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

Felicity Thomas

In this exclusive Drug Digest video interview, Meg Rivers and Felicity Thomas, 

editors, interview experts in sterilization and aseptic processing. Alex Van Hagen of Watson-Marlow Fluid Technology Solutions discusses how to approach selecting sterilization methods, installation of aseptic machinery, how single-use technology factors into aseptic processing, and areas for improved automation. In a quick-fire interview, Hamish Hogg of Cherwell Laboratories talks about the eagerly anticipated publication of the revised EU GMP Annex 1 guidance, potentially problematic aspects of the revised guidance, and tips and tricks for companies to ensure compliance.

 is a molecular biologist by training and the current North UK life sciences sector specialist for Watson-Marlow Fluid Technology Solutions. In this position, Alex provides experience-based consultation to the life sciences sector, taking each project from cradle to gate. Previously, Alex worked in academic research centered on producing sustainable microbial cell factories for the production of fossil-fuel-based chemicals using renewable carbon sources, and his work has been presented internationally. In addition, Alex has been a guest lecturer at bioscience continued professional development courses within the UK and sits on an industry expert liaison panel at the University of Lincoln.

 has been the microbiology product specialist at Cherwell Laboratories since January 2019. He has a background as a biomedical scientist for the NHS in microbiology. Later, he expanded his career into medical devices companies, delivering technical support to end users and training to the internal and external corporate teams and customers.

This episode of Drug Digest is sponsored by:

Drug Digest is a tech talk video series with the 

 editors, who interview industry experts to discuss the emerging opportunities, obstacles, and advances in the pharmaceutical and biopharmaceutical industry for the research, development, formulation, analysis, upstream and downstream processing, manufacturing, supply chain, and packaging of drug products.

Automating pharma and biopharma processes

Videos

Pharmaceutical Technology editors interview aseptic and sterilization experts from Watson-Marlow Fluid Technology Solutions and Cherwell—diving into sterilization, aseptic processing, and the revised EU GMP Annex 1 guidance.

Drug Digest: Sterilization’s Horizon: Improving Automation, Single-Use Technologies, and Annex 1

Poor solubility and low bioavailability have hindered the development pipeline for some time and are set to continue to challenge drug companies in the future. As more new chemical entities enter development with complex needs, it is becoming more pressing for the industry to employ innovative and effective solutions to overcome solubility and bioavailability challenges.

To find out more about the issue of poor solubility and bioavailability, current approaches aimed at helping advance poorly-soluble drugs through the clinical pipeline, and best formulation practices for poorly-soluble drugs in development, 

 spoke with Michael Morgen, R&D director, Lonza Small Molecules, and Craig Grant, global director, solid form and particle engineering, Veranova.

 Could you explain why solubility/bioavailability is still such a big issue in bio/pharmaceutical drug formulation?

 Compounds with low solubility or low bioavailability fall into Biopharmaceutical Classification System (BCS) II (low solubility–high permeability) and IV (low solubility–low permeability) regions. Over time, the industry has observed that these types of molecules are becoming the rule rather than the norm, as around 90% of preclinical compounds are now estimated to have bioavailability challenges (1).

There are several market factors that contribute to this continuing trend. For example, disease targets and associated API chemistry are being driven towards low solubility drug candidates. Many targets have pushed discovery chemists to molecules that are very hydrophobic, have high melting points, and/or high molecular weights—trends that have been clearly seen in Lonza’s portfolio of client compounds. The first two issues lead to low water solubility, while the third can limit solubility but also permeability, and therefore put a premium on solubilization. As examples, kinases have become important targets for oncology, and the kinase inhibitors often have rigid planar structures with high melting points. Many recent antivirals, however, tend to be larger, hydrophobic molecules having molecular weights >500 Da. High molecular weights are also typical of the newer classes of protein degraders being developed for a range of therapeutic areas.

Another market factor having an impact is that patients prefer the convenience, non-invasiveness, and lower cost of oral tablets or capsules. This is because orally-administered drugs are much easier to adhere to compared to those delivered parenterally. This is critical, as patient compliance is a paramount priority in drug development. The challenge, however, is the low intrinsic permeability of the API in the gastrointestinal (GI) tract, which results in poor bioavailability.

