Susan Haigney

Mitragyna speciosa or kratom leaves with medicinal products in capsules and powder in white ceramic bowl and wooden table, top view | Image Credit: ©Yanawut Suntornkij - stock.adobe.com

On July 29, 2025, FDA published recommendations for the control of concentrated 7-hydroxymitragynine (7-OH) products under the Controlled Substances Act (1), because a concentrated byproduct of the kratom plant has been recognized as having the potential for abuse due to its ability to bind to opioid receptors. The agency also released a report, “7-Hydroxymitragynine (7-OH): An Assessment of the Scientific Data and Toxicological Concerns Around an Emerging Opioid Threat,” detailing concerns over these products. FDA’s recommendations now go to the Drug Enforcement Agency, which has authority over drug classification.

On Aug. 14, 2025, Florida Attorney General James Uthmeier issued an emergency rule filing to classify certain 7-OH products as Schedule 1 controlled substances in Florida. The rule makes it illegal to sell, possess, or distribute certain 7-OH drugs in the state (2).

® interviewed C. Michael White, distinguished professor and Chair of the Department of Pharmacy Practice at the UConn School of Pharmacy and chair of the Kratom Consumer Advisory Council, to find out how these regulatory actions may impact the pharmaceutical industry and consumers.

 Can you please explain what kratom is and how it is used in the development of opioids?

 tree in Southeast Asia that was called kratom by indigenous people when Western explorers arrived in the 1800s. The leaves contain many phytochemical alkaloids that can act on receptors in the body. Mitragynine is the most abundant alkaloid and stimulates serotonin, alpha-1 and alpha-2 adrenoceptors, and indirectly and mildly stimulates opioid receptors. Mitragynine is a unique opioid receptor stimulator because it is a mild stimulator rather than a depressant and is unlikely to cause reductions in respiratory rate or minute ventilation as the dose escalates. One of the metabolites of mitragynine is 7-OH, which is a very potent but short-acting opioid receptor stimulator, and the metabolite of 7-OH is mitragynine pseudoindoxyl, which is also a potent opioid receptor stimulator but possibly with a longer duration of action.

Instead of following the normal process where chemicals derived from natural products are pre-clinically tested to support an IND [investigational new drug] application followed by Phase I, II, and III clinical trials, manufacturers simply extracted mitragynine, oxidized it to make 7-OH, and then chemically converted it to make mitragynine pseudoindoxyl. [They] started putting it into products and selling it to consumers with no involvement of health professionals.

Consumers could self-select if they wanted to take it, even if it was just to experience euphoria, choose the duration of therapy, and choose their own dose. This seems to be against FDA’s drug approval process and sets a horrible precedent for drug development. These products were never approved as new dietary ingredients and should not have been legally sold as dietary supplements, but they were.

While 7-OH is found in trace amounts (less than 2% of total alkaloids) in the dried kratom powder, it is not in the fresh leaf, so whether it would qualify as a dietary supplement is unclear. However, it is clear that mitragynine pseudoindoxyl is not found in fresh or dried kratom leaves and should never be allowed as a dietary supplement.

[This situation] is similar to the recent sales of tianeptine as a dietary supplement. Tianeptine is a fully synthetic molecule and used as a drug in some European countries but appeared on gas station, convenience store, and smoke shop shelves as a dietary supplement. This exposes a major vulnerability in our drug and dietary supplement market where dietary supplements do not need to notify FDA before they are sold, and it is up to the overworked and understaffed FDA to discover them and then start testing, warning, and enforcement actions. Additionally, 7-OH products are actually being sold in vape pens, sublingual strips, and buccal pouches even though dietary supplements can only be swallowed. This is blatant disregarding of federal law.

 How do the recommendations by FDA, and Florida’s emergency ruling to reclass certain concentration 7-OH opioids as controlled substances, impact the pharmaceutical industry, patients, and consumers?

