Aligning mRNA Progress with Regulatory Streamlining

BioPharm Peer Exchange

Dosage Forms: Roundtable on Oral Solid Dosage Trends

Drug Solutions Podcast: 

Pharmaceutical packaging must advance to adapt to new, complex modalities

Out-of-the-Box Packaging Advancements

From Theory to Reality: Automating Process Development

Drug Digest: 

The Importance of Appropriate Supplier Oversight

Ask the Expert

Siegfried Schmitt, PhD, is Vice President Technical at Parexel International, Siegfried.Schmitt@parexel.com.

Question mark background | Image Credit: © Leigh-Prather - © Leigh Prather - stock.adobe.com

Q: There appear to be a lot of recent changes in the requirements for aseptic processing. Are there any other key developments in this field we should expect in 2025?

A: The two issues that will most likely be top of the list are compliance and competitiveness. Regarding compliance, although Annex 1, the European Union’s guide to the manufacture of sterile products (1), has been in force for over a year, many companies are still somewhat unsure as to how to comply with certain aspects of this document. In particular, establishing the contamination control strategy (CCS) proves to be more complex and resource intensive than many expected (2,3). Creating this document requires access to many disparate sources of information from several departments. Unless this information is accessible electronically, the task will be made excessively difficult.

When it comes to competitiveness, increasing demands from regulatory bodies, including those governing environment and health, place a burden on industry to find solutions (e.g., minimize waste even when using single-use equipment) that do not compromise compliance.

A good source to keep abreast of developing trends is to look at events and activities organized by leading industry associations that traditionally cover aseptic processing; for example, the International Society for Pharmaceutical Engineering (4,5) or the Parenteral Drug Association (6).

These and other organizations (7) are also providing fora for interested parties that prepare guidance documents (e.g., technical reports, good practice guides, points to consider, or similar) from industry experts for industry peers. Active participation in such groups provides early access to these highly valuable documents.

An area of special interest is to bring manufacturing as close as possible to the points of need or care. Rather than shipping product from a central manufacturing hub to a large number of locations, the idea is to establish more manufacturing sites, or even mobile manufacturing units (8) that will bring a lot more flexibility to manufacturing schedules, and deliver resilience to interrupting factors like environmental disasters or new trade barriers. Aseptic processing validation under these circumstances may need careful consideration.

Annex 1 Manufacture of Sterile Medicinal Products, 

Schmitt, S. Contamination Control Strategy–Are We There Yet? 

Schmitt, S. Creating a Contamination Control Strategy. 

ISPE. Building Resilience in ATMP Manufacturing: Insights and Innovations at the 2025 ISPE Aseptic Conference, 

PDA Good Aseptic Manufacturing Conference 2025

Regulatory Affairs Professionals Association. Fundamentals of Pharmaceutical and Biologics Regulations, A Global Perspective. 2nd edition, 

PDA. PDA Points to Consider Mobile Manufacturing, 2025. www.pda.org, [publication planned for 2025].

Siegfried Schmitt, PhD, is vice president, Technical at Parexel.

When referring to this article, please cite it as Schmitt, S. Developments in Aseptic Processing. 

Articles

Compliance and competitiveness are key factors in aseptic processing, says Siegfried Schmitt, PhD, vice president, Technical at Parexel.

Developments in Aseptic Processing

Mike Hennessy Jr. is the President and CEO of 

High Angle Shot of a Working Desk of an Successful Person in Office with Cityscape Window View. | Image credit: © Gorodenkoff - stock.adobe.com

Technological advances are continuing to push boundaries for global industries. Artificial intelligence (AI) is one such advancement and is being increasingly employed in research and scientific work across multiple disciplines as a result of its ability to improve efficiencies.

A recent example of how AI is improving efficiency at the research stage has been demonstrated by co-scientist, Google’s new AI research tool, which solved a complex problem about superbugs—that had taken microbiologists a decade to work out—in a mere 48 hours (1). Google’s AI tool, built on Gemini 2.0, has been created to help scientists generate novel hypotheses and research proposals, which it does through a combination of specialized agents based on scientific methodology (2).

“The AI co-scientist represents a promising advance toward AI-assisted technologies for scientists to help accelerate discovery,” said Juraj Gottweis, Google Fellow, and Vivek Natarajan, Research Lead, in a blog post (3). “This project illustrates how collaborative and human-centered AI systems might be able to augment human ingenuity and accelerate scientific discovery.”

On the theme of collaboration, earlier this year, in January 2025, accelerated computing company, NVIDIA, announced new partnerships with IQVIA, Illumina, Mayo Clinic, and Arc Institute, to transform the healthcare and life sciences industry with AI (4). Using AI agents, NVIDIA’s partners are seeking to accelerate clinical trials, advance drug discovery, and support industry growth.

