Susan Haigney

Ask the Expert: Quality Control Units

After an FDA inspection of a pharmaceutical manufacturing facility, any deviations the inspector might find during the inspection are reported on a Form 483 and sent to the manufacturer. If the company fails to properly respond to the agency, FDA will follow up with a warning letter. A common theme seen on warning letters is that companies fail to properly establish a quality control unit. So how should a company respond if they receive such a citation?

“Well, you see the mere fact that they actually received a warning letter means that their initial response to the observations by the FDA inspectors were considered inadequate or incomplete,” Siegfried Schmitt, vice president of Technical at Parexel, explains. “I think it's therefore essential to admit that this shortcoming has happened, and so they should make sure that the response they now give to this warning letter is really a complete and convincing one and provides a remediation plan that will be acceptable to the authorities.

 video series, Susan J. Schniepp, distinguished fellow at Regulatory Compliance Associates, and Siegfried Schmitt, PhD, vice president, Technical at Parexel, discuss what manufacturers should do when they receive a warning letter from FDA for an insufficient quality control unit.

Click the video above to watch Sue and Siegfried answer the following question:

“My company received an FDA warning letter for failure to create a quality control unit. What is the best way to respond to FDA?”

Susan J. Schniepp is distinguished fellow at Regulatory Compliance Associates and a member of 

Siegfried Schmitt is vice president, Technical at Parexel and a member of 

Welcome to the Ask the Expert video series. This series is an extension of the PharmTech Group’s long-running print column in which industry experts answer common quality and regulatory questions from the industry. This new video series will expand on topic areas to include development and manufacturing concerns to help those working in the industry better understand bio/pharmaceutical requirements. Have a question you would like answered? Send it to PTProjects@mmhgroup.com, and it may appear in a future episode or print column.

Videos

In this episode of the Ask the Expert video series, Susan J. Schniepp, distinguished fellow at Regulatory Compliance Associates, and Siegfried Schmitt, PhD, vice president, Technical at Parexel, discuss how to address an FDA warning letter citation for a failure to establish a quality control unit.

A laboratory technician performing a quality control test on a batch of pharmaceutical tablets, highlighting the importance of ensuring drug safety. | Image Credit: ©MAY -stock.adobe.com

The API is, one might say, the most important element in a pharmaceutical product. Poor-quality APIs that do not meet potency levels and/or those that harbor impurities can create safety risks for the patient. Drug formulations may be destabilized by poor-quality APIs, which could shorten the drug’s shelf life. Poor-quality APIs may result in regulatory actions or recalls that can create production delays for the manufacturer that can impact the supply chain, therefore, keeping drugs from the patients that need them. Poor API quality may also leave the door open for counterfeit drugs to reach the market.

“From a supply chain perspective, poor-quality APIs increase the likelihood of production interruptions, which disrupt the supply to the market,” says Qixuan Lu, vice-president of Process Chemistry at BioDuro. “Because of the poor-quality API, additional quality control measures become necessary, driving up costs and diminishing profit margins. If such issues arise repeatedly, they can harm a company’s reputation and undermine market confidence in its products. Beyond these commercial setbacks, manufacturers also face considerable legal and regulatory risks if they fail to meet the standards required for pharmaceutical quality and patient safety.”

Impurities may result from a lack of a robust process and inadequate quality control, which often evolves from a lack of understanding of critical quality attributes (CQAs). This can manifest in poorly defined design spaces and analytical methods that fail to detect impurities, according to Dirk-Jan van Zoelen, Drug Substance Business Unit director, Ardena. “Moreover, when new impurities are identified, out-of-specification (OOS) results can lead to production delays, affecting the stability and reliability of the supply chain,” van Zoelen explains.

“Poor quality API presents several risks to the drug product, supply chain, and ultimately patients. These risks range from a lack of efficacy to the possibility of toxicity. Poor efficacy may result from low potency API, whereas toxicity may be related to the presence of uncontrolled impurities,” Richard Castledine, head of Drug Substance Operations at Quotient Sciences, says. “Additionally, simple batch-to-batch variability of quality attributes such as particle size and residual solvent concentration may result in differences in downstream manufacturing processes.”

