Daria G. Husni

Pharmaceutical researcher making dissolution test | Image Credit: © Kadmy - stock.adobe.com

Dissolution testing plays an important role within the bio/pharma sector, providing critical information for quality control and drug development. In an interview with 

, Shailesh Vengurlekar, senior vice president, quality and regulatory affairs, LGM Pharma, provides more details on the role of dissolution testing, recent innovations in the space, and potential upcoming trends.

What key roles does dissolution testing play, especially regarding quality control?

 Dissolution testing assesses the absorption of a drug after oral consumption through the release of the drug substance from the drug product. The dissolution result of a product lot determines the ability of the lot to dissolve at the specified time (e.g., immediate, extended, or delayed) as intended.

During the formulation and development stage, dissolution data are utilized to assess different formulations and identify one that delivers the drug most effectively based on the dissolution criteria (as mentioned, immediate, extended, or delayed release). Consistent, reproducible dissolution data of a drug product can provide a level of assurance about its quality. Dissolution testing is also utilized to perform any equivalency study during changes or development of new formulations, ensuring continuous demonstration of product quality. FDA expects that new drug applications (NDAs) submitted to the agency contain bioavailability data and 

 dissolution data, which, together with chemistry, manufacturing, and controls (CMC) data, characterize the quality and performance of the drug product. Acceptable bioequivalence data, and comparable 

dissolution and CMC data, are all required for approval of abbreviated new drug applications.

What are some recent innovations in dissolution testing? Can you describe their impact?

To my experience, dissolution equipment is more advanced and continues to evolve to meet user demands—for example, the equipment's ability to autosample, including multiple timepoints. Dissolution media have evolved over the years to mimic physiological conditions; media such as water, acid solution, simulated intestinal fluid, and simulated gastric fluid, including enzyme additions, have been developed and implemented. These tests help predict and simulate the 

 movement of the drug product through the gastrointestinal (GI) tract.

What are some chief concerns in dissolution testing?

Dissolution testing has to be accurate and reliable each and every time it is performed, regardless of when, where, or by whom. Thus, the method should be validated to demonstrate accuracy and precision. Dissolution method validation should be performed similarly to potency and purity method validation, which includes but is not limited to specificity and selectivity, accuracy, precision, linearity, range, and solution stability and robustness (including apparatus functionality: speed, temperature, and media type or volume). Acceptance criteria must be defined prior to performing the validation. Additionally, method validation must be performed in accordance with regulatory guidelines, such as 

] and ICH [International Council for Harmonisation].

How do the trends of the industry affect dissolution testing? Are there any upcoming trends that professionals should be on the lookout for?

The industry is coming out with more innovative drugs, such as biologics and cell and gene therapy, which are not the traditional oral solid dose, and the current standard dissolution techniques are not suitable for these innovative drugs. New innovative drugs will require the development of innovative and new dissolution approaches and analytical techniques. Some considerations affecting the development of such new techniques are the formulation (e.g., tablet, capsule, or powder), particle size, solubility, hardness, and stability of the drug substance.

What do you see in the future for dissolution testing? Is there one change in particular that could have an impact on analytical testing?

Dissolution testing is an important quality control parameter to assess absorption of a drug, as described above, and thus will continue to be important in the analytical space. However, changes to dissolution techniques, method, and instrument may be necessary for new and innovative drugs developed in the future.

Articles

Advances in dissolution testing equipment are helping to meet user demands to a certain degree; however, more innovation in the space may be necessary for novel therapies, such as biologics.

Dissecting Dissolution Testing

Considerations in Pharmaceutical Facility Design

The Pharmaceutical Technology Group spoke with John Bertagnolli, vice-president of Commercial Operations, at the 2024 CPHI North America event, about what it takes to create a new pharmaceutical facility. According to Bertagnolli, the building of greenfield facilities by contract manufacturing organizations (CMOs) is a new trend in the outsourcing industry. “It's usually an aging … pharma-owned, Big Pharma-owned facility [that is] repurposed as a contract manufacturing organization, or an existing company has … other parts of it built on so that they can do different parts of contract manufacturing,” Bertagnolli says.