Looking a little further along the development lifecycle, towards the larger-scale commercial manufacturing end, the benefits of smarter technology and AI implementation are also being seen. However, as highlighted in this issue’s Focus piece, which can be found on pages 10–13, while technological advances are accelerating progress, there are still hurdles to overcome. “Plenty of challenges stand in the way, including cost of implementation, regulatory compliance, and more. We have heard from experts who anticipate that fully automated, ‘lights-out’ biomanufacturing facilities could become a reality within the next five to 10 years,” explains Anthony Christopher, commercial manager of bioprocessing at Kent Elastomer Products (5).

Gerken, T. AI Cracks Superbug Problem in Two Days that Took Scientists Years. 

Haigney, S. Google Launches AI Co-Scientist System. 

Gottweis, J.; Natarajan, V. Accelerating Scientific Breakthroughs with AI Co-Scientist. Blog Post. Google Research. Research.google. Feb. 19, 2025.

NVIDIA. NVIDIA Partners with Industry Leaders to Advance Genomics, Drug Discovery, and Healthcare. Press Release, Jan. 13, 2024.

Mirasol, F. Accelerating Adoption of Smart Tools to Advance Manufacturing. 

Mike Hennessy Jr is President and CEO of MJH Life Sciences®

When referring to this article, please cite it as Hennessy, M. Pushing Tech Boundaries. 

Artificial intelligence, among other technological advances, is pushing innovation boundaries.

Pushing Tech Boundaries

Patrick Lavery is an Editor for the MJH Life Sciences brands 

. Previously at MJH, he filled the same role for 

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Eli Lilly and Company (Lilly) announced on Feb. 28, 2025 that its Jaypirca (pirtobrutinib), a non-covalent or reversible Bruton's tyrosine kinase (BTK) inhibitor, was given a positive opinion by the European Medicines Agency (EMA)’s Committee for Medicinal Products for Human Use (CHMP), for treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) previously treated with a BTK inhibitor (1).

one of 16 drugs for which CHMP extended therapeutic indications

 at its February meeting, EMA said on February 28 (2).

"We are pleased to receive a positive opinion from the CHMP, signaling that the European Union may lead the way in broadening patient access to Jaypirca for those with relapsed or refractory CLL in the post-BTK inhibitor setting," said Jacob Van Naarden, executive vice president and president of Lilly Oncology, in a Lilly press release (1). "There are currently no treatment options that have been specifically studied in a randomized Phase III trial in this patient population, and we are hopeful Jaypirca will be a meaningful new option for patients. We look forward to the European Commission [EC]'s decision in the coming months."

It could be one to two months for that decision from the EC, according to Lilly, following the release of data from—as Van Naarden alluded to—a Phase III trial (BRUIN CLL-321) that is the first randomized study in CLL ever to be conducted specifically among patients previously treated with a BTK inhibitor (1). Included in those results was a 46% reduction in the risk of disease progression or death after treatment with pirtobrutinib versus two global standards of care, either idelalisib or bendamustine plus rituximab.

 at its July 2024 meeting, for treatment of not only CLL but also rheumatoid arthritis, in the form of Ituxredi, a biosimilar referencing Roche’s MabThera (3).

In its press release, Lilly detailed CLL as a slow-growing form of non-Hodgkin lymphoma developed from lymphocytes, and for which cancer cells are present in the blood (1). There are approximately 100,000 new global cases of CLL each year, and it is one of the most common types of leukemia in adults.

"Results from the BRUIN CLL-321 trial show that Jaypirca delivers clinically meaningful outcomes in a post-BTK inhibitor setting with markedly prolonged time to next treatment, including in those with high-risk characteristics often associated with poor prognosis," Paolo Ghia, MD, professor of medical oncology at Università Vita-Salute San Raffaele and IRCCS Ospedale San Raffaele, Milano, Italy, said in the Lilly press release (1). "Jaypirca allows for continued targeting of the BTK pathway following treatment with a covalent BTK inhibitor and has the potential to be an important new option in a setting with significant unmet need. The CHMP opinion is an important step toward bringing Jaypirca to patients in the European Union."

In the United States, Jaypirca was approved by FDA in 2023 under an accelerated approval pathway for treatment of adult patients with CLL or small lymphocytic lymphoma who have received at least two prior lines of therapy including a BTK inhibitor and BCL-2 inhibitor, or for treatment of adults with relapsed or refractory mantle cell lymphoma after at least two lines of systemic therapy (1).

 of four new US manufacturing sites, more than doubling its manufacturing investment in the country since 2020 to in excess of $50 billion total (4).

1. Eli Lilly and Company. Lilly's Jaypirca (pirtobrutinib) Recommended by CHMP for Approval in the European Union for Adults with Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL) Previously Treated with a BTK Inhibitor. Press Release. Feb. 28, 2025.
2. EMA. Meeting Highlights from the Committee for Medicinal Products for Human Use (CHMP) 24–27 February 2025. Press Release. Feb. 28, 2025.
3. EMA. EMA. Meeting Highlights from the Committee for Medicinal Products for Human Use (CHMP) 22–25 July 2024. Press Release. July 26, 2024.
4. Eli Lilly and Company. Lilly Plans to More Than Double US Manufacturing Investment Since 2020 Exceeding $50 Billion. Press Release. Feb. 26, 2025.

