Behind the Headlines Episode 27

Ask the Expert

Small Molecules, APIs, and Excipients—Trends, Challenges, and Opportunities

Drug Digest September 2025

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Enhancing Bioanalysis and Drug Development with Advanced Tools and Technologies

J.P. Morgan Report Lists Biologics, Obesity, China

Top Trends Reshaping Pharma R&D

Don Henry is director of the Office of Program and Regulatory Operations in FDA’s Center for Drug Evaluation and Research’s Office of Pharmaceutical Quality.

In 1992, FDA’s Center for Drug Evaluation and Research (CDER) was struggling. Due to a lack of capacity and resources, new drug application reviews took longer than two years to complete, and more than 70% of medicines were first approved outside of the United States (1). Driven by the desire to better serve the US public, CDER made drastic changes to bolster its new drugs program. Within 10 years, CDER cut new drug approval timelines in half (2). Now, FDA approves the average new drug in well under one year and 75% of novel drugs before any other country (3). What fueled this dramatic turnaround?

Every five years, FDA and industry negotiate agreements on user fees to help fund FDA’s mission of protecting and promoting public health. FDA collects user fees from companies that produce certain products, including human drugs that require a marketing or licensing application, to generate funding for regulatory activities. These programs involve commitments made by FDA, such as predictable timelines to evaluate applications and release guidance on important topics to industry. FDA doesn’t operate on user fees alone; federal law authorizes FDA to collect user fees to supplement the annual funding Congress provides. User fees fund 65% of human drugs regulatory activities, which account for one-third of FDA’s total budget (4). Importantly, FDA decisions, such as whether to approve an application, do not depend on the ability to collect user fees. Since 1992, the mixture of public and user fee funding has enabled the timely availability of drugs for US patients without compromising scientific integrity or public health. In September 2022, President Biden reauthorized certain user fee programs through 2027 including the Prescription Drug User Fee Act (PDUFA VII), Generic Drug User Fee Amendments (GDUFA III), and Biosimilar User Fee Amendments (BsUFA III).

Over the years, user fees have delivered clear value to public health. Owing to the accomplishments under PDUFA I, the first user fee program authorized in 1992, the availability of new drugs increased. Thus, demand for more affordable generic drugs also rose. GDUFA I, enacted in 2012, enabled FDA to bring greater predictability to generic-drug reviews and promote timelier generic-drug availability for patients. At the start of GDUFA I in 2012, FDA was staring at a backlog of more than 4500 pending generic-drug submissions. FDA was able to take first action on greater than 90% of these backlog applications, while acting on more than 90% of new applications, before the end of GDUFA I (5). User fees have similarly expanded the availability of biosimilars. Before the enactment of BsUFA in 2012, there were approved biosimilars in Europe but none in the US. Now there are more than 40 approved biosimilar products for US patients. User fee programs have helped provide the resources and scientific expertise to improve the availability of high-quality drugs.

If one were to consider the FDA’s human drugs program as a business, because CDER does not make or sell a physical product, one might reasonably conclude that one of CDER’s core products is communication. Consider the myriad ways in which CDER communicates: industry meetings, application correspondence, public engagement, policy documents, scientific papers, public workshops, listening sessions, and conferences. A retrospective look at the now 13 authorizations of the above user fee programs supports this notion; many of the programs’ elements focused on high-quality communications. In examining the developments most relevant to manufacturing and pharmaceutical quality in the recent user fee authorizations, it is no surprise that many continue to focus on communication.

Overall, GDUFA III emphasizes the importance of high-quality communication to drive the submission of high-quality applications and the availability of high-quality drug products. One of the aims of GDUFA III is to enable generic-drug approvals in fewer review cycles. In part, this requires guidance from FDA on ways to maximize the efficiency and utility of the first assessment cycle. Within days of reauthorization, CDER released two quality-related draft guidance documents that were GDUFA III commitments. The first relates to facility readiness and goal date decisions and provides information to applicants on how FDA assigns goal dates based on a manufacturing facility’s readiness for inspection. Applications citing facilities that are not ready for inspection can slow an application’s approval, so CDER will now defer substantive application assessment if a facility is not ready for inspection at the time of submission. While most facilities are found to be compliant with current good manufacturing practice (CGMP) requirements, noncompliant facilities can impede the approval of otherwise worthy applications. Under GDUFA III, certain noncompliant facilities cited in generic-drug applications may be eligible to meet with FDA after receiving a Warning Letter to obtain preliminary feedback regarding corrective actions prior to a reinspection (6). Transparent communication regarding facilities will encourage effective steps toward enabling a drug approval.

Facilities are not the only element of an application that can slow or impede generic drug approvals. CDER also needs to find drug master files (DMFs) cited in drug product applications to be adequate in order to approve the application. CDER’s second draft guidance addresses the early assessment of DMFs, up to six months prior to the submission of certain abbreviated new drug applications (ANDAs) or supplements that will reference the DMF. Eligible ANDAs include, for example, drug products related to a drug shortage or a public health emergency (7). This earlier engagement on the assessment of DMFs can increase the likelihood that a DMF will be found adequate and thus that the associated ANDA will be found approvable. Of course, CDER will not find all ANDAs approvable. In these cases, GDUFA also expands the scope of controlled correspondence. After receipt of a complete response letter stating the reasons why a drug application was not approved, generic-drug manufacturers can now submit controlled correspondence to seek regulatory and scientific feedback and clarify deficiencies identified for the ANDA (8).

In general, improved communication improves generic-drug development. CDER’s Pre-ANDA program, first introduced in GDUFA II, assists applicants and prospective applicants developing complex generic products (9). Although GDUFA II set standards for communication through the Pre-ANDA program, GDUFA III enhances the dialogue between CDER and potential ANDA applicants (10). A critical element of the Pre-ANDA program is the release of Product-Specific Guidances (PSGs) that provide the agency’s current thinking and expectations on how to develop drug products that are therapeutically equivalent to reference listed drugs. This transparency can be especially beneficial for stakeholders eyeing complex generic drugs that are difficult to develop. GDUFA III establishes goal timelines for releasing PSGs for complex innovator drug products to speed generic-drug development. For example, a GDUFA III goal is to issue PSGs for 75% of complex products within three years of the innovator product approval date. Under GDUFA III, when a new or revised PSG is published, a potential applicant may now request a teleconference to obtain CDER feedback on the potential impact of the PSG on its development program (11). These additional Pre-ANDA communications promote a more efficient ANDA review process for complex generic-drug products, and aim to reduce the number of review cycles and facilitate approvals.

