Felicity Thomas is Associate Editorial Director of Pharmaceutical Technology, Pharmaceutical Technology Europe, BioPharm International.

Felicity Thomas

Within the bio/pharma industry, there is a certain expectation for companies to maintain required levels of cleanliness within their facilities to ensure products that are manufactured are at minimal risk of contamination. All cleaning processes must also be validated for effectiveness and reproducibility.

As drug products become more complex and sensitive to potential contaminants, there is an increasing demand for cleaning validation throughout industry. According to market research, the cleaning validation market is forecasted to grow by a compound annual growth rate of 5.7% between 2021 and 2027 (1).

Of course, the requirement for manufacturing equipment to be clean is nothing new; as Andrew Kolbert, PhD, senior leader, Technical Solutions, Element, points out, this facet of drug production has been a necessity for 70 years since the introduction of the 21 Code of Federal Regulations (CFR) 210 Part 133.4 (2). “Early efforts [in this field] were focused on avoiding microbiological contamination or just filth, as seen at food manufacturers,” he states.

“In 1978, the GMPs [good manufacturing practices] were amended to 21 CFR Part 210.67, which specifically addressed the issue of cross contamination, as opposed to mere unsanitary conditions, with particular focus on manufacturers that made penicillin and other pharmaceutical products on the same equipment train,” Kolbert continues. The issue of cross contamination was brought to the fore by a case in 1988, he highlights, where a drug product, Cholestyramine Resin, was recalled due to contamination with pesticides as a result of insufficient cleaning of solvent drums (3).

“Cleaning validation is a subject that receives a great deal of attention within biopharmaceuticals, not least due to the risks presented in terms of product adulteration from cross-contamination and, hence, patient harm from improperly cleaned surfaces (and noting additional concerns such as operator protection),” specifies Tim Sandle, head of microbiology at Bio Products Laboratory (BPL) in Elstree, UK.

Sandle also highlights microbial proliferation as an area of importance because of the risk it poses in terms of the numbers of organisms adhering to surfaces and the release of microbial toxins. “Under the least desired conditions, a combination of organic residues and the presence of microorganisms can lead to a biofilm developing,” he says. “Biofilms are difficult to detect, and they are challenging to remove.”

Therefore, it is expected, by the regulatory bodies, such as FDA, that a drug manufacturer has a cleaning process in place for all equipment to ensure that no drug residue exceeds the maximum allowable carryover (MACO) level—a level that is determined based on toxicological risk—and that there are no cleaning agent residues and so forth, Kolbert asserts. “The cleaning process must also be validated to ensure it is consistently reproducible and effective. The exact form of this validation depends on the nature of the equipment as well as the cleaning process,” he says. “If cleaning is to be done manually, the reproducibility across workers will be need to be explored. If solvents or detergents are used, reduction to an acceptable level must be demonstrated.”

“Approaching cleaning validation should always begin with a risk assessment,” emphasizes Sandle. “To be effective, the risk assessment needs to be built upon a thorough understanding of the equipment to be cleaned and the cleaning reagents and mechanisms.”

Additionally, any residue(s) that needs to be removed must be identified and the optimal method to remove the residue(s) must be considered, Sandle continues. “For example, some residues are best cleaned by either an alkaline or acidic cleaner (or both types of cleaning agent may be required). To ensure the designed process has a greater chance of being effective, it is also important to understand how the residue is actually being removed (which requires detail of the residue chemistry),” he states.

“The next step is whether to use product residues or an alternative soil to challenge the designed cleaning process,” Sandle adds. “Users need to assess whether product residues are suitable for the cleaning validation because some process soils pose little challenge to the cleaning system, and it may be more appropriate to use a surrogate with greater viscosity and binding characteristics.”

Furthermore, Sandle points out that consideration should be made to how much residue may be permitted to be left, which will impact the level of cleaning that is required. “This [consideration] means selecting appropriate sampling methods, typically based on rinsing and swabbing, and the appropriate test methods for microbial and chemical analysis,” he says. “With methods, there needs to be an understanding about the metrology of the test instruments and the likelihood they can quantify the minimum acceptable residue. In addition to typical analytical method validation parameters (specificity, accuracy, linearity, limit of detection, precision), the actual sampling procedure must be qualified.”

For Kolbert, swabbing all of the drug product contact surfaces along the manufacturing train using the simplest analytical finish that will achieve an appropriate limit of detection is the most common approach. “If the drug product has a chromaphore, HPLC [high-performance liquid chromatography] or even UV [ultraviolet]/vis [visible] may be sufficient,” he says. “It is important to detect not only the drug product but any degradants or by-products that may be created.”

Also, if a detergent mix or solvent is required for the cleaning process then merely analyzing the rinsate does not suffice, Kolbert admonishes. “The product path components must also be tested for residue by direct swabbing,” he states. “A commonly used metaphor is if you are cooking in a pot, it is not enough to analyze the water rinse, you also need to look at the pot for old product residue that may break off over time.”