 The biotech and pharmaceutical industries are continually looking for novel and efficacious APIs to meet the needs of the growing and aging global population. During early-stage development, innovators often focus on potency or efficacy for candidate selection, meaning that downstream solubility/bioavailability considerations are often overlooked. This oversight can lead to time and effort being spent on overcoming developability deficiencies of a compound that can increase time to market. Despite that, there have been many technological advances in recent years making the development of poorly soluble drug moieties more attainable.

 Is the issue of poor solubility/low bioavailability getting increasingly difficult?

 The issue has been growing for a number of years now. As of 2018, it was estimated that around 90% of APIs in the development pipeline are poorly soluble (1). This is fuelled by drug discovery turning towards candidates derived from more complex core molecular scaffolds, with increased molecular weight and often an increased number of chiral centres. Here, the introduced chirality provides developers with a tool to improve stereoselectivity, target specificity, and increase drug activity—as such, it’s likely this trend will continue.

However, many larger molecules typically don’t want to crystallize at all, and chiral drug molecules can present potential challenges from a chemical synthesis perspective.

Fortunately, solid form screening approaches with complex chiral APIs can aid syntheses via resolution methods, and once chirally-pure entities are in hand, absolute stereochemical assignments can be made using single crystal X-ray diffraction.

Looking ahead, the industry has become more accustomed to working with complex molecules; so, it’s likely that further advancements in technology and solid form methods will continue to evolve. Perhaps one day it will be possible to screen these larger, more complex molecules to understand—through predictive techniques—if they are likely to crystallize and determine the most thermodynamically stable form as well as the number of potential polymorphs, to speed up analysis.

 While we anticipate that oral bioavailability will continue to be a common challenge, there are a number of bioavailability-enhancing technologies that can be leveraged to deliver small molecules orally. The key is to have a solid scientific understanding of the target drug product profile to be able to

select and utilize the appropriate enabling technology to address this challenge and create the most efficacious small molecule drug. Even as compounds entering the pipeline are becoming more complex over time, proven scientific methods and understanding will continue to be at the heart of solutions.

 Are there ‘conventional’ and ‘non-conventional’ approaches to overcome solubility/bioavailability issues during formulation?

 There are several technologies that have been developed to improve bioavailability. However, two of the most commonly used for commercially-viable compounds are particle size reduction (jet milling) and amorphous solid dispersions (ASDs).

Micronization, often performed using a jet mill, reduces the particle size of APIs (typically to <10 µm) to enhance bioavailability by increasing the surface area, and therefore the dissolution rate. ASD formulations are typically manufactured using either spray drying or hot-melt extrusion, depending on physical-chemical properties. ASD prevalence is driven by its broad applicability across a diverse drug compound property space and its scalability, offering the flexibility and control needed for an optimized drug product.

In terms of unconventional approaches, there are several opportunities for formulation and process innovation to extend the applicability of ‘conventional’ ASDs technologies to a broader range of APIs. One approach is the use of solvent technologies to enable spray drying of ‘brick dust’ compounds that have poor solubility in typical process solvents, as well as process improvements to thermal-based methods to reduce the thermal exposure while achieving a homogeneous system. On the formulation side, there is an opportunity to use existing excipient materials in novel engineered architectures to increase drug loading and to aid in the dissolution and sustainment of high drug concentrations.

Highly impermeable compounds—for example, high molecular weight ‘small molecules’ or biologics—continue to be a difficult challenge to deliver orally. A number of academic labs and start-up companies, especially, are working on innovative technologies to address these molecules. The specific challenges are to find ‘permeation enhancing’ approaches that are safe and that are broadly useful, as opposed to very specific to a particular active molecule.

 Fundamentally, the formation of an optimal solid form is the most important step in creating a drug product that has good solubility and bioavailability. For crystalline materials, optimal refers to the best salt, cocrystal, or parent-free form of an API that is developable. However, when it comes to the most ‘conventional’ or ‘non-conventional’ methods, these are wholly dependent on individual attitudes towards solid form techniques. Beyond selecting the ‘optimal’ solid form, we routinely overcome solubility issues using particle engineering approaches as well as enabling formulation techniques. These include excipient screening, the use of surfactants, and other related methods.