User fees continue to play an important role in expediting the development and approval of new drugs. With the PDUFA reauthorization, industry now has additional tools to overcome chemistry, manufacturing, and controls (CMC) challenges in product development. Improved communication is also a hallmark of PDUFA VII, which establishes two new types of meetings to expand communication and feedback during drug development. In addition to the traditional development meetings (Type A, B, and C), there is now a Type D meeting for quick discussion on a narrow set of issues. Another new meeting option is Initial Targeted Engagement for Regulatory Advice on CBER/CDER ProducTs (INTERACT) to facilitate successful investigational new drug applications. Early input from FDA to a sponsor, regarding novel and unique challenges in the development phase, might prevent delayed entry into the clinic (12).

In October 2022, FDA announced a CMC Development and Readiness Pilot program to further expedite the development of products that address unmet medical needs. Products with accelerated clinical development timelines often face CMC development and CGMP compliance challenges. Under the pilot, FDA can provide product-specific CMC advice during product development by including an option for two additional CMC-focused meetings (Type B) and additional CMC-focused discussions based on readiness and defined CMC milestones. For those sponsors who request to participate in the pilot, FDA will evaluate the anticipated clinical benefits of facilitating earlier access, the novelty of the product, the complexity of the manufacturing process, the sponsor’s overall manufacturing experience, and the sponsor’s experience with the product.

PDUFA VII also aims to advance the implementation of innovative manufacturing technologies. Over the course of PDUFA VII, FDA will conduct a workshop that includes industry and public feedback and publish a draft strategy document for public comment on innovative manufacturing technologies. This document will outline the strategy to facilitate the implementation of innovative manufacturing technologies, including addressing barriers to their adoption (13). These engagement opportunities will help FDA encourage the submission of products made using innovative manufacturing technologies to assure process and product quality.

Over the past decade, BsUFA has enabled the approval of the first biosimilars in the US, including four interchangeable biosimilars that can be more easily substituted for innovator products. Biosimilars provide more treatment options for patients and improve the availability of biological products. As science often drives biosimilar product development, in addition to sharing several goals with PDUFA VII, BsUFA III establishes a regulatory science pilot program to improve the efficiency of developing biosimilar and interchangeable products. Five projects have already been funded to help advance these goals (14). Three projects focus on improving biosimilar product development by addressing aspects of the similarity assessment. These assessments might be aided by advanced or standardized analytical methods and improved understanding of the impact of the product formulation and container. The two other projects advance the development of interchangeable products by using 

 methods, rather than switching studies, to predict immunogenicity risks that can arise when a patient switches products. The overall objective of the BsUFA regulatory science pilot program is to improve the availability of biological treatment options for patients.

It turned out that the reauthorizations of GDUFA, PDUFA, and BsUFA were just a start. Many other provisions were later included as reforms in the Consolidated Appropriations Act 2023 under the Food and Drug Omnibus Reform Act of 2022 (FDORA). Many of these provisions also relate to communication including, for example, issuing guidance and holding a public meeting related to the designation of advanced manufacturing technologies (15). A theme seems clear: high-quality communication is an enabler of CDER’s approval of high-quality drug products. This is why FDA strives to engage with applicants and manufacturers developing products and technologies, provide clear expectations and feedback, and minimize deficiencies in the application assessment process. User fees provide the resources and engagement opportunities to do so and expand the availability of high-quality medicines to patients. Although the implementation of the recently reauthorized user fee commitments and FDORA provisions is still in progress, they build on a foundation of successful progenitor programs. User fee programs have been a significant asset to US healthcare and have undoubtedly increased the availability of safe, effective, and high-quality medicines for the American public.

Food and Drug Administration: Effect of User Fees on Drug Approval Times, Withdrawals, and Other Agency Activities

https://phrma.org/policy-issues/Research-and-Development/PDUFA

5. FDA. Implementation of the Generic Drug User Fee Amendments of 2012 (GDUFA). (2016) (testimony of Janet Woodcock). 

6. FDA. GDUFA III Changes for Facilities, 

7. FDA. FDA Revises Generic Drug Application Prioritization Policy to Ensure Fairness to Applicants, Efficiently Allocate Limited Agency Resources, and Protect the Public Health. 

Guidance for Industry, Post-Complete Response Letter Clarification

Teleconferences Between FDA and ANDA Applicants Under GDUFA

GDUFA Reauthorization Performance Goals and Program Enhancements Fiscal Years 2023-2027 

 Product-Specific Guidances for Generic Drug Development 

SOPP 8101.1: Regulatory Meetings with Sponsors and Applicants for

Drugs and Biological Products, Version 11 

PDUFA Reauthorization Performance Goals and Procedures Fiscal Years 2023 through 2027 

14. FDA. BsUFA Regulatory Research Pilot Program New Research Awards, 

15. H.R.2617 - 117th Congress (2021-2022): Consolidated Appropriations Ac

When referring to this article, please cite it as Henry, D. High-Quality Communication Enables High-Quality Drug Products. 

Articles

User fee programs have improved FDA’s approval timeline for important therapies.

High-Quality Communication Enables High-Quality Drug Products

Ken Boda is dissolution product specialist at Agilent Technologies.

Dissolution is a crucial aspect of drug product development and characterization. It is the only pharmaceutical test which is capable of determining how a formulation will perform in a patient. Over the years, the science of dissolution has needed to adapt to advances in pharmaceuticals.
At the beginning of dissolution, medicines were primarily immediate release drugs where a United States Pharmacopeia (USP) Apparatus 1 (baskets) or 2 (paddles) worked quite well at assessing how a product would perform in vivo.

As pharmaceuticals have advanced, a wide variety of new formulations have been developed, which all need dissolution testing. Dissolution evolved to accommodate dosage forms that required extended-release times, multiple
media changes, and more. More recently, drug-device combination products
further challenged dissolution testing by needing to test extremely low volumes for several days or weeks for implants. Now, making the APIs smaller into nanoparticles is the new challenge for dissolution testing.

When referring to this article, please cite it as Boda, K. The Next Challenge in Dissolution–Nanoparticles. 

Nanoparticles are becoming more prevalent to overcome low solubility and poor permeability.