Jaypirca (pirtobrutinib) has received a conditional marketing authorization from EMA for mantle cell lymphoma. The drug was approved in the United States in 2023 for several indications.

EMA Gives Positive Opinion to Lilly Treatment for Chronic Lymphocytic Leukemia

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February 28, 2025 marked the annual edition of Rare Disease Day, established in 2008 by the European Organization for Rare Diseases (EURORDIS) (1,2). On leap years, Rare Disease Day has been recognized on February 29, the rarest date on the calendar.

The day’s official website said that more than 70 patient organizations partner with EURORDIS on a yearly basis to help build an international community with the objectives of achieving “equity in social opportunities, healthcare, and access to diagnosis and therapies for people living with a rare disease”—some 300 million people worldwide, according to the site (1).

According to the Rare Disease Day website, a “rare disease” is defined as that which affects fewer than one in 2000 people (1). More than 6000 such diseases are known to exist, 72% of them being genetic in nature.

With February 2025 drawing to a close, positive trial results and regulatory approvals have been reported for numerous rare diseases. The following is a brief and non-exhaustive rundown of the latest developments:

While congenital deafness present at birth affects approximately 1.7 in 1000 children born in the United States, a specific condition caused by variations in the otoferlin (OTOF) gene is considered ultra-rare, according to Regeneron (3). That information was part of an announcement that the company’s investigational gene therapy, DB-OTO, showed 72-week progress in speech and development in a first child diagnosed at 10 months of age, and a “notable response” in 10 out of 11 other children enrolled in a Phase I/II study (CHORD) so far. A surgical procedure that administers DB-OTO is similar to that of a cochlear implementation, Regeneron said in a press release, allowing it to be deployed in young infants. DB-OTO has received orphan drug designation from both FDA and the European Medicines Agency, and additional fast track, rare pediatric disease, and regenerative medicine advanced therapy designations from FDA.

DM1 affects an estimated one in 8000 people, and there are approximately 40,000 patients in the US, 75,000 in Europe, and 15,000 in Japan (4). That’s according to Boston-based PepGen, which on February 24 announced positive initial results from a Phase I trial (FREEDOM-DM1) of its investigational candidate PGN-EDODM1.

DM1 is a monogenic, autosomal dominant, and progressive disorder primarily affecting skeletal, cardiac, and smooth muscles, as well as the central nervous system. In severe cases, life expectancy may be reduced due to the increased mortality rates that accompany pulmonary and cardiac complications—alongside the customary symptoms of muscle weakness, myotonia, cardiac and respiratory abnormalities, gastrointestinal problems, early cataracts, cognitive or behavioral issues, or fatigue (4).

CTX is a lipid storage disease caused by a mutation in the CYP27A1 gene. This results in a deficiency of an enzyme that is important insofar as the body’s ability to break down cholesterol in a normal way, exacerbated by the gene mutation causing reduced bile production in the liver. When that happens, atypical cholesterol metabolites are deposited and cause damage in places in the body such as the brain, liver, skin, and tendons. 

 that it had approved Ctexli (chenodiol), from California-based Mirum Pharmaceuticals, as the first drug authorized by the agency to treat CTX (5). The recommended dosage for chenodiol is 250 milligrams, taken orally three times a day. Prescribing information includes a warning for liver toxicity in all patients, and increased risk of liver damage in patients with pre-existing liver disease or bile duct abnormalities.

PBC is defined as a chronic, autoimmune disease of the bile ducts, for which there is no cure. In Europe specifically, it affects approximately 22 out of every 100,000 people. Women are more commonly affected than men, and the disease if left untreated can cause liver disease and ultimately liver failure. Gilead Sciences, of California, 

 that its seladelpar, an oral, peroxisome proliferator-activated receptor (PPAR)-delta agonist, was granted conditional marketing authorization by the European Commission for treatment of PBC, either in combination with ursodeoxycholic acid (UDCA) in adults who have an inadequate response to UDCA alone, or as a monotherapy in patients unable to tolerate UDCA (6). (The drug is marketed as Livdelzi in the US.)

The pruritus, or chronic itch, and fatigue that are often symptoms of PBC—related to cholestasis, or impaired bile flow—can be debilitating, and a Phase III trial showed that improvement of pruritus was more pronounced after six months of treatment with seladelpar than with placebo (6).

TGCT is a non-malignant type of tumor that forms within or near joints. It is caused by the dysregulation and subsequent overproduction of the CSF1 gene and, if recurring or left untreated, can damage or degenerate the affected joint and surrounding tissues, leading to the potential of significant disability. 

 Ono Pharmaceutical of Osaka, Japan announced that FDA had approved its subsidiary Deciphera Pharmaceuticals’ Romvimza (vimseltinib), a treatment in capsule form for adults with symptomatic TGCT for whom surgical resection would cause potential worsening functional limitation or severe morbidity (7).