Having strict quality checks, supplier audits, and strong compliance measures are important to maintain a safe and smoothly run system, according to M. Damodharan, chief quality officer, Sai Life Sciences.

A comprehensive control strategy is key for ensuring API quality, according to van Zoelen. This strategy should address an in-depth understanding of the processes involved (e.g., chemical, physical, and cleaning) with defined critical process parameters (CPPs) and acceptable ranges. These processes should then be validated. The critical material attributes of raw materials and starting chemicals should be evaluated using comprehensive fit-for-use assessments to determine impurity clearance. A rigorous supplier qualification process should be put in place to ensure material quality and regulatory compliance. Analytical methods should be developed and validated in accordance with International Council for Harmonisation (ICH) guidelines, and a quality assurance department should be created that has an established quality management system to monitor regulatory compliance, van Zoelen says.

“A strong quality management system, aligned with good manufacturing practice (GMP) requirements, should define detailed production processes and quality control procedures to ensure that every stage of manufacturing is consistently supervised,” Lu agrees. “By actively monitoring the manufacturing workflow, manufacturers can guarantee that each critical step meets the required specifications and prevents potential quality deviations.”

Once parameters are set, they must be understood within the manufacturing process, says Castledine. “By understanding the edge of failure of any given process checks and controls can be implemented to ensure the process remains within the target ranges to produce high quality drug products,” he says. “Establishing a high-quality supply chain for all materials used in the manufacturing operation reduces the risk of introducing substandard materials to the process. Finally, the manufacturing process should be supported by internal analytical capabilities to assess critical quality attributes.”

“When designing a synthetic route for an API, process route design involves finding and selecting a pathway with favorable characteristics to maintain high quality CGMP [current good manufacturing practice] production when the API is manufactured at larger scale,” Castledine continues. “Modification or redesign of the process is often required to prepare for larger batch sizes and ensure that API can be produced in a compliant, efficient manner. Early on, drug developers should be mindful of identifying and developing control strategies for process and degradation impurities which may otherwise remain in the API. Additionally, avoiding niche or expensive starting materials and reagents for API synthesis is recommended; these can result in supply chain difficulties later and possibly lead to poorer quality substitutions being made.”

Sourcing from GMP-certified suppliers can help ensure API quality, according to Subbareddy Inta, vice-president and head of Quality, Dr. Reddy’s Laboratories North America. “Regular audits and inspections of supplier facilities ensure compliance with safety and quality standards,” Inta says.

“To secure high-quality APIs, manufacturers should implement a rigorous supplier evaluation system that carefully selects qualified raw material providers and conducts periodic audits. Incoming raw materials must undergo thorough inspections to confirm compliance with specified standards,” Lu stresses.

“Suppliers should be seen as an extension of internal manufacturing controls and standards, aligning with the drug manufacturer’s quality and compliance goals/objectives,” Timothy Buckley, vice-president of Global Quality, SK pharmteco, says. “Supplier qualification is critical, not only from a quality perspective, but also to ensure reliable supplies to eliminate potential drug shortages and supply interruptions.”

Materials used that are obtained from a third-party vendor must be rigorously qualified to ensure quality. This can be done through spike/fate and purge studies conducted on multiple lots, according to van Zoelen.

The physical and chemical characteristics of these materials, including crystal form, particle size, solubility, purity, residual solvents, and heavy metals, must be tested for CQAs to determine that they meet requirements. “Moreover, understanding the synthetic route used by the vendor is crucial, since the reagents, reaction conditions, and by-product removal methods should be compatible with the downstream manufacturing process,” Lu states. “This alignment ensures efficient conversion of starting materials or intermediates and minimizes impurities that might otherwise compromise the finished product’s quality.”

Tests performed on third-party-sourced materials, according to Ragavendran Vasudevan, director and head of Operations C2 Pharma India Ltd., include identity testing, purity and impurity profiling, assay testing, physical and chemical characterization, microbial and endotoxin testing, and stability and storage condition studies.