The Next Challenge in Dissolution–Nanoparticles

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

Novel and emerging biotherapeutics are commanding a larger portion of the development pipeline at an inflated rate. As drug companies focus greater efforts on these complex therapies, regulatory authorities have been working on various guidelines to ensure these drugs are manufactured to a high level of quality with minimum risks. Focusing on good manufacturing practices (GMPs) for emerging therapies across the United States and the European Union (EU) in particular, 

 spoke with Elena Meurer, principal consultant at Biopharma Excellence, to learn more about current regulatory expectations, the evolution of guidelines, and potential regional variances.

 Could you provide an overview of current GMP expectations for emerging therapies?

 Both FDA and the European Medicines Agency (EMA) have published regulatory guidelines related to the implementation of GMP across the different clinical phases (1,2). Many emerging therapies fall under the definition of advanced therapeutic medicinal products (ATMPs) in the EU or cell and gene therapies in the US. Only EMA has published specific GMP guidance that is applicable to the manufacture of ATMPs.

When assessing the required application of GMP in clinical phases, there are many similarities between the EU and US GMP requirements in that they both focus on the identification and assessment of the risks to the quality of an investigational phase medicinal product. The main difference between the EMA and FDA approaches is the recognition by EMA that ATMPs require explicit GMP guidelines that take the specifics of this product class into consideration, and places a heavy emphasis on a risk-based approach for the broad application of GMP across the product lifecycle (2). It is important to note that not all emerging therapies are classified as ATMPs. Nevertheless, as with ATMPs, such novel therapeutics may also require specific manufacturing solutions that should be addressed case by case in a risked-based manner.

The vast majority of emerging therapies are developed as sterile drugs and, due to the heat sensitivity of many of these therapies, final sterilization is not feasible. Therapeutics in this class are usually sterile filtered (unless they are cell-based therapies and this is not possible) and are manufactured through aseptic processing using modern barrier technology including single-use fluid pathways and isolators, for instance.

Early clinical research is likely to be more relevant for the discussion about emerging therapies. While quite a few cell and gene therapies have moved into later clinical phases and beyond, there are new examples of emerging therapeutics such as extracellular vesicles, peptide-based vaccines, complex molecules produced by chemical synthesis, or approaches using combinations of different technologies in the development/research phases.

For early clinical phases, patient safety is a primary focus. For many emerging therapies that are sterile, fully validated aseptic manufacturing processes are required to support clinical supply, even for Phase I. There is more flexibility in areas that do not have a direct impact on patient safety such as QC [quality control] method validation, where verification may be sufficient but, at the outset, a phase-appropriate GMP assessment is required—to determine the areas where full GMP is required to ensure patient safety, and balance these areas with others that may require less rigor for the clinical program. This approach is valid for both regulatory regions—EU and the US—but in practice expectations can differ depending on the inspector and their knowledge of the product. This can be one benefit of the expedited pathways available from FDA and EMA which include built-in scientific meetings for exchanges of information between inspectors and clinical researchers—long before an MA/IND [marketing authorization/investigational new drug application] is granted and an inspection is scheduled.

 How has the guidance for GMPs for emerging therapies evolved over recent years?

 Over recent years, the landscape for the regulation of GMP has changed in response to innovation and the broader range of therapy types being developed. Due to the huge variety of platforms and technologies, a ‘one size fits all’ approach is no longer practical nor feasible. With this change, the emphasis is being placed on the identification, assessment and control of risk. This has been a major focus in the revision of key guidance documents such as the 

 Volume 4 Annex 1 ‘Manufacture of Sterile Products’ and the recent revision of ICH [International Council for Harmonisation] Q9 on quality risk management (QRM) (3,4). Each revised guidance document includes a much more focused emphasis on managing the risk to product quality to safeguard patients.

The introduction of the European guidelines on GMP specific to ATMPs demonstrates a recognition of the difficulty in legislating for ATMPs, and of the important role QRM plays in the future regulation of all emerging therapies (2).

 Are any major changes to GMP guidance for emerging therapies expected in the near future?

 The GMP for ATMP guidance published for the EU was a good start, in recognizing that GMP manufacturing of innovative drugs requires more flexible guidance to account for all different modalities. However, not all emerging therapies are covered by the ATMP guideline. One good example is personalized cancer vaccines consisting of peptide-based neoepitopes. Such therapies do not fall under the ATMP definition, yet share many common features—such as manufacturing and testing challenges imposed by their small batch sizes. Most importantly, the composition of each batch of such a personalized therapeutic differs, which requires a special approach (e.g., to their validation and stability studies).

Another important development is the increased use of prediction programs using artificial intelligence in designing personalized therapeutics. These emerging applications should drive adaptations of existing GMP regulations to further develop approaches for algorithm validation in a GMP environment, for example.

There are also more subtle changes that are already occurring such as the widening of the scope of Annex 1 in terms of applicable territories and manufacturing platforms. This further highlights the acceptance, particularly between the US and EU, that a more common approach is needed for the regulation of GMP for all product types, not just emerging therapies.

It is also evident, based on the focus on QRM in the industry, that this will be the driver for future GMP regulation—rather than relying on unilateral instructions for an industry that is now highly diverse.

 Are there specific differences between the GMP guidance for emerging therapies in the US versus Europe and other parts of the world?

 There are no specific GMP regulations for emerging therapies in the US; this is a gap currently. The GMP applied to US emerging therapies is interpreted from existing regulations, and the US is now placing more focus on the application of QRM for emerging therapies that have unique or unusual characteristics that impact GMP. In the EU, there is an existing document (2), which although set apart from the existing GMP regulations contained in EU GMP Volume 4, is largely an amalgamation of existing documents, in addition to references relating to application of QRM where black and white guidance is impossible or unavailable.

The situation in other territories is very similar, where there is a recognition that emerging therapies can be unique in terms of the practical application of GMP. The US and EU are leading the way in recognizing the unique challenges posed by emerging therapies, and the standards that need to be applied during their manufacture.

However, it should be noted that The Pharmaceutical Inspection Convention Scheme (PIC/S) has adopted the relevant EU guidance documents including the guidance entitled ‘Manufacture of advanced therapy medicinal products for human use’ which is denoted as Annex 2A and is equivalent to the standalone 

 guidance (5). This adoption brings these regulatory expectations to a large cohort of global regulatory authorities. With the availability of this guidance across a large part of the global pharmaceutical industry, the main difference will be in the local application and interpretation of these industry standards.

 Will there be greater harmonization between regions on GMP guidance for emerging therapies in the future in your opinion?

