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 has more than 20 years of experience in the pharmaceutical industry. She has built her career in the areas of computer system validation, IT quality, and computer systems quality assurance. And while her current role focuses on data integrity, DI has been an important driving force throughout her entire career. She is an audit trail review subject matter expert, a leader in process improvement, and happily challenges the status quo.

Document Review and Quality Control Concept. Document with a checkmark, quality assurance, and process control. auditing, compliance, verification, data inspection, and business workflow management. | Image Credit: © Supatman - stock.adobe.com

What would it be like to reduce the audit trail review (ATR) burden in laboratories and manufacturing spaces all while satisfying inspector expectations? With more than 100 external inspections of Eli Lilly and Company’s commercial manufacturing sites conducted in the two years since the company published a novel and enhanced ATR assessment process, Lilly has established a sustainable and tested approach. This article describes how the company was able to achieve this.

Based on both external evaluation and internal assessment, the need to examine the data integrity (DI) governance program to ensure it remains in alignment with current regulatory expectations was determined. One area identified for further review was ATR. At that time, a need to make the ATRs more consistent was recognized, and the global requirements also needed to be enhanced. Additionally, requirements for data review needed to be more standardized. These enhancements were essential to maintaining trusted data and meeting ALCOA+ (attributable, legible, contemporaneous, original, accurate, complete, consistent, enduring, and available) principles.

Desiring to upgrade the approach across all sites, external consultants were hired to help build an enhanced global ATR process. However, the implementation of this global process was not specific enough, and uncovered potential inconsistencies in implementation, confusion from site and global teams, and frustration about the global process being too open-ended. Because the implementation strategy was open to local interpretation, information technology (IT) support teams were responsible for determining how to assess their systems and independently determined the DI gaps that needed an ATR. They also determined the justification for DI gaps that would not have an ATR. These independent assessments of the global ATR process were not sufficient to support an overall implementation, so a more holistic approach was needed. With the advances in technology in the pharmaceutical industry, as well as evolving regulatory expectations, a more specific and global process was warranted.

As a result, a centralized data management team was added to the organization to ensure sustainable DI processes were developed and maintained. This team is an independent, strategic, global quality and compliance-level team that supports all functions across operations, research, and commercial. This team is fully dedicated to DI governance and is a key organizational component that establishes DI policy.

To create a more robust ATR process, the original process’ authors were interviewed to understand theprocess state, and site and global teams that had started to use the first version were also consulted. It was determined that global data management needed to provide more specific ATR tools to the local manufacturing teams so they could continue to focus on producing high-quality products. The available regulations and industry guidance were then studied that govern ATR (

). Lastly, a deep dive into the existing established DI requirements was performed, and it was determined that they were strong and well-developed. The conclusion of the research was that the company needed an ATR assessment process that was comprehensive and robust, but also easy to follow, keeping in mind the end users’ experience with ATR.

 Regulations and industry guidance utilized in the ATR process design.

Cross-referencing the company’s DI requirements with the industry regulations and guidance, a specific set of logical controls were documented as expected controls for identified DI vulnerabilities. If systems could not be configured with the expected logical control, minimum ATR activities are expected to be performed and were consequently outlined for each DI vulnerability. Therefore, the result of following this process would mean that DI requirements are either met through a logical control or ATR is performed to mitigate the vulnerability, ensuring no compliance gaps.

The workflow for developing an ATR assessment process is represented in 

Workflow for developing an audit trail review (ATR) assessment process.

The following process was designed for areas to use when evaluating their ATR responsibilities. A lead assessor from the quality, business, or IT group would be appointed and organize the appropriate team of subject matter experts (SMEs) to assess the system. Assessment teams would then:

evaluate potential DI risks based on the established minimum DI requirements

determine if there are the specified logical controls in place that mitigate each risk

document the ATR expectations when those controls do not exist.

This three-part assessment process was expanded upon in a global standard operating procedure (SOP), and an assessment template was created to make it easy for teams to pick up and utilize. When ATR is required, teams follow the process in 

Workflow for determining and executing ATR requirements.

 shows two hypothetical examples of how the process can work with this ATR process flow if the requirement is “end users must not have the ability to modify or delete output data.” These examples are provided for illustrative purposes only, as each company will have its own systems and controls and should not rely on these specific examples.

The assessment process would look like this:

Workflow showing a hypothetical example of an ATR assessment.

Notice the template phrasing above is “Do users have the ability…?” It is not “Will they…?” Phrases like “Will they…?” or “Can they…?” imply a procedural control is acceptable, and a procedural control is not an acceptable control strategy in the industry. Although a determination of “No Audit Trail Review required” is made in the second hypothetical example, keep in mind there may be additional data reviews for batch release based on other requirements or different regulations. However, if there are logical controls in place that have been validated, the data integrity risk drops significantly.