He points to three milestones that CMOs should meet when building a new facility: completion of the facility, completion of the first aseptic process simulation (APS), and regulatory approval and manufacture of the first product. “[W]hen we're talking about the APS, it's what used to be referred to as the media fill, but [FDA] has put some much … tighter bounds around what they call aseptic process simulation. And because of that, it truly is the final exam for a facility to say, yes, we know we can manufacture sterile product to the correct level that would meet [FDA] requirements. [I]n the case of building a brand-new greenfield site, that also means that you've done all of the characterization of the site from a microbiological perspective, so that you know how all the monitoring is done, that all of the utilities have been established and validated, and you have data to make sure that they're doing exactly what they should be doing.”

Click the video above to watch the full interview. CPHI North America occurred May 7–9 in Philadelphia.

Videos

John Bertagnolli, vice-president of Commercial Operations at Selkirk Pharma, discusses considerations when building and scaling up pharmaceutical facilities, including contamination control and aseptic processing challenges.

Considerations in Pharmaceutical Facility Design (CPHI North America 2024)

Communication between the manufacturing plant and retail stores. | Image Credit: © Cagkan - © Cagkan - stock.adobe.com

Cresset, a UK-based company focused on solutions for computational drug discovery and development, announced on May 13, 2024, that it is opening a new headquarters in Bangalore, India. This news follows the establishment of Cresset’s new facility in Boston earlier in 2024. The facility in Bangalore, one of India’s leading areas for biotechnology and pharmaceutical research, is intended to expand Cresset’s existing Asia-Pacific presence, increasing its reach across the region to include markets such as South Korea, Japan, China, and Australasia.

Cresset intends to take advantage of the nearby chemistry talent available in Bangalore. New staff appointments in India will encompass a range of areas, including sales, support, and development.

“Launching our new site in India marks a major milestone in our international growth and expansion as a company,” said Mark Mackey, PhD, co-founder, chief scientific officer, Cresset, in a press release (1). “The talent pool and centers of excellence available in the region will enable us to expand our existing service offering to clients and develop strong relationships through face-to-face contact on the ground.”

“We already have a satellite office space in Bangalore, where a high proportion of our Indian staff are currently based,” Mackey continued. “The new office will allow us to grow our overall business and gain access to grant funding in the Indian market.”

Bangalore is a popular area for expansion. On Oct. 30, 2023, Aragen, a contract research development and manufacturing organization, announced its new biologics manufacturing facility in the city, as part of a $30 million investment (2). The planned 160,000-square-meter facility is set to include process development labs and multiple good manufacturing practice (GMP) suites, as well as supporting functions such as quality control labs. It is designed to facilitate solutions across the biomanufacturing lifecycle and will be equipped to develop and manufacture monoclonal antibodies, therapeutic proteins, and fusion proteins.

Aragen has since operationalized the first phase of the facility, which it announced in a press release on Mar. 27, 2024 (3). It also executed its first small-scale manufacturing project for a US-based organization, a novel anticancer monoclonal antibody. The facility can process batch sizes up to 50 liters and includes process development and analytical labs.

“We are happy to announce the commissioning of the first phase of our biologics manufacturing facility at Bangalore, India as per schedule and the successful completion of the first project at this facility,” said Manni Kantipudi, CEO of Aragen Life Sciences and director of Aragen Biologics, in the press release (3). “This brings us one step closer to offering full-scale Gene-to GMP solutions to our customers. Once the facility’s expansion is fully operational by the end of this calendar year, we will be able to do internal tech transfer from our R&D labs in California to the manufacturing site in India, thereby enabling end-to-end integrated service offering to customers.”

Cresset Group. Cresset Targets Global Growth with New India HQ. Press Release, May 13, 2024.

Establish $30 Million Biomanufacturing Facility in India

Aragen Operationalizes First Phase of its Biologics Manufacturing Facility in India

The drug discovery company intends for this new site to increase its reach in the region, supporting growing demands from its Asia-Pacific consumers.

Cresset to Open New Headquarters in Bangalore, India

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At its April 2024 meeting, the European Medicines Agency’s (EMA) human medicines committee (CHMP) recommended eight medicines for approval: Altuvoct, Fruzaqla, Jeraygo, Obgemsa, Truqap, Tofidence, Wezenla, and Eribulin Baxter (1).