Increasingly, companies are utilizing highly potent drugs in biopharmaceuticals, which is creating challenges in terms of cleaning validation, asserts Kolbert. These drugs have extremely low MACO, which has driven analytical limits of detection to barely achievable levels, he adds. As a result, it is becoming necessary to use liquid chromatography coupled with tandem mass spectrometry to hit the toxicologically driven thresholds, Kolbert states.

In Sandle’s opinion, the main challenges in cleaning validation are in relation to residue removal, which is partially dependent upon the required level of cleanliness and the level of cleanliness that can actually be achieved—which relates to the design of the equipment. “Ideally, equipment selection will have embraced quality-by-design and there will be no inaccessible parts,” he continues. “However, in reality, some areas of large items of equipment are easier to clean than others and the main challenges that arise are often cantered on developing cycles that can reach challenging locations [such as] narrow pipes, u-bends, valves, and so on.”

Another area that is sometimes neglected is consideration of the age of equipment, Sandle specifies. “Manufacturing activities have the potential to induce abrasion and corrosion,” he says. “Hence, consideration must be given to ageing equipment with any aspect of cleaning.”

Regulators expect companies to conduct a risk assessment, Sandle points out. “With the risk process, it is good practice to use a multi-disciplinary team. The team should assess indirect product contact pars in relation to: the ability to build-up residues and the ability to transfer residues to product contact sites,” he explains.

Additionally, there is an expectation from regulators that all sample locations selected are represented and that potential ‘worst cases’ are indicated, Sandle notes. “I have seen several regulatory findings for cleaning validation that has been undertaken using locations that are not sufficiently challenging,” he says.

“A common regulatory issue also relates to manual cleaning,” Sandle continues, “especially around verification [as to whether] the operators can continue to undertake manual cleaning to a reliably high standard.”

Essentially, the cleaning process needs to be documented and demonstrated to be valid as per the regulatory bodies’ guidance, such as FDA outlined in Validation of Cleaning Processes (7/93) (3), confirms Kolbert. “There are a number of pitfalls that must be avoided, such as an overreliance on rinse analyses instead of direct observation of the equipment product contact paths; lack of sufficient evidence of reproducibility of any manual steps in the cleaning process; and verification of the absence of cleaning agents at the conclusion of cleaning,” he emphasizes.

“Perhaps the most important lesson from regulatory findings is the importance of running a risk assessment to manage the process, focusing on the proactive identification of hazards, selecting the optimal process to reduce the risk presented by these hazards, and with that ensuring there is a suitable measure of detection in place to verify the outcome,” Sandle says.

Sandle hopes that there will be increased use of rapid methods in cleaning validation that can provide real-time assessments in the near future. 

“Adenosine triphosphate (ATP), protein residue, and glucose residue swabs are among the more useful rapid methods, although further development is required to improve accuracy and repeatability,” he highlights. “Of the different ‘PAT [Process Analytical Technologies] methods’, ATP bioluminescence technology offers a higher sensitivity compared with colorimetric methods.”

In terms of management of cleaning validation processes, software developments are piquing Sandle’s interest, including some that are employing artificial intelligence. “Such packages can help to sort equipment into types where a matrix approach is preferred, as well as enabling scheduling and for setting re-validation targets,” he states.

At its very essence, cleaning validation will require greater consideration, simply as a result of the evolving therapeutic landscape, Kolbert asserts. “The increased use of biological therapeutic agents in pharmaceutical manufacturing will require increased complexity of analytical techniques as activity of the residue is as important as chemical presence,” he summarizes.

1. MMR. Pharmaceutical Cleaning Validation Market: Industry Analysis and Forecast (2021–2027) by Product Type, Validation Test, and Region. Report,.October 2021.
2. CFR Title 21, 210 Part 133.4 (Government Printing Office, Washington, DC).
3. FDA. Validation of Cleaning Processes (7/93), Inspection Guide. Aug. 26, 2014.

Felicity Thomas is the European/senior editor for Pharmaceutical Technology Group.

Articles

Analytical techniques for validating cleaning methods must evolve to match the pace of an increasingly complex manufacturing landscape for new therapeutics.

Validating Cleaning Methods in Bio/Pharma Processes

Towards the latter half of 2022 (on 27 Sep. 2022), CRB launched its 

 industry report, providing a snapshot of how the industry is doing and how it might progress (1). To create the report, CRB surveyed a wide selection of the top companies in the life sciences industry and then combined those views to create and overarching perspective into the status of the industry and future prospects.

The 2022 report marks the first one to include an expanded audience, as many European countries were also included in the survey, which has raised some interesting insights. To learn more about the report and the outcomes revealed, 

spoke with Peter Walters, Fellow—Advanced Therapies, CRB.

 Based on the results of CRB’s latest report, what are the biggest challenges facing European pharma companies over the next five years?