 The vast majority of emerging therapies address very specific patient groups that require global recruitment (e.g., rare diseases) or unmet medical need which is of high interest for all regulatory regions. Thus, harmonization in the GMP guidance is of the utmost importance and should be driven by the therapeutic needs, as it would significantly simplify clinical manufacturing and supply in addition to safeguarding patients and ensuring a global standard of care for equivalent patients in different countries. The agencies of major regulatory regions are in regular contact, and must be aware of these emerging needs.

Several actions are needed to progress the regulation for emerging therapies, such as the need for scope expansion for mutual recognition agreements between the EU and several other countries globally to include ATMPs and blood products. The adoption of Annex 1 by FDA and PIC/S shows the direction of travel in terms of harmonization, and is a positive step in ensuring that future regulation is likely to be global rather than local. This promises to benefit patients in all countries, while reducing the regulatory burden of trying to satisfy a myriad of differing expectations when trying to get an emerging therapy to patients.

Current Good Manufacturing Practice for Phase 1 Investigational Drugs

. Guidance for Industry, July 2008.
2. EC. 

Guidelines on Good Manufacturing Practice Specific to Advanced Therapy Medicinal Products.

Manufacture of Sterile Medicinal Products

. Final Version, January 2023.
5. PIC/S. 

Annex 2A Manufacture of Advanced Therapy Medicinal Products for Human Use

Felicity Thomas is the European/senior editor for Pharm Tech Group.

When referring to this article, please cite it as Thomas, F. Optimizing the Manufacture of Emerging Therapies. 

Guidance for GMP manufacture of emerging therapies has evolved to accommodate innovation and the broader spectrum of products in development, but greater harmonization is still needed.

Optimizing the Manufacture of Emerging Therapies

Cynthia A. Challener is a contributing editor to Pharmaceutical Technology.

Continuous manufacturing has the potential to offer benefits in terms of reduced costs, footprint, raw material consumption, and byproduct and emission generation combined with increased process consistency and product quality. Regulatory submission timelines can also be advanced by more than 12 months and approval times by three months compared to products generated via batch manufacturing (1). Not surprisingly, the US Food and Drug Administration (FDA) encourages the development of continuous processes, and these processes are slowly becoming more prevalent in both small-molecule and biologics manufacturing. It is expected, in fact, that in the near future continuous operations will be the norm rather than the exception, according to Hibreniguss Terefe, director of research and development at Catalent. As such, outsourcing providers that develop continuous manufacturing expertise and leverage this technology can establish a differentiating competitive advantage.

Editor's Note: This article was published in 

Hot-melt extrusion (HME) by its nature is a continuous process, and its integration with other continuous manufacturing operations has the potential as an amorphous solid dispersion (ASD) solution to offer more benefits than just enhanced solubility and bioavailability for poorly soluble APIs. “Given that HME is one of the best tools for enhancing solubility, linking HME processes effectively with other unit operations such as tableting/capsule filling will reduce the number of unit operations, ease scale-up to commercial production, and ultimately help patients realize earlier access to products with positive economic impacts for sponsors as well,” states Purushottam Singnurkar, vice-president and head of formulation development at Syngene International Limited.

Formulating drug substances into ASDs is a widely accepted approach to enhancing the solubility and bioavailability of poorly soluble molecules, according to Terefe. “The conversion of a crystalline API into an amorphous form by dispersing and immobilizing it in a polymeric carrier can be achieved through solvent- or fusion-based technologies. Spray drying is a solvent-based process, while HME is fusion-based technology,” he observes.

In addition to improved solubility, other benefits of using HME are good process control, scalability, and avoidance of solvents, notes Hannes Fuderer, technical operations manager with AbbVie Contract Manufacturing. “Good process control enables balancing of incoming variability into the extrusion process and reduces the variability of the extrudate itself to improve the performance of downstream processing. Good scalability provides the opportunity for faster development and transfer from
lab through pilot to commercial scale and affords flexibility to accommodate volume and extruder-scale changes during life-cycle management,” he explains.

“The ability to practically transfer material inputs continuously and have them transformed into output materials that are continuously removed leads to increased product quality assurance and enhanced product capability and control,” adds Singnurkar. He also comments that the fact that HME is a “green technology” that involves fewer processing steps than spray drying and freeze drying provides further advantages.

HME takes place in a twin-screw extruder, which is, according to Terefe, a continuous, versatile, and highly efficient self-wiping small mass mixer amenable to process analytical technology (PAT). That is why process parameters can be well controlled and HME processes can be readily scaled from R&D to commercial-scale equipment. “Once process parameters are established at a given equipment scale, the batch size is then a function of time and can be easily changed by running the process for a longer or shorter period without needing to change other process parameters,” he notes.

In addition, HME offers a high degree in flexibility and many use cases. “Based on the HME process design, there are many options to integrate an HME process into a fully continuous process or combine it with discontinuous up- and/or downstream processes if required, such as batch blending to feed the extruder or storage of extrudate intermediate prior to further (batch-wise) processing into final drug product,” Fuderer says. HME can also be used for potent compounds and due to the equipment design it typically results in high yields.

An HME unit operation is usually performed as a continuous process through a sequentially assembled equipment system consisting of powder feeder(s), optional liquid pump(s), a twin-screw extruder, a conveyor, and a pelletizer (or a chill roll flaker) working in a harmonized and continuous manner, Terefe notes. The extrudate, however, is typically handled as an intermediate and further processed as a batch, limiting HME to a semi-continuous process.

On the upstream side, the material feed can be a mixed powder blend or individual streams of different ingredients (API and excipients) fed directly. Either approach can be performed continuously, according
to Fuderer.He also notes that, based on material properties or to increase the throughput, the blend can be densified prior to extrusion by a continuous roller compactor or side-stuffer.

The extrudate, meanwhile, can be shaped into nearly any form by the design of the extruder die in combination with several cutting and shaping technologies that are also all continuous processes, Fuderer says. Common shapes are flakes, pellets, and beads depending on the downstream unit operation. “It is possible rather than collecting and buffering the shaped and cooled extrudate in containers prior to further processing, it can be dosed immediately to the next unit operation as the mass flow is still controlled,” he adds.

Integrating the extrusion process with other upstream and downstream semi-continuous unit operations such as continuous blending, milling, tablet pressing (direct compression), and tablet coating would, Terefe says, create a fully end-to-end continuous solid-oral-dosage-form manufacturing process. “Combining a continuous HME process with continuous downstream operations could be envisioned as a viable means for taking full advantage of a continuous process to manufacture solubility- and bioavailability-enhanced products,” he concludes.