Altuvoct (efanescotocog alfa) was recommended for a marketing authorization for the treatment and prophylaxis of bleeding in patients with hemophilia A, which is a rare genetic bleeding disorder cause by a lack of factor VIII. Fruzaqla (fruquintinib) received a positive opinion for the treatment of patients with previously treated metastatic colorectal cancer. Jeraygo (aprocitentan) also received a positive opinion, for the treatment of resistant hypertension. CHMP gave a positive opinion to Obgemsa (vibegron) for the treatment of adult patients with overactive bladder syndrome. Truqap (capivasertib) received a positive opinion for the treatment of locally advanced or metastatic breast cancer with one or more specific mutations.

Tofidence (tocilizumab) and Wezenla (ustekinumab), both biosimilar medicines, received positive opinions from the committee. Tofidence received a positive opinion for the treatment of COVID-19, rheumatoid arthritis, systemic juvenile idiopathic arthritis, and pediatric plaque psoriasis. Wenzela received its positive opinion for the treatment of plaque psoriasis, including pediatric plaque psoriasis, psoriatic arthritis, and Crohn’s disease. Erubulin Baxter (eribulin), a generic medicine intended to treat breast cancer and liposarcoma, a rare disease which develops in fatty tissue, also received a positive opinion from the CHMP.

In addition to the positive opinions, two applications for marketing authorization were withdrawn. The first was for GeGant, a radionuclide generator that doctors can use to label diagnostic medicines. A question-and-answer document on the withdrawal of GeGrant is available 

. The second was Upstelda, a biosimilar treatment for plaque psoriasis, psoriatic arthritis, and Crohn’s disease, which is a duplicate of Wezenla. The committee also recommended extensions of indication for six medicines already authorized in the European Union: Alescensa, Opdivo, Rozlytrek, Rybrevant, Sirturo, and Triumeq. The committee recommended new contraindications on the co-administration of Reyataz (Atazanavir) with ivosidenib and encorafenib, and with phenobarbital, phenytoin, and carbamazepine.

In regulatory updates, EMA is currently reviewing the impact of the appellate judgement of the Court of Justice (March 14, 2024) on the evaluation of Hopveus, the subject of the court case, as well as other regulatory procedures. Because of this, CHMP has created a new ad-hoc expert group (AHEG) for Syfovre and will reset the evaluation procedure for this treatment from the point of reset to day 180 of the initial assessment. The judgement reviewed questions related to the organization of EMA’s Scientific Advisory Groups and AHEGs, which are both groups that are called upon by EMA to respond to questions from the EMA’s committees during a medicine evaluation. The agency wrote that it is “considering the impact of the appellate judgment on the evaluation of other regulatory procedures,” and “will further communicate as appropriate” (1).

Meeting Highlights from the Committee for Medicinal Products for Human Use (CHMP) 22-25 April 2024

EMA’s CHMP recommended treatments for hemophilia A, colorectal cancer, hypertension, overactive bladder, and metastatic breast cancer.

EMA Recommends Eight Medicines for Approval in April

Science laboratory test tubes, laboratory equipment | Image Credit: © BillionPhotos.com - © BillionPhotos.com - stock.adobe.com

® sat in on a panel by Rachel Harris, product engineer, AstraZeneca, on enabling industry consensus and action for sustainability with drug delivery devices (1). Harris spoke specifically on her work with BioPhorum, which is a member-lead collaborative company made up of industry leaders and experts with the aim of accelerating progress in the pharmaceutical field through connection and collaboration. One of the company’s biggest objectives is cultivating greater sustainability within the industry through supporting an industry-wide transition to a low carbon future.

Harris said that there are three main areas where the BioPhorum team is focused on driving positive change: access to healthcare, environmental protection, and ethics and transparency. To improve public access to healthcare, Harris underlined the need for promoting prevention of disease, increasing access to life-changing treatments, and strengthening the resilience and sustainability of healthcare systems. To mitigate environmental impact, BioPhorum is focused on expediting the delivery of net-zero healthcare and investing in nature and biodiversity. Harris also emphasized the need to manage the environmental impact of the industry, where companies take a proactive approach in recording and reducing their own waste. Finally, Harris spoke on the importance of ethical and transparent action across the industry, in a way that is safe and inclusive.