Some of the biggest challenges reported by our European respondents were: attracting and retaining key talent—talent shortages are at a high right now, and companies are struggling to get the staff they need to progress forward; financing—strapped by investment issues worldwide, companies are being forced to scrutinize and optimize their spending a lot more than in the previous couple years; innovative technologies—European clients are facing a need for better, more effective technological solutions to their manufacturing challenges.

 Where might the biggest opportunities lie for European pharma companies over the course of the next five years?

 Attracting and retaining key staff is becoming critical within the life science industry. The continued evolution of therapy approaches, and the resultant needs for development and new technologies, means having the right staff to lead and drive your organisation. Building the right personnel foundation can make all the difference in your ability to move forward or get caught in a talent trap.

How do the challenges and opportunities for European pharma line up with the rest of the world?

We received survey responses that showed much better global alignment than we anticipated. The report saw regulatory perception, including around global harmonization efforts, closely aligned. The report also saw close alignment around companies’ intentions for Pharma 4.0 and digitalization initiatives.

 How has the COVID-19 pandemic shaped the European pharma landscape and what continuation of these changes should we expect to see over the next five years?

Financial constraints have become far more prevalent post-COVID. Companies are indicating they are still expecting company growth and expansion, but at a much more conservative, methodical pace than pre-COVID.

When will the next report be scheduled and how can European companies be involved?

 report every year, so keep an eye out for the 2023 edition, most likely on shelves around Q4. For companies interested in specifically taking part in our industry survey, please reach out and we will do our best to incorporate them in our survey effort when that goes out.

Felicity Thomas is the European/senior editor for Pharmaceutical Technology Group.



CRB’s latest industry report includes an expanded audience to include many European countries, which has provided some interesting insights.

Providing a Snapshot of the Industry

The bio/pharmaceutical industry has made it through 2022—a year that started off with the unrelenting COVID-19 pandemic, continued with Russia’s invasion of Ukraine, and culminated in global economic struggles—evolving and adapting to each difficulty, reasonably unscathed. However, as the challenges and opportunities of next year start cresting on the horizon, the bio/pharma industry must look to bolster operations to ensure it can weather the forthcoming storms and reap the potential benefits of change appropriately.

Looking back over the year, Adam Sherlock, CEO of Rephine (a good manufacturing practice [GMP] compliance specialist company), remarks on the continual evolution of the industry, which has experienced an increased focus on digital health and broadening uses of artificial intelligence (AI) and the progressive shift of many traditional companies towards biological products. However, he also notes that there have been persistent issues also, compounded by global disruptions.

The bio/pharma supply chain has continued to experience problems in 2022, Sherlock continues. “As in many other areas, [these issues have been] compounded by the war in Ukraine and the remaining COVID restrictions in China, which as well as physically disrupting many supply chains are dramatically increasing transport costs and routes,” he says. “In some cases, this [disruption] has led to drug shortages, which, added to existing pricing policies in certain European countries, is influencing supply preferences to the detriment of some markets.”

“Stabilizing the supply chains will not be a quick feat, and cost and efficiency are slated to take an even more prominent position in companies’ plans [in the future],” forecasts James Kelleher, founder and CEO of Generis—a company that specializes in content and information management systems.

Additionally, the complexity of the bio/pharma industry’s current supply chains can be problematic when there is a break or alteration in one or several of the links of the chain, requiring reorganization, Sherlock emphasizes. “The complexities of each stage of the lifecycle of a product create a need for highly specialized ‘one-stop shops’ for services, spanning regulatory, analytical, supply chain control, and in product terms covering biological, intermediates, and so forth,” he states.

“On top of continued challenges for the supply chain, [industry has seen] the coming into force of several regulations,” Kelleher asserts. “Companies are keeping their head above water with new expectations of speed and efficiency that came out of the pandemic, which requires a broad review of processes, the downside of which can be further delays in delivering visible progress to management in meeting those expectations.”

An obvious regulatory change in Europe, set to happen in 2023 after some delays, is that of the submission process for the identification of medicinal products (IDMP), stresses Kelleher, who believes that the requirements of these standards will add pressure on technology companies to work directly with healthcare authorities. “When you think about it, the real industry requirements are pretty much driven by these authorities, so the expectation that solutions are developed in absolute accordance with those [bodies] will only grow,” he says.

This collaborative effort is already being seen with certain data exchange/gateway mechanisms across regulatory and safety applications such as the E2B (R3) standard, remarks Kelleher (1). “The ongoing journey to standardization on more aspects of submission and data exchange will continue to have an impact,” he notes.

Ian Crone, business unit director Europe—fme Life Sciences, which provides business and technology services, points out that the web-based human variations electronic application form (eAF) for centrally authorized products (CAPs) has been available for use since 4 Nov. 2022 on the European Medicines Agency’s (EMA’s) new product lifecycle management (PLM) portal. “The formal transition period will start after the anticipated March 2023 release when nationally authorized products (NAPs) features will be added to the form,” he confirms. “The current interactive PDF eAF will remain available until the end of the transition period.”