“Identity testing using FTIR [Fourier transform infrared spectroscopy], NMR [nuclear magnetic resonance], HPLC [high-performance liquid chromatography], or GC–MS [gas chromatography–mass spectrometry] confirms chemical structure. Purity and impurity profiling detect unwanted byproducts, while potency is measured through titration, UV-Vis [ultraviolet-visible], or HPLC. Residual solvent analysis via GC-HS [headspace-gas chromatography] ensures no toxic solvents remain,” Damodharan explains. “Water content is checked using Karl Fischer titration, and microbial testing screens for bacteria and endotoxins. Particle size and polymorphism studies assess bioavailability impact. Stability testing evaluates degradation risks, and elemental analysis using ICP-MS [inductively coupled plasma mass spectrometry] checks for toxic metals. These steps ensure the API meets safety and regulatory standards.”

Validation is a crucial step in ensuring the quality of APIs and applies to the regulatory compliance requirements of facilities, equipment, and infrastructure, according to Lu. “Stability testing should also be carried out to track changes in the physical and chemical properties of the API, as well as the formation of any degraded products or impurities over time,” Lu says. “These tests help determine appropriate shelf life and storage conditions, ensuring that the API retains its intended quality and efficacy until it is used.”

Other validation exercises, according to Vasudevan, include supplier qualification, raw material testing, process validation, analytical method validation, and regulatory documentation.

“Validating test methods, such as chromatography and spectrometry, ensures accurate purity and potency analysis,” Inta says. “Conducting stability studies under various storage conditions ensures the API remains stable over time. Ensuring compliance with pharmacopeial standards and regulatory requirements maintains high-quality standards.”

“Confirmation of the manufacturing process used is also essential to ensure that methods used for testing are suitable,” Castledine says. “For example, some manufacturing processes have the potential to generate potentially mutagenic impurities (PMI) which need to be controlled to PPM [parts per million] levels, often requiring the development of specialized HRMS [high-resolution mass spectrometry] methods.”

Quality validation of APIs should be a phase-appropriate approach, according to van Zoelen, with analytical methods getting partial validation in early phase development that focuses on process-related impurities and safety data. “As development progresses to later clinical phases, a more comprehensive validation is required, including full validation of the analytical methods for the API, starting materials, and intermediates,” van Zoelen says. “Impurity profiles are set during early-stage development, with tox-batch validation and process validation as essential milestones. Throughout this process, supplier qualifications should also be conducted to ensure consistency and reliability of materials.”

A transparent supply chain is achieved by good distribution practices, according to Damodharan, and helps prevent counterfeit drugs. “Regulatory compliance is a must, including accurate documentation and real-time monitoring. Staying updated on compliance changes and maintaining data integrity [can] ensure long-term quality,” Damodharan says.

Maintaining accurate CGMP records for APIs is necessary to assure regulators of compliance, traceability, and product quality. However, according to Vasudevan, many companies lack complete and accurate documentation and have poor record keeping practices. They also have data integrity violations and insufficient training on compliance with CGMPs.

Poor documentation, including incomplete records or backdating, violate CGMPs and data integrity requirements. “Illegible batch records, unverified calculations, and outdated SOPs [standard operating procedures] lead to errors,” Damodharan says. “Failing to record deviations, corrective actions, or equipment calibrations weakens oversight. These slip-ups can trigger compliance issues, recalls, or even regulatory shutdowns.”

It is important to avoid gaps in impurity data in CGMP records. A mistake some manufacturers make, according to van Zoelen, is not aligning analytical methods with an API’s impurity profile in clinical phases. “As development progresses, particularly through the clinical phases, new impurities may emerge, such as genotoxic or mutagenic impurities,” van Zoelen says. “Multiple analytical methods may be employed at different stages, and these may change as the development advances. It is critical to ensure continuous alignment of these methods with impurity data to avoid gaps or discrepancies in CGMP records, especially as the product progresses through clinical phases.”

“Failing to capture batch-specific information or variations in production conditions can compromise data integrity,” Inta says. “Inadequate documentation of deviations or corrective actions can leave issues unresolved. Lastly, not adhering to proper data integrity protocols, such as avoiding falsification or improper handling of electronic records, can severely compromise data quality.”