 The actions from FDA and [the] Florida Attorney General are desperately needed by the pharmaceutical industry, patients, and consumers. Pharmaceutical companies following FDA guidance and spending billions of dollars to bring a drug to market that is proven to have a positive benefit-to-risk profile in human clinical trials should not be competing against competitors that are circumventing the process and directly reaching consumers. Patients are being denied access to well-tested, novel drugs because prescribers cannot be certain if the risks of these new products are better or worse than current options, how to use the drugs in unique patient types, and what the risk of drug interactions are. Consumers are taking products that animal studies show are highly addictive with no protections. Many of the products are being sold next to the Gatorade and Mentos and are fruit-flavored, sugar-enhanced candy formulations with names that would appeal to children or drug seekers.

 What actions will pharmaceutical companies need to take to respond to the new regulations?

 I hope that pharmaceutical companies would become more aware of competitors that are cutting corners and directly reaching consumers with their drug products or are selling dietary supplements in ways that are clearly illegal but compete with prescription products (like natural GLP-1s given in transdermal patches). These are not counterfeit drug makers, which pharmaceutical companies are adept at combatting; but companies selling products for the same indications but are unique chemical entities, or are using legal loopholes like saying they are ‘peptide’ companies to sell counterfeit versions of drugs to consumers, pretending that they are only selling them for ‘research purposes.’ Another great example is people selling THC [tetrahydrocannabinol], used to help people sleep, reduce stress, etc., but use a loophole in the Farm Bill to create THC and THC-like chemicals from extracts of ‘hemp’ cannabis plants. FDA does not have the bandwidth to combat these entities unless this type of enforcement becomes prioritized.

FDA. FDA Takes Steps to Restrict 7-OH Opioid Products Threatening American Consumers. Press Release. July 29, 2025. 

https://www.fda.gov/news-events/press-announcements/fda-takes-steps-restrict-7-oh-opioid-products-threatening-american-consumers

Makary, M.A. Statement from FDA Commissioner Marty Makary, MD, MPH, on Florida Restriction of 7-OH Opioid Products. 

https://www.fda.gov/news-events/press-announcements/statement-fda-commissioner-marty-makary-md-mph-florida-restriction-7-oh-opioid-products

Articles

The FDA has recommended controlling concentrated 7-hydroxymitragynine (7-OH) products under the Controlled Substances Act due to their potential for abuse, as they bind to opioid receptors. Florida has classified certain 7-OH products as Schedule 1 controlled substances, making their sale, possession, or distribution illegal. These regulatory actions aim to protect consumers and the pharmaceutical industry from unapproved products that bypass FDA's drug approval process. The pharmaceutical industry must remain vigilant against competitors exploiting legal loopholes to market unapproved or potentially harmful products.

FDA’s recommendation to control 7-OH products under the Controlled Substances Act should help prevent competition between legitimate pharmaceutical medicines and those companies looking to circumvent FDA regulations, says Michael White, Distinguished Professor and Chair of the Department of Pharmacy Practice at the UConn School of Pharmacy and Chair of the Kratom Consumer Advisory Council.

Kratom and the Impact of 7-OH Reclassification

Text sign showing Industry News. Business photo text delivering news to the general public or a target public | Image Credit: © Artur - © Artur - stock.adobe.com

FDA published a draft guidance document on Aug. 18, 2025 titled 

Oncology Therapeutic Radiopharmaceuticals: Dosage Optimization During Clinical Development

 that was created to assist drug sponsors with identifying an optimized dosage for radiopharmaceutical therapies (RPTs) for oncology indications during clinical development. The guidance addresses clinical development before submitting a marketing application for a new indication and usage. The new draft guidance should be used alongside recommendations provided in the August 2024 guidance, 

Optimizing the Dosage of Human Prescription Drugs and Biological Products for the Treatment of Oncologic Diseases.

The new draft guidance, however, does not cover selection of the initial RPT administered activity in first-in-human trials. Other aspects of clinical development of RPTs, such as dosimetry software, fixed administered activity dosing for a population versus dosing determined by personalized dosimetry, and theranostic co-development, are not addressed in the guidance document.