Within five years, Crone specifies that bio/pharma companies should have a solution implemented within their organization that can provide a streamlined approach across all stages of the product development life cycle. “Meaning that IDMP data, RIM [regulatory information management] data and eCTD [common technical document in electronic format] (submission) should be managed together as required by EMA guidelines; managing and tracking of data should go together with submission,” he says.

A potential weak point within the bio/pharma industry for Crone is actually the management of labelling documents. “I expect that software vendors will introduce industry solutions that will assess, revise, and track labelling changes,” he states.

“The process of revising the guidelines and regulations is ongoing,” emphasizes Sherlock. “This revision is bringing important challenges for the industry as it moves away from the positive checklist of must-have measures and focuses regulations on concrete solutions arising from the knowledge of processes and technologies, and risk analysis, to fine-tune what needs to be done to ensure the quality of medicines.”

And, of course, regulations are not going anywhere, Kelleher asserts. “So, companies have no choice but to adapt,” he says. As discussed earlier, submissions to regulatory bodies are undergoing change through PLM and IDMP for example, which will be happening over the next six to 12 months, Kelleher adds. “This [change to submissions] means an additional challenge in improving processes to meet heightened expectations around efficiency, which were probably not realistic via traditional ways of working; and learning new processes and trying to merge those into existing improvements,” he says.

“In the area of digital solutions for regulatory operations, the industry is starting the transition from a content to a data-centric model,” reveals Renato Rjavec, director of Product Management, Amplexor Life Sciences—a global provider of regulatory, quality, and safety software solutions. “This means that regulatory data [are] becoming an asset which is enabling not just data submissions but also data-driven content and processes management.”

CRB’s latest industry report includes an expanded audience to include many European countries, which has provided some interesting insights. Read 

interview with Peter Walters, Fellow—Advanced Therapies, CRB, on the report and its outcomes 

A key driver for this shift has been the product data submission requirements related to IDMP, Rjavec continues. “The progress on the overall IDMP implementation in Europe has been so watered down that the industry now seems to take the lead in recognizing that the benefits of data-centric approach go far beyond compliance. Quality and operational efficiency seem to be the most impactful areas,” he says. “This [understanding] is also driving implementation of holistic RIM platforms which bring end-to-end connectivity to regulatory affairs and beyond.”

“Many biopharmaceutical functions have spent the last decade modernizing their base technologies, most often in a cloud/software as a service environment platform that brings foundational benefit to individual functions,” states Steve Gens managing partner, Gens & Associates—a global life sciences advisory and benchmarking firm focused on the regulatory ecosystem.

Currently, the industry is in the early stages of its ‘data connectivity’ era where critical data from multiple functions are being slowly connected, explains Gens. Internal productivity and external regulatory requirements are both driving this data connectivity within industry, he adds, which “requires a clear cross functional digitization strategy and focus on cross-functional data governance, master data management, and ensuring all data from these various authoritative systems [are] at the same high level.”

The COVID-19 pandemic has also accelerated adoption of digitalization within the bio/pharma industry, Gens specifies. Referring to the COVID-19 Regulatory Impact Studies that were performed by Gens & Associates in 2020 and 2022 (2,3), Gens reveals that many companies with pandemic-related products, when compared with those that did not have COVID-19 products, actually accelerated their digitization and system modernization plans, mainly to reduce the time from clinical development to patient product access without sacrificing quality.

“Digitalization has indeed experienced a significant boost because of the pandemic, particularly with regard to tools providing an alternative to traditional business relationships—collaborative tools, remote audits, virtual meetings,” confirms Sherlock. “The use [of these tools] has been consolidated now and will remain to a large degree.”

However, dramatic change in other areas, such as digital health, medical devices, remote diagnosis, real-world evidence/data, communication with suppliers, and control of the supply chain, is also being seen, Sherlock adds. “It seems clear that [digitalization] is the direction being taken towards healthcare now, and we can expect to see all kinds of further developments. One of the fastest-growing areas here is AI; we will see many new applications of this in the healthcare and pharma industry,” he says.

When done correctly, digitalization is a big enabler that has the potential to make companies more agile and resilient, asserts Kelleher. “The actual adoption of cross-functional platforms for managing content and data, rather than armchair appreciation of this concept, has already been unprecedented. Companies are engaged in a digital ‘arms race’ to ensure they can capitalize on reaction time and efficiency over the coming five years,” he says. “Digitization of the ‘core’ aspects of managing content and data has become a commodity now, and fairly standard. The next stage in the evolution is to link all these capabilities via business process management and unified structured data/information lakes, and to use this seamlessly inter-connected scenario to enable many more robotic processes and automation use cases that are not possible when data and content remain separate.”