“While GMP expectations such as data integrity, GDP [good documentation practices], and facility/personnel controls are the same for APIs and drug products, a key issue for API manufacturers is ensuring appropriate documentation and evaluation of supplier changes,” Buckley explains. “Changes in the route of synthesis for critical raw materials, such as regulatory starting materials, can lead to a new or altered impurity profile of existing impurities. This may introduce concerns related to nitrosamines, heavy metals, and/or PEG [polyethylene glycol] residues. Therefore, while there are many GMP considerations, change control and supplier qualification are especially critical in API manufacturing.”

Highly potent APIs (HPAPIs) have increased pharmacological activity and safety risks according to Vasudevan. Safe production and handling of HPAPIs can be done by implementing stringent quality measures. These include dedicated production areas or isolators and closed-system processing. Using segregated facilities that have independent heating, ventilation, and air conditioning (HVAC) systems can prevent contamination. Maintaining negative pressure environments may contain potent compounds, and using automated handling systems reduces manual intervention, insists Vasudevan.

“More drugs in development than ever are classed as highly potent,” Helen Baker, director of Formulation Design, Quotient Sciences, explains. “HPAPIs present additional CMC [chemistry, manufacturing, and controls] challenges due to the containment requirements to protect both the operators and manufacturing facilities. The production processes may also require greater precision and control due to the very small quantities of drug present in the final dosage form.”

Preventing cross-contamination in the manufacture of HPAPIs is the main concern with ensuring quality for pharmaceutical products that contain these types of ingredients, especially when manufactured in multipurpose facilities, according to van Zoelen, who stresses that stringent cleaning protocols must be adhered to. “The maximum allowed carryover (MACO) should be defined based on health-based occupational exposure limits (HBOEL) to ensure safe transitions between high-potency and low-potency APIs,” van Zoelen says. “Additionally, a comprehensive cross-contamination strategy is essential, including facility design considerations, dedicated equipment, and validated cleaning procedures to mitigate the risk of HPAPI contamination in subsequent batches.”

“If potent compounds are produced in the same facility as less potent products, dedicated production lines or segregated manufacturing areas are essential to eliminate the risk of contamination and to uphold stringent safety standards,” Lu agrees.

“EH&S [environmental, health, and safety] audits are critical to ensure that HPAPIs continually meet CGMP compliance standards and regulatory requirements,” Baker says. “The HPAPI manufacturer should also have a robust risk management program that includes ongoing environmental health monitoring and surrogate monitoring to ensure consistent control over our processes, facilities, cleaning procedures, and SOPs is also critical to ensure that HPAPIs are being manufactured consistently.”

Drug shortages can impede access to life-saving medications, and quality issues are one reason drug shortages may occur (1). Regulatory agencies have guidelines that should be followed to mitigate the risk of poor-quality ingredients, such as APIs. By following these guidelines, having a robust quality system, and qualifying API suppliers, drug manufacturers can help keep the supply chain healthy.

 March13, 2025 (accessed April 11, 2025). 

https://www.fda.gov/drugs/drug-safety-and-availability/drug-shortages

When referring to this article, please cite it Haigney, S. Poor API Quality Threatens a Healthy Supply. 

Articles

Poor API quality may often lead to delays in production and a shortage of supply.

Poor API Quality Threatens a Healthy Supply

Industry Outlook 2025: European Political Impacts on the Supply Chain

The instability in the European geopolitical climate, as well as other areas of the world, has created some nerves in many industries, but the increased focus on the need to have a healthy and safe supply chain for pharmaceuticals is one positive outcome of a tumultuous time, according to Edwin Stone, CEO of Cellular Origins.