Novel, enhanced, sustainable approach for ATR

The newly structured ATR SOP has been well-received, and teams were eager to use the assessment template. There is an added benefit in that the SOP has transformed employees’ understanding that if a system can be designed and validated to meet the expected controls in the assessment, a review is not needed, and the time and expense of performing non-value-added data reviews is drastically cut. An in-depth training program was also established and rolled out to every manufacturing site and global support team. The training program introduced the novel and enhanced process and instructed teams on how to effectively assess systems for their ATR needs. This process has directly translated into other improvement initiatives and is another tool to complement the DI by design approach when implementing new systems. This means that systems are designed to meet the expected control instead of the required long-term reviews that would otherwise be required. And when an ATR is required, there is a globally consistent approach that can stand up to external audits.

In conclusion, a more sustainable ATR assessment process was developed and implemented that reduced the ATR burden, enhanced DI compliance, and aligned with current good manufacturing practice expectations. The process involved a three-part evaluation of potential DI risks, logical controls, and ATR expectations based on a set of internal DI requirements and industry standards. The process also led to improved system designs that meet the expected controls and more specifically define when an ATR is needed. The procedure has been completely integrated into the manufacturing space and has been able to withstand external scrutiny.

Diana Russo has more than 20 years of experience in the pharmaceutical industry. She has built her career in the areas of computer system validation, IT quality, and computer systems quality assurance. And while her current role focuses on data integrity, DI has been an important driving force throughout her entire career. She is an audit trail review subject matter expert, a leader in process improvement, and happily challenges the status quo.

Articles

Eli Lilly and Company developed an innovative and sustainable approach to audit trail review (ATR) aimed at reducing the ATR burden while adhering to regulatory expectations and data integrity (DI) principles. The process has transformed employees' understanding of ATR and complemented the DI by design approach, leading to better system designs that meet expected controls and reduce non-value-added data reviews.

A Novel, Enhanced, and Sustainable Approach to Audit Trail Review

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

medicine and vision concept - woman closeup and eye diagram, future technologies | Image Credit: ©Julia - stock.adobe.com

Aging of the global population and the rise of chronic diseases, particularly diabetes, have contributed to an increase in the occurrence of eye diseases, such as glaucoma, keratitis, age-related macular degeneration (AMD), dry eye disorder (DED), and diabetic retinopathy (DR). Pharmaceutical companies have responded with growing investment in the research and development of novel eye treatments and drug delivery systems designed to address key challenges in ocular therapy. Current treatments range from traditional small-molecule and antibody-based drugs to cell and gene therapies and nanoparticle delivery solutions, along with various types of ocular implants and the use of drug-eluting contact lenses (1,2).

One area of focus has been the development of solutions for the sustained delivery of treatments, particularly to the posterior part of the eye. Many ocular therapies are formulated as eye drops that must be administered frequently to overcome the many physical and mechanistic barriers in the eye and ensure sufficient dosing. Sustained and targeted delivery products are helping reduce the dosing frequency by overcoming ocular barriers and increasing bioavailability.

Delivery of therapeutics to the anterior, or front of the eye, is generally simpler than delivery to the posterior part, because topical eye drops are an option. There are limitations to their effectiveness, however. “Drops do not maintain good bioavailability and are relatively quickly flushed out by nasolacrimal drainage,” explains Jeffrey S. Heier, chief scientific officer with Ocular Therapeutix. “While they are a convenient mode of delivery,” he adds, “they present challenges in terms of not only bioavailability, but limited duration of therapeutic effect, both of which contribute to inconsistent patient compliance and suboptimal outcomes.”

Treatments for glaucoma (high eye pressure), as well as infections and inflammation of the eye, are good examples. Glaucoma eye drops typically need to be administered at least once daily, and in many cases, multiple times a day. For some conditions, Heier observes, drops must be delivered on an hourly basis. “Such a dosing frequency is only sustainable for a short period of time. In fact, it is readily accepted that even with easy-to-administer options like eye drops that must be applied just once daily, adherence remains a major issue due to the frequency of this regimen,” he says.

Another option for treatment of the anterior segment of the eye is straightforward intracameral injections, according to Heier. This method of administration delivers ocular therapies directly into the anterior chamber of the eye, allowing for targeted delivery and resulting in enhanced bioavailability (3).

While treatments for infection, inflammation, high eye pressure, and neovascularization have been shown to be effective, this method of delivery is considered “off-label,” as FDA has not approved products specifically for this use, except two intracameral implants (see below). In addition, many patients are hesitant to receive eye injections.

Targeting the back of the eye presents unique challenges, not only in achieving therapeutic durability but also in navigating complex regulatory expectations, Heier comments. Indeed, delivery to the posterior segment is anatomically more complicated, especially when the durability of treatment is a primary objective.

“Although advances in intravitreal medicines have shown incremental increases in durability compared to prior standard of care, current retinal therapies rely on frequent intravitreal injections to maintain their effect,” observes Peter Jarrett, chief technical officer for Ocular Therapeutix.

For many patients, even therapies that require administration every three to four months can be challenging, as this type of regimen places a significant burden on patients and care partners, according to Jarrett. “To treat the full spectrum of patients with retinal disease or other conditions affecting the posterior segment, there is still a need for more durable treatments, and the development of longer-lasting treatments is such a critical focus,” he says.