Given the fact that the COVID crisis remains apparent for now, certainly in China, and that the global economy is experiencing high inflation, pressure will be felt on manufacturing margins, particularly for generics manufacturers, Sherlock stresses. “Companies with traditional quality and manufacturing management processes will need to implement immediate and important changes to improve efficiency,” he says.

Kelleher points to reshoring of manufacturing as a further increasing trend thanks to the pandemic and economics, with some companies relocating their manufacturing operations from Asia to European options, such as Spain and Portugal. “Companies in all industries are learning that keeping your operations geographically close—despite the increased [outlay] cost—drastically reduces risk, supply chain cost, and costs driven by rapidly changing geopolitics,” he notes. “Fundamentally, when the geopolitical and economic outlook are positive, companies look to globalization for economic savings, but when the outlooks are negative, they operate a form of ‘protectionism’ over their business, partners, and suppliers.”

In light of this ‘protectionism’, Kelleher points out that many bio/pharma companies will also seek to bring more processes in-house, impacting the outsources services market too. “After all, [bio/pharma companies] should now have platforms that allow low-code, rapid implementation of new processes,” he says. “In this case, demand will increase for specialized knowledge, while more general processes will be automated or reassigned.”

Furthermore, investment into biologics manufacturing projects has been witnessed in recent years, especially through acquisitions, Sherlock adds. “The pressure on the margins of generics-focused companies is influencing this shift to other types of investments. Companies that are not large enough to realign in this way will either have to implement intensive changes to how they operate now, to gain efficiency, or wait to be bought out by larger generics groups,” he affirms.

As a result of the market pause, an outcome of the COVID-19 pandemic, and with smaller companies being forced to navigate choppy fiscal waters, Kelleher believes that M&A opportunities should be opening up again once more in 2023 and beyond. “The drive for cost savings, particularly with the current economic climate declining, should continue to fuel the appetite for M&A—although values may be affected,” he says.

“This activity may not only be about purchasing additional lines/areas of business, but more about acquiring talent and processes,” Kelleher continues. “As noted earlier, if you want to rapidly scale your abilities to perform processes that were previously performed on a different continent, but don’t necessarily want to pay for the number of resources you were previously relying on for outsourcing, then you are left with the option of acquiring smaller but highly efficient companies with strong subject matter expertise, and swallowing the cost—to reduce risk, reduce supply chain cost, and increase domestic or near-shore capabilities.”

For Sherlock, there will be further evolution and consolidation of changes in the industry that began several years ago. “On the one hand, the decreasing number of companies of generic products [will continue], with dwindling profit margins and the need of increasing productivity and reducing costs,” he summarizes. “On the other hand, [there will be an] increasing role of biologic products, and the need for huge investments for the development and launch of new products here, leading to M&A—until we end up with a small number of generic[-drug] companies with large production capacities and optimized costs; and powerful groups with sufficient financial muscle to cover the costs of R&D of new products—most of them in the biotech area.”

. Version 5.02 (2016).
2. Gens & Associates. 2020 COVID-19 Regulatory Impact Survey Results Whitepaper. Whitepaper, 8 Feb. 2021.
3. Gens & Associates. 2022 COVID-19 Regulatory Impact Follow-up Survey Whitepaper (Summer 2022). Whitepaper, 31 Aug. 2022.


Vol. 35, No. 1
January 2023
Pages: 9–11, 18

When referring to this article, please cite it as F. Thomas, “Opening Up Opportunities in 2023,” 

Bio/pharma has evolved and adapted to a variety of challenges in 2022, but what might be on the cards for the industry in 2023?

Opening Up Opportunities in 2023

Pharmaceutical Cleaning Validation Market: Industry Analysis and Forecast (2021–2027) by Product Type, Validation Test, and Region

 Title 21, 210 Part 133.4 (Government Printing Office, Washington, DC).
3. FDA. 

Pharmaceutical Technology
Volume 47, No.1
January 2023
Pages 36-37


When referring to this article, please cite it as Thomas, F. Cleaning Up in Bio/Pharma 47 (1) 2023. 

As the therapeutic landscape grows more complex, so too must the analytical techniques for cleaning validation to ensure the utmost cleanliness is achieved.



Cleaning Up in Bio/Pharma

Environmentally conscious business practices are much more prominent nowadays in many parts of the world and across all industries. For Europe, in particular, a common goal that has been set out by national governments and regulatory authorities is to achieve sustainability in the near future (i.e., in the next decade), and the bio/pharma industry is no exception to this objective.

To learn more about the sustainability requirements that bio/pharma companies in Europe are facing, what companies have been and should be doing to meet relevant objectives, and how Europe matches up to the rest of the world in sustainability progress, Pharmaceutical Technology Europe spoke with Andre Valente and Verena Ahnert, both partners at L.E.K Consulting—a global strategy consulting firm.