About 20 years ago, cocrystals were seen as a novel approach to overcoming poor solubility and bioavailability. Although they are more widely accepted today, there is still some hesitancy in the industry towards their use. This hesitancy is mostly due to a lack of understanding or experience in developing cocrystals. Hopefully, with increasing regulatory approvals of novel cocrystal products, they will become more conventionally accepted, as they are a valuable solution when no ionizable groups are present. As such, it is preferred, at Veranova, to run salt and cocrystal studies in parallel.

 What technological advances have there been in terms of aiding solubility/bioavailability in drug formulation? Are there any advances in the pipeline that will be impactful in your opinion?

 As the industry has been forced to adapt to the increasing complexity of novel APIs and new chemical entities, technology to characterize and evaluate these compounds has also evolved.

Oral dosage forms continue to be the most preferable delivery route—due to self-administrative convenience and ease of manufacture. Therefore, advancements in the methods used to monitor their dissolution in the GI tract have been invaluable. Small-scale in situ dissolution is one such technology that has helped improve understanding of the solubility and bioavailability of BCS Class II compounds, those which are highly permeable in the GI tract but have poor solubility. When issues with the dissolution of APIs are highlighted earlier in development, it’s much easier for innovators to identify the potential developability issues and look to understand if the optimal solid form of a drug moiety will solve solubility and bioavailability issues. There have also been some advancements in the use of porous excipients, such as mesoporous silica, and metal-organic frameworks. Although there are still no FDA [US Food and Drug Administration]‑approved drugs utilizing these technologies, it’s likely the research in this area will advance in the coming years.

 Improved in-silico prediction of formulation performance will be a significant opportunity going forward. There have been recent advances in using physiologically-based pharmacokinetic modelling in conjunction with more targeted in-vitro tests to select formulation technologies and compositions that will help aid bioavailability-enhancement strategies.

In addition, artificial intelligence approaches will likely play an increasingly important role in pharmaceutical development going forward. Machine learning approaches that have been broadly applied to drug discovery and clinical trial design are beginning to find applications in formulation selection and optimization.

 Could you provide some best practices for formulators when dealing with poor solubility/bioavailability?

Addressing poor solubility and low bioavailability is often a critical need in commercializing a small-molecule drug.

Characterize the target product profile well. This information, along with extensive institutional knowledge of molecules with similar properties and target product profiles, can be used to develop a formulation strategy and choose which enabling technology to use.

Strategically choose drug delivery technologies early in the development process, based on preclinical, and then verified by first-in-human clinical success. Making this choice can be time- and resource-intensive; so, it is critical to base this decision on science and data. Depending on the target drug product profile, this will determine which bioavailability enhancing technology is needed to effectively formulate your compound.

Keep commercialization in the line of sight. As the product is moved through the development pipeline, it is important to demonstrate the ability to scale that formulation to the next phase. Early clinical trials can require significant quantities of drug products that may be challenging to provide under accelerated timelines without a well-planned scale-up strategy.

Minimize company-to-company transfers. Working with multiple outsourcing partners can result in duplicated efforts, longer timelines, and increased costs. This can be addressed with a single outsourcing model, where the right partner can optimize a formulation, progress a compound through clinical trials, and rapidly scale the drug product to launch.

 Optimizing the properties and performance of the drug substance is one of the most important things for formulators to consider when dealing with poorly soluble APIs. It’s vital to get as much information about the end goals of a novel drug product; things like the route of administration, drug target, and so on can impact the type of experimental design and yield the best value-added data. At Veranova, a hierarchical approach is employed, following the molecule through every stage of development to gather as much data as possible.

However, it’s unlikely that a single partner will be a ‘one-stop-shop’ expert; so, it’s important that developers consider their needs, requirements, and the complexity of their molecule when outsourcing. This consideration ensures the selection of the right expertise for a particular drug candidate.

With modern technology being able to work on a smaller scale without compromising quality, pertinent data can be captured earlier in development so that leading candidates pose fewer solubility and/or bioavailability issues that need to be overcome through formulation.

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


Vol. 34, No. 8
August 2022
Pages: 16–18

When referring to this article, please cite it as F. Thomas, “Adapting to Solubility/Bioavailability Challenges” 

Articles

Industry is adapting to the increasing complexity and poor solubility and bioavailability of molecules in the pipeline.

