Pharmaceutical Technology Is Now PharmTech: A Sharper Name for a Smarter Industry

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Behind the Headlines Episode 28

Ask the Expert

Closing the Gap in Modern Process Control and Automation for QC/QA

Drug Digest December 2025

How It Helps Avoid Facility and Equipment Problems

A “Plan, Prevent, Prove” Approach

Kevin M. Kane, PhD, is CMC strategy director, Strategic Development Consulting, at PPD, part of Thermo Fisher Scientific.

Eugene J. McNally, PhD, is vice-president, early engagement and regulatory strategy, Strategic Development Consulting, at PPD, part of Thermo Fisher Scientific.

Jeff L. Garwin, PhD, MD, is associate clinical science director, Strategic Development Consulting, at PPD, part of Thermo Fisher Scientific.

Debra A. Schaumberg is vice-president and global head, Strategic Development Consulting, at PPD, part of Thermo Fisher Scientific.

Drug development is a risky business. For a drug entering Phase I clinical trials, there is an estimated 10% probability of eventual FDA approval (1). At each milestone, the financial stakes increase for the next development phase: average costs are $30 million in Phase I, $70 million in Phase II, and $310 million in Phase III (2). These increasing stakes demand robust, strategic scientific and regulatory support for each transition.

Even big pharmaceutical companies (collectively, Big Pharma) have challenges in managing the end-to-end development process of new molecular entities (NMEs). For example, in 2016, Pfizer’s cumulative probability of success from start of Phase I (first-in-human [FIH] study) through approval was 4%, versus 8% for the entire industry (2). By 2020, Pfizer had revived their R&D pipeline (2) to achieve greater end-to-end success in the clinic, achieving a cumulative success of 21%, versus 11% for the industry (2). Pfizer has attributed their improvement in success rate to their increased early investments in understanding the biology of the target disease and the pharmacology of an NME, including exposure at the site of action, binding to the pharmacological target, and expression of pharmacological activity. Having a portfolio of NMEs enabled Pfizer to use this enhanced understanding to weed out failures early and take calculated risks to accelerate “winners” (2,3). Eli Lilly and Company (Lilly) (4,5) and AstraZeneca (6) have employed similar “truth-seeking” early development strategies that prune portfolios early of NMEs that are likely to fail during Phase II due to lack of efficacy. Lilly claims similar success for its autonomous Chorus early-stage drug development unit (4,5). AstraZeneca has published their framework of determinants for project success and for effective decision-making: right target, right patient, right tissue, right commercial potential, and right culture (6).

In contrast, the business model for most small pharma—include emerging, virtual, and small biotechnology companies—is different than those of Big Pharma and frequently anticipate investment tranches upon achievement of certain developmental milestones, such as opening an investigational new drug (IND) application, initiation of the FIH study, or the completion of a Phase II proof-of-concept (POC) study. Frequently, the achievement of the next value inflection point for development milestones results in activity for executing a strategic plan to attempt to sell and/or license the asset, make a public offering, or take on a partnership arrangement that can enable product commercialization. Reaching these milestones for the one (or few) small pharma-owned assets is sometimes at odds with the type of “truth-seeking” early development strategies that have allowed Big Pharma’s improved odds of success at the portfolio level.

This paper describes an intelligent drug development paradigm that enables small pharma to implement a truth-seeking early development approach such as those used by progressive Big Pharma companies, aimed at efficiently maximizing the value of information needed to inform key milestone decision points and optimize the probability of success.

All pharma developers face challenges in early clinical development (Phase I and Phase II) associated with drug substance manufacture, drug product formulation and manufacture, and anticipating the doses needed for clinical trials. These challenges arise from a lack of communication of and adherence to a common overall drug development strategy, generally as defined in the clinical development plan (CDP) to address the target product profile (TPP) across the siloed disciplines.

Historically, Big Pharma companies established standard operating procedures and ways of working within and across siloed disciplines, approaching drug development largely sequentially, handing an NME off from one siloed discipline to the next, with collaboration occurring at the end of each task. Big Pharma companies run programs in-house, and/or contract with contract development and manufacturing organizations (CDMOs) and clinical research organizations (CROs) for development services, and they have in-house teams with diverse expertise who build a robust early development strategy to accelerate entry into the clinic and keep the development program on track (4).

