Daria G. Husni

Purna Thakker, founder and CEO of ADPT Solution, discusses common issues that companies face with FDA regulations at CPHI North America.

Interpreting Regulations and Meeting FDA Requirements at CPHI North America

 sat down with Purna Thakker, founder and CEO of ADPT Solution, to discuss common issues that companies face when following FDA regulations. Thakker went over the rising trends in FDA 483s during the past few years, how to interpret older regulatory documents with modern terminology, and how companies can reduce the potential for non-conformance.

When asked how companies can reduce the potential for non-conformance, Thakker said, “There are CAPA [corrective and preventive action] procedures written by every company. And FDA does recommend in their guidance documents [from 2006] about CAPA [that] they do expect companies to do preventive action. However, there are no regulations written about preventive action. So, the non-conformities written in [

] 820.100 for CAPA is very different than CGMP [Current Good Manufacturing Practice] 211.192. The thorough investigation is written very specific to CGMP, and that is [ missing in] CAPA procedure.”

“If [your] company and FDA recommended that you need to have a CAPA procedure, when you investigate then you need to read 192 and put all components that [are] required for investigation into your procedure,” Thakker continued. “That will help reduce the nonconformities or CAPA or thorough investigation issues [related to] 192. There are 483s written and warning letters are also given.”

“If I want to give a message to everybody: it’s a hard road, but read the regulation,” Thakker said. “You need to read [the] regulation yourself, interpret it, and implement [it]. Because your organization is not the same as other organizations. So, taking anything from a different organization, you might bring some issues from the other organization with it. So, you need to read, understand, and interpret the regulation in your company.”

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The United States Federal Trade Commission (FTC) is seeking more information on Novo Nordisk parent’s $16.5 billion proposed acquisition of Catalent, a US-based contract development manufacturing organization (CDMO). Catalent stated on May 3, 2024 that both companies were gathering information in order to respond to the FTC’s request (1), which was received on May 2. This request was submitted weeks after an application to the FTC was refiled to approve the deal.

Novo Nordisk announced its decision to acquire Catalent in early February 2024 (2). Under a planned merger of Novo Holdings, the parent company of Novo Nordisk, and Catalent, Novo Nordisk would receive three of Catalent’s fill/finish sites and related assets. Those three sites, located in Anagni, Italy; Bloomington, Indiana (US); and Brussels, Belgium, would be advantageous for Novo Nordisk, which has been steadily increasing production of Wegovy as demand for the drug explodes.

Novo Nordisk emphasized its goals of expanding Wegovy production in its own press release on the acquisition (3). The deal would enable the company to expand manufacturing capacity while allowing flexibility for its existing supply network. “We are very pleased with the agreement to acquire the three Catalent manufacturing sites which will enable us to serve significantly more people living with diabetes and obesity in the future,” said Lars Fruergaard Jørgensen, president and chief executive officer, Novo Nordisk (2). “The acquisition complements the significant investments we are already doing in active pharmaceutical ingredients facilities, and the sites will provide strategic flexibility to our existing supply network.”

Demand for Wegovy, Novo Nordisk’s obesity and cardiovascular disease treatment, has skyrocketed over the last year, alongside its sister diabetes therapy, Ozempic. Wegovy was approved in the US in early March of 2024 to reduce risk of major adverse cardiovascular events (MACE) including cardiovascular death, non-fatal heart attack (myocardial infarction), or non-fatal stroke in either overweight or obese adults with established cardiovascular disease (CVD) (4). Novo Nordisk also filed for a label expansion in the European Union.

Both Novo Nordisk and Catalent still expect to close the deal by the end of 2024, but doubts were raised when Novo Nordisk refiled the application in April. According to a Reuters press release, David Ricks, CEO of Eli Lily, a major competitor to Novo Nordisk and Wegovy, raised potential antitrust concerns, calling Novo Nordisk’s proposal to buy the plants “unusual” (4). Novo Nordisk did not disclose details about why the application was refiled.

US SEC. Form 8-K. Current Report Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934, Catalent, Inc. May 3, 2024. https://www.sec.gov/Archives/edgar/data/1596783/000119312524129990/d797118ddefa14a.htm

Novo Holdings to Acquire Catalent in Deal Valued at $16.5 billion

Novo Nordisk to Acquire Three fill-finish Sites from Novo Holdings A/S in Connection with the Catalent, Inc. Transaction

Wegovy Approved in the US for Cardiovascular Risk Reduction in People with Overweight or Obesity and Established Cardiovascular Disease

US FTC Seeks More Information on Novo Nordisk Parent-Catalent Deal

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The request for more information was received weeks after an application to the FTC was refiled to approve the deal.

US Federal Trade Commission Seeks Additional Information on Novo Nordisk Parent-Catalent Deal

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Cormica, a UK-based medical device and pharmaceuticals testing group, announced on May 1, 2024 that it has completed its seven-figure acquisition of TPM Laboratories (TPM), an independent contract testing laboratory based in New Jersey. Cormica is backed by Limerston Capital, a UK mid-market private equity investment firm, and is focused on expansion across the United States and Europe. According to Cormica (1), the deal is intended to use Cormica’s expertise and broad service line to help TPM grow organically and reach its full potential.