According to the FDA guidance document, RPTs share characteristics with external beam radiation therapy (EBRT) and systemic drug therapy. RPTs adhere to absorbed dose limits to critical organs determined by prior experience with EBRT. FDA states, however, that the differences between RPTs and EBRT in physical properties and treatment delivery lessen the applicability of EBRT-derived organ absorbed dose limits to RPTs. The optimized RPT dosage, therefore, may be greater than or less than a dosage limited by EBRT organ tolerances. Radiation absorbed dose limits also may differ between different isotopes or RPTs based on their physical properties. “Empiric determination of RPT-specific organ tolerances, or full assessment of dose-response relationships for a specific RPT, may not be possible if the evaluated dosages are limited based on EBRT organ tolerances,” the guidance document states (1).

The new draft guidance provides considerations for dosage optimization. According to the document, if there is adequate rationale that the optimized dose of an RPT cannot be identified at lower dosages, administered activities per cycle and/or cumulative RPT-administered activities that result in absorbed dosages exceeding EBRT organ tolerances can be studied in clinical trials of RPTs.

“Proposals to expose participants to RPT dosages that exceed EBRT organ tolerances or previously characterized RPT dosages could be justified based on existing clinical data or other approaches, as applicable, and should be discussed with FDA during formal meetings, including early in clinical development,” the agency states in the document (1). “Trials should include safeguards such as appropriate participant selection, trial design, safety monitoring, and radiation dosimetry evaluation.”

The guidance goes on the discuss participant population, trial design, safety monitoring, and dosimetry for dosage optimization trials.

According to Mike Ritchie, chief commercial officer at Champions Oncology, radiopharmaceuticals have been used in the past to treat superficial tumors, but they have evolved to treat internal tumors as well (2).

“There's so much [that goes] into pharmaceutical development into making something that can be manufactured at scale. It can sit on a shelf for a while. We can administer it to a patient, and it behaves in the way that we want,” Ritchie said in an interview with 

®. “We're just learning how to apply what we learn from anybody drug conjugates into radio drug conjugates, so the chemistry of how to link this radio ligand to an antibody, something that will continue to evolve, and there's a real opportunity there to improve that, to improve the therapeutic activity. From the biology perspective, again, we're in our infancy and understanding what are the tumor types, or the molecular cohorts within a tumor that are more sensitive to radio ligands. Like any chemotherapy or any therapy, certain tumors will respond. Others will not. They'll develop resistance. And so really understanding the right cohorts of patients to treat is something that we're still learning, and I think we'll continue to learn as the clinical development of these programs evolves.”

PharmTech’s interview with Mike Ritchie can be found 

https://www.fda.gov/regulatory-information/search-fda-guidance-documents/oncology-therapeutic-radiopharmaceuticals-dosage-optimization-during-clinical-development

Haigney, S. The Evolving Field of Radiopharmaceuticals. 

https://www.pharmtech.com/view/the-evolving-field-of-radiopharmaceuticals

The FDA's draft guidance document, released in August 2025, aims to assist drug sponsors in optimizing dosages for radiopharmaceutical therapies (RPTs) in oncology during clinical development. It emphasizes dosage optimization before marketing applications and should be used alongside the 2024 guidance on oncologic drug dosage. The guidance does not cover initial RPT dosages in first-in-human trials or other clinical development aspects like dosimetry software. It highlights the differences between RPTs and external beam radiation therapy (EBRT) and suggests that optimized RPT dosages may exceed EBRT organ tolerances.

The guidance document provides recommendations for identifying an optimized dosage for radiopharmaceutical therapies for cancer treatment during clinical development. 

FDA Releases Guidance on Oncology Therapeutic Radiopharmaceuticals

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

Telstar, part of the Syntegon Group that provides aseptic process solutions, announced on Aug. 18, 2025 that it will be showcasing its integrated good manufacturing practice (GMP) services during Farmaforum in Madrid, which is being held Sept. 17–18. The company has grouped their engineering, consulting, equipment qualification, and facility validation under one division within a 4.0 environment of process automation and digitalization. Telstar can be found at Farmaforum at Booth G42-H41.

Telstar’s GMP services includes an in-house multidisciplinary team of experts available throughout the project lifecycle, from concept to final inspection approval. These services include engineering, GMP facility construction, and supply chain support, as well as quality and safety services. GMP digitalization is available to connect and integrate plat operations which can enhance supply chain security and traceability of components, products, and processes. Preventive and predictive maintenance, equipment upgrades, process optimization, validation and qualification, and design solutions are also available.