 Could you highlight how the sustainability requirements of regulatory authorities have changed over the past few years for European pharma companies?

We would distinguish between regulations related to drug development, marketing authorization, and monitoring set by the EMA [European Medicines Agency] and national pharmaceutical regulators, such as the MHRA [Medicines and Healthcare products Regulatory Agency] in the UK [United Kingdom], and sustainability-related legislation passed by national governments or the European Union (EU).

There has been a tightening of regulatory/legislative changes in both areas—from medicines regulators and governmental bodies—a few examples include [the following].

 We observe a tightening of requirements in the environmental space: environmental risk assessments (ERAs) have been an integral part of marketing authorizations by EMA for a long time—an ERA is required for all new marketing authorization applications for medicinal products. An ERA does not constitute a criterion for refusal of a marketing authorization, but EMA can require specific arrangements to limit a drug’s environmental impact (1). While this requirement was introduced in 2006, a more recent revision of the guideline in 2018 has led to a tightening in some areas (e.g., inclusion of medicinal products previously exempted; efforts to avoid unnecessary repetition of animal studies; review of monitoring requirements, and so on) (2).

Other guidelines relate to ‘social’ aspects of ESG [environmental, social, and government], for example to ensure drug quality and safety or to incentivise the development of medications for rare diseases. A key example is the pharmacovigilance legislation which defines the monitoring requirements for marketed drugs to ensure drug quality and safety, a critical consideration under the ‘social’ dimension of ESG. This was introduced in its current form in 2012 and had a significant impact on strengthening patient protection.

 In recent years there has been increasing pressure both nationally and at the European level in relation to sustainability, both within the pharmaceutical industry and across sectors. For example, Germany introduced its Supply Chain Due Diligence Act in 2021 (3), which seeks to ensure that human rights and environmental standards are met across the entire global pharma supply chain, from the extraction of raw materials to the delivery of medicines to customers. The requirements are internationally compatible and are based on the ‘due diligence standard’ of the UN [United Nations] guiding principles. The requirements will apply from 2023 for companies with at least 3000 employees in Germany and from 2024 for companies with at least 1000 employees in Germany.

In the UK, as part of a broad UK Government commitment to net zero, the NHS [National Health Service] has published ambitious plans to reach net zero by 2045 (4). These plans include profound changes to its procurement process with a view to limit scope 3 emissions, including those coming from pharma and medtech vendors.

At the EU level, we observe a tightening of ESG-related reporting requirements. At present, non-financial reporting is regulated by the EU NFRD (non-financial reporting directive; first introduced in 2014), a sustainability reporting legislation to which the largest EU-based companies are currently held and which requires companies to disclose ESG impact information in their non-financial statements (5). The NFRD is expected to be replaced by the more widely applicable and more stringent Corporate Sustainability Reporting Framework (CSRF). The CSRF will widen the scope of companies included (from approximately 12,000 to 49,000), notably including large non-EU-based companies with subsidiary activity in the bloc. It will also expand reporting requirements, now mandating inclusion of further information such as supply chain emissions, and the entity’s wider impact on society and the environment (6).

More broadly, the Pharmaceutical Strategy for Europe, defined by the European Commission (EC) and adopted in November 2020, aims to create a regulatory framework to support the availability of medicines in Europe (7). This strategy goes beyond ESG requirements and aims at ‘future-proofing’ the pharmaceutical sector in Europe in the face of global challenges (e.g., supply chain concerns and pandemic preparedness). However, a few topics are directly touching on ESG priorities (e.g., ensuring access to affordable medicines, including in rare diseases, tackling antimicrobial resistance, and environmental sustainability of drug manufacturing). As part of this strategy, the EC plans to revise general legislation on medicines in a few key areas (e.g., legislation on medicines for children and rare diseases to address unmet needs; legislation to improve access to generics and biosimilars).

 What are the current regulatory goals for sustainability in pharma for Europe? Are these goals achievable in your opinion?

 Considering varying regulatory goals between countries and the variety of regulations that are applicable across sectors, we are focusing our answer on pharma‑specific Europe-wide regulatory goals; this is best summarized in the European Commission’s Pharmaceutical Strategy for Europe (7).

As stated above, not all aspects of the Pharmaceutical Strategy for Europe are ESG-related; however, a few are directly linked to ESG and are expected to lead to legislative changes, including: legislation to improve accessibility of medicines for children and rare diseases; review of legislation to introduce measures to restrict and optimise the use of antimicrobial medicines; enforcement of EU competition rules to counter some pharma activities hindering the entry or expansion of affordable medicines (generics/biosimilars); reviewing the provisions on environmental risk assessments to be submitted as part of a marketing authorization application; reviewing the manufacturing and supply provisions to improve transparency and oversight of the supply chain and clarify responsibilities to ensure overall environmental sustainability and safeguard the quality of medicines.

