Ahead of this year's Extractables & Leachables Asia, we spoke with William Bello, Analytical Pharmacist at Lausanne University Hospital to get a sneak peek of what we can expect from his presentation on 'The risk of unmonitored leachables in hospital pharmacy compounding due to the off-label use of plastic primary packaging: A cause for concern?' Here's what he had to say…



Q1. Why is this message particularly critical for industry professionals to hear right now?
The risk of unmonitored leachables in hospital pharmacy compounding due to the off-label use of plastic primary packaging is a pressing concern that industry professionals should learn. As the hospital demand for compounded drug product continues to rise, driven by drug shortages, withdrawal and specific patient treatments, hospital pharmacies are increasingly relying on plastic containers as parenteral route delivery systems, such as syringes and intra-venous bags. These plastics, while convenient, are often used in off-label ways not validated for compatibility with specific drug formulations. This creates a critical blind spot in the quality assurance process.
These plastic materials may leach unmonitored potentially harmful plastic-related substances such as industrial in-process contaminants into the drug formulation. This risk is particularly acute when drug products are stored in these devices for extended periods i.e. weeks or months. These devices, as per their technical sheets, are meant to be used for immediate action, specifically for administration and withdrawal of fluid in patients. Therefore their current use brings about added risk to patients. While large pharmaceutical manufacturers rigorously test for extractables and leachables (E&L), hospital compounding environments often lack the resources, infrastructure, or standardised procedures to perform such evaluations. As a result, patients may unknowingly be exposed to harmful substances, therefore posing potential health risks.
Currently, there is no formal regulatory framework from major authorities such as the FDA, and the EMA, specifically addressing the appropriate use of plastic primary packaging in hospital pharmacy batch compounding and the need for leachables risk assessments. This regulatory gap presents both a challenge and an opportunity. With the support and technical expertise of the pharmaceutical and packaging industries, clear regulatory drafts could be made in the form of evidence-based guidelines to ensure patient safety. Such frameworks could mandate the appropriate selection of packaging and require leachables risk assessments for high-risk preparations. In my view, this collaborative regulatory evolution is long overdue. It would bring much-needed consistency and safety standards to hospital compounding, reducing variability and preventing avoidable harm to vulnerable patient populations.
Finally, the ethical implications cannot be overlooked. In a healthcare environment where transparency and patient safety are paramount, the failure to assess and monitor leachables can lead to serious consequences—including patient harm, lawsuits, and damage to institutional credibility. For hospital pharmacy leaders and quality professionals, the time to act is now. Prioritizing education in the form of awareness programs, adopting validated materials, and establishing robust risk assessment protocols for packaging in compounding practices is essential to uphold the integrity of care.
In summary, the silent threat of unmonitored leachables in off-label plastic packaging is a multifaceted risk that demands immediate attention. It is not just a regulatory or technical concern—it is a matter of public trust and patient safety.



Q2. Can current industrial E&L guidelines be applied on hospital pharmacy batch compounding?
Yes, they can and should be applied, but with a tailored “adopt and adapt” approach. While existing industrial guidelines for extractables and leachables (E&L), such as those developed by the FDA, USP <1663>/<1664>, PQRI, and ICH, are designed for large-scale pharmaceutical manufacturing, their underlying principles are directly relevant to hospital pharmacy compounding. These guidelines provide a robust framework for understanding how packaging materials can interact with drug products, and they offer valuable tools to systematically assess and mitigate the risk of harmful leachables reaching the patient.
In the hospital setting, compounded drugs, especially sterile preparations, involve high-risk routes of administration (e.g., intravenous, ophthalmic), inappropriate use of plastic packaging and vulnerable patient populations (e.g., neonates, chronic patients). Many of these compounded drugs are stored in off-label plastic containers. Despite these high-risk scenarios, leachables are never evaluated and documented, in hospital compounding. This creates a clear and urgent patient safety gap.