Adapting to Solubility/Bioavailability Challenges

Production of high-quality, defect-free finished products is a top priority in the bio/pharmaceutical industry, primarily to ensure the safety of the end-user—patients. The automation of finished product inspection is leading to gains in efficiency for companies and, as such, is being widely adopted.

To find out more about automated finished product inspection, some of the common tools used, potential pitfalls of approaches, the impact of increasing complexity of therapeutics in development, and regulatory changes, 

 spoke with Tyler Harris, applications engineer, and Oliver Stauffer, CEO, both from PTI—a specialist in packaging inspection technologies.

 Could you provide a little bit of background into automated finished product inspection, its importance, and where the industry currently sits on its use?

 Automated finished product inspection has been widely adopted by the pharmaceutical industry with the use of various test methods. Additionally, not all these test methods are container closure integrity technology (CCIT) methods, non-deterministic, or likely to be accepted by regulatory agencies in the near future.

Visual inspection, torque testing, high-voltage leak detection (HVLD), headspace analysis, vacuum decay, and airborne ultrasound all inspect finished products in some form from label alignment to leak detection, and seal quality. No one test method is suitable for all applications, and more than one test method may be required.

Although methods such as visual inspection are widely adopted by the industry, CCIT methods have not yet become commonplace, although [they are] gaining traction. The newfound increase of CCIT in the automated finished product inspection space comes from the development of scalable test methods and regulatory pressure. Benchtop, offline inspection methods validate automated sampling and 100% inline inspection systems. The practice of offline benchtop quality testing will never dissolve or be replaced by automated inspection; scalability decreases validation time, risk, and analysis time.

 What sort of analytical tools are commonly used in automated finished product inspection?

 The technologies used for automated inspection are application driven and depend heavily on the package format and container contents. Typically, headspace analysis, vacuum decay, or high-voltage leak detection (HVLD) are the go-to inspection technologies for parenterals.

 Are there any pitfalls/analytical shortcomings that need to be addressed?

 The most critical aspect of inspection is selecting the best test method for the application at hand. Some methods are suitable for a variety of applications while others have specific characteristics the applications must have to be effective. In regard to deterministic non-destructive CCIT methods, each have shortcomings that prevent robust, reliable, and repeatable results. Headspace analysis can only test transparent/translucent rigid applications before labeling and the package must have headspace.

One of the more common automated inspection technologies is traditional AC HVLD. Applications suitable for HVLD must be cylindrical, glass or plastic, and conductive liquid with low viscosity. High voltage can have negative effects on active drug product and produce large amounts of ozone.

Over the last half decade, MicroCurrent HVLD (HVLDmc) has been proven to greatly reduce the voltage exposure to the product and reduce ozone to near negligible amounts. Since the mid-1980s, vacuum decay has been utilized to test full container integrity of non-porous flexible and rigid containers. Although widely adopted for benchtop applications, it is not without pitfalls. Vacuum decay is only suitable for non-porous packaging and has difficulty testing large-molecule liquid products. Vacuum decay is often used for automated sampling systems but rarely used for 100% inline testing due to its long test cycles. Shortcomings are overcome by necessary innovation in this regulatory driven climate.

 How has automated finished product inspection adjusted to the increasingly complex therapeutic landscape?

 Therapeutics require far more attention than standard pharmaceutical products. With small batch sizes and costly product, non-destructive methods are mandatory in this market segment. Therapeutics are typically large molecule and sometimes viscous liquids stored in vials, syringes, and intravenous (IV) bags. The increase in large-molecule, high risk products has led to the need for HVLD, and HVLDmc in the automated inspection space, further leading to new innovations in handling, test cycle speed, and reliability.

Although superior to vacuum decay for large-molecule and viscous liquid products, HVLD struggles to effectively test the entirety of an IV bag. During an HVLD test, liquid must cover every interior surface of the package. IV bags are not easily rotated and typically contain a large air bubble. These two issues lead to false negatives and inconsistent results. This is where vacuum decay is highly effective. Although limit of detection (LOD) may be higher due to the molecule size, vacuum decay is able to detect leaks in IV bags in automated sampling inspection systems and offline systems.