These goals build on existing legislation and industry practices; this is particularly the case for the incentivisation of R&D on rare disease, environmental risk assessments and the expansion of affordable medication. Further improvements in these areas are achievable, but specific targets have yet to be defined.

In a broader sense, we believe that there is sufficient interest from a wide set of stakeholders, including patients, investors, governments, and staff, in the reduction of carbon emissions. The goal of reducing emissions seems achievable, the bigger question is by when.

 What should pharma companies be doing now to meet these regulatory goals? What might the outcome be if these goals are not met?

 Given the increasing stringency of regulatory requirements, paired with growing pressure from stakeholder groups such as shareholders, customers, and the general public, pharma companies need to formulate an ESG strategy which prioritizes the areas that are most material to their stakeholders. Careful prioritization will be important given the volume and diversity of ESG demands. In this prioritization, regulatory requirements will of

We would, however, stress that fulfilling regulatory requirements is not enough—beyond these, pharma companies have to comply with increasingly stringent demands by their customers. Fulfilling these will become a table stake to be able to compete.

One example is the NHS’ Net Zero roadmap with the goal to reach net zero for all emissions across scopes, including from the supply chain, by 2045 (4). This will require all suppliers to the NHS to formulate plans to reduce carbon emissions by 2024, to publicly report targets for emissions reductions by 2027, and to demonstrate progress in achieving these targets by 2030. Failing to do so will disqualify them from selling into the NHS.

The introduction of ethical considerations into pharmaceutical supply contracts by statutory health insurance funds in Germany is another example. Last year, Germany’s largest statutory health insurance fund, the AOK, launched a tender for the supply of five antibiotics. This tender included a number of ESG conditions, including protection of workers’ rights and environmental standards. Unlike in previous tenders, the principal criterion was not price: companies that had invested in higher environmental standards had a higher chance to win the contracts.

 Has there been an overriding sense that pharma companies within Europe are doing enough or does more need to be done?

 Pharma companies are increasingly aware of the importance of setting and working towards sustainability targets. Whilst many have already incorporated ESG standards and criteria across their value chain (R&D, manufacturing, supply chain), more can be done with regards to setting targets and reporting on individual progress.

L.E.K. conducted a survey of circa 50 pharma companies this year [2022] which shows a clear divergence in ESG maturity between the largest pharma companies (revenues of >US$10 billion [>€9.5 billion]) and the smallest ones (revenues of up to US$500 million [€471 million]). While all reported that they are in the process of defining policies to address ESG concerns (measured across a set of 42 ESG metrics), Big Pharma was most advanced in implementing these policies. Our survey showed that the difference in maturity was particularly pronounced on setting environmental standards for suppliers, water resource use, energy efficiency, and drug availability in low and middle‑income countries.

As an outcome of the recent COP27 in Egypt, seven global pharma companies (as part of the SMI Health Systems Task Force) have come together to commit to reduce GHG [greenhouse gas] emissions and accelerate the transition to net zero healthcare. Although this represents a minority of global players, it is an indication of the future as the industry looks to take greater ownership of its sustainability agenda and work with the public sector to achieve wider sustainability and decarbonization goals.

 How does Europe match up to the rest of the world in terms of sustainability in pharma? Are there any lessons to be learned, either by Europe from other regions or vice versa perhaps?

 Europe has been a leader with respect to widespread legislation requiring the disclosure of climate-related risks and emissions irrespective of industry. The CSRD looks to extend the mandate of disclosure from circa 11,000 EU companies (in the NFRD) to circa 50,000 from 2024 and to widen the scope of reporting requirements to include scope 3 emissions. This momentum has also seen the United States Securities and Exchange Commission table a new proposal which would bring US climate-related disclosure in line with European requirements (8).

In addition, the inclusion of ESG‑related criteria as common practice in the payer decision-making process across the EU5 (France, Germany, Italy, Spain, and the UK) is something which many other European states are reviewing if not already implementing (e.g., recent decision by the Nordic states) and is a strong driver of momentum for the wider sustainability agenda. Pharma companies are likely to increase their investment in environmental standards and policies to be able to continue competing for European tenders.

Guideline on the Environmental Risk Assessment of Medicinal Products for Human Use

 15 Nov. 2018.
2. EMA. EMA/CHMP/SWP/65429/2016. 

Concept Paper on the Revision of the ‘Guideline on the Environmental Risk Assessment of Medicinal Products for Human Use’ (EMEA/CHMP/SWP/4447/00 corr 2)

 28 April 2016.
3. BMWK. Lieferkettensorgfaltspflichtengesetz. 

BMWK.de/Redaktion/DE/Gesetze/Wirtschaft/lieferkettensorgfaltspflichtengesetz

. 3 March 2021 (accessed 15 Dec. 2022).
4. NHS England. Delivering a Net Zero NHS. 