The climate crisis is recognized as one of the greatest threats to global health, Harris said, and the health sector is responsible to 4–5% of total global emissions. Because the biopharmaceutical industry exists to advance human health, it’s natural for the industry to be concerned about environmental impact. BioPhorum’s current focus is on the drug delivery devices market, which is rapidly growing and presents an opportunity to separate impact from growth. Harris stated that because the industry operates in a complex global value chain, collaboration is critical to a successful sustainability practice.

As investors, customers, and employees demand more impactful sustainability performance, there are opportunities across the drug delivery field to reduce environmental impact. From engineers, who can design devices and packaging that create less waste, to regional/global leads, who are at the front of corporate environmental programs, there is a role for everyone to play. To illustrate this, Harris outlined the stages in the life cycle of a drug delivery product, and what opportunities for impact reduction exist in each stage.

The development and manufacturing of a product, or the beginning of the device life cycle, impacts all other stages. It’s crucial to think about sustainability, according to Harris, from the very beginning of the cycle, where the device can be designed with reuse or recyclability at end-of-life in mind. An important step is to minimize the complexity of materials, and to embed sustainability practices into the manufacturing process. In the middle stage of a product’s life cycle, during distribution, key practices include optimizing packaging and distribution networks, collecting data on the impact of the process, and decreasing waste by reusing components. At the end of a product’s life, collaborative programs can be created around the recovery and disposal of devices and materials.

BioPhorum’s first deliverable, an industry consensus paper, is due for publication in the second quarter of 2024. The paper details industry consensus on the challenges and opportunities in decarbonizing the value chain and incorporating circularity of materials in drug delivery devices. Moving forward, Harris said that it will be important to standardize assessments across the industry. Companies should understand and interact with regulatory systems, utilize tools for measuring impact, and lean toward new materials and technology that are more sustainable. According to Harris, through collaborative efforts and keeping sustainability in mind, the industry can move towards a greener future. 

Harris, R. Enabling Industry Consensus and Action for Sustainable Drug Delivery Devices. Presentation at the 2024 CPHI North America Conference, Philadelphia, Pennsylvania, United States, May 7, 2024.

At CPHI NA, Rachel Harris, AstraZeneca, spoke on her work at BioPhorum to enable industry consensus and action for sustainability with drug delivery devices.

Embedding Sustainability in Drug Delivery through Industry Consensus at CPHI NA

Tara Dougal, content director, Pharma, Informa Markets, discusses successes and insights from this year’s CPHI NA and the agenda for the upcoming CPHI Milan.

CPHI North America: Industry Trends, Agenda Additions, and What to Expect at CPHI Milan

 sat down with Tara Dougal, content director, Pharma, Informa Markets, to discuss successes and insights from CPHI North America 2024 and the agenda for the upcoming CPHI Milan.

“So, there's a lot to be excited about this year,” Dougal said, in reference to CPHI North America. “One thing that I'm really excited about is that we've moved a lot of our content to the show floor. Attendees will notice we have two theatres on the show floor this year, more content than has ever been at the show before. And the theatre being situated on show floor really creates a great buzz. So really excited to see that development.”

“The other thing I'm really excited about is a new feature for us, which is our startup market. So, we have launched it at some of our other events. It's brand new for North America. This year, we brought 16 young innovative companies to the show to showcase their products and their solutions. It's been such a busy zone all day; I've seen people filing through, chatting to all our startups, and it shows a real interest from the industry on where innovation is coming from.”

“I think when we're talking about the US pharma market, we talk a lot about supply chain resilience, [and] I think a lot of that is still a bit of a COVID hangover,” Dougal said, when asked about industry trends present at CPHI NA. “We're looking at how we can build resilience in supply chains, how we can re-shore or near shore manufacturing. And that still seems to be a pretty prevalent trend for this year.”

On changes to the CPHI NA conference agenda, Dougal said, “So actually, this year, we have a brand-new conference track on sustainability. And this is something which obviously is a huge buzzword in pharma. We cover it at a lot of our conferences and our events, but it's such an important issue. And what we see is that people are really hungry for knowledge around sustainability. They want to know what targets they should be setting, how they can achieve those targets, and how they can make actionable change. So, it's really great to see a whole track dedicated to sustainability this year.”

Tara Dougal, content director, Pharma, Informa Markets, discusses successes and insights from this year’s CPHI North America and the agenda for the upcoming CPHI Milan.