One example provided by Singnurkar involves transfer of the hot extrudate directly to dies of suitable sizes for the manufacture of 3D tablets. “Integration eliminates many process steps such as cooling and milling of the extrudate and mixing with excipients, among others,” he says. Any integration of continuous operations without a centralized computer system for control and the implementation of PAT tools for constant process monitoring will, however, reduce the likelihood of success, Singnurkar stresses.

Understanding the critical material attributes (CMAs) of the API and polymer, such as the melting and glass-transition temperatures is also important for developing high-performing HME processes. “The machine settings, including the screw configuration, screw diameter-to-length-ratio, barrel-free volume, distribution of heating and cooling zones, die-orifice size and shape, and the cooling system are equality important. Critical process parameters include the barrel temperature, screw speed, residence time, and throughput,” Singnurkar from Syngene observes.

Controlling material inputs often presents the greatest challenge for HME process optimization, according to both Fuderer and Terefe. “Blend homogeneity, dosing accuracy, and risk of blend segregation during powder conveying are important issues that must be managed,” Fuderer stresses.

Inconsistent and inaccurate feeding of input material into the twin-screw extruder may be caused by poor flow properties of certain raw materials, or very low amounts of certain excipients such as plasticizers and surfactants, Terefe notes. “Feeding all of the components separately at an appropriate ratio of feed rates, as reflected in the formulation composition, would be ideal for a well-harmonized continuous
process, but this assumes that no additional pre-extrusion unit operations are necessary,” he says. Poorly flowing APIs may need to be preblended with a carrier polymer, and often, with additional flow-enhancing excipients, Terefe adds.

Fuderer does point out, though, that one advantage of the HME process is that variances in blend homogeneity and dosing are smoothened to a certain extent, and therefore, variances will not immediately impact extrudate quality.

Blend segregation, however, must be avoided during powder conveying into the extruder, according to Fuderer. This issue is particularly associated with discontinuous batch blending, as it poses higher risk for segregation at bin changes or if the upstream equipment runs empty.

In cases where the poor flow properties of the API or any excipient cannot be overcome by simple blending, Terefe observes that a pre-extrusion granulation step may be required. “Appropriate selection of the powder feeders with suitable feeder screw designs and the choice of liquid pumps for accurate liquid feeding without pulsation can help alleviate many of the input material feeding challenges,” he comments. Introducing a continuous blending process upstream of the extrusion step can also be beneficial for formulations for which simple blending cannot overcome these challenges, Terefe says.

Optimum HME processes generate extrudate with acceptable critical quality attributes (CQAs), such as amorphicity, content uniformity, and purity. Many CQAs impact downstream unit operations, according to Terefe, and thus it is crucial to have online monitoring capabilities (such as near-infrared spectroscopy for evaluating an extrudate’s crystallinity and content uniformity) to track these properties. Fortunately, says Fuderer, if HME processes are properly developed, they are robust and have good process control, and thus typically exhibit only minor variances in physical properties of extrudate intermediate that could impact downstream processing due to HME process performance.

Improper identification of critical material attributes and CQAs for HME processes can, believes Singnurkar, impact the uniformity, degradation profile, and dissolution behaviour of the final drug products. Misidentification of CPPs, meanwhile, can impact the milling of extrudates which can affect compressibility and thus make tabletting difficult. In addition, the API loading and miscibility of the API with the polymeric carrier can also, he says, significantly impact downstream processing.

It is the physical properties of the extrudate that are most important for downstream processing, Fuderer agrees. He adds, however, that they are mainly dependent on the product composition and less dependent on the HME process parameters such as the temperature profile. “As long as the product composition is controlled (e.g., blend homogeneity or ratio of solid and liquid feeds), no impact is expected on downstream processing,” he states.

In addition to product composition, Terefe emphasizes the importance of achieving consistent and controlled material throughput that is harmonized with downstream processes. For example, he points out that the material feed rate into a mill impacts particle size distribution, which may lead to inconsistency in the dissolution of the final product. Inconsistent material input into the continuous direct blending process downstream may also lead to poor blend uniformity, resulting in poor content uniformity of the final tablets.

Here again, the HME process benefits from good monitoring and control technologies. “Twin screw extruders typically have features for controlling and monitoring material throughput consistency, allowing the feed rate, extrusion load, and melt pressure to be continuously measured and monitored in real time,” Terefe explains. Any fluctuation in one of these parameters is a direct indication of material throughput inconsistency and the need to adjust the process.

Ultimately, the successful use of HME to enhance solubility and bioavailability of poorly soluble APIs manufactured in a fully continuous process, as is the case of any continuous manufacturing process, requires a well-engineered process design that can be controlled, Terefe contends. “When developing an HME process, there is a broad choice in polymers, equipment design, and development and scale-up approaches. It is important to involve appropriate subject matter experts at each stage to ensure the highest quality and most robust process for commercial manufacturing,” adds Fuderer.

The polymer and composition as well as the equipment and screw design are typically defined in early development at small extruder scale, according to Fuderer. At this stage, it is very important to understand how the material behaves in the extruder to prevent any issues to product quality or processability during scale-up because the opportunities to make changes to the composition later on are limited, he observes.

The processibility of the input material must be considered, says Terefe. For example, he highlights the need to understand the flow properties of the excipients in order to select appropriate feeders and determine pre-extrusion blending requirements.

“Investigating all possible variables that can impact product quality at the early stage can be challenging, however,” Fuderer comments. “Defining a design space that ensures product quality and processability, but also gives enough flexibility for post-development changes performed during lifecycle management (process and cost improvements, yield increases, supplier notifications for raw materials, etc.) is essential,” he concludes.

A well-planned process design that considers all technical and commercial perspectives and the company’s long-term strategy is fundamental, Terefe agrees. “The type of product(s) to be manufactured, the process flow, and unit operations need to be well understood, and the core equipment, along with necessary accessories, process control for each unit operation, and the CQAs of intermediate output material must be identified,” he states.

An effective means for achieving these goals is to use a quality-by-design (QbD) approach, according to Terefe. “A thorough risk assessment of CMAs and CPPs that impact CQAs for each unit operation must be conducted, along with identifying mitigation and control strategies,” he explains.

In addition, because continuous manufacturing aims to facilitate real-time batch release, a good understanding of each unit operation, both independently, and in combination with all other unit operations working in tandem, is essential, according to Terefe. In addition to PAT and real-time process analytics, he notes that model-based process optimization using relevant output data from sensors and processes is important.

It is also highly recommended, notes Fuderer, to keep process requirements for continuous processing in mind when developing HME processes to ensure that not only the HME process is developed to its optimum, but also that the interfaces to the up- and downstream unit operations guarantee final drug product meeting the desired quality.