GMP environment process automation solutions

The company will be promoting its digitalization and process automation solutions, including Telstar Insights, a preventive and predictive maintenance platform. The platform is a non-intrusive cloud platform that collects and analyzes real-time operating equipment data to anticipate potential production problems. “Capable of providing comparative data of assets of the same type in similar production conditions, this platform allows for the generation of a customized specific predictive and preventive maintenance plan and improve overall equipment efficiency (OEE),” the company stated in a press release (1).

Telstar offers solutions for maintaining traceability of materials, processes, and resources at a manufacturing or distribution plant with its Ip6 industrial software platform. Ip6 digitalizes processes in regulated sectors and is designed to be fitted into logistics and materials management. It is parameterizable and scalable and is GMP and FDA validatable.

“The ability to develop complete solutions in engineering, process and GMP consulting, construction, and manufacturing processes with automation technologies for the life sciences market has led the Telstar brand to be [well] recognized as one of the [major providers for] the development of aseptic process solutions for the pharmaceutical industry,” the company stated in the release.

Syntegon Group provides pharmaceutical process and packaging solutions for liquid and solid pharmaceutical products. Syntegon acquired Telstar in June 2024, giving Syntegon an expanded portfolio for seamless line solutions.

“With the acquisition of Telstar, we will enhance our portfolio of innovative technologies and many successful references in the market. Our customers will benefit from even more comprehensive solutions, seamless processes, and lifecycle services,” said Torsten Türling, CEO of the Syntegon Group, in a press release at the time of acquisition (2). “At the same time, we can jointly capture growth opportunities and expand our market presence.”

Automation in sterile drug product manufacturing

During CPHI Milan in 2024, Klaus Ullherr, senior product manager at Syntegon, spoke with 

® about challenges companies may face when working to comply regulatory requirements for aseptic processing and how automated systems can help manufacturers achieve their goals (3). In the interview, Ullherr details the challenges involved in maintaining clean air and ensuring that the air that flows onto a machine does not come into contact with product. He stresses that automated solutions can reduce human intervention and protect product from contamination.

https://www.pharmtech.com/view/cphi-milan-2024-compliance-and-automation-in-aseptic-processing

1. Telstar. Telstar Integrated GMP Services for the Pharmaceutical Industry Will Be Promoted at Farmaforum. Press Release. Aug. 18, 2025.

2. Syntegon. Set for Future Growth: Syntegon Announces Acquisition of Testar. Press Release. June 7, 2024.


https://www.syntegon.com/press/set-for-further-growth-syntegon-announces-acquisition-of-telstar

3. Thomas, F. CPHI Milan 2024: Compliance and Automation in Aseptic Processing. 

Telstar, part of the Syntegon Group, will showcase its integrated GMP services at Farmaforum in Madrid. These services encompass engineering, facility construction, and supply chain support, enhanced by digitalization and process automation. Telstar Insights, a cloud platform, offers predictive maintenance by analyzing real-time equipment data. The Ip6 software ensures traceability in manufacturing processes. Syntegon's acquisition of Telstar in 2024 expanded its portfolio, enhancing its aseptic process solutions. Automation in sterile drug manufacturing reduces human intervention, addressing regulatory compliance challenges in aseptic processing.

The company will highlight how its GMP services combine engineering, consulting, equipment qualification, and facility validation to better integrate its services during Farmaforum, which is being held in Madrid from Sept. 17–18, 2025.

Telstar to Showcase Integrated GMP Services at Farmaforum

On Aug. 4, 2025, the European Commission (EC) published a working document announcing its findings on the use of titanium dioxide (TiO

) in medicinal products (1). According to the EC document, TiO

 is used in 91,000 human drug products to add whiteness, accentuate color, ensure uniformed color, maintain color during shelf life, and preserve the API (1).

In 2021, after an assessment of potential safety concerns, the European Food Safety Authority determined TiO

 was not safe to use as an additive in food because genotoxicity could not be ruled out. To assess the potential concerns of using TiO

 in drug products, EC asked the European Medicines Agency (EMA) to provide scientific analysis of the reason for using it in drug products and the potential alternatives to its use.