TPM provides analytical services to the pharmaceutical and chemical industries, such as quality control, research and development, and stability storage and testing services. Its facility is 8000 sq ft of office and laboratory space and can handle anti-cancer products. Rupa Iyer, president and founder of TPM, will continue to lead TPM’s US team with support from Cormica.

“The acquisition marks a milestone moment for Cormica and clearly demonstrates our ambitions to grow our international footprint and increase our market share in a highly competitive market,” said Mark Hammond, Cormica Group CEO in a press release (1). “TPM boasts a highly skilled laboratory team with extensive pharmaceutical experience which has helped it to build a strong reputation for excellence. We are looking forward to working with Rupa and her team as we explore how we can help support the expansion of the business and use it to further our aims in the US, both organically and via further acquisitions.”

“I am proud of the success TPM has had to-date, but I also recognise that the business has the ability to scale-up,” Iyer added. “Cormica has a compelling offer, driven by people who understand the industry and how to create opportunities. This marks a new chapter in our story, and we are keen to work more closely with our colleagues in the UK and Europe.”

Cormica recently expanded its own testing facilities in January 2024, with an expansion to its Cormica Bradford division. The expansion added two Agilent 1260 Infinity II LCs (liquid chromatography) to the company’s suite of high-performance liquid chromatography instruments. Cormica also upgraded its particle size distribution analysis capabilities with the Microtrac S3500 Laser Diffraction power spectral density instrument, which was equipped with both wet and dry dispersers, joining the company’s range of particle size analyzers. Finally, the company added the Copley JVT100i Tapped Density Tester to bolster its powder density testing capabilities.

In a press release on the expansion, Caroline German, technical director at Cormica, said, “By expanding our equipment range and updating our capabilities, we’re not just enhancing our capacity; we’re aligning more closely with our clients’ hardware and methodologies. This streamlines the method development, validation, and transfer process, allowing for more efficient and seamless service delivery.”

Limerston Capital Backed Cormica Announces First US Acquisition With New Jersey Based TPM Laboratories

Cormica Bradford Expands Testing Capabilities with State-of-the-Art Equipment

Cormica’s first US Acquisition is intended to support to organic growth of TPM laboratories.

Cormica Announces Seven-Figure Acquisition of TPM Laboratories

Santander UK, a retail and commercial bank based in the United Kingdom, has announced it has provided Ennogen Healthcare International, a UK-based pharmaceuticals manufacturer, with a £30 million loan to support its international expansion plans. Ennogen, which was established in 2011, is focused on dermatology, respiratory, and pain relief therapies, especially those with chronic conditions. The loan package is intended to support the company’s rapid growth as it invests in purchasing bolt-on pharmaceutical products in appropriate therapeutic areas and targets future acquisitions. The approved funding may be extended to £50 million as Ennogen considers international expansion opportunities, although this is subject to future approvals.

“Santander quickly understood our business and came up with an innovative and flexible approach to meet our acquisition and product development needs,” said Jason Tate, chief financial officer at Ennogen, in a Santander press release (1). “With offices and specialism in key locations around the world, Santander are best placed to support our international expansion strategy. Working with both the team in Manchester and Liverpool, it is clear they have a strong knowledge of the pharmaceutical and healthcare industry.”

Ennogen is based in Dartford and has a regional office in Northwich, Cheshire. Over the past few years, it has grown both organically and through acquisitions, resulting in its current staff totaing over 50 members. Its growth so far has been funded through cashflow and shareholder injections; this loan is intended to give the company a flexible approach to its growth strategy.

“We are delighted to support Ennogen with this new £30m facility, which will help deliver their acquisition plans,” said Sarah Laverty, Structured Finance director at Santander UK in the press release. “The business has a strong management team and clearly articulated strategy, which is exactly the type of business Santander looks to support.”

Santander Provides Pharma Manufacturer Ennogen with £30 Million Credit Facility for Growth

The loan is intended to support Ennogen’s growth as it looks to international acquisitions.

Santander UK Grants £30 Million Loan Package to Ennogen Healthcare

FDA’s Center for Drug Evaluation and Research (CDER) has published the 2023 Office of New Drugs (OND) Annual Report. The report details the office’s major achievements of 2023, including notable drug approvals, publications, guidances, workshops, webinars, and meetings. Specifically, these achievements contain over 3400 formal meetings between sponsors of new drug development programs and CDER staff; 25 public Advisory Committee meetings; 55 novel drug approvals; 34 issued guidances; 651 OND speaking engagements; and OND representations at meetings, including Patient-Focused Drug Development meetings, Critical Path Innovation meetings, and Patient Listening Sessions.

Also featured are innovations in drug design and development, as well as OND’s partnerships with FDA and external stakeholders to tackle obstacles in drug development and regulation. The report demonstrates OND’s efforts in supporting drug development, pushing forward important drug approvals through substantial application reviews, using workshops and new guidances to promote policy, and maintaining careful post-approval drug assessments.