New sustained-delivery therapies, however, must be proven to be as safe and effective as existing treatments that may require much more frequent administration. In addition, Jarrett notes that targeted delivery to the retina and posterior segment of the eye necessitates overcoming several blood-ocular barriers, including the blood-aqueous barrier and the blood-retina barrier.

“Historically,” Jarrett explains, “overcoming these physiological defenses has required delivering drugs at high concentrations. However, this approach often results in increased systemic exposure, which in turn can lead to a higher incidence of adverse events and toxicities. Striking the right balance between effective ocular delivery and systemic safety remains a focus in the development of retinal therapies.”

Potential for better treatments with greater convenience

While small steps taken to enhance ocular delivery have had positive impacts, there is still real potential for innovative solutions, particularly those leveraging sustained-release delivery technologies, to have dramatic effects on patient outcomes.

“While incremental improvements can be achieved through sophisticated formulations, such as enhancing solubility, prolonging ocular surface retention, or improving penetration through ocular barriers, these refinements often reach a ceiling in terms of clinical impact,” Heier remarks. “In contrast, transformative advances in treating chronic eye diseases are more directly realized through sustained-release delivery technologies, which bypass many of the pharmacokinetic limitations of topical or injectable drugs by providing continuous, controlled delivery of therapeutics directly to targeted intraocular tissues over extended periods,” he contends.

In addition, Jarrett emphasizes how important it is for developers to realize that results obtained in clinical trials often do not translate to the real world for treatments with dosing regimens patients have difficulty consistently maintaining as part of their daily lives. “A durable therapy that reduces treatment burden could offer not just convenience, but potentially better long-term outcomes for patients who would otherwise fall through the cracks of an intensive treatment schedule. Recognizing this balance between ideal clinical trial conditions and the real-world experience of patients is key to advancing more durable treatment options,” he states.

Nanoscale drug-delivery systems are recognized to achieve enhanced bioavailability and targeted and sustained delivery of many types of therapeutics addressing a wide variety of conditions, including eye diseases (2). Examples of different types of nanoparticles used for ocular drug delivery include nanomicelles, liposomes, polymeric nanospheres, and peptide-based nanoparticles (2).

Nanomicelles in preclinical testing have been shown to experience good uptake by corneal cells and when administered topically to achieve sustained delivery of drugs to treat DED, neovascular AMD, inflammation, and other eye disorders (1). Biocompatible lipid nanoparticles can deliver drugs with both hydrophobic and hydrophilic properties for extended periods. In one animal model of glaucoma, large unilamellar liposomes achieved sustained delivery of latanoprost, a common drug used to reduce eye pressure, for up to five days (4).

Peptide-based nanoscale delivery systems are particularly attractive because they are not only biocompatible, but can be used to target specific cell receptors, disrupt endosomal membranes, and carry drug payloads to the nucleus (1). Of the two main types of systems (elastin-like polypeptides and silk fibroin polymers), the former have been investigated for sustained release of drug substances from contact lenses due to their ability to remain adhered to their surfaces.

Researchers continue to investigate the potential of nanoscale materials for the formulation of extended-release ocular therapeutics, with efforts focused on increased drug-loading capacity, ocular residence time, and release periods while reducing potential toxicities (1).

Drug-eluting contact lenses and canalicular plugs

Given the limitations and issues associated with the use of eye drops and intracameral injections for treatment of conditions in the anterior segment of the eye, other options for delivery are looking to leverage the accessibility of this portion of the eye, according to Heier. Examples include drug-eluting contact lenses and canalicular plugs.

As indicated previously, sustained, topical delivery of ocular therapies to the anterior of the eye is possible using contact lenses loaded with active drug substances, such as peptide-based nanoparticles carrying drug payloads. It is even possible to improve drug loading by incorporating non-covalent binding sites into the lenses when they are manufactured (1). Delivering drugs using contact lenses is attractive because this approach is non-invasive and can potentially support increased drug uptake compared to topical applications (eye drops, creams, ointments). ACUVUE Theravision contact lenses (Johnson & Johnson Vision Care), which provide sustained delivery of ketotifen for the treatment of itchy eyes, are the first FDA-approved drug-eluting contact lens product (5).

Canalicular plugs belong to a class of treatments known as punctal plugs, which are inserts designed to slow or block the outflow of tears from the eye (6). Punctal plugs can be temporary, semi-permanent (resorbable), or permanent (synthetic, usually silicone), and some are able to provide sustained release of drug substances. They are most widely used to treat DED and have been shown over three decades to be generally safe and effective; although, they can fall out, become partially displaced, or lead to watery eyes.

Recent developments have helped address many of these issues. One example is a canalicular gel device (Lacrifill, Nordic Pharma) introduced in June 2024 (7). The chemically crosslinked particulate hyaluronic acid (HA) hydrogel device is designed to completely fill the canaliculus regardless of its size in different patients, preventing dislodgement and the buildup of stagnant tears and mucus that can result in infection. It is meant to be used for up to six months and can be easily removed by applying a sterile solution.