In EMA’s conclusions, the agency stated TiO

 is used in several essential oral solid and semi-solid dosage forms, but alternatives should be able to be used; however, it was not yet confirmed if use of those alternatives would be feasible. EMA also stressed the impact on the supply chain if alternatives were used because of the number of products that would be impacted. Therefore, at the time, it was decided to continue its use while the EC reviewed the situation after an updated analysis was done by EMA.

Further analysis concludes alternatives not a viable option

The findings of EMA’s updated analysis were released in April 2024 concluded that while some alternatives to TiO

 performed well when evaluated under certain key performance indicators (KPIs), all were inferior when assessed against all KPIs. Therefore, EMA stated that the use of TiO

 was necessary for some medicines to ensure safety and efficacy, and it would only be feasible to remove TiO

“The investigations performed by the pharmaceutical industry thus far have confirmed the view reflected in the EMA response in 2021 that it is not considered technically feasible to replace TiO

 across the board in all medicines, without negatively impacting the quality, safety and efficacy of some, or all, of those medicines and thus their availability,” EMA stated in its findings (2). “With respect to new products currently under development, the same technical challenges are expected to apply. Given its widespread use and acceptability, TiO

 will have been the material of choice in coating materials, capsules, etc., and is likely to have been included very early in product development and in early formulation development and clinical studies. Therefore, its removal from medicines under development is expected to raise the same technical challenges as for authorized medicines.”

As a result of these findings, “the Commission takes the view that the use of titanium dioxide as a color in medicinal products, as provided for in Regulation (EU) 2022/63 amending Regulation (EC) No 1333/2008, should be maintained” (1).

On Aug. 13, 2025, ACG, a supplier of capsules and allied solutions, commented on the EC’s decision (3). ACG worked to inform the pharmaceutical community on the challenges of TiO

 and cooperated with the IQ Consortium to create a database of the potential impact of a ban on TiO

 in drugs. The company also prepared for a ban by investing in the development of TiO

“This is a wise and pragmatic decision for the pharmaceutical sector,” Dr. Subhashis Chakraborty, general manager, Head–Global Product Management at ACG Capsules, said in an emailed statement. “We remain fully committed to supporting the nutraceutical industry in navigating the ongoing ban through innovative TiO₂-free capsule solutions.” 

EC. Commission Staff Working Document on the Use of Titanium Dioxide in Medicinal Products. 

https://health.ec.europa.eu/document/download/34542b69-8507-4fc2-b106-bd15b481e40d_en?filename=mp_working-doc-titanium-dioxide_en.pdf

EMA. Feedback from European Medicine Agency (EMA) to the EU Commission Request to Evaluate the Feasibility of Alternatives to Replace Titanium Dioxide (TiO

) in Medicinal Products and its Possible Impact on Medicines’ Availability. 

https://www.ema.europa.eu/en/documents/report/feedback-european-medicine-agency-ema-eu-commission-request-evaluate-feasibility-alternatives-replace-titanium-dioxide-tio2-medicinal-products-its-possible-impact-medicines-availability_en.pdf

ACG. ACG Welcomes European Commission’s Decision on Titanium Dioxide in Pharmaceuticals. Statement Emailed to Pharmaceutical Technology. Aug. 13, 2025.

The European Commission's 2025 findings on titanium dioxide (TiO2) in medicinal products highlight its widespread use in 91,000 human drug products for color and stability. Despite safety concerns raised by the European Food Safety Authority in 2021, the European Medicines Agency (EMA) concluded that alternatives to TiO2 are not feasible for most medicines without compromising quality, safety, and efficacy. Consequently, the EC decided to maintain TiO2 use in pharmaceuticals. Industry stakeholders, like ACG, support this decision, emphasizing the challenges of replacing TiO2 and the need for innovative solutions.

Based on an analysis done by the European Medicines Agency on the feasibility of alternatives, the European Commission maintains use of titanium dioxide in drug products.

In Europe, the Use of Titanium Dioxide in Drugs Will Continue

FDA Commissioner Marty Makary, MD, MPH, released a statement on Aug. 13, 2025 commending Florida Attorney General James Uthmeier’s emergency rule filing to classify certain concentrated 7-hydroxymitragynine (7-OH) opioid drugs as Schedule 1 controlled substances in Florida. The rule makes it illegal to sell, possess, or distribute certain 7-OH drugs in the state.