Even though Rare Disease Day comes around just once annually, news on treatments for rare diseases is always developing, and is a genre worth following year-round.

1. Rare Disease Day. What is Rare Disease Day? 

 (accessed Feb. 27, 2025).
2. EURORDIS. Who We Are. 

 (accessed Feb. 27, 2025).
3. Regeneron. Latest DB-OTO Results Demonstrate Clinically Meaningful Hearing Improvements in Nearly All Children with Profound Genetic Hearing Loss in CHORD Trial. Press Release. Feb. 24, 2025.
4. PepGen. PepGen Announces Positive Initial Results, Including Robust Splicing Correction, from Ongoing FREEDOM-DM1 Trial in Patients with DM1. Press Release. Feb. 24, 2025.
5. FDA. FDA Approves First Treatment for Cerebrotendinous Xanthomatosis, a Rare Lipid Storage Disease. Press Release. Feb. 21, 2025.
6. Gilead Sciences. Gilead’s Seladelpar Granted Conditional European Marketing Authorization for the Treatment of Primary Biliary Cholangitis. Press Release. Feb. 20, 2025.
7. Ono Pharmaceutical. U.S. FDA Grants Full Approval of Deciphera’s Romvimza (vimseltinib) for the Treatment of Symptomatic Tenosynovial Giant Cell Tumor (TGCT). Press Release. Feb. 14, 2025.

More than 6000 rare diseases—those which affect fewer than one in 2000 people each—are acknowledged in the medical community, with 72% of them being genetic.

Rare Disease Day Celebrated on February 28

Rare Disease Day, which is recognized on the final day of February each year—hence, February 29 in leap years, the rarest date on the calendar—shines a light not only on the 

6000 or more diseases that affect some 300 million people

 around the world, but also the medicines and therapies in development to help those impacted (1).

On Feb. 28, 2025, the European Medicines Agency 

 to Vyjuvek (beremagene geperpavec), a topical gene therapy for the ultra-rare genetic skin-blistering condition, dystrophic epidermolysis, which is caused by mutations in the collagen type VII alpha 1 chain (COL7A1) gene (2).

Earlier in February, FDA granted breakthrough therapy designation to radiprodil, GRIN Therapeutics’ investigational, potent negative allosteric modulator selectively targeting the N-methyl-D-aspartate receptor subtype 2B (NR2B or GluN2B), for treatment of seizures associated with GRIN gene-related neurodevelopmental disorder with gain-of-function mutations (3).

Meanwhile, FDA’s Center for Drug Evaluation and Research’s Accelerating Rare Disease Cures program, established in 2022, released its Year Two Annual Report in October 2024, and the Learning and Education to Advance and Empower Rare Disease Drug Developers initiative continues to offer insights to those inquisitive about the design and conduct of rare disease clinical trials, according to an FDA update (4).

According to data from Elsevier’s Scopus, the amount of literature on rare diseases experienced a steady climb starting in 2018 and hit a peak in 2021 after the onset of the COVID-19 pandemic, having leveled off since then but still well above pre-2018 levels (5). The United States has been dominating other countries in terms of rare disease research output, although China is a clear second and outpaces the US in most other disease areas. And since 2020, there has been an explosive increase in inquiries as to how artificial intelligence can be used to shape this research.

Yet despite this increased focus, challenges remain when it comes to ensuring effective clinical trials for rare diseases, as outlined by Phesi in a February 2025 report (6). The five main obstacles listed in that report are: limited patient populations or difficulties with recruitment; geographic dispersion and uncertainty of investigator site selectivity; heterogeneity in disease presentation and progression; a lack of historical clinical trial data in many cases; and regulatory and/or ethical concerns.

Growing uncertainty at the federal level may also become a mounting challenge for the rare disease community. Just this week, the FDA and NIH-sponsored Rare Disease Day 2-day event was postponed (7) with little explanation in the wake of sweeping layoffs within the FDA and NIH. The event "seeks to bring together a broad audience including patients, patient advocates, caregivers, health care providers, researchers, trainees, students, industry representatives, and government staff," according to the event website, but the postponement has left many in the community concerned about the future support for rare diseases. 

This adds to growing concern about future federal support for rare disease research and drug development, as the Rare Pediatric Disease Designation and Priority Review Voucher Programs also ended in December 2024 and were not renewed (8), leaving little financial motive for pharmaceutical companies to fund rare disease drug development. 

Rare Disease Day Celebrated on February 28.