In contrast, today’s small pharma companies often have deep expertise in narrow areas, but they may lack internal expertise, infrastructure, and operating procedures to conduct many core drug development activities in-house, necessitating engagement of external vendors such as CDMOs, CROs, and consultants (7). This multi-vendor outsourcing approach often leads to fragmented operational challenges, loss of continuity, and failure to maximize information at each stage of development. In most cases in small pharma, the CDMO vendor is not responsible for creating the overall development strategy. Small pharma sponsors are often ill-equipped to define this strategy and yet are responsible for choosing the strengths/doses to manufacture, bearing the risk if development fails due to improper dose or formulation selection.

Further complicating this stage of development, the manufacturing of drug substance and drug product often occur in separate locations and on highly variable timelines. Drug substance and drug product manufacturing vendors have no incentive to align their schedules, leading to schedule adjustment at the Phase I clinic if drug product delivery is delayed.

With far fewer resources than Big Pharma, small pharma sponsors often feel pressure to minimize expenditures by limiting the scope of chemistry, manufacturing, and controls (CMC), nonclinical, and activities preparatory to start of an FIH or other Phase I study until the next investment tranche. Speed-to-clinic feels critical because a small pharma sponsor’s next round of funding may be tied to an upcoming development milestone, such as enrollment of the first subject in an FIH trial. The primary objectives of FIH clinical studies are to assess the safety, tolerability, and pharmacokinetic (PK) behavior of a compound, but due to financial and time pressures, sponsors may delay some critical tests until later POC studies. This rush through Phase I is often at the expense of gathering critical data that would lead to stronger Phase II trials with better chance of achieving POC and a higher probability of eventual marketing approval.

More than a decade ago, CDMOs aimed to address these inefficiencies by creating end-to-end service networks, promising efficiency to deliver cost and time savings to sponsors (8). These networks delivered compressed timelines but brought on new challenges because sites within the network communicated and collaborated poorly. Today’s CDMO networks typically market the speed of their integrated offerings to deliver drug product to the clinic but fail to address the core challenge of choosing which doses or formulations the sponsor should manufacture.

A few CMDOs have also combined manufacturing to provide small-scale good manufacturing practice (GMP) batches of drug product (9) with clinical trial services to eliminate some time gaps between findings in the clinic and adjustment of dose at the manufacturing and drug product finishing sites. This “mini-GMP” setting enables iterative manufacture and clinical testing that is faster than the traditional GMP “make and ship-to-clinic” approach and may yield a more optimized formulation.

The intelligent drug development paradigm for small pharma

Small pharma sponsors frequently hire one or more independent consultants across a variety of disciplines to coordinate the early interactive phase between manufacturing and early clinical development. Such consultants play a vital role by providing nonclinical, manufacturing, regulatory, clinical, and technical support, often acting as liaisons between sponsors and vendors. However, when consultants operate from within their individual areas of expertise strategic value can be lost, mirroring the siloed model of Big Pharma approaches that increases development risk. In addition, the task of managing multiple independent consultants across disciplines is often challenging for a small pharma sponsor.

Instead of that fragmented approach, many of the challenges of typical small pharma development can be addressed by an intelligent drug development paradigm that is functionally integrated, dynamic, parallel, and iterative. Such a paradigm is like the paradigm followed by progressive Big Pharma companies such as Pfizer (2,3), Eli Lilly (4,5), and AstraZeneca (6).