Significant advances have also been made over the past two decades in ocular implant technology for sustained release of drugs that treat a number of eye diseases. Implants can be biodegradable, although some are not (8). The former can suffer from the rapid release of remaining active drug substance upon degradation, while the latter require surgical removal when the drug substance is fully released.

Bioerodable implants are thus receiving more attention. These products are slowly solubilized upon exposure to biological fluids, leading to slow release of the drug and absorption of the implant material into the eye, avoiding a final “burst” release (8). The rate of dissolution can also be controlled by modifying the chemical composition of the polymer used in the implant. Theoretically, these devices could provide sustained release of therapeutics for months to years.

Jarrett highlights the use of degradable or erodible matrix materials for the sustained delivery of small-molecule drugs. “The choice of drug and implant material are extremely important in designing such a sustained-release system,” he says. “Challenges include drug potency, safety, control of drug release rate, local and systemic drug concentrations, implant biocompatibility and bioresorption, implant size and placement position, and the injection technology utilized,” Jarrett denotes.

As an example, Jarrett points to bioresorbable hydrogel technology as offering a long-term option for delivering small molecules to the posterior segment. Hydrogels, he says, are well-suited to deliver extremely low solubility, lipophilic drugs because the release rate is being controlled by drug solubility. “Drug solubility in both the hydrogel matrix and in the vitreous humor fluid are important rate control factors. These factors may be combined to create a constant release rate in the eye,” he explains.

In addition, the bioresorbable hydrogel vehicle can be designed to break down into water soluble molecules that are neutral pH, non-reactive, and readily cleared from the eye, with timing of resorption tailored to synchronize with drug depletion, allowing repeat injections without crowding the vitreous with empty vehicles or “shells” from earlier injections.

Implants have, in fact, been developed for insertion into both the anterior and posterior segments of the eye. The devices are either implanted surgically or via injection (intracameral for anterior and intravitreal for posterior applications). Injected implants are typically smaller as they must be able to fit into a needle (7).

Two examples of FDA-approved intracameral implants are Durysta (Allergan) and iDoseTR (Glaukos), both of which provide sustained release of drugs (bimatoprost and travoprost, respectively) to treat intraocular pressure in open-angle glaucoma/ocular hypertension.

There are also several intravitreal implants approved by FDA, including Ozurdex (AbbVie) for macular edema and Dexycu (EyePoint Pharmaceuticals) for post-operative inflammation. Encelto (Neurotech Pharmaceuticals), which leverages an encapsulated cell therapy technology to continually deliver therapeutic doses of ciliary neurotrophic factor to the retina to treat macular telangiectasia type 2, received FDA approval in early 2025 (9).

FDA approval was also granted in early 2025 to Susvimo (Roche) for the treatment of DME, which continuously delivers ranibizumab via the Port Delivery Platform, a refillable (every six months) eye implant surgically inserted into the eye (10).

While there remain many challenges to effectively treating diseases of the eye, significant strides have been made with recent advances in technologies supporting sustained, targeted release of effective ocular therapies. With many additional, innovative solutions in preclinical through late clinical development, additional progress is expected.

Whalen, M.; et al. Seeing the Future: A Review of Ocular Therapy. 

Chandel, A. and Kandav, G. Insights into Ocular Therapeutics: A Comprehensive Review of Anatomy, Barriers, Diseases, and Nanoscale Formulations for Targeted Drug Delivery. 

https://doi.org/10.1016/j.jddst.2024.105785

Gautam, M.; et al. Intracameral Drug Delivery: A Review of Agents, Indications, and Outcomes.

 39 (2), 102-116. DOI:10.1089/jop.2022.0144

Natarajan, J.V.; et al. Sustained Release of an Anti-Glaucoma Drug: Demonstration of Efficacy of a Liposomal Formulation in the Rabbit Eye. 

Johnson & Johnson Vision. Johnson & Johnson Vision Care Receives FDA Approval for ACUVUE® Theravision™ with Ketotifen - World's First and Only Drug-Eluting Contact Lens. Press Release, March 2, 2022. 

https://www.prnewswire.com/news-releases/johnson--johnson-vision-care-receives-fda-approval-for-acuvue-theravision-with-ketotifen--worlds-first-and-only-drug-eluting-contact-lens-301493964.html

Cleveland Clinic. Punctal Plugs. ClevelandClinic.org (accessed June 20, 2025). 

https://my.clevelandclinic.org/health/treatments/25249-punctal-plugs

Charters, L. New Canalicular Gel Shows Promise for Dry Eye Treatment. 

https://www.ophthalmologytimes.com/view/new-canalicular-gel-shows-promise-for-dry-eye-treatment

Wykoff, C.C.; Kuppermann, B.D.; and Saïm, S. Extended Intraocular Drug-Delivery Platforms for the Treatment of Retinal and Choroidal Diseases. 