Industrial standards, if adapted thoughtfully, can fill this gap. E&L guidelines provide clear expectations around the control of leachables, particularly for products with long shelf lives or high-exposure risk. Although not written with hospital compounding in mind, it signals a broader shift toward risk-based, data-driven assessment of packaging material safety. In my opinion, it's only a matter of time before regulators begin to expect similar levels of justification in clinical settings.
From a practical standpoint, hospitals do not need to fully replicate the scale or cost of industrial E&L testing. Instead, they can take a tiered approach: using existing E&L data from packaging suppliers, performing basic risk assessments for high-risk compounds, and incorporating leachables considerations into quality assurance processes. This doesn’t require reinventing the wheel, but it does require awareness, training, and collaboration.
This shift will necessitate closer collaboration among stakeholders, including packaging suppliers, hospital compounders, analytical labs, and regulatory experts. Hospitals need access to material data (e.g., extractables profiles), and suppliers must be ready to share it in a usable format, although there is a risk that it may be confidential. Analytical labs can offer scaled-down or targeted E&L assessments and even provide expert opinions to support hospital pharmacy decision-making.
In my opinion, the lack of regulatory requirements today should not be a reason to delay action. Rather, it is an opportunity for the hospital compounding community to lead with best practices, demonstrate proactive risk management, and align more closely with industry standards. In other words, E&L field is not an industrial field anymore. Waiting for regulators to impose requirements could lead to rushed, costly changes. Acting now, by adapting industrial E&L guidelines to the hospital context, will enhance patient safety, ensure preparedness for future regulation, and help foster a culture of quality and accountability in healthcare.


Q3. Why is hospital pharmacy compounding underregulated in terms of batch compounding concerning the proper selection of plastic primary packaging and the assessment of leachables?
Hospital pharmacy compounding, especially batch production, remains significantly underregulated when it comes to the selection of plastic primary packaging and the assessment of leachables. Here are my opinions shared with hospital pharmacists worldwide.
Compounding in hospitals is not the same as large-scale pharmaceutical manufacturing, and yet, many regulators approach it with the same lens. Some inspectors may lack a full understanding of hospital pharmacy workflows, particularly batch compounding practices. They may underestimate the clinical importance of such preparations, assuming that hospital pharmacies only produce low-risk personalised medications. This results in a lack of pressure for improvement in areas like packaging material selection or leachables assessments, areas that are absolutely critical for ensuring patient safety in more vulnerable populations, such as neonates or chronically-ill patients.
Moreover, regulatory bodies are often heavily industry-oriented. This leads to situations where hospital pharmacy is either overlooked or over-scrutinized in ways that aren’t constructive. Over-inspection based on irrelevant industrial standards can become burdensome for hospital teams, discouraging them from innovating or implementing more rigorous risk assessments like those used in industry. This regulatory disconnect creates a vacuum, hospital pharmacists know that improvements are needed, but without regulatory frameworks to back them, it's difficult to allocate the time, resources, or funding for implementation.
Another key issue is the stagnation of regulatory innovation at the national level. National regulatory authorities often shy away from initiating these changes due to fear of criticism, political friction, or resource limitations. Therefore, changes in guidelines, particularly those concerning E&L testing or plastic packaging, need to be implemented at an international or supranational level, such as through the European Commission and the FDA. Without top-down harmonization and leadership, hospitals remain stuck with outdated or irrelevant frameworks.
Additionally, hospital pharmacies themselves are partially isolated in this problem. The widespread off-label use of plastic packaging in compounding is a symptom of progress happening in silos. Hospitals have been advancing rapidly in clinical and compounding capabilities, adapting formulations for highly specific patient needs. However, regulators have failed to keep pace with these developments, and hospital pharmacists, on the other hand, have not always effectively communicated the risks associated with off-label packaging choices. This mutual disconnect creates a cycle of under recognition and inaction.