A resource-constrained small pharma stands to derive great benefit through contracting with an integrated strategic team comprised of scientific experts across core disciplines, including clinical science, regulatory, CMC, biopharmaceutics, pharmacology, and toxicology, and operating under a unified goal with the sponsor to get an asset into the clinic, successfully through Phase I and beyond. This core team serves as thought partners with the sponsor’s internal experts on scientific and regulatory matters in an on-demand manner. The strategic team works with the sponsor to define the near- to long-term objectives, and then builds a strategic clinical plan to strengthen the information available to inform key milestone development decisions. In this intelligent drug development approach, the joint sponsor/vendor strategic team’s development plan covers scenarios and contingencies that make it possible to adjust strategies and tactics based on emerging data in CMC, non-clinical, and clinical spaces. With a comprehensive and adaptive clinical plan supported by evolving, phase-appropriate CMC resources, the development program runs more efficiently and on a more predictable timeline. The evolving CMC needs are supported in parallel by one or more vendors that are qualified and directed by the strategic team. This new service model is designed with small pharma companies in mind, getting faster and more intelligently into POC clinical trials with robust data support at each milestone transition. 

illustrates how the same level of expertise possessed by a Big Pharma entity could be deployed for resource-constrained sponsors, with examples shown for two consecutive phases of development: the first for progressing a compound from discovery into clinical development and the second for transitioning from Phase I into Phase II POC studies. 

 Planning and oversight activities of a strategic consulting team at two consecutive phases of drug development. IND is investigational new drug. POC is proof-of-concept.

In the intelligent drug development paradigm, the focus of Phases I and II is to achieve POC as efficiently as possible, completing all learning required to plan an efficient and complete Phase III program. Efficiency may mean parallel development of validated outcome and biomarker assessments while Phase I studies are in progress (or even before), so that they can be incorporated into Phase II studies. Efficiency may sometimes mean careful analysis of Phase I results to confirm a decision to advance the drug candidate to Phase II or Phase III.

The technical and financial failure risks of drug development add significant pressure to small, rapidly developing sponsors, making the POC a critical milestone in their business models. In many cases, partnering or selling the asset after POC is critical to carrying an asset toward commercialization. To realize these ends, small pharma sponsors need reliable and efficient execution of POC trials with deliberate speed to develop a robust data package that makes the asset attractive to potential buyers or partners. In this new intelligent clinical development paradigm, the strategic team also oversees the development of the due diligence data package, ensuring it includes all relevant efficacy, safety, and CMC data.

Around 2005, Lilly established Chorus, a small, operationally independent clinical development organization within the company that has specialized in drug development from candidate selection to POC (5). “The mission of Chorus is to achieve [POC] rapidly and at a low cost while positioning successful projects for ‘pharma-quality’ late-stage development. Chorus uses a small internal staff of experienced drug developers and a network of external vendors to design and implement CMC processes, preclinical toxicology and biology, and Phase I/II clinical trials” (5). “Since it was established, Chorus has demonstrated substantial productivity improvements in both time and cost compared to traditional pharmaceutical research and development” (5).

The intelligent drug development paradigm provides small pharma with access to an aligned and integrated multi-disciplinary team that builds and drives a strategic plan as seen in leading Big Pharma drug development. Aligned with a sponsor’s clinical and business objectives, the strategic team ensures maximum flexibility, coordination, and speed for efficiently executed Phase I and II studies, supported by robust preparatory nonclinical and CMC work. The team coordinates partners from the fragmented vendor space and directs activities to enhance the scientific knowledge by maximizing interaction and rapid iterative cycling across disciplines, more efficiently using resources. The resulting robust and more complete datasets across disciplines facilitate better go/no-go decisions at development milestones that are value inflection points.

1. Takebe, T.; Imai, R.; Ono. S. The Current Status of Drug Discovery and Development as Originated in United States Academia: The Influence of Industrial and Academic Collaboration on Drug Discovery and Development. 

 (6), 597–606. DOI: 10.1111/cts.12577
2. Fernando, K.; Menon, S.; Jansen, K.; et al. Achieving End-to-End Success in the Clinic: Pfizer’s Learnings on R&D Productivity. 

 (3), 697–704. DOI: 10.1016/j.drudis.2021.12.0101/cts.12577
3. Wu, S. S.; Fernando, K.; Allerton, C.; et al. Reviving an R&D Pipeline: A Step Change in the Phase II Success Rate. 

 (2), 308–314. DOI: 10.1016/j.drudis.2020.10.019
4. Bonabeau, E.; Bodick, N.; Armstrong, R. W. A More Rational Approach to New-Product Development. 

, 96–102.
5. Owens, P. K.; Raddad, E.; Miller, J. W.; et al. A Decade of Innovation in Pharmaceutical R&D: The Chorus Model. 