The report is largely divided into individual office reports, including the offices of: cardiology, hematology, endocrinology, and nephrology (OCHEN); drug evaluation sciences (ODES); immunology and inflammation (OII); infectious diseases (OID); neuroscience (ON); nonprescription drugs (ONPD); oncologic diseases (OOD); rare diseases, pediatrics, urologic and reproductive medicine (ORPURM); specialty medicine (OSM); therapeutic biologics and biosimilars (OTBB); and the non-clinical offices of program operations (OPO), regulatory operations (ORO), administrative operations (OAO), and new drug policy (ONDP). Each section includes a brief overview of the department, followed by its major achievements from the year. The report also features a message from the director, OND’s senior leadership team, an organizational chart of the office, publications from each office, and a list of acronyms and key terms.

Over 2023, OND organized 21 patient listening sessions, 18 of which were organized with the office of the commissioner and the office of patient affairs, and 3 of which were organized with professional affairs and stakeholder engagement. OND’s drug approvals in 2023 included new molecular entity (NME) new drug applications (NDAs), and biologics applications (BLAs), with additional efficacy supplement approvals and approvals to breakthrough therapy requests and fast track requests.

“This report documents the diverse efforts of OND staff, beyond the regulatory actions to approve important drugs,” stated Peter Stein, Director, Office of New Drugs in the report (1). “These efforts include holding many public meetings both to inform our OND staff of cutting edge science, and for OND staff to contribute to the knowledge of those in the pharmaceutical industry, in academics, and for patients and other stakeholder groups about advances in regulatory science, the biology of disease, and advances in clinical drug development; publishing numerous guidances that give insight to drug developers about the pathways and approaches to development that can provide the data FDA needs to support the effectiveness and safety of new drugs; the careful monitoring of drug safety post-approval to assure that drug’s prescribing information is kept updated with the safety information that health care practitioners and patients need.”

Center for Drug Evaluation and Research (CDER), 

2023 OND Annual Report: Breaking Barriers to Advance Public Health

The report covers the major achievements of the office during 2023, including notable drug approvals, publications, guidances, workshops, webinars, and meetings.

CDER Releases Office of New Drugs 2023 Annual Report

Adare Pharma Solutions, a global contract development and manufacturing organization (CDMO) focused on oral dosage forms, has announced plans to expand its high potency handling capabilities in the United States and Europe. This expansion will include a second high potency suite to Adare’s facility in Philadelphia, upgrades to R&D suites in its Ohio facility, and high potency upgrades to its facility in Milan, Italy.

Adare’s 128,000 sq ft Orthodox Street facility in Philadelphia will receive a second high potency suite, which will add encapsulation, blending, high-shear granulation, and other manufacturing processes. These processes will bolster the site’s existing potent suite, which provides bin blending, roller compaction, milling, and tablet compression. Construction is set to complete by Q4 of 2024.

Work has already begun on the company’s 179,000 sq ft Vandalia facility in Ohio and is also scheduled to complete by Q4 of 2024. The Ohio facility is receiving upgrades to several of its R&D-to-clinical stage production suites to provide high potency handling. Capabilities will include microencapsulation, dry roller compaction, and fluid bed processing.

The expansion to Adare’s 220,000 sq ft Pessano facility in Milan, Italy will add high potency upgrades to its formulation and analytical laboratories, which include bin blending, fluid bed processing, compression, encapsulation, and pan-coating capabilities. Additionally, the facility recently announced plans to add packaging capabilities and more warehouse capacity (2). A two-story, 2800 square-meter extension is underway to accommodate a new packaging line in a specially built packaging hall, which is projected to be installed by Q4 2024. The expansion also contains a 1000 square-meter warehouse with capacity for 900 pallets and space for a second future packaging line.

A week after its packaging and warehouse expansions were announced, Adare revealed further expansions to the Milan site, adding a high-shear mixer granulator to its existing fluid bed capabilities (3). The granulator, an IMA 600-L Roto Mix high-shear mixer with IMILL and Hydrowash, provides wet granulation with either aqueous or organic-based solutions. The mixer’s design allows for lower changeover times and lower water and energy consumption as compared to traditional machine clean-down routines. These expansions, as well as the high potency upgrades, are expected to be operational by the end of 2024.

“We have seen demand for high potency handling and packaging continue to increase, with around half of solid dose drugs in development being highly potent,” said Tom Sellig, CEO of Adare Pharma Solutions, in a company press release (1). “This proactive investment across our global network of sites will ensure we continue to provide customers with the oral dose capabilities and capacity they will need both now and in the future.”

Adare Pharma Solutions, Adare Expands Global High Potency Handling and Packaging Capabilities. Press Release, May 1, 2024.

Adare Pharma Solutions, Adare Pharma Solutions to Expand Packaging and Warehousing Capabilities in Europe. 

Adare Pharma Solutions, Adare Pharma Solutions Expanding Oral Dose Capabilities in Europe. 

The CDMO plans to expand and upgrade its Philadelphia, Ohio, and Milan facilities to meet the continued growth in demand for high potency handling capabilities.