Neurotech Pharmaceuticals. Neurotech’s ENCELTOTM (revakinagene taroretcel-lwey) Approved by the FDA for the Treatment of Macular Telangiectasia Type 2 (MacTel). Press Release, March 6, 2025. 

https://www.neurotechpharmaceuticals.com/wp-content/uploads/Neurotech_Press-Release_BLA_Approval_FINAL.pdf

Roche. FDA Approves Roche’s Susvimo as the First and Only Continuous Delivery Treatment for the Leading Cause of Diabetes-related Blindness. Press Release, Feb. 3, 2025.

https://www.roche.com/media/releases/med-cor-2025-02-04#:~:text=Susvimo%C2%AE%20(previously%20called%20Port,edema%20(DME)%20that%20continuously%20delivers

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

Hydrogels, drug-eluting contact lenses, and other implant technologies show real promise.

Advanced Solutions for Sustained Delivery of Ocular Therapies

Patrick Lavery is an Editor for the MJH Life Sciences brands 

. Previously at MJH, he filled the same role for 

Old rusty shovel in the ground on the building | Image Credit: © photolink - stock.adobe.com

 the contract development and manufacturing organization within Mumbai-based 

 held a groundbreaking ceremony on June 25, 2025, for its new sterile injectables development and manufacturing facility in Lexington, Ky. (1). The new construction in Lexington, as well as in Riverview, Mich., comprise 

 first announced by Piramal Pharma in May 2025 (2).

However, the expansion of the Lexington site accounts for $80 million of that amount, and the Lexington plans 

 in September 2024, well prior to the disclosure of the updated May 2025 plan (3).

Piramal Pharma’s $80 million expansion in Lexington, Ky., will more than double sterile injectable production capacity and add 40 full-time manufacturing jobs.

The Lexington site will serve as Piramal's dedicated fill/finish facility, featuring new lyophilizers, a modern filling line, and expanded lab capabilities.

The investment aligns with US onshoring trends and regulatory shifts, supporting commercial-scale manufacturing amid projected sterile injectables market growth.

At the time of the May announcement, Piramal Pharma said it was responding to what it called a trend toward onshoring of drug supply in the United States. Earlier that month, US President Donald Trump signed an executive order directing FDA and the Environmental Protection Agency (EPA) to reduce certain regulatory barriers—including urging EPA to accelerate construction of prescription drug manufacturing sites—after which FDA said it intended to expand unannounced inspections at foreign manufacturing facilities (4,5).

Piramal Pharma said its Lexington site is designed to be the company’s dedicated fill/finish facility, providing fill/finish services for all integrated programs and specializing in sterile compounding, liquid filling, and lyophilization for sterile injectable drug products (1). The expansion, which is expected to be completed by late 2027 and which will eventually create 40 new, full-time jobs, will accommodate commercial-scale sterile injectable manufacturing with 24,000 additional square feet, plus a new laboratory, and state-of-the-art machinery: a new filling line, specialized capping machine, external vial washer, and two commercial-size lyophilizers.

As such, the Lexington site will more than double its manufacturing capacity upon completion of the expansion, from a current peak utilization of 104 product batches annually to more than 240, according to Piramal Pharma (1).

“We prioritize patient, consumer, and customer centricity in all our operations, engaging with the populations we serve to better understand, anticipate, and address their needs,” Nandini Piramal, chairperson, Piramal Pharma, said in a company press release (1). “Our research has revealed that the sterile injectables market is projected to exceed $20 billion by 2028, underscoring the urgent need for us to enhance our offerings in this segment. We are confident that this strategic $90 million investment will empower us to meet the demands of this market, reinforcing our position as a trusted global partner in biologic manufacturing. By enhancing the services we provide to our partners, we can reduce the burden of disease for more patients around the globe.”

Piramal Pharma said the expansion at the Riverview site is expected to be complete by the end of 2025; at this location, a commercial-scale suite is being added that is specifically designed for development and manufacturing of payload-linkers (1).

Piramal Pharma Solutions Breaks Ground on $90M Expansion Plan

. Press Release. June 30, 2025.
2. Piramal Pharma. 

Piramal Pharma Ltd. Continues to Invest In USA; $90M in Expansions of Two US Sites.

 Press Release. May 12, 2025.
3. Piramal Pharma Solutions. 

Piramal Pharma Solutions Announces $80M Expansion Plan for Sterile Injectables Facility in Lexington, Kentucky.

 Press Release. Sept. 30, 2024.
4. The White House. 

Fact Sheet: President Donald J. Trump Announces Actions to Reduce Regulatory Barriers to Domestic Pharmaceutical Manufacturing.

FDA Announces Expanded Use of Unannounced Inspections at Foreign Manufacturing Facilities.

The expansion of the Kentucky site accounts for $80 million of the announced investment, with the remaining money earmarked for facilities in Michigan.

Piramal Pharma Holds Groundbreaking at Kentucky Facility, Part of $90 Million Investment Plan

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

FDA announced on June 27, 2025, that Sandoz, Inc. is voluntarily recalling one lot of cefazolin for injection, USP, 1 gram per vial after customers complained that four penicillin G potassium for injection, USP, 20 million units labeled vials were incorrectly included in a carton of Cefazolin for Injection vials (1). While the company states it has not received any reports of adverse events associated with the recall, they did receive one complaint of the wrong product being given to a patient.

Four vials of penicillin G potassium for injection, USP were wrongly included in a lot of cefazolin for Injection, USP.