Furthermore, well-organized and planned process integration into a computerized system that complies with GMP and good automated manufacturing process requirements needs to be established, as do proper IT structures and supervisory and control systems, Tenefe says. Such a centralized computer system that is integrated with various unit operations and PAT tools and provides real-time quality and process control is, in fact, essential for achieving consistent and optimum continuous HME processes, contends Singnurkar.

1. Mahesh R. An FDA Self-Audit of Continuous Manufacturing for Drug Products. FDA Podcast, 

. 28 June 2022. (Accessed March 30, 2023).

Cynthia A. Challener, PhD, is a contributing editor to 

When referring to this article, please cite it as Challener, C.A. Continuous Hot-Melt Extrusion for Poorly Soluble APIs. 

Process control is essential for using continuous hot-melt extrusion to enhance solubility.

Continuous Hot-Melt Extrusion for Poorly Soluble APIs

FDA released a new draft guidance that provides recommendations aimed at sponsors, investigators, and other stakeholders regarding the implementation of decentralized clinical trials (DCTs) for drugs, biological products, and devices. This specific guidance refers to a DCT as a clinical trial where some or all the trial-related activities occur at locations other than traditional clinical trial sites.

According to the draft guidance document, in a fully decentralized clinical trial, all activities take place at locations other than traditional trial sites. Further, these trial-related activities may take place at the homes of trial participants or in local health care facilities that are convenient for trial participants. In terms of a hybrid DCT, some trial activities involve in-person visits by trial participants to traditional clinical trial sites, while other activities are located at places other than traditional clinical trial sites, like a participants’ homes.

This new guidance provides suggestions that are related to FDA’s requirements for investigations of medicinal products when applied to DCTs and fulfills the requirement set forth in section 3606(a)(1) of the FDORA.

This specific guidance refers to a DCT as a clinical trial where some or all the trial-related activities occur at locations other than traditional clinical trial sites.



FDA Gives Guidance for Decentralized Clinical Trials for Drugs, Devices

LEON (eon-nanodrugs GmbH) announced on April 27, 2023 that the establishment of their own lab facilities at IZB (Start-Up Center for Biotechnology) in Munich has been initiated. The new research and development capacities set the stage for completion of product development for LEON’s manufacturing devices and will be used to showcase the devices and provide process development services to clients using LEON’s equipment.

The product platform at LEON is built on their proprietary, innovative FR-JET technology that enables a huge efficiency increase in the formulation process of active ingredients into nanodrug carriers, like lipid nanoparticles (LNPs). Further, their devices, the NANOme and NANOus, are designed for aseptic processing, GMP-compliance, and quick scale-up. NANOme is intended for small-scale, individual patient and clinical trial-size production, whereas NANOus is a fully automated, aseptic device enabling the LNPencapsulation of APIs from medium- to large-scale with high throughput using process analytical technology.

“We are truly excited about moving into the IZB. As one of the key biotech hubs in Germany, the IZB provides not only lab facilities, but also an unparalleled environment to foster innovation and growth,” said Setu Kasera, PhD, head of Science and Engineering, in a press release. “The local proximity to biotech start-ups, academia, VCs, and Big Pharma creates an ecosystem that facilitates networking in- and outside of your peer group, setting the stage for future cooperations and partnerships. We are looking forward to using our new capacities to complete the development of our devices for the market, while we pursue and build on opportunities for collaborations by providing access to our devices and process development services.”

The new research and development capacities set the stage for completion of product development for LEON’s manufacturing devices and will be used to showcase the devices and provide process development services to clients using LEON’s equipment.

LEON Sets Lab Facilities at IZB in Munich

On April 27, 2023, Sanofi completed its acquisition of Provention Bio, which adds TZIELD (teplizumab-mzwv), a first-in-class therapy in type 1 diabetes treatment, to Sanofi’s core asset portfolio in General Medicines and further drives its strategic shift toward products with a differentiated profile.

“We are excited to finalize our acquisition of Provention Bio, Inc.,” said Olivier Charmeil, executive vice president of General Medicines at Sanofi, in a press release. “This strategic fit for Sanofi lies at the intersection of our growth in immune-mediated diseases and disease-modifying therapies in areas of high unmet need.”

FDA approved TZIELD injection on Nov. 17, 2022 to delay the onset of stage 3 type 1 diabetes in adults and pediatric patients eight years and older who currently have stage 2 type 1 diabetes, according to the press release.

The acquisition was completed through the merger of a wholly owned subsidiary of Sanofi with and into Provention Bio, pursuant to Section 251(h) of the General Corporation Law of the State of Delaware, and Provention Bio continuing as the surviving corporation and becoming an indirect, wholly owned subsidiary of Sanofi.

The acquisition was completed through the merger of a wholly owned subsidiary of Sanofi with and into Provention Bio.

Sanofi Acquires Provention Bio 

Feliza Mirasol is the science editor for 

Returning to the office on the back of a successful INTERPHEX 2023, and it seems the return of in-person conferences has been solidified as the world wakes up after an extended hibernation period of COVID quarantine. Spring is back, not just in the weather, but also in conference-goers’ steps!

INTERPHEX was back in its usual haunt at the Javits Center in New York City, where engineers, manufacturers, c-level executives, and others came together to forge new and nurture already established pharma and biotech relationships. For the 

 team, the Keynote stage was the platform where the editors shed light on specific key trends set to shape the industry moving forward.

Leading the charge, on April 25, 2023, was a session on mRNA Supplier-developer Relationships and Technical Advances, where discussion revolved around the continued progress of mRNA-based therapies, which, thanks to the mRNA vaccines, have been largely optimized for stability, structure, and delivery. The industry is looking to novel delivery methods for these innovative therapies as efforts to ramp up dose-loading capabilities have led to new intellectual property filings. The second session on Tuesday, Cell and Gene Therapy Scale Up and Process Optimization, saw experts exploring issues around the manufacturing of viral vectors, whose complexity requires components not needed in stable, recombinant protein-expressing production systems.

The morning of April 26, 2023, saw the exciting dialogue continue with the Organ on a Chip for Pharmaceutical Development session. Here, experts shared their insights and experiences in the up-and-coming technology of organ-on-a-chip, which is poised at a tipping point in the drug discovery arena as well as in the shift toward personalized medicine. The afternoon session on Wednesday, and close of the keynote sessions for INTERPHEX, focused on Applied Continuous and Modular Manufacturing Innovations, where experts evaluated how the bio/pharma industry is building on the small successes of continuous manufacturing (CM). With new industry guidance on CM (1), there may likely be increased use of CM technologies for a variety of therapeutics, including small molecules, biologics, vaccines, and other modalities.