“The proliferation of concentrated 7-OH products is a major concern for the FDA. I am particularly concerned with the growing availability of concentrated 7-OH products appealing to children and teenagers, such as fruit-flavored gummies, candies, and ice cream cones,” Makary said in the statement (1). “These concentrated 7-OH products have snuck into every community in America, and I'm glad to see Florida's local leaders fighting back and educating Floridian parents, law enforcement professionals, teachers and community leaders about this threat to public health. I encourage other states to act now and use common sense regulation to safeguard the well-being of our youth and Make America Healthy Again.”

In July 2025, FDA recommended a scheduling action to control certain 7-OH products under the Controlled Substances Act (2). A concentrated byproduct of the kratom plant, 7-OH has the potential for abuse, according to the agency, because it can bind to opioid receptors. FDA released a report about the health concerns (3) of 7-OH and how it differs from the kratom plant leaf. The agency also warned about vape and other products that contain 7-OH, calling these products a major concern for the agency, especially those that might appeal to children and teenagers. Labeling for these products might not be accurately labeled, the agency stated, and they might be disguised as kratom.

“Vape stores are popping up in every neighborhood in America, and many are selling addictive products like concentrated 7-OH. After the last wave of the opioid epidemic, we cannot get caught flat-footed again,” said Makary in a press release (2).“7-OH is an opioid that can be more potent than morphine. We need regulation and public education to prevent another wave of the opioid epidemic.”

FDA also announced labeling changes in July for all opioid pain medications that emphasize the risks with long-term use of these products.Data from two large FDA-required observational studies, postmarketing requirements (PMR) 3033-1 and 3033-2, provided new data on how long-term opioid use can lead to serious side effects. These data combined with public comments, medical research, and a lack of studies on the long-term effectiveness of opioids led the agency to require the safety labeling changes so that health care professionals and patients can make more informed treatment decisions.

“The death of almost one million Americans during the opioid epidemic has been one of the cardinal failures of the public health establishment,” said Makary, in a press release (4). “This long-overdue labeling change is only part of what needs to be done—we also need to modernize our approval processes and post-market monitoring so that nothing like this ever happens again.”

“I know firsthand how devastating addiction is—not just for individuals, but for entire families and communities,” said Health and Human Services Secretary Robert F. Kennedy, Jr., in the release. “Today’s FDA action is a long-overdue step toward restoring honesty, accountability, and transparency to a system that betrayed the American people.”

Makary, M.A. Statement from FDA Commissioner Marty Makary, M.D., M.P.H., on Florida Restriction of 7-OH Opioid Products. 

FDA. FDA Takes Steps to Restrict 7-OH Opioid Products Threatening American Consumers. Press Release. July 29, 2025. 

Reissig, C. J.; et al. 7-hydroxymitragynine (7-OH): An Assessment of the Scientific Data and Toxicological Concerns Around an Emerging Opioid Threat. 

FDA. FDA Requires Major Changes to Opioid Pain Medication Labeling to Emphasize Risks. Press Release. July 31, 2025. 

https://www.fda.gov/news-events/press-announcements/fda-requires-major-changes-opioid-pain-medication-labeling-emphasize-risks

FDA Commissioner Marty Makary praised Florida's emergency rule to classify concentrated 7-hydroxymitragynine (7-OH) as a Schedule 1 controlled substance, addressing concerns over its appeal to youth. The FDA had recommended this scheduling action due to 7-OH's potential for abuse, as it binds to opioid receptors. The agency also announced labeling changes for opioid pain medications, emphasizing risks associated with long-term use. These actions aim to prevent another opioid epidemic wave and enhance public health safety by promoting informed treatment decisions and regulatory oversight.

Florida’s emergency rule will classify certain concentration forms of 7-hydroxymitragynine opioid products as Schedule 1 controlled substances in Florida, a step FDA recommended for 7-OH opioids in July 2025.