The two antibiotics have different indications. Using penicillin G potassium for injection, USP instead of cefazolin for injection, USP could be life threatening.

Sandoz’s new facility in Slovenia will produce injectable products for both existing and upcoming biosimilars.

The new facility is part of a $1.1 billion investment the company has planned through 2029.

The impacted lot number is PG4360, vial national drug code (NDC) number 0781-3451-70, with an expiration date of 2027-NOV (1). The lot was manufactured by Sandoz GmbH and distributed by Sandoz Inc. The vials that were incorrectly included have the vial NDC 0781-6136-94 and an expiration date of 2027-NOV.

The two antibiotics have different indications

Cefazolin for injection USP is indicated for the treatment and/or prevention of bacterial infections in different parts of the body in adults, the elderly, and children (1). Penicillin G potassium for injection treats certain serious infections, such as septicemia, skin infections, and wound infections, and can be used to treat diphtheria, community-acquired pneumonia, peritonitis, meningitis/brain abscesses, osteomyelitis, infections of the genital tract, anthrax, tetanus, gas gangrene, listeriosis, pasteurellosis, rat bite fever, fusospirochetes, actinomycosis, complications in gonorrhea and syphilis, and Lyme. It should be used to only treat or prevent infections caused by susceptible bacteria to reduce the chance of drug-resistant bacterial from developing.

According to an FDA press release (1), the two antibiotics have different indications despite being part of the same beta-lactam group of antibiotics and having overlapping patient populations. The dosing regimens for each may also differ.

Administration of penicillin G potassium injection instead of cefazolin injection may have life-threatening consequences that include lack of efficacy resulting in less than optimal treatment of severe infections, antibiotic resistance, allergic reactions, drug interactions, and cardiac arrhythmias caused by high potassium.

Sandoz is asking customers to return the recalled product, which was shipped to select wholesalers for nationwide distribution. The company recommends providers stop using the product immediately. Adverse events may be reported to FDA through its 

In other Sandoz news, the company broke ground on a new facility in Slovenia in July that will produce injectable products for both existing and upcoming biosimilars. The project adds $440 million to a $1.1 billion investment the company has planned through 2029.

"Biosimilars is the fastest-growing segment of our pipeline as the need of patients and healthcare systems for these critical medicines continues to grow rapidly,” Richard Saynor, chief executive officer of Sandoz, said in a press release (2). “As the global leader in the field, we are investing to meet rapidly growing patient demand. With a commitment of over US$1.1 billion, we are proud to significantly expand our biosimilar manufacturing capacity in Europe as Slovenia’s largest direct foreign investor. This is another major step that will position Sandoz uniquely to capitalize on the unprecedented biosimilars market opportunity of the next decade."

"Our investment in biomanufacturing in the heart of Europe marks another important milestone in building our own independent manufacturing network—one that enhances our control, resilience and agility across the global supply chain,” Glenn Gerecke, chief manufacturing and supply officer at Sandoz, said in the release. “We recognize the strategic value Slovenia brings for us as a company: a highly skilled talent pool in natural sciences and engineering; a central location with world-class logistics infrastructure; cost-competitive production; and a stable, innovation-driven environment closely connected to academia and research."

FDA. Sandoz Inc. Issues Voluntary Nationwide Recall of One Lot of Cefazolin for Injection Due to Product Mispackaging. Press Release. June 27, 2025. 

https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/sandoz-inc-issues-voluntary-nationwide-recall-one-lot-cefazolin-injection-due-product-mispackaging

Sandoz. Sandoz Further Asserts Leadership in Biosimilars, Breaking Ground on New Slovenia Facility to Expand European Biosimilar Hub and Global Market Reach. Press Release. July 1, 2025. 

https://www.sandoz.com/sandoz-further-asserts-leadership-biosimilars-breaking-ground-new-slovenia-facility-expand-european/

The company is voluntarily recalling one lot of cefazolin for injection, USP, 1 gram per vial due to customer complaints of the wrong product being included in a carton.

Sandoz Recalls Cefazolin Due to Mispackaging, Opens Biosimilar Facility in Slovenia

NÜRNBERG / GERMANY - APRIL 7, 2019: Siemens Logo on an office building in Nürnberg. Siemens is a German engineering company | Image Credit: © filmbildfabrik - stock.adobe.com

Siemens AG has completed its $5.1 billion acquisition of Boston-based Dotmatics, a provider of research and development software for the life sciences sector (1). The deal brings Dotmatics under the umbrella of Siemens’ Digital Industries Software division and marks a significant expansion of Siemens’ artificial intelligence (AI)-driven product lifecycle management (PLM) portfolio into the life sciences domain.

Originally announced in April 2025 (2), Siemens described the transaction as a “strategic milestone” that aligns with structural changes in healthcare—such as aging populations, broader access to medical care, and increasing demand for collaborative, data-integrated R&D environments (1). The acquisition is part of Siemens’ ONE Tech Company strategy, aimed at enhancing digital capabilities across high-growth industrial sectors.