With small batch sizes and high risk of therapeutic products, benchtop systems are capable of successfully testing product to ensure sterile barrier is intact and no leaks in the package are present. With small batch sizes and frequent changes to the production process/line, validation must be completed with every change. Automated inspection system validation can stretch across multiple weeks and hold up processing of time sensitive live product. Benchtop offline testing stretches across a few days and can be easily completed by a trained operator without the need for validation of the automated handling mechanisms. Testing offline allows for increased attention to the package and lower machine costs. Additionally, many of these therapeutic products are manufactured in a manual process which does not warrant a need for automated inspection.

 What regulatory changes have impacted automated finished product inspection, in your expert opinion?

 Foundational regulatory guidance documents have been updated in both the [United States] and European market space. United States Pharmacopeia (USP) <1207> was recently updated and reflects the shift away from probabilistic test methods to more reliable and traceable deterministic methods. USP <1207> is prescriptive about the technologies that should be considered as improved alternatives to traditional, less effective methods such as dye ingress.

In Europe, the European Medicines Agency (EMA) is updating its Annex 1 guidance, which is less prescriptive around the suggested technologies, but with guidance that frequency of testing and the method of testing should be scientifically appropriate for the commensurate level of risk associated with the application. The need to test fused containers still stands, and the proposed language further clarifies that IV bags also fall within that category. The final draft will most likely have some leniency related to that requirement. Regardless, in both the US and Europe, the regulatory guidance documents are driving towards increased testing frequency using deterministic test methods.

 Are there further regulatory changes, particularly pertaining to analytical analysis, in the near future that you believe will impact automated finished product inspection?

 The regulatory space is forever in a constant state of flux. The most recent proposed changes revolve around the European Union’s (EU’s) Annex 1 and its drafted revisions. The proposed changes call for 100% testing and deterministic test methods for package integrity on all fused containers. This refers to products such as ampoules, pre-filled syringes, and IV bags. The draft specifies that visual inspection alone is not suitable for these types of packages and must be used in conjunction with a deterministic method. At this moment, IV bags are the most difficult application to test whether automated or benchtop and there are two possible outcomes to the final revision of EU Annex 1. Regulatory demands can force innovation, or regulation must wait for further development of the aforementioned deterministic inspection methods.

 Could you highlight any future trends that you deem to be important within automated finished product inspection in terms of analytics?

 Inspection trends are driven by reliability, [regulations], and most commonly, cost. An uptick in automated sampling systems and scalable test methods is on the horizon. The ability to have the same technology in an automated format and in a laboratory setting is critical in being able to compare results, analyze data, validate, and ensure automated systems are functioning properly. Automated sampling systems allow for less human interaction, rapid inspection, and a decrease in inspection time. These benefits ultimately lead to a decrease in cost despite a larger capital expense.


Vol. 46, No. 8
August 2022
Pages: 42–43

When referring to this article, please cite it as F. Thomas, “Inspecting Finished Products with Precision,” 

Automated finished product inspection has been widely adopted in the bio/pharmaceutical industry.

Inspecting Finished Products with Precision

In this episode of the Drug Solutions podcast, Felicity Thomas, European/Senior Editor, talks to Fernando Muzzio, Distinguished Professor, Chemical and Biochemical Engineering, Rutgers University, about a novel approach to improving drug solubility—continuous melt coating. Fernando talks about the technique in some detail, a little about some of the results that have been achieved in research, and provides information about the current patent filing and what companies can do to start working with this new approach.

Curia is a global contract research, development, and manufacturing organization offering products and services across the drug development spectrum to help their partners turn ideas into real-world impact—from curiosity to cure.

Fernando J. Muzzio, Distinguished Professor, Chemical and Biochemical Engineering, Rutgers University.

 presents the Drug Solutions podcast, where the editors will chat with industry experts from across the pharmaceutical and biopharmaceutical supply chain. Join us as experts share insights into your biggest questions—from the technologies, to strategies, to regulations related to the development and manufacture of drug products.

Podcasts

In this episode, Fernando Muzzio provides greater insight into a novel approach to improving drug solubility—continuous melt coating.

Drug Solutions Podcast: Overcoming Poor Solubility Through Accelerated Dissolution

In mid-July 2022, GSK announced the completion of its demerger from the consumer healthcare business, now formed under the moniker of the Haleon Group (1). However, market conditions and an overriding concern about inflation have proven less than favourable for Haleon’s listing debut on the London Stock Exchange, the biggest listing for a decade, with a small but rapid drop in share price seen (2). Shares in the newly reduced company GSK, which is now solely focused on biopharmaceuticals, also experienced a drop, but through consolidation, the price was roughly brought back in-line with that seen before the demerger (2).