If you missed out on INTERPHEX, session information and further conference coverage can be found on 

Guidance for Industry, Q13 Continuous Manufacturing of Drug Substances and Drug Products

When referring to this article, please cite it as Mirasol, F. Springing Forward. 

INTERPHEX was back in full swing with Keynote sessions highlighting cutting-edge technologies that are setting the stage for the bio/pharma industry’s future.

Springing Forward

At the time of writing, countries throughout Europe are being brought to their knees through strike action being taken by employees from various sectors who are unhappy about low pay and poor working conditions. Teachers, nurses, doctors, train drivers, pilots, airport staff, and civil servants, to name a few, are holding mass walkouts from their jobs, ensuring that their demands are heard by the relevant authorities.

Over the years, the bio/pharma industry has not been subjected to much industrial action from its workers, particularly not when compared with professions based in the public sector. In fact, when looking back, the most notable disruption to the industry occurred in 2010 when there was a spate of disputes affecting three major pharma companies—AstraZeneca, Sanofi, and Merck—where employees fought back against job cuts and unfavourable benefits (1).

However, this year is proving to be bucking the trend. At the beginning of May 2023, GSK employees staged a series of walkouts that, at the time of writing, were expected to last throughout the month and impact a number of the company’s plants in the United Kingdom. Strike action started at Montrose on 2 May and spread to GSK’s plant in Irvine on 4 May, with the Ware, Barnard Castle, Worthing, and Ulverston facilities following suit at later dates in the month (2).

Indeed, it was only a year ago, in May 2022, that GSK managed to narrowly avoid strike action due to a dispute over pay, when negotiations with the workers’ union, Unite, ended in an improved offer that was accepted (3). This new action by GSK workers in 2023 demonstrates the current financial strain many people are facing in the UK and Europe as a result of the rate of inflation and general cost of living increases. To that point, according to the UK’s Office for National Statistics, when taking inflation into consideration, the real value of regular wages has actually fallen by 2.5% between October and December 2022 alone (4).

Inflation in Europe—although declining slightly from the peak level—is set to remain high for now, and economic growth is spluttering along at a painfully slow pace (5), meaning that the cost of living will not improve for working people in the region for some time. Only time will tell whether the bio/pharma industry will succumb to further industrial action by its workforce or not.

1. Reuters. European Staff Fight Back as Drugmakers Hack Costs. News Release, 17 Aug. 2010.
2. Unite. GSK Strike Wave Across the UK Begins in Montrose. News Release, 1 May 2023.
3. Unite. Strike Off as Unite Secures Pay Lift for GSK Workers. News Release, 23 May 2022.
4. King, S.; Crees, M.; Ball, C.; Gabriadze, M. The Impact of Strikes in the UK: June 2022 to February 2023. 

, Article, 8 March 2023.
5. Kammer, A. Europe’s Knife-Edge Path Toward Beating Inflation Without a Recession. 

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

When referring to this article, please cite it as Thomas, F. On Strike! 

Strike action is impacting numerous sectors across Europe, including the bio/pharma industry.

On Strike!

Jennifer Markarian is a contributing editor for 

Pharmaceutical manufacturers should be familiar with the terms “Smart Factory,” or “Pharma 4.0,” which is the International Society for Pharmaceutical Engineering (ISPE)’s trademarked name for Industry 4.0 in pharmaceutical manufacturing. Pharma 4.0 moves beyond automation and strives to use digital technology, including the Industrial Internet of Things (IIoT) and software tools that mine data from large datasets in the cloud, to increase productivity. These tools can be implemented in pharmaceutical process development and in clinical and commercial manufacturing, and many manufacturers in the bio/pharma industry are using them to aid in digital transformation. Yet, misconceptions and limited knowledge remain a barrier for some because digitalization is a new way of thinking and working.

At its essence, Pharma 4.0 is a paradigm shift, says Gilad Langer, industry practice lead at Tulip Interfaces. He is currently leading an ISPE Pharma 4.0 Community of Practice subgroup that is preparing to publish a Pharma 4.0 best practice guide in 2023. Industry 4.0 equipment—such as a smart sensor—is autonomous (i.e., plug and produce) and collaborative (i.e., communicates with other equipment or with people using the IIoT), explains Langer. “Pharma 4.0 is a concept that, if adopted wholly and effectively, has the promise of an order-of-magnitude productivity increase,” he asserts.

“The connectivity of smart devices changes where, how, and by whom decisions are made in the manufacturing process,” adds Sandra K. Rodriguez, senior industry analyst at life-science consultancy Axendia. “The efficiencies gained by smart manufacturing techniques cannot be achieved using paper-based, paper-on-glass, or manual processes that rely on people. The use of manufacturing execution systems (MES) is a key component in smart manufacturing. People supervise the manufacturing process in the new standard, as opposed to driving it.”

Axendia researched the state of digital transformation in life sciences manufacturing (1) and found that 43% of respondents (representing
pharmaceutical, biotech, and medical device companies) are currently undergoing digital transformation, reports Rodriguez.

Business drivers for digital transformation initiatives include “speed to market, enabling data-driven decisions, enhanced operational excellence, improved regulatory compliance, and addressing sustainability goals,” adds Mark-John Bruwer, senior director of strategic product marketing, pharma, at AspenTech. Digital transformation is being accelerated by the need for more supply chain agility, the increase in remote work, and the tight labor market, he adds. “Pharma companies are increasingly adopting digital tools for continuous process verification (CPV), advanced planning and scheduling, electronic batch records, convergence of information technology (IT) and operational technology (OT) functions, process analytical technology, and predictive maintenance,” says Bruwer. Barriers to using digital tools persist, however, including limited knowledge or skill gaps, he adds.

Moving away from paper-based records and collecting digital data (i.e., digitization) so that it can be used is a crucial early step in digitalization. One of the roadblocks to implementing this shift is that people who are not “digital natives” (generally workers born before 1980) are still most comfortable with paper.

“If a non-digital native is asked a question in an audit, they want to point to data on a piece of paper. A digital native, however, is comfortable with the idea that a picture stored in the cloud and viewed on a device is tangible evidence,” suggests Langer. He says that a picture of a temperature reading or a video of an operator performing a task are examples of digital evidence that can be collected with Tulip’s apps. “We must move beyond a ‘document mindset’. Document-based data—whether on physical paper or a pdf file—can’t be mined the way digital data can,” says Langer.