, Feb. 27, 2025.
2. EMA. Meeting Highlights from the Committee for Medicinal Products for Human Use (CHMP) 24–27 February 2025. Press Release. Feb. 28, 2025.
3. GRIN Therapeutics. GRIN Therapeutics Receives FDA Breakthrough Therapy Designation for Radiprodil. Press Release. Feb. 25, 2025.
4. FDA – CDER. FDA Continues to Make Inroads in Rare Disease Drug Development. Press Release. Feb. 28, 2025.
5. Elsevier – Scopus – Rare Disease Research. Received via email correspondence on Feb. 27, 2025.
6. Phesi Rare Disease Showcase, 

5 Challenges of Delivering Effective Clinical Trials for Rare Diseases—And Strategies for Overcoming Them

; Phesi, February 2025.
7. FDA-NIH Rare Disease Day 2025. FDA.gov. Updated February 25, 2025. https://ncats.nih.gov/news-events/events/rdd
8. Rare Pediatric Disease Designation and Priority Review Voucher Programs. FDA.gov. Update September 27, 2024. https://www.fda.gov/industry/medical-products-rare-diseases-and-conditions/rare-pediatric-disease-designation-and-priority-review-voucher-programs

Regulatory clearances and approvals continue as agencies work to disseminate literature, raise awareness, redouble research efforts, and improve the efficacy of clinical trials.

Rare Disease Day 2025: Pharmaceutical Treatments Advancing in the US, EU

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The European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) recommended marketing authorization approval for four medicines in February 2025. The recommended drugs treat a number of types of cancer, immunodeficiencies, and a rare genetic skin blistering disease.

Conditional marketing authorization was given to Lynozyfic (linvoseltamab) for the treatment of the bone marrow cancer, relapsed and refractory multiple myeloma. The generic drug, Trabectedin Accord (trabectedin), was granted approval to treat advanced soft tissue sarcoma and relapsed platinum-sensitive ovarian cancer.

Deqsiga (human normal immunoglobulin) was granted approval as areplacement therapy for primary or secondary immunodeficiencies and immunomodulation in patients with certain autoimmune diseases.

A treatment for the ultra-rare genetic skin blistering condition, dystrophic epidermolysis bullosa, was given a positive opinion. The orphan drug, Vyjuvek (beremagene geperpavec), went through the agency’s PRIority MEdicines scheme, which offers early and enhanced regulatory support. Dystrophic epidermolysis bullosa is caused by mutations in the collagen type VII alpha 1 chain (COL7A1) gene.

In addition to the new drug approval recommendations, CHMP extended therapeutic indications for 16 drugs, including Abrysvo, Calquence, Columvi (an orphan drug), Darzalex (an orphan drug), Enhertu, Imfinizi, Jaypirca, Prevymis (an orphan drug), Rinvoq, Stelara, Supemtek Tetra, and Tremfya.

The indications for Kaftrio (ivacaftor/tezacaftor/elexacaftor) and Kalydeco (ivacaftor) were extended to include patients aged two years and older who have at least one non-class I mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. “This positive opinion brings disease-modifying treatment to all cystic fibrosis patients with modulator responsive mutations,” the agency said in a press release (1).

Ixchiq’s (chikungunya vaccine (live)) indication was extended to include immunization for adolescents 12 years and older to protect against the Chikungunya virus, a viral disease transmitted to humans by infected mosquitoes. 

The orphan drug, Fabhalta (iptacopan), had its indication extended to include treatment of adult patients with the ultra-rare kidney disease, complement 3 glomerulopathy.

At the meeting, CHMP also provided the results from its re-examination of the initial opinion for the indication extension for Keytruda (pembrolizumab) to treat unresectable non-epithelioid malignant pleural mesothelioma. The committee’s original decision was upheld. CHMP also held up its rejection of marketing authorization for Kizfizo (temozolomide) to treat neuroblastoma.

EMA also noted that the application for Pelgraz Paediatric (pegfilgrastim), for the treatment of neutropenia and prevention of febrile in children with cancer was withdrawn. The application of Rilonacept FGK Representative Service GmbH (rilonacept) to treat idiopathic pericarditis was also withdrawn.

The application to extend the indication of Dupixent to treat moderate-to-severe chronic spontaneous urticaria in adults and adolescents was withdrawn as well. In addition, the authorization holder for the COVID-19 vaccine, Bimervax, withdrew the application to include an adapted version to target the JN.1 strain of SARS CoV-2.

At the February meeting, CHMP also stated that the marketing authorization for Leqembi (lecanemab), which received a positive opinion in November 2024 for the treatment of mild cognitive impairment or dementia due to Alzheimer’s disease, does not need to be updated. “In January 2025, the European Commission (EC) asked the committee to consider information on the safety of Leqembi that became available after the adoption of the positive opinion and whether this would require an update of their recommendation. The CHMP has now concluded that its opinion recommending the marketing authorization does not need to be updated and has provided a response to the EC, which will now resume the decision-making process for this medicine,” EMA stated in the press release.

EMA. Meeting Highlights from the Committee for Medicinal Products for Human Use (CHMP) 24-27 February 2025. Press Release. Feb. 28, 2025.

Treatments for autoimmune diseases, multiple cancers, and skin blistering have been recommended for marketing approval.