·Siemens’ acquisition of Dotmatics enhances AI-driven drug development, connecting R&D to manufacturing through a unified digital thread.

·Dotmatics’ Scientific Intelligence Platform will streamline pharmaceutical workflows, accelerating discovery, development, and production cycles.

·Pharma manufacturers gain access to Siemens’ expanded digital twin and PLM tools, enabling scalable, data-integrated, and compliant operations.

“By acquiring Dotmatics, we’re strategically strengthening our position in Life Sciences and creating a world-leading AI-powered PLM software portfolio as part of Siemens Xcelerator,” said 

Roland Busch, president and CEO of Siemens

 AG (2). “Artificial intelligence has emerged as a transformative force across various industries, and its application in life sciences is becoming increasingly important.”

Connecting R&D to manufacturing in the pharma value chain

The Dotmatics platform centers around its Scientific Intelligence Platform, Luma, which supports AI-powered, multimodal drug development and data contextualization (1). The software facilitates seamless collaboration, connects previously siloed data across R&D and manufacturing, and creates a continuous digital thread through the pharmaceutical development lifecycle.

“With Dotmatics, we’re building a new era of innovation in Life Sciences,” said Busch. “From research through to production—we’re creating a unique, end-to-end digital thread: We combine Dotmatics’ scientific intelligence with our industrial AI technologies and digital twins. This will allow us to help our customers accelerate breakthroughs, reduce development cycles, and bring life-saving pharmaceuticals faster and more affordably to the market.”

For Siemens, the acquisition opens up an additional $11 billion in total addressable market within industrial software (1). Dotmatics is expected to generate more than $300 million in revenue in fiscal year 2025. Siemens projects medium-term revenue synergies of around $100 million annually, scaling up to more than $500 million in the longer term. The acquisition is expected to be immediately accretive to growth, profitability, and cash flow.

“The acquisition of Dotmatics drives strong revenue synergies and is highly profitable and cash generative,” said 

Ralf P. Thomas, chief financial officer of Siemens

 AG (2). “Financing will be provided primarily through the sale of shares in listed companies, including Siemens Healthineers.”

Siemens’ push into scientific innovation

The transaction also reflects the evolution of Dotmatics itself. Formerly known as Insightful Science, the company rebranded as Dotmatics in April 2022 following its acquisition of Protein Metrics and a period of expansion under the ownership of Insight Partners (2). 

, emphasized the strategic alignment in the press release announcing the deal.

“Following an exciting journey with Insight Partners, where Dotmatics achieved remarkable growth and portfolio expansion, we are thrilled to announce our new chapter with Siemens,” said Swalla (2). “Combining our next-generation scientific intelligence platform and industry-leading scientific applications together with Siemens' digital twin and AI capabilities, we’ll drive a new wave of innovation in life sciences R&D.”

Latest in high-profile software acquisitions

The Dotmatics acquisition follows closely on the heels of Siemens’ $10 billion acquisition of Altair Engineering, completed in April (3). That deal brought new simulation, high-performance computing, and AI capabilities into Siemens’ industrial software offerings and was similarly integrated into the Siemens Xcelerator platform.

“We welcome the Altair community of customers, partners and colleagues to Siemens,” Busch said at the time of that acquisition (3). “Adding Altair’s groundbreaking innovations to the Siemens Xcelerator platform will create the world's most complete AI-powered design, engineering and simulation portfolio.”

Together, these back-to-back deals underscore Siemens’ aggressive push into domains in which digital twin technology, data integration, and AI are reshaping complex product development. With Dotmatics and Altair, Siemens now commands an expanded portfolio capable of supporting highly regulated industries like pharmaceuticals with the digital tools needed to meet rising demand, tighter timelines, and greater product complexity.

Siemens Completes Acquisition of Dotmatics

Siemens Acquires Dotmatics, Extending AI Software Portfolio into Life Sciences

Siemens Acquires Altair to Create Most Complete AI-powered Portfolio of Industrial Software

Siemens expands AI-driven pharma software portfolio, integrating Dotmatics’ platform to connect drug research, development, and manufacturing digitally.

Siemens Finalizes $5.1B Dotmatics Acquisition

Chris Spivey is director of Industry Relations and Strategic Partnership, MJH Life Sciences.

Behind the Headlines, Episode 20: CAR-T Milestones, Abbvie and Eli Lilly M&A Moves, and More

 is a bi-weekly panel discussion examining the latest trends, readouts, and other factors that drive pharmaceutical news and innovation. Each episode features consultants, venture capitalists, scientists, patient advocates, and journalists discussing the prior weeks’ top news while seeking to highlight the more enduring lessons that hide behind the headlines. 

In episode 20, the panel explores a new wave of developments in CAR-T innovation, biopharma dealmaking, and the evolving role of information in translational medicine. Sascha Berger, private biopharmaceutical investor; Shannon Eaker, CTO of Xcellbio; Edwin Stone, CEO of Cellular Origins; and Bryce Sady, VP of Product Development at PSL Group, unpack key headlines and examine the long-term implications shaping scientific progress and patient access.