 (1),17–28. DOI: 10.1038/nrd4497
6. Cook, D.; Brown, D.; Alexander, R.; et al. Lessons Learned from the Fate of Astrazeneca’s Drug Pipeline: A Five-Dimensional Framework. 

 (6), 419–431. DOI: 10.1038/nrd4309
7. Nayler, S.; Pritchard, K. The Reality of Virtual Pharmaceutical Companies. 

, 8–15.
8. DiMasi, J. A.; Smith, Z.; Getz, K. A. Assessing the Financial Benefits of Faster Development Times: The Case of Single-Source Versus Multi-Vendor Outsourced Biopharmaceutical Manufacturing. 

 (6), 963–942. DOI: 10.1016/j.clinthera.2018.04.011
9. DiMasi, J. A.; Wilkinson, M. The Financial Benefits of Faster Development Times: Integrated Formulation Development, Real-Time Manufacturing, and Clinical Testing. 

 (6), 1453–1460. DOI: 10.1007/s43441-020-00172-w.

Kevin M. Kane, PhD, is CMC strategy director; Eugene J. McNally, PhD, is vice-president, early engagement and regulatory strategy; Jeff L. Garwin, PhD, MD, is associate clinical science director; and Debra A. Schaumberg is vice-president and global head; all at Strategic Development Consulting, PPD, part of Thermo Fisher Scientific.

Articles

An intelligent drug development paradigm can enable small pharma to implement an effective early drug development approach.

Exploring an Intelligent Drug Development Paradigm

Manufacture of medicines is most often required to be performed in a sterile environment to ensure the quality and safety of these products. Microorganisms lurking in the air or on surfaces may degrade APIs and impact their effectiveness, according to Anne-Grit Klees, PhD, BioMonitoring Portfolio Manager for The Life Science business of Merck KGaA, Darmstadt, Germany. “Furthermore, pathogenic and even many non-pathogenic microorganisms can cause serious and life-threatening infections in patients, especially if immunodeficient. For this reason, particularly injectable drugs must be sterile. This can be achieved by final sterilization of the drug or, if not possible, by aseptic manufacturing.”

It is recommended by regulators that microbial monitoring of cleanrooms and isolators is performed by a combination of methods, says Klees. “Air monitoring is performed with a combination of volumetric microbial air samplers (active air monitoring) and settle plates (continuous passive air monitoring). Surfaces and personnel should be monitored with contact plates or swabs. Using alternative methods is also permissible if these have been validated and show comparable or superior efficacies.”

® spoke with Anne-Grit Klees to find out some environmental monitoring (EM) best practices manufacturers can follow to ensure the safety of their products.

What are the differences between environmental monitoring in aseptic versus non-aseptic manufacturing?

Anne-Grit Klees (The Life Science business of Merck KGaA, Darmstadt, Germany):

 The environmental monitoring methods are usually the same for both. The higher the cleanroom grade, the higher the monitoring frequency and number of sample locations. The monitoring equipment and culture media should possess features to match the cleanroom-grade requirements. For air samplers, features such as cleanability, resistance towards disinfectants, emission of particles, and disturbance of the unidirectional air flow are important to consider and should match the cleanroom concept. For culture media, there is a choice between single bagged ones for lower risk areas and irradiated, double, or triple bagged ones for the different manufacturing lines.

 What are some best practices for air monitoring?

Anne-Grit Klees (The Life Science business of Merck KGaA, Darmstadt, Germany): 

When selecting an air sampler, important features to consider are sampling volume accuracy, a good efficiency of the method to collect small particles, and whether damage to microorganisms is avoided during the sampling process. The recovery efficiency should be validated by the supplier according to ISO [International Organization for Standardization] 14698. What also matters is ease-of-use to minimize the risk of human errors, low particle emissions to prevent contamination of the cleanroom, good cleanability, and minimal disturbances of the unidirectional air flow. If the air sampler can be integrated into external tracking software systems, all data can be handled. This helps to observe trends.

What are some best practices for surface monitoring?