EMA Recommends Four Medicines for Approval in February

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

Industry Outlook 2025: Interesting Relations and Detailed Discussions on Data

The political landscape in the United States has shifted, and while industry is learning about the various changes and new appointments, the full impact is hard to predict, not least because of the continuation effect from previous governments, points out Preeya Beczek, managing director and co-founder of Beczek.COM Ltd. However, there are three or four areas that she believes will be of potential interest with the new administration in place.

“I'm quite interested to think about China relations with the US and this BIOSECURE Act. I think that's going to perhaps impact the import tariffs, and then this could have a ripple effect on the global pharma industry, pharma economy,” Beczek explains. “The second thing, and this is not a new thing, is around anti-vaccine, anti-pharma sentiments, perhaps with the RFK [Robert F. Kennedy, Jr.] influence.”

Additionally, there is also discussion around the cost of drugs and provision of care and privatization that will continue throughout 2025, Beczek adds. “And then this final point I'm going to make is around digital health, health technology, AI [artificial intelligence], and mix that in the balance with data privacy,” she says.

Looking across the Atlantic, towards Europe, which has also undergone political shifts in 2024, industry is still working to get to grips with recent legislative changes, such as the new pharmaceutical legislation and the European Union clinical trials regulation, Beczek remarks. “So, coming back to that thing around information, data security, and what data [are] out in the public domain, right? There're still decisions that need to be made there at the very detailed level, and companies can expect to have detailed discussions around this,” she says.

Preeya Beczek, Managing Director and Co-Founder of Beczek.COM Ltd

Preeya Beczek is Managing Director and Co-Founder of Beczek.COM Ltd, a specialist in regulatory affairs and compliance. Preeya has worked in the regulatory affairs and compliance space for over 25 years, focusing on regulatory affairs activities at a strategic and operational level. Prior to her current role, Preeya worked in industry performing a lot of infrastructure and process development to support companies with new systems, initiatives with AI automation, regulatory, information management, system software modernization, and so on.

Videos

Preeya Beczek from Beczek.COM gives her thoughts on the areas to watch with the new US administration and how Europe might be finalizing preparations for previous legislative changes in an interview with Pharmaceutical Technology®.

Global pharmaceutical manufacturer Eli Lilly and Company, whose headquarters are in Indianapolis, Indiana, recently announced that it will be building four new domestic manufacturing sites in the United States, less than a month 

after President Donald Trump announced the intention to impose steep tariffs

 on imports from Canada, Mexico, and China (1,2).

The news from Lilly came the same day that Trump also threatened a 25% tariff on goods imported from the European Union, the 

After Trump announced the initial penalties on Canada, Mexico, and China on February 1—against which only the latter country has taken effect so far, pending ongoing negotiations—the Brookings Institution predicted that if the Canada and Mexico tariffs wind up being imposed, pharmaceutical exports from Mexico could fall by 61% (4). Should Canada and Mexico eventually enact retaliatory tariffs, as China has done, Brookings estimates the dropoff to climb to 72%. In addition, The Council on Foreign Relations calculated that US exports of vaccines, blood antisera, toxins, and cultures could collectively be one of the top five export categories most affected by the tariffs to the tune of $5 billion in exports to China, $2 billion to Canada, $994 million to Mexico, and $41 billion to the rest of the world (5).

In Lilly’s announcement on February 26, company chair and CEO David A. Ricks said an incentive passed during the prior Trump Administration was the impetus for the company’s decision to expand nationally—provided that incentive is continued during Trump’s current term.

"The Tax Cuts and Jobs Act legislation passed in 2017 during President Trump's first term in office has been foundational to Lilly's domestic manufacturing investments, and it is essential that these policies are extended this year,” Ricks said (1). “We believe that our investments in America and upskilling our nation's workforce will spark a significant ripple effect. For every job we create, many more will be generated, positively impacting the communities that host our innovative new sites."

Previous total domestic capital expansion commitments, made from 2020 to 2024, included both Research Triangle Park and Concord, in North Carolina; at the LEAP Innovation District in Lebanon, Indiana, the site of a new Lilly Medicine Foundry; Kenosha County, Wisconsin, where a manufacturing site has been acquired and expanded; and the company’s home city of Indianapolis, throughout which expansions and updates were made to multiple manufacturing facilities (1).

Three of the new sites will focus on API manufacturing, particularly bolstering small-molecule chemical synthesis capability and strengthening Lilly’s supply chain (1). The fourth is intended to extend Lilly’s global parenteral manufacturing network for future injectable therapies, according to the press release.

Negotiations on where the sites will be located are currently ongoing, and those locations should be announced later in 2025.

In total, Lilly’s capital expansion commitments in the US since 2020 now exceed $50 billion, with the February 26 announcement representing more than half that figure, as commitments from 2020 through 2024 totaled $23 billion (1).

Lilly said roughly 13,000 high-wage jobs could be created through the new sites: 3000 for highly skilled workers at the sites, when completed, among them engineers, scientists, operations personnel, and laboratory technicians (1). Close to another 10,000 construction jobs are expected to be needed.