“I think for a long time, people took [supply chains] for granted. There was a narrative that has been born over the last 20-plus years that just in time, was the right model,” says Edwin Stone, CEO of Cellular Origins. “And of course, that's very true in a situation where you're putting a box of corn flakes on a shelf, and every extra week that corn flakes packets on the shelf is probably knocking a quarter off of your margin on it. So, by week four, effectively you're giving away for free. That's not so true in medicines. In medicines, we need to take a bigger picture view. We need to look at the accounts differently. I know companies that took very pragmatic views 10 years ago, to set up facilities where they would hold stock of 18-month supply of certain consumables. And it took a lot of warehousing to do it. This was equipment, supply people. But what it meant was, through the construct supply constraints, we saw, for example, through COVID, that they were able to actually continue to supply where others couldn't. The rationale, actually, the shelf space of these high-value consumables was a fraction compared with the value when they sold them to the customer. So, I think what's been really good is [the instability] has caused that focus on supply chain. I think it's managed to remove some of the assumptions of certainty and some of the lack of risk consideration that we'd got into.”

Click the video above to watch the full interview.

The PharmTech Group interviewed Edwin Stone, CEO of Cellular Origins, about how geopolitical instability in Europe, and beyond, has impacted the bio/pharmaceutical supply chain.

Text sign showing Industry News. Business photo text delivering news to the general public or a target public | Image Credit: © Artur - © Artur - stock.adobe.com

FDA Director Martin Makary announced on May 6, 2025 that he has appointed Dr. Vinay Prasad, MD, MPH as the director of FDA’s Center for Biologics Evaluation and Research. Prasad is a hematologist-oncologist and was previously a professor in the department of Epidemiology and Biostatistics at the University of California San Francisco (UCSF).

In a post on X, FDA Director Martin Makary stated (1), “I’m proud to welcome Dr. Vinay Prasad, MD, MPH, as the new head of FDA’s Center for Biologics Evaluation & Research. With 500+ peer-reviewed publications and two books, Dr. Prasad brings the kind of scientific rigor, independence, and transparency we need at CBER—a significant step forward. Welcome aboard, Dr. Prasad.”

According to an online biography, Prasad has run the VKPrasad lab at UCSF, “which studies cancer drugs, health policy, clinical trials and better decision making”, hosted an oncology podcast, and has authored more than 500 academic articles. He graduated from the University of Chicago Pritzker School of Medicine, Johns Hopkins Bloomberg School of Public Health, and Michigan State University (2).

According to media reports, Prasad has criticized the response to the COVID-19 epidemic and certain FDA proposals (3, 4). In March 2025, former CBER Director Peter Marks resigned, citing an “assault on scientific truth” and the current administration’s views on vaccines (4).

“Over the past 13 years I have done my best to ensure that we efficiently and effectively applied the best available science to benefit public health,” Marks said in his resignation letter (5). “As you are aware, I was willing to work to address the Secretary's concerns regarding vaccine safety and transparency by hearing from the public and implementing a variety of different public meetings and engagements with the National Academy of Sciences, Engineering, and Medicine. However, it has become clear that truth and transparency are not desired by the Secretary, but rather he wishes subservient confirmation of his misinformation and lies.”

https://x.com/DrMakaryFDA/status/1919802781466079264

Sagonowsky, E. FDA Commissioner Marty Makary Taps Vinay Prasad to Head Up CBER. 

https://www.fiercepharma.com/pharma/fda-commissioner-marty-makary-taps-vinay-prasad-head-cber

Lawrence, L.; Mast, J.; and Herper, M. Vinay Prasad Tapped to Run FDA Center that Regulates Vaccines, Gene Therapies. STAT. May 6, 2025.

Marks, P. Letter to Sara Brenner, MD, MPH Acting Commissioner of Food and Drugs U.S. Food and Drug Administration. March 28, 2025. Posted by 

FDA chooses Dr. Vinay Prasad, MD, MPH, a hematologist-oncologist, to lead the Center for Biologics Evaluation and Research at FDA.

New CBER Director Appointed

n-nitrosodimethylamine molecular structure, 3d model molecule, n-nitrosamines, structural chemical formula view from a microscope | Image Credit: © Сергей Шиманович - stock.adobe.com

In January 2025, FDA posted “Determining Recommended Acceptable Intake Limits for N-nitrosamine Impurities in Pharmaceuticals: Development and Application of the Carcinogenic Potency Categorization Approach” in the Spotlight on CDER Science section of the FDA.gov website (1). The presence of nitrosamines, which are cancer causing chemicals, in pharmaceuticals has been an ongoing concern since 2018 (2).