This situation forms a kind of regulatory ouroboros: a closed loop where the lack of regulations makes the process easier and less burdensome, so no one is incentivized to push for change. Because adverse events are rare or underreported, the perceived need for regulation remains low, and the cycle continues. But this is dangerous thinking. As medicine evolves toward more personalized therapies, the formulations used in hospitals are becoming increasingly complex. This, in turn, raises the stakes. Without proper assessment of leachables and appropriate packaging choices, these innovations could introduce new and unpredictable risks to already frail patients.
In my opinion, breaking this cycle will require coordinated effort. Regulators must be educated on the clinical significance and specific technical challenges of hospital batch compounding. Hospital pharmacists must also be more proactive in identifying risks and demanding change. Only through mutual acknowledgment of these issues, combined with updated, hospital-specific regulatory frameworks, can the gap between compounding practice and patient safety truly be closed.


Q4. How to properly mitigate these risks?
To mitigate these risks, the answer is to perform risk assessments on leachable compounds in hospital pharmacy high risk compounding no matter the label of the primary packaging, but how? The debate intensifies: should assessments be outsourced to external experts, or should hospital networks build independent capabilities through regional or national centralization?
Subcontracting to specialized experts can be a practical and flexible solution. However, it must be approached strategically. Hospital pharmacy batch compounding is fundamentally different from industrial-scale drug manufacturing. The number of units produced is small, and the production cycles are variable. As such, subcontracting to large commercial laboratories may not be viable or cost-effective. Instead, partnering with small-to-medium-sized enterprises (SMEs) that specialize in compounding and understand the unique demands of hospital pharmacy could be far more suitable. They are industrial in nature but adaptable to client’s requests. These SMEs can provide targeted, high-quality services such as leachables testing for prefilled syringes, parenteral nutrition bags, and dose-banded chemotherapy preparations. They can also assist in medical device selection and compatibility testing, areas in which hospital pharmacies often lack internal expertise. The advantage is that these services are tailored, efficient, and well-integrated into hospital workflows. The downside, however, is the cost—outsourcing to SMEs can be more expensive than in-house assessments. Moreover, such a model is only financially feasible for medium- to large-volume preparations, which may fluctuate depending on hospital demand and clinical practices.
An alternative and potentially more sustainable solution is centralizing E&L assessments through dedicated hospital pharmacy laboratories at a regional, national and even international levels. These centres could be equipped with the instruments and expertise needed to perform both extractables studies on medical devices and leachables assessments on container-closure systems used in batch compounding. Such laboratories would bring a higher level of standardization, enable shared cost structures across multiple hospitals, and ensure consistent quality in testing practices. Centralised laboratories could also foster strong collaborations with medical device manufacturers—such as syringe and intra-venous bag producers—who are eager to demonstrate that their products meet hospital compounding standards. In this way, manufacturers benefit from validated use-cases, and hospitals gain access to safer, pre-evaluated packaging solutions. This model mirrors the rigor of industrial practices but operates on a smaller, hospital-focused scale. Samples from various hospitals could be sent to these laboratories for routine or case-specific testing, improving safety and compliance across the board. That said, building such a laboratory requires significant upfront investment. Recruiting professionals with expertise in both E&L science and hospital pharmacy compounding is challenging, and training them will take time. However, these are short-term barriers. Once established, such laboratories could serve not only hospital systems but even facilitate international partnerships, particularly in countries with shared regulatory frameworks or procurement systems. Over time, this would be cost-effective, and strategically beneficial for the entire healthcare system.
In my opinion, a hybrid model is the most practical path forward. In the immediate term, high-risk compounding scenarios should be addressed through partnerships with SMEs who can provide rapid, specialized support. Meanwhile, healthcare systems should begin investing in the development of centralised hospital pharmacy laboratories for long-term sustainability. Governments and professional bodies can accelerate this transition by offering funding, policy incentives, and educational programs to train the necessary workforce.
Ultimately, this is not just about regulatory compliance—it’s about patient safety. Hospital compounded products needs the same safety assessments and material checks as industrially manufactured drugs. By strategically combining subcontracting with centralised capability-building, hospital pharmacies can rise to meet this challenge efficiently and responsibly.