"To deliver on our big bets on next-generation modalities like small molecules, biologics, and nucleic acid therapies, Lilly is investing in the state-of-the-art manufacturing infrastructure needed to deliver tomorrow's safe and reliable medicines," said Edgardo Hernandez, executive vice president and president of Lilly Manufacturing Operations, in the press release (1). "We are not just building facilities. We are creating a future where American innovation leads the world in pharmaceutical manufacturing, requiring a highly skilled workforce prepared to shape the future of health care. This is a significant step for our company, our communities, and the patients we serve."

1. Eli Lilly and Company. Lilly Plans to More Than Double US Manufacturing Investment Since 2020 Exceeding $50 Billion. Press Release. Feb. 26, 2025. https://lilly.mediaroom.com/2025-02-26-Lilly-plans-to-more-than-double-U-S-manufacturing-investment-since-2020-exceeding-50-billion
2. The White House. Fact Sheet: President Donald J. Trump Imposes Tariffs on Imports from Canada, Mexico and China. 

, Feb. 1, 2025 (accessed Feb. 4, 2025). https://www.whitehouse.gov/fact-sheets/2025/02/fact-sheet-president-donald-j-trump-imposes-tariffs-on-imports-from-canada-mexico-and-china/
3. Politi, J. and Inagaki, K. Donald Trump Threatens to Impose 25% Tariffs on EU Goods. 

, Feb. 26, 2025. https://www.ft.com/content/2f0288f6-3f6a-4334-b666-3f0122981842
4. Meltzer, J.P. Trump’s 25% Tariffs on Canada and Mexico Will Be a Blow to All Three Economies. 

, Feb. 3, 2025 (accessed Feb. 4, 2025). https://www.brookings.edu/articles/trumps-25-tariffs-on-canada-and-mexico-will-be-a-blow-to-all-3-economies/
5. O’Neil, S. K. and Huesa, J. What Trump’s Trade War Would Mean, in Nine Charts. 

, Feb. 1, 2025 (accessed Feb. 4, 2025). https://www.cfr.org/article/what-trumps-trade-war-would-mean-nine-charts

Previous domestic capital expansion commitments since 2020 had been made in Research Triangle Park and Concord, both in North Carolina; Kenosha County, Wisconsin; Lebanon, Indiana; and Lilly’s home city of Indianapolis.

In Wake of Trump Tariffs, Lilly Plans New US Pharmaceutical Manufacturing Sites

businessman working with sign of the top service Quality assurance, Guarantee, Standards, ISO certification and standardization concept. | Image Credit: ©Looker_Studio– stock.adobe.com

Process development is a key factor in the development and manufacture of biologics. Processes must be developed and validated so that product specifications can be met to create a safe and effective biologic drug. Contract development and manufacturing organizations (CDMOs) offer sponsor companies the expertise to develop these processes, which then must be validated. Process validation is a necessity to be sure the manufacturing process produces the desired, safe product.

For cell culture processes, process validation must be performed before good manufacturing practice (GMP) batches can be produced for commercial production, according to Daniel Giroux, vice-president of Biologics Development at Abzena. Formal process characterization studies must then be performed before the process validation so that one can understand the impact of variations of product parameters from their targets. Small-scale studies are performed on a validated scale-down model, and the information obtained is then applied to large-scale production.

Characterization and Qualification of Processes

Bio/Pharma Outsourcing Innovation eBook 2025

“You need to understand what are allowable ranges of process parameters and what will have an impact on your process or on the product quality, and those [parameters] that won’t [have an impact]. Then you define your process envelope …the combination of all these parameters, such as agitation, temperature, feed timing, feed amounts, and so on. [These are determined with] design-of-experiment approaches, because you have to measure [the variations’] impacts, both individually, as they change, but also when they change in combination,” says Giroux.

After process characterization and studies are performed and acceptable ranges established, batch records can be drafted, and validation protocols can be created, says Giroux. “And then you have to run multiple at-scale batches, so you know if your commercial process is going to be at the 2000-L scale, then your validation protocol will dictate how many batches you want to run. A typical number is three. It doesn’t have to be three. It could be more. Possibly could be less, rarely,” Giroux explains. “And then you execute your production batches, and you analyze heavily the impact on the product that’s coming out. You do more analysis than you normally would, something like this, and then you basically show that you met the acceptance criteria that you set up in your validation protocol.”

An essential part of process characterization is the establishment of critical process parameters (CPPs), according to Bob Schrock, PhD, senior director, Global Head of Process Development, at Lonza. Proposed critical process parameters (PCPPs) are obtained after process characterization studies are carried out.