FDA Commissioner Applauds Florida Restriction on 7-OH Opioids

FDA announced on Aug. 7, 2025 a new program to increase regulatory predictability and facilitate construction of drug manufacturing facilities in the United States, with the purpose of strengthening the country’s domestic drug supply chain. FDA PreCheck was created in response to an executive order directing the agency to streamline review of domestic manufacturing plants and eliminate unnecessary regulatory requirements.

According to FDA, more than half of pharmaceuticals distributed in the US are made overseas, and the US is reliant on foreign API manufacturers, with only 11% of API manufacturers located domestically. The PreCheck Program will have a two-phase approach to the development of new manufacturing facilities in the US.

The Facility Readiness Phase will allow more frequent communication between manufacturers and FDA at critical stages, such as facility design, construction, and pre-production. Companies will be encouraged to provide the agency with comprehensive facility-specific information through a Type V drug master file (DMF) that should include site operating layout and description, quality system elements, and quality management maturity practices. The DMF can be used in a drug application as appropriate.

The Application Submission Phase will focus on streamlining development of the chemistry, manufacturing, and controls section of a drug application through pre-application meetings and feedback.

“Our gradual overreliance on foreign drug manufacturing has created national security risks,” said FDA Commissioner Marty Makary, MD, MPH, in a press release (1). “The FDA PreCheck initiative is one of many steps FDA is taking that can help reverse America's reliance on foreign drug manufacturing and ensure that Americans have a resilient, strong, and domestic drug supply.”

A public meeting, “Onshoring Manufacturing of Drugs and Biological Products", will be held on Sept. 30, 2025 that will feature a presentation of the FDA PreCheck program, stakeholder discussion, and additional considerations for overcoming onshoring challenges (2).

Pharma companies may be responding to the current administration’s push to move drug manufacturing to the US, with some major names announcing new and/or expanded locations in the US. 

 in February that it would be building four new domestic manufacturing sites in the US (3). In July, AstraZeneca announced it was investing $50 billion in US manufacturing and development, including a multi-billion-dollar facility in Virgina (4). Hikma Pharmaceuticals USA announced in June that it is investing $1 billion by 2030 to expand generic-drug manufacturing at its Ohio and New Jersey facilities (5). Also in June, BASF opened a good manufacturing practice (GMP) facility in Wyandotte, Mich., as part of the company’s commitment to providing a reliable supply of bioprocessing ingredients and excipients (6).

FDA. FDA Announces New FDA PreCheck Program to Boost US Drug Manufacturing. Press Release. Aug. 7, 2025. 

https://www.fda.gov/news-events/press-announcements/fda-announces-new-fda-precheck-program-boost-us-drug-manufacturing

FDA. Hearings, Meetings, Proceedings, etc.: Onshoring Manufacturing of Drugs and Biological Products. Federal Register. Aug. 8, 2025. 

https://www.federalregister.gov/public-inspection/2025-15083/hearings-meetings-proceedings-etc-onshoring-manufacturing-of-drugs-and-biological-products

Eli Lilly and Company. Lilly Plans to More Than Double US Manufacturing Investment Since 2020 Exceeding $50 Billion. Press Release. Feb. 26, 2025.

AstraZeneca Plans to Invest $50 Billion in America for Medicines Manufacturing and R&D

Hikma Pharmaceuticals USA Announces $1 Billion of New US Investment to Further Expand its Domestic Manufacturing and Development of Essential Generic Medicines

BASF. BASF Strengthens Its Commitment to the Biopharma and Pharmaceutical Ingredients Industries through a New Investment in North America. Press Release. June 17, 2025.

The FDA has launched the FDA PreCheck program to enhance regulatory predictability and support the construction of drug manufacturing facilities in the US, aiming to bolster the domestic drug supply chain. This initiative addresses the reliance on foreign pharmaceutical manufacturing, with only 11% of API manufacturers based domestically. The program involves a two-phase approach: the Facility Readiness Phase and the Application Submission Phase, focusing on streamlining processes and enhancing communication. Major pharmaceutical companies are responding by investing in new and expanded US manufacturing sites, aligning with the administration's onshoring efforts.

The agency’s new program is designed to increase regulatory predictability and streamline review of domestic manufacturing facilities.