CAR-T’s Next Chapter: From Solid Tumors to Regulatory Streamlining

The panel begins by examining the growing promise of CAR-T in solid tumors—a space long considered too complex or hostile for cell therapies. Recent data and development activity are challenging that view: Gilead Sciences reports 62% tumor shrinkage in glioblastoma (1); Affini-T Therapeutics is targeting KRAS mutations (2); and Immatics is advancing its pipeline into PRAME-positive tumors (3).

In parallel, the FDA announced it has removed Risk Evaluation and Mitigation Strategies (REMS) requirements for autologous CAR-T cell therapies. This decision, widely welcomed by the ATMP field, is expected to reduce the reporting burden on healthcare providers, broaden access, and help drive down overall treatment costs (4).

Strategic Acquisitions: AbbVie and Eli Lilly Bet Big

The panelists also explore the rationale behind two major acquisitions. AbbVie announced a $2.1 billion deal to acquire Capstan Therapeutics, strengthening its cell therapy and immunology portfolio (5). Meanwhile, Eli Lilly acquired Verve Therapeutics, whose VERVE-102 program is being positioned as a potential first-in-class in vivo gene editing therapy for cardiovascular disease. According to Lilly’s leadership, the treatment could help shift care from a chronic model to a one-time intervention (6).

The discussion closed with reflections on two systemic shifts: the ongoing talent exodus from the United States—driven in part by cuts to basic research funding—and the transformation of how research findings are shared and applied. Panelists discussed how modern publishing models, data capture technologies, and changes in information flow influence the pace and impact of translational medicine.

Watch the full episode above for more insights into the evolving biopharma landscape and catch up on previous episodes of 

Bagley, S.J., Desai, A.S., Fraietta, J.A. et al. Intracerebroventricular bivalent CAR T cells targeting EGFR and IL-13Rα2 in recurrent glioblastoma: a phase 1 trial.

. Published online June 1, 2025. DOI:10.1038/s41591-025-03745-0

Affini-T Therapeutics presents preclinical data from its programs targeting oncogenic drivers KRAS and TP53 at AACR. Press release. Affini-T Therapeutics. April 24, 2025. 

https://affinittx.com/press-releases/affini-t-therapeutics-presents-preclinical-data-from-its-programs-targeting-oncogenic-drivers-kras-and-tp53-at-aacr/

Immatics IMA203 PRAME cell therapy data presented at 2025 ASCO annual meeting continues to show strong anti-tumor activity and durability in patients with metastatic melanoma. Press release. Immatics. May 31, 2025. https://investors.immatics.com/news-releases/news-release-details/immatics-ima203-prame-cell-therapy-data-presented-2025-asco 

FDA Eliminates Risk Evaluation and Mitigation Strategies (REMS) for Autologous Chimeric Antigen Receptor (CAR) T Cell Immunotherapies. FDA Safety Communication; June 26, 2025. https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/fda-eliminates-risk-evaluation-and-mitigation-strategies-rems-autologous-chimeric-antigen-receptor

AbbVie to Acquire Capstan Therapeutics, Further Strengthening Commitment to Transforming Patient Care in Immunology. Press release. AbbVie. June 30, 2025; https://news.abbvie.com/2025-06-30-AbbVie-to-Acquire-Capstan-Therapeutics,-Further-Strengthening-Commitment-to-Transforming-Patient-Care-in-Immunology

Lilly to Acquire Verve Therapeutics to Advance One-Time Treatments for People With High Cardiovascular Risk. Press release. Eli Lilly & Company. June 17, 2025; https://investor.lilly.com/news-releases/news-release-details/lilly-acquire-verve-therapeutics-advance-one-time-treatments

Videos

Sascha Berger, private biopharmaceutical investor; Shannon Eaker, CTO of Xcellbio; Edwin Stone, CEO of Cellular Origins; and Bryce Sady, VP of Product Development at PSL Group go behind the headlines to talk CAR-T advancements, exciting M&A developments, and the impact of lost research funding on innovation. 

BIO 2025 - Political Climate Compilation

® Group was able to interview more than a half dozen executives in the biopharmaceutical industry 

 of the Biotechnology Innovation Association (BIO) International Convention, which took place in Boston June 16–19, 2025.

The conference was bookended by major developments with impacts to healthcare within United States government agencies, namely US Health and Human Services Secretary Robert F. Kennedy Jr. 

 of the Advisory Committee on Immunization Practices, a Centers for Disease Control and Prevention-affiliated body responsible for guiding vaccine policy, followed by 

FDA suspending certain new clinical trials,

 pending review, in which US citizens’ living cells are sent to China and other “hostile countries.”

With those policy and personnel changes in mind, the key opinion leaders shaping some of the content presented at BIO were asked how much attention they and their companies were giving to US developments, how those developments figured to impact their business, and the larger implications to their employees and the industry at large.

 in April, there was not one unifying theme expressed by this group; the changes—which by no means are complete—have affected companies small and large, as well as foreign and domestic, in varying ways.

In contrast to earlier conferences in 2025, experts interviewed as part of the BIO conference in Boston did not come to a consensus about lasting impacts of recent changes in US government policy.

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