England.nhs.uk/greenernhs/a-net-zero-nhs/

Directive 2014/95/EU of the European Parliament and of the Council of 22 October 2014 Amending Directive 2013/34/EU as Regards Disclosure of Non-Financial and Diversity Information by Certain Large Undertakings and Groups

 (October 2014).
6. BDO. EU Sustainability Reporting—Comparison of Draft CSRD to NFRD Requirements. 

, 24 May 2022 (accessed 15 Dec. 2022).
7. EC. Pharmaceutical Strategy for Europe; November 2020.
8. Allen & Overy. U.S. Securities and Exchange Commission Proposes Extensive Climate-Related Disclosure Regime Covering All SEC Registrants. 

. 23 March 2022 (accessed 15 Dec. 2022).


Vol. 35, No. 1
January 2023
Pages: 31–33

When referring to this article, please cite it as F. Thomas, “Setting Goals for Sustainability,” 

In light of increasingly stringent sustainability requirements, bio/pharma companies need to make sure they formulate effective ESG strategies.

Setting Goals for Sustainability

For the past 10 years, Clarivate has published its 

report annually, highlighting therapies that are deemed to have blockbuster potential (i.e., achieving sales of more than US$1 billion [€931 million] within five years). However, as patient populations being targeted by industry are becoming smaller and disease areas more niche, the methodology employed by Clarivate to create its ‘watch list’ has required some adjustment. Therefore, for the 2023 report, Clarivate has expanded its methodology to also recognize therapies that have the potential to transform treatment paradigms, even if those treatments are forecasted to fall short of the annual sales required to classify them as blockbusters (1).

 report, published on 10 Jan. 2023, has produced a list of 15 therapies—more than double that of 2022—that are, for the most part, treatments targeted to a specific biomarker (1). The drugs that have been selected for 2023 as ones to watch are: bimekizumab for plaque psoriasis; capivasertib for breast cancer; daprodustat for chronic kidney disease-related anaemia; deucravacitinib for plaque psoriasis; foscarbidopa/foslevodopa for Parkinson’s disease; lecanemab for Alzheimer’s disease; donanemab for Alzheimer’s disease; lenacapavir for HIV; mirikizumab for Crohn’s disease; pegcetacoplan for Paroxysmal nocturnal haemoglobinuria and geographic atrophy; ritlecitinib for alopecia; sparsentan for treat rare kidney disorders; teclistamab for multiple myeloma; teplizumab for Type 1 diabetes mellitus; and valoctocogene roxaparvovec for haemophilia A. 

Additionally, in the report, the Clarivate analysts highlight their trends to watch in 2023. For the analysts, some key trends include the US patent expiration for HUMIRA (AbbVie)—with the expectation that there will be an influx of biosimilars to the drug launching in the United States throughout the year—and the growing drug market in mainland China—where oncology drugs comprise the majority of the potential blockbusters, driven by the country’s latest healthcare reforms (1).

To learn more about upcoming innovations, read this month’s cover story, ‘

,’ which provides an overview of European-specific bio/pharma industry trends, as highlighted by several industry experts.

When referring to this article, please cite it as F. Thomas, “Getting Personal,” 

bimekizumab (BIMZELX) from UCB, developed to treat plaque psoriasis;

capivasertib (AZD5363) from AstraZeneca, which is a treatment for breast cancer;

daprodustat (GSK1278863/Duvroq) from GSK for the treatment of chronic kidney disease-related anaemia;

deucravacitinib (SOTYKTU/BMS-986165) developed by Bristol Myers Squibb to treat plaque psoriasis;

foscarbidopa/foslevodopa (ABBV-951) from AbbVie to treat Parkinson’s disease;

lecanemab (BAN2401) developed by Eisai and Biogen for Alzheimer’s disease treatment;

donanemab (LY-3002813) from Eli Lilly, which has also been developed to treat Alzheimer’s disease;

lenacapavir (Sunlenca/GS-6207) from Gilead Sciences, developed to treat HIV;

mirikizumab (LY-3074828) developed by Eli Lilly to treat Crohn’s disease;

pegcetacoplan (EMPAVELI/ASPAVELI/APL-2) from Apellis Pharmaceuticals for the treatment of Paroxysmal nocturnal haemoglobinuria and geographic atrophy;

ritlecitinib (PF-06651600) from Pfizer for the treatment of alopecia;

sparsentan developed by Travere Therapeutics to treat rare kidney disorders;

teclistamab (TECVAYLI/JNJ-64007957) from Janssen Pharmaceutical Companies of Johnson & Johnson for multiple myeloma;

teplizumab (TZIELD/PRV-031) from Provention Bio for the treatment of Type 1 diabetes mellitus;

valoctocogene roxaparvovec (ROCTAVIAN/BMN-270) developed by BioMarin Pharmaceutical for the treatment of haemophilia A.

The latest report from Clarivate has been published, highlighting 15 potential blockbusters to watch out for in 2023, the majority of which are personalized medicines.