® asked Amit Chivate, senior market manager, Greater Asia and China, Roquette, to give us his perspective on FDA’s recommendations on how manufacturers should approach nitrosamines.

What can you tell us about the recommendations FDA published in January 2025 for the development and application of the Carcinogenic Potency Categorization Approach (CPCA) to nitrosamines?

The CPCA provides a comprehensive framework for assessing the carcinogenic potential of and acceptable intake limits for N-nitrosamine drug substance-related impurities (NDSRIs) (1). The need for such specific advice stems from the fact that, in contrast to simpler, small-molecule nitrosamines, NDSRIs present complex and unique chemical structures, which make the establishment of accurate acceptable limits (AI) particularly challenging. The CPCA proposes a new protocol that predicts the carcinogenic potency of an NDSRI by analyzing its chemical make-up—whether known or merely theoretical. The first step is a review of available science from animal studies and human epidemiological data to determine the relative risk associated with each nitrosamine compound. Next, scores are awarded according to the structure of α-hydrogen atoms, and the presence of activating or deactivating features are combined to assign the NDSRI to a potency category, which then dictates its acceptable daily intake limit. This approach represents a notable breakthrough because it allows for a precise, risk-based assessment—even in the absence of specific long-term carcinogenicity data for a particular NDSRI–—making it an ideal case study for how regulatory updates can simplify the drug development process.

The CPCA also brings a dose of much needed clarity and transparent scientific process to the field of nitrosamine mitigation, making it a win for consistency, quality and— above all—patient safety.

What makes determining acceptable intake so challenging?

Determining an acceptable daily exposure limit for any given drug impurity is an incredibly complex task—especially in the case of NDSRIs, which are usually unique to each individual drug. Extreme specificity, in this instance, means increased uncertainty, as there is unlikely to be enough tailored safety information on each NDSRI for manufacturers to determine safe exposure levels. As a result, formulators often turn to information gathered on structurally similar compounds or apply a conservative default acceptable intake limit, neither of which yield perfectly accurate results and can force drug companies to make unnecessary changes to their production practices to meet disproportionately strict standards.

Inconsistent regulatory guidelines across different countries, limited long-term epidemiological data, and the difficulty of quantifying cumulative risk from multiple sources all add another layer of complexity. FDA, for instance, sets its AI limits based on safety assessments that evaluate the mutagenic and carcinogenic potential of nitrosamines. Here, it uses rodent carcinogenic potency data or structure-activity relationships (SAR) to identify comparable compounds in the absence of robust data. In contrast, the European Medicines Agency (EMA) predicts carcinogenic potency categories and corresponding AI limits based on the presence of activating or deactivating structural features in the molecule, which influence carcinogenic potency. The recently published CPCA was developed to harmonize and simplify these approaches, with the aim of giving drug manufacturers a simpler, faster and more precise strategy for remaining compliant and protecting patients, without always having to resort to the most extreme safety measures.

NDSRIs are a subset of nitrosamine genotoxic impurities with complex chemical structures that typically mirror that of an API. They form when secondary or tertiary amines in the drug substance or formulation interact with nitrosating agents during manufacturing and storage. NDSRIs are particularly concerning because they are probable human carcinogens, as classified by the International Agency for Research on Cancer. In contrast to simpler, small-molecule nitrosamines, which are more general contaminants that can affect any drug formulation, NDSRIs are formed through the nitrosation of the API in response to specific production or storage conditions. In short, NDSRIs are complex, unique, and, therefore, more difficult to manage.

 What can pharma manufacturers do to manage the nitrosamine risk?

At this point, manufacturers are well versed in nitrosamine risk mitigation, but there are some underreported strategies that we think should be brought into the spotlight. First is the benefit of weaving the compliance process throughout the entire production line, start to finish. Though testing to determine whether drugs meet AI limits is typically carried out on finished products, we advise that all raw materials should first be evaluated for their potential to introduce nitrosamine impurities—either during production or on their way to patients’ medicine cabinets. This initial step can help save time and potential expense through the early identification of contaminated raw materials, as well as speed up the verification process of the final product.