GSK’s own reported second quarter results demonstrated healthy growth, and as a result of demand in vaccines, the company is increasing its sales growth outlook in this area, with Shingrix, the company’s shingles vaccine, expected to do very well (3). “This is GSK’s first set of results as a newly focused biopharma company, and we have delivered an excellent second quarter performance, with strong growth in Specialty Medicines, including HIV, and a record quarter for our shingles vaccine Shingrix,” said Emma Walmsley, CEO, GSK, in a company press release (3). “With this momentum in sales and operating profit growth, we have raised our full-year guidance and are confident in delivering the long-term growth outlooks we set out for shareholders last year.”

Additionally, GSK announced on 28 July 2022 that it had signed an agreement with the European Commission’s Health Emergency Preparedness and Response Authority (HERA) for the reservation of future production and supply of Adjupanrix (4). This latest agreement follows on from others made by GSK with the United States, the World Health Organization (WHO), and Canada for the pandemic influenza vaccine.

“I’m delighted that HERA has chosen GSK as a key partner in pandemic flu preparedness. This contract follows three other agreements GSK has made, in the US, Canada, and with the WHO,” said Roger Connor, president Vaccines and Global Health, GSK, in a press release (4). “These agreements leverage GSK’s world-class global vaccine manufacturing network to continue our long-standing partnerships on pandemic preparedness and response. We have all seen the devastating human, economic and social consequences of a pandemic and the important part that vaccines are playing in helping us return to normal life. Through this agreement for 85 million doses, we can help the [European Union] and European countries, as well as other countries and regions, be better prepared for future pandemics.”

1. GSK, “Completion of the Demerger of Haleon and Share Consolidation of GSK,” Press Release, 18 July 2022.
2. J. Evans, “Debut of GSK Consumer-Health Spin-Off Haleon Disappoints,” 

, 18 July 2022.
3. GSK, “GSK Delivers Strong Q2 2022 Sales of £6.9 Billion +19% at AER, +13% at CER and Total EPS from Continuing Operations 17.5p -42% AER, -58% CER; Adjusted EPS of 34.7p +23% AER, +6% CER,” Press Release, 27 July 2022.
4. GSK, “GSK Signs Agreement to Support Pandemic Preparedness in Europe,” Press Release, 28 July 2022.

When referring to this article, please cite it as F. Thomas, “Demerger and the Future” 

GSK has completed its demerger of Haleon and has signed an agreement to help support future pandemic preparedness in Europe.

Demerger and the Future

In this episode of the Drug Solutions podcast, Felicity Thomas, European Editor, talks to a couple of experts on drug packaging advances that have been impactful in recent years and those that may have an impact in the future. Some talking points include sustainable packaging, tailored and patient-centric packaging options, the packaging challenges that arise when dealing with biologics, technological advances making packaging more convenient, and some interesting insights from events. The experts involved in this discussion were Aurelio Arias, who is part of the EMEA thought-leadership group at IQVIA, and Josh Brooks, the marketing and community director for a new event called Connect in Pharma.

LabVantage Solutions, a leader in intelligent laboratory informatics serving Top 20 pharma.

Aurelio Arias, engagement manager, European Thought Leadership, IQVIA

Aurelio creates topical and forward-looking strategic content relevant to pharma executives and publishes articles, blogs and white papers on a regular basis. He is involved in numerous projects related to increasing access to medicine as well as the interface between healthcare and digital technology. He is considered a subject matter expert in these areas and speaks at numerous conferences worldwide, presents at board-level meetings and engages with consulting projects.

Prior to IQVIA, Aurelio has worked in R&D and in various strategy consulting roles. He holds an MSci in Chemistry from Imperial College London.

Josh Brooks, marketing & community director, Packaging at Easyfairs

Josh heads marketing and communication activities across an international portfolio of agenda-setting packaging events in the UK, France, Switzerland and Italy. He joined Easyfairs in 2018 after an early career in business journalism and publishing, where he covered a wide range of sectors including packaging, printing, construction, property and electronics.

In this episode, experts share their insights into important drug packaging advances of the past, present, and future.  