Langer adds that in Pharma 4.0, all digitalization software will use the cloud, and eventually it will look different from the current MES and enterprise resource planning software. “In the new paradigm, programs will be app-based, intuitive, and democratized so that anyone can use them. All programs will reside in the cloud, and people will use devices in the edge to interact with data in the cloud,” he explains.

This shift is happening, says Bryon Hayes, director of smart manufacturing solutions at Grantek. “Companies are moving from ‘paper on glass’ toward a vertically integrated approach,” Hayes explains. “Many companies see the value of having a cloud-hosted data hub from which they can run analytics or populate dashboards.”

Rodriguez adds that, based on Axendia’s research and interactions with FDA officials, industry executives, and MES software vendors, “we are finally seeing a much-needed shift from paper batch records to implementing MES and electronic batch records (EBR) in support of release/review by exception.” Axendia’s research found that 32% of companies surveyed plan to digitally streamline batch execution and release in the next two years (1).

Automating EBR review is a key benefit of modernizing manufacturing operations, but some companies have held back because of misconceptions regarding FDA’s acceptance of review by exception, says Rodriguez. “In an Axendia ‘Straight from the Source’ webcast [2], Francisco (Cisco) Vicenty, program manager, case for quality at FDA, debunked many industry myths including that the agency requires EBR print outs for official records and the agency requires validation of every feature in MES.”

Another misconception is that cloud storage could raise data integrity concerns not found in on-premise storage methods. To the contrary, says Bruwer, “cloud-based solutions reduce data integrity challenges by having the cloud data repository be the single source of the truth, with global access easily and securely provided to properly authenticated individuals. In addition, cloud service providers have the critical mass to ensure cutting-edge cyber-security technology and best practices are employed, which an IT department at a bio/pharma company or contract development and manufacturing organization may be more challenged to deliver, especially at smaller organizations with smaller budgets. Similarly, the software underpinning the data warehousing solution can more easily be kept current in a centralized cloud environment versus across multiple servers distributed geographically.”

Bruwer reports that survey respondents in an AspenTech study performed in collaboration with FT Longitude (3) listed cloud and software-as-a-service as key initiatives to improve operational agility in the next three to five years. “Pharma and biopharma companies are looking for long-term technology partnerships with key vendors rather than transactional software purchases,” concludes Bruwer.

Bruwer says that a data integrity challenge—in the cloud or in on-premise storage—can arise if data sources are integrated point-to-point, with many bespoke OT-IT connections accruing across sites. “These disparate implementations can become unmanageable over time, increasing the risk for data corruption,” he explains. “In response, the robust way to ensure long-term data integrity and regulatory compliance over a growing number of OT and IT nodes is to implement an intermediary data platform that
connects the disparate data sources, securely bridging firewalls, contextualizing and cleansing data in transit, and reliably delivering it to a centralized repository that provides a single source of the truth.”

Digitalization is important not only for GxP manufacturing processes, but also for process development and efficient technical transfer. “Documents and spreadsheets tend to be the norm for data collection, process knowledge capture, and the technical transfer process between the lab and production floor,” says Rodriguez. She adds, however, that there is a growing need to eliminate paper and manual processes to meet the increasing pressure to get to market faster. The ongoing shift to broader product mix portfolios, which include large-molecule products and smaller production volumes, adds to the need for digitalization.

Digital product lifecycle management (PLM) tools can accelerate commercialization and improve knowledge transfer (4). “With product and process data predominantly stored across siloed systems and paper on glass documents, data [are] difficult to maintain, reuse, and share with stakeholders across extended, global value chains,” says Rodriguez. “Managing data in a system like PLM helps biopharma companies transition from document-centric to data-centric materials and process knowledge management, establishing a seamless data flow from lab to plant. Structured data [are] easily and quickly evolved and enriched throughout the product lifecycle as the process moves across functional stakeholders, systems, and sites, both internal and external.”

Bruwer reports that nearly half of the 400 pharma professionals surveyed by AspenTech (3) listed data silos between departments as a challenge in digital transformation. “[These divides] can hinder effective information sharing across the product lifecycle, including during technology transfer and commercial manufacturing,” explains Bruwer.

In the new Pharma 4.0 paradigm, knowledge can be stored as data in a repository (i.e., a data lake) that can be mined by digital tools, adds Langer.

Software validation is moving into “Validation 4.0” with the use of computer software assurance (CSA) processes to achieve computer system validation. “Software that can be validated for intended use instead of following the traditional stepwise process will be prominent in life science manufacturing in 2023,” predicts Langer. In CSA, the burden falls on the software providers to show that critical data have integrity and are controlled, and manufacturers demonstrate control of their process using the software, he explains. “The new CSA methods use risk-based approaches to reduce the validation burden by orders of magnitude,” says Langer.

Pharma 4.0 technologies are also being applied to CPV, to enable predictive monitoring of manufacturing processes. “The cloud is a huge enabler for CPV,” says Hayes. “It’s elastic, so resource-intensive applications like CPV are perfect for the cloud. Gathering, storing, contextualizing, and analyzing large volumes of data requires heavy storage, memory, and processing power, and the cloud can scale up and down as needed.” Hayes says that the quality team should first identify their needs and then digital solutions can be found to meet these requirements. “Keep in mind that CPV is a quality-led function that is supported by technology, and not the other way around,” he cautions.

Perceptions are beginning to shift toward greater acceptance, according to AspenTech, as only 35% of respondents to their 2022 survey said that the digital transformation process was hindered by risk aversion (3), compared to a 2021 survey in which risk aversion was considered the top barrier among digital culture leaders (5).

Digital transformation is not a simple or quick change. The benefits, however, are clear, and the tools are available. 

Axendia Research Report: The Needle is Moving–Digital Transformation in Life Sciences Manufacturing

Axendia Straight from the Source Webcast: FDA Debunks Industry Myths on Electronic Batch Records and Review by Exception

Seizing New Opportunities: Pharma’s Roadmap for Smarter Manufacturing

Axendia Market Research Report: Accelerating Time to Market with Biopharma PLM

Culture Reimagined: How Pharmaceutical Firms Can Use Data and AI with

When referring to this article, please cite it as Markarian, J. Envisioning Digital Pharma Manufacturing. 

Digital transformation to the Pharma 4.0 paradigm moves forward in process development and clinical and commercial manufacturing. 

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