Surface monitoring is usually performed either with contact plates or swabs, depending on the accessibility of the sample location. Culture medium selection should be based on the ability over the complete shelf-life to detect a broad range of microorganisms. Furthermore, the media formulation should ensure that any potential growth-inhibiting substances such as disinfectant residues or antibiotics are inactivated. To maintain the cleanliness of the sampled surface any culture media residues should be removed after sampling.

 What are some best practices for personnel monitoring?

Personnel monitoring is always performed on the gloves, but also on gowning. The growth promotion properties of the selected media must [often] allow in-house skin flora of the personnel to grow. It is important that contact plate samples are taken of the personnel’s gowning or gloves before leaving the cleanroom. If glove tests are performed after critical interventions, the outer gloves should be replaced before continuing manual work.

 What are the latest advancements in processes and workflows for environmental monitoring?

 These are stated in the current 2022 version of the EU [European Union] CGMP [current good manufacturing practice] Annex 1. While the well-established volumetric air samplers, settle plates, contact plates, and swabs are still recommended to be used frequently, a new focus is on the importance of a contamination control strategy of the pharmaceutical company. This should include a risk-based sample plan that states the frequency and sample locations for those methods. There are additions about using validated rapid or automated technologies, also for continuous volumetric air sampling. These need to be equal to or superior to the above-described methods.

What are some of the best tools for performing environmental monitoring of cleanrooms?

Some portable microbial air samplers (e.g., the MAS-100 NT) offer high accuracy and excellent sampling efficiency. It is small enough to sample close to critical sample locations, can take up to 30 samples in one cleanroom, is easy to disinfect and available with an exhaust filter. It minimizes disturbance of the unidirectional air flow and is compatible with several EM software systems. Triple-bagged and gamma-irradiated ICR or ICR+ culture media for grade A and B cleanrooms reduce the contamination risk because outer bags can be removed in the material lock. Plate versions with locks allow safe transportation for incubation after sampling.

 What are some of the best tools for performing environmental monitoring of a restricted-access barrier system (RABS)?

In a RABS the same environmental monitoring tools can be used as in a cleanroom. However, if a RABS system is decontaminated with vaporized hydrogen peroxide (VHP), it must be ensured that the culture media within the RABS during decontamination are protected by VHP-impermeable bags. These can be hung up during decontamination. To prevent false negative results, all ICR settle plates, contact plates and ICR swabs are formulated to neutralize VHP residues. The MAS-100 NT can also withstand VHP decontamination if in switched-off mode. Alternatively, MAS-100 air samplers specially designed for isolators can be used.

 What are some of the best tools for performing environmental monitoring of isolators?

 In isolators, space is limited, so the control unit of the dedicated air samplers (e.g., MAS-100 Iso line) for isolators are positioned on the outside, saving space inside. The distance can be up to 10 m. A double-valve system prevents cross-contamination and the air tubing can be decontaminated with VHP (e.g., with the MAS-100 Iso MH, one control unit can handle up to four sampling locations.)

Certain packaging designs (e.g., IsoBag rapid transfer bags) save space in isolators. They readily provide ICR settle or contact plates in a DPTE [differential pressure transmitter for air] beta bag. Plates can be safely transferred via rapid transfer alpha ports whenever needed.

How are data obtained from environmental monitoring? How are these data used in pharma manufacturing?

 The data are usually obtained as colony forming units from the culture media used in active and passive air sampling as well as surface and personnel sampling. The new EU GMP Annex 1 suggests using the data both for batch release decisions and for trending analyses. It is possible to detect adverse trends by increasing excursions from action limits or consecutive excursions from alert levels. Also, noticing changes in the microbial flora is important. This helps to maintain the level of cleanliness and address issues by corrective and preventive actions.

Are there specific analytical tools that work best for different types of environmental
monitoring?

As the amount of data generated by environmental monitoring is huge, the PDA [Parenteral Drug Association] Technical Report No. 13 outlines computer-based tracking tools as essential. Specific software systems designed for environmental monitoring help to find adverse trends, and the stored data may allow conclusions as to what the root cause is. One important feature of the sampling equipment is that it should allow data transfer into such software systems, so that all tracked data are handled in a single database