Excipients are another essential, yet often overlooked, element to the nitrosamine compliance conversation. Fillers, binders, disintegrants, and diluents make up as much as 90% of a drug’s overall volume, so it stands to reason they receive at least some of the scrutiny when it comes to product safety (3,4).One of the simplest and most effective safeguarding options for pharma producers is to select excipients with a demonstrated low nitrate content. The drawback with this strategy, however, is that since regulators do not yet mandate their assessment for nitrosamine risk, comprehensive or consistent data on the nitrite content of many excipients can be hard to pin down. This is where the support of an experienced formulation partner can be invaluable, not only for providing drug manufacturers with high-quality information and products, but also with tailored advice on how to optimize production conditions, for safety and productivity.

FDA. Determining Recommended Acceptable Intake Limits for N-nitrosamine Impurities in Pharmaceuticals: Development and Application of the Carcinogenic Potency Categorization Approach. Spotlight on CDER Science. 

https://www.fda.gov/drugs/spotlight-cder-science/determining-recommended-acceptable-intake-limits-n-nitrosamine-impurities-pharmaceuticals

FDA. FDA Statement on the FDA’s Ongoing Investigation into Valsartan and ARB Class Impurities and the Agency’s Steps to Address the Root Causes of the Safety Issues. Press Release. Jan. 25, 2019.

Abrantes, C.G.; Duarte, D.; Reis, C.P. An Overview of Pharmaceutical Excipients: Safe or Not Safe. 

. 2016;105:2019–2026. DOI: 10.1016/j.xphs.2016.03.019

Haywood, A.; Glass, B.D. Pharmaceutical Excipients—Where Do We Begin? 

2011;34:112–114. DOI: 10.18773/austprescr.2011.060

Amit Chivate is senior market manager, Greater Asia and China, at Roquette.

Amit holds an MBA and a PhD in pharmaceutical drug delivery, and has more than 20 years of experience working across R&D, strategy, sales, marketing, and product management in both India and the United States. At Roquette, Amit serves as the senior marketing manager for the APAC region, leveraging his technical and business expertise to drive marketing initiatives and strategic growth.

Amit Chivate, senior market manager, Greater Asia and China, Roquette, provides his perspective on FDA’s recommendations regarding nitrosamines. 

Strategies for Mitigating Nitrosamine Risk

AAPS National Biotechnology Conference 2025: High-Concentration Biologics

Biologic drugs typically have a higher dosage than small-molecule drugs, according to Lun Xin, associate director at WuXi Biologics, and sometimes patients will need to spend hours at an infusion center to receive these treatments. “That's a growing experience for a lot of people, especially folks that [are] dealing with things like cancer or long-term arthritis disease or something of that nature, which is lot of time … So, there's a good amount of need for a patient to take [the drug] home and then be able to use pre-filled syringes or autoinjector cartridges, where they can deliver the dose by themselves in the comfort of their home,” says Xin. “Now the limitation with that is you can only put in so much drug into the subcutaneous space using a prefilled syringe or auto injector. And a lot of that's believed to be about two milliliters to be a good benchmark. So now that you have the ideas, and you have to deliver several 100 milligrams of those into a two milligram, two milliliters of volume, right? So, there's a need to develop the concentration of the protein therapeutics to several 100 milligram per mL.”

 spoke with Xin about these challenges associated with the formulation of high-concentration biologics ahead of his presentation at the AAPS National Biotechnology Conference, which is being held May 4–7, 2025 in Boston. Xin’s presentation, “Accelerating High Concentration Formulation Development with Big Data-Driven High-Throughput Technologies”, occurred on Tuesday, May 6 .

Click the video above to watch part one of our interview with Lun Xin.

Lun Xin is associate director at Wuxi Biologics.

BioPharm International® spoke with Lun Xin, associate director at WuXi Biologics, about high-concentration biologics and some of the biggest challenges associated with their formulation.