gravity/density will generally also ensure compliance with 

 requirements. The acceptance criteria associated with the selected method should be applied.

Assessment: differences in specific rotation/optical rotation methods typically involve sample preparation, solvent, measurement temperature, path length, and detection wavelength. The general trends expected are that the higher the concentration and the longer the path length for the test, the higher the expected rotation result. Despite differences in methods, the specific rotation/optical rotation result, as a fundamental physical property, is expected to comply with the corresponding, appropriately established acceptance criteria.

 method for specific rotation/optical rotation will generally also ensure compliance with 

requirements. The acceptance criteria associated with the selected method should be applied.

Assessment: the tests for sulphated ash/residue on ignition in the 

. method for sulphated ash will also ensure compliance with 

 requirements. The tightest acceptance criteria should be applied to ensure multi-compendial compliance.

Assessment: differences in total ash/LOI methods typically involve sample size, ignition temperature, and ignition time used in the procedure. The 

 carry out the test to constant weight, which should provide the highest loss on ignition result (i.e., a more stringent assessment).

 method for total ash/LOI will generally ensure compliance with 

Assessment: differences in rotational viscometer (e.g., Brookfield) methods typically involve sample concentration, measurement temperature, spindle, speed, and instrumentation. Use of capillary viscometers (e.g., Ubbelohde-Type and Ostwald-Type) is also very common in excipient monographs and methods may differ in sample concentration and temperature. The expected trends are that the higher the sample concentration, the higher the resulting viscosity, and the higher the temperature, the lower the resulting viscosity. It is difficult to compare rotational and capillary viscosity methods. Despite differences in methods, the viscosity result, as a fundamental physical property, is expected to comply with the corresponding, appropriately established acceptance criteria.

 method for rotational or capillary viscosity will generally ensure compliance with the corresponding 

 methods. The acceptance criteria associated with the selected method should be applied.

Assessment: differences in water determination using titrimetric methods include sample amount, solvent, titrant, titrant concentration, and end-point determination (potentiometric or coulometric). These differences are not expected to have a substantial impact on the result obtained using a suitably qualified and calibrated instrument that is appropriate for the expected amount of water in the sample. For determination of low levels of water, a coulometric/micro procedure is preferred.

 method for water will generally ensure compliance with 

 requirements. The tightest acceptance criteria should be applied to ensure multi-compendial compliance. Appropriate consideration for the method, sample amount, and acceptance criteria should be given for low-level water determinations.

Waxes, fats, and fixed oils—typical properties (e.g., acid value, hydroxyl value, iodine value, saponification value)

Assessment: differences in the wet chemical procedures used to determine particular properties of waxes, fats, and fixed oils may include the sample preparation, reagents, indicators, titrants, and test conditions. However, for a particular procedure, differences in the compendial methods would not typically be expected to produce a different result. The acceptance criteria may be different in the different compendial monographs.

 method for a particular procedure, (e.g., saponification value) will generally ensure compliance with the 

 requirements for the same procedure (e.g., saponification value). The tightest acceptance criteria should be applied to ensure multi-compendial compliance.

Section 2. Additional tests to be considered

Assessment: residual solvents in pharmaceuticals are defined in the International Council for Harmonisation (ICH) Q3C guideline (2) as organic volatile chemicals that are used or produced in the manufacture of drug substances or excipients, or in the preparation of drug products. The guideline recommends acceptable amounts for residual solvents in pharmaceuticals for the safety of the patient. The approach to limit residual solvents as specified in the ICH guideline is also included in the 

 general notices, general monographs, and general chapters. A manufacturer needs to demonstrate that the levels of residual solvents comply with the limits established in ICH Q3C, and that solvent levels are maintained using an appropriate control strategy that encompasses the drug product and all of its components. As such, residual solvents in excipients must be controlled to comply with the ICH and pharmacopoeia requirements.

Selection: the harmonized approach to residual solvent control listed in the pharmacopoeias should be used for an excipient, including the appropriate test method and acceptance criteria.

Assessment: the ICH Q3D guideline (3) presents a process to assess and control elemental impurities in the drug product using the principles of risk management as described in ICH Q9 (4). Although focused on the drug product, the guideline recognizes that, among other potential contributors, elemental impurities may be present in the excipients used in the preparation of the product and must therefore be considered in the overall risk assessment. The ICH Q3D guideline is also being incorporated into the pharmacopoeias, and consideration of elemental impurities is required by the pharmacopoeial general notices. The harmonized general chapter by PDG is being implemented, with the 

 being the last to make it official in July 2026 (5). For pharmaceutical manufacturers, adoption of the harmonized approach to elemental impurities is recommended for acceptance into major markets. Whenever the elemental impurities risk assessment for a drug product requires testing a particular excipient for a specific element, or if a test for a specific metal impurity is listed in the excipient monograph, the test method from the pharmacopoeia should be used whenever possible and appropriate.

Selection: the test method recommendations listed in the harmonized chapter “Elemental Impurities” as published in the pharmacopoeias should be used in the determination of elemental impurities, as needed for an excipient. Acceptance criteria listed in the harmonized pharmacopoeia chapter for a specific elemental impurity should be applied to the excipient being tested, ensuring the limit is appropriate for the overall drug product risk assessment.