“Once we do all the process characterization studies—and there can be literally thousands and thousands of samples, and [you have] done 12 or 15 different process characterization studies—the results are discussed with PD (process development) and MSAT (manufacturing, science, and technology) and from these, the actual CPPs can be determined,” says Schrock. “These CPPs are integrated into the process, and the validation of the process is then basically what we call the PPQ [process performance qualification] runs, the PPQ runs that are done just prior to commercialization. For [much of the] processes, the cell culture portion is only part of the process, for example, [with] viral vector manufacturing. There’s, of course, purification steps downstream from the [cell] culture portion.”

According to Schrock, PPQ runs show that a process is validated and robust and the number of runs needed depends on the variability of the process. “For a viral vector program that uses a large and well-characterized cell bank, you can do the minimum of three runs if they run perfectly. But for something [such as] autologous cell therapy, where you are starting with different cells from patients or healthy donors, you may need to do more,” says Schrock. “And then, of course, the question of using healthy donors to validate a process that is intended to start with patient samples and patient leukopaks packs, that’s always a deep and spirited discussion where you need to get creative on how you justify that. But at the end of your PPQ runs, you write a huge report that’s part of your BLA [biologics license application] submission, and it’s a cornerstone of your BLA. [It] proves that your process is validated.”

Pharmaceutical Technology®/Pharmaceutical Technology® Europe/BioPharm International

®
eBook: Bio/Pharma Outsourcing Innovation 2025
February 2025
Pages: 22–24

When referring to this article, please cite it as Haigney, S. Characterization and Qualification of Processes. 

Pharmaceutical Technology Bio/Pharma Outsourcing Innovation

Contract manufacturers have special expertise in the characterization and validation of biopharmaceutical manufacturing processes.

Cosette Pharmaceuticals, of Bridgewater, NJ, announced on Feb. 20, 2025 that it has an agreement in place to buy all remaining shares of Australia-based Mayne Pharma Group (1). The current price per share is AUD$7.40, which equates to approximately US$4.69; when the transaction is completed, the total consideration will be an approximate US$430 million.

In a press release, Cosette said that the acquisition will strengthen its dermatology and women’s health businesses, furthering its pharmaceutical footprint in the United States while also asserting a presence in international markets (1). Chiefly, Cosette said it wants to expand access to women’s health therapies. The company said that upon the close of the deal, it will be able to market 12 patent-protected products centering on women’s health and dermatology—some well-known brand names Cosette mentioned in the press release include Annovera, Bijuva, Imvexxy, Intrarosa, Nextstellis, Rhofade, and Vyleesi—plus have numerous programs in clinical development.

“This acquisition marks a transformational step for Cosette, adding patented, high-growth products to solidify our leadership in women’s health in the US and expanding our reach globally,” Apurva Saraf, president and CEO of Cosette Pharmaceuticals, said in the press release (1). “By combining Cosette’s strong portfolio with Mayne Pharma’s proven commercial expertise, the combined company will be well positioned to further invest in innovation, portfolio expansion and better serve our patients. We look forward to a timely closing and welcoming Mayne Pharma to the Cosette family.”

Cosette reports a staff of more than 350 employees, while Mayne Pharma employs more than 480, suggesting that the workforce of the combined company will more than double (1). Two state-of-the-art, FDA-approved manufacturing sites will be operational as a result of the merger, in Salisbury, South Australia, and in Lincolnton, NC, in the US.

“Joining the Cosette team amplifies our shared mission to improve lives through innovative and accessible women’s health and dermatology medicines,” said Shawn Patrick O’Brien, Mayne Pharma CEO, in the Cosette press release. “This transaction represents a unique opportunity for our employees, customers, and patients. Together, we will extend the reach of important therapies, drive innovation, and improve patient access.”

 was announced in May 2024, when the United Kingdom-based retail and commercial bank Santander UK said it was providing a £30 million (approximately US$38 million) loan to UK-based Ennogen Healthcare International, which focuses on not only dermatology but also respiratory and pain relief therapies, especially among those with chronic conditions (2).

 Metrics Contract Services, which had been its full-service specialty contract development and manufacturing organization, to Catalent in August 2022 for $475 million (3).

In this latest transaction, the boards of directors of both Cosette and Mayne Pharma have approved Cosette’s share purchase agreement, and Mayne Pharma has directed its shareholders to vote in favor of the merger, according to the press release (1). The acquisition is expected to close in the second quarter of 2025.

1. Cosette Pharmaceuticals. Cosette Pharmaceuticals Announces Acquisition of Mayne Pharma, Transforming Company into a Leader in Women’s Health and Dermatology. Press Release. Feb. 21, 2025.
2. Santander. Santander Provides Pharma Manufacturer Ennogen with £30 Million Credit Facility for Growth. Press Release. May 2, 2024.
3. Catalent. Catalent to Acquire Metrics Contract Services for $475 Million to Expand High-Potent Capabilities and Oral Development and Manufacturing Capacity. Press Release. Aug. 9, 2022.

While the boards of directors of both companies have approved the transaction, it is not expected to close until the second quarter of 2025, as Mayne Pharma’s shareholders must still vote in favor of the acquisition.

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