Assessment: the test for heavy metals is a wet-chemistry limit test that has long been included in pharmacopoeia monographs. The test is intended to detect the presence of metal impurities that form insoluble precipitates with sulfide ion. The metals that respond to this test typically include lead, mercury, bismuth, arsenic, antimony, tin, cadmium, silver, copper, and molybdenum. Long-standing questions about the test’s usefulness to accurately detect these metals contributed to the introduction of the ICH/PDG risk-based assessment of elemental impurities that are likely to be present. (See above.)

Selection: it is possible that a test for heavy metals may still be listed in the pharmacopoeia monograph for a particular excipient, especially in national pharmacopoeias that are not currently part of PDG; although, this should become increasingly rare. Applying the superior, risk-based approach for control of elemental impurities (including appropriate test methods and acceptance criteria) and testing particular excipients to limit specific metals that may be present, should in all cases be considered an acceptable alternative to the wet-chemistry test for heavy metals.

 have introduced controls for a risk-based N-nitrosamine evaluation for drug substances and excipients. Many N-nitrosamines are classified as probable human carcinogens and regulators are taking action to ensure these impurities are minimized or eliminated from substances and final drug products. The requirements for control of N-nitrosamines are being captured in pharmacopoeial general chapters. 

. General Monograph 2034 Substances for Pharmaceutical Use includes a requirement to establish a control strategy for N-nitrosamines. The control strategy is listed in 

 General Chapter <1469> Nitrosamine Impurities provides recommendations regarding: a) the establishment of controls of nitrosamine levels in order to ensure their elimination or reduction; and b) analytical procedure performance characteristics for procedures used to monitor nitrosamine levels. Many health authorities have also issued guidance documents that are applicable for the evaluation of nitrosamine levels.

Selection: manufacturers should consider whether control of nitrosamines is necessary for the excipients used in their drug products, including the selection of appropriate test methods and acceptance criteria. Manufacturers should also remain vigilant to current nitrosamine requirements, given the dynamic state of regulatory expectations and the lack of harmonization to date among the pharmacopoeias.

Tests for ethylene glycol (EG), diethylene glycol (DEG) and triethylene glycol (TEG)

 have all introduced testing to control EG, DEG, or TEG in several high-risk monographs in response to the public health concerns posed by the potential presence of these contaminants in medicinal products (6-11). Regulatory agencies around the world are also issuing guidance for control of these toxic impurities. To date, the pharmacopoeia and regulatory approaches have not been harmonized.

Selection: manufacturers need to be aware of these monograph changes as well as the regulatory guidance documents for controlling EG, DEG, and TEG that are being issued directly by global health authorities to combat adulteration of drug products. For example, FDA has issued a guidance document (12) that targets several high-risk excipients and requires that each drum of the material be sampled and tested to comply. Companies will need to execute testing required in individual monographs to ensure compliance with the testing for these contaminants. Given the intense focus of pharmacopoeias and regulators on this area, companies should ensure compliance with country or regional requirements as they continue to evolve.

This article provides a comprehensive technical assessment of compendial tests from the European Pharmacopoeia, United States Pharmacopeia–National Formulary, and Japanese Pharmacopoeia, focusing on differences in methods and acceptance criteria. It offers recommendations for selecting appropriate methods to ensure multi-compendial compliance, emphasizing the importance of standardizing on Ph. Eur. methods for various tests. The article also discusses additional considerations for residual solvents, elemental impurities, heavy metals, nitrosamines, and specific contaminants like ethylene glycol. This guidance aims to streamline testing processes and enhance regulatory compliance.

This paper provides a technical assessment of compendial tests commonly found in the European Pharmacopoeia, the United States Pharmacopeia–National Formulary, and the Japanese Pharmacopoeia, detailing differences between the methods and acceptance criteria, and the potential impact of these differences on multi-compendial compliance.

Multi-Compendial Compliance for Pharmaceutical Excipients–Part 2: A Detailed Assessment for Specification Equivalence

Embryonic stem cells , Cellular therapy , Regeneration , Disease treatment | Image Credit: ©Giovanni Cancemi -stock.adobe.com

On Jan. 5, 2026, the Fujifilm Life Sciences Group announced that FUJIFILM Irvine Scientific has been officially rebranded as 

FUJIFILM Irvine Scientific has rebranded as FUJIFILM Biosciences, reflecting its 55-year legacy in cell culture solutions. The company emphasizes its commitment to innovation and customer experience, leveraging its global manufacturing network. Significant investments include a $3 billion agreement with Regeneron to expand biopharmaceutical production in North Carolina, aiming to create 1,400 jobs by 2031. FUJIFILM's strategic focus on reagents, materials, and bioprocessing performance underscores its dedication to supporting customers across key global regions, enhancing the quality of biologics and expanding its life sciences capabilities.

FUJIFILM Irvine Scientific has changed its name to FUJIFILM Biosciences to better align with the company’s work in cell culture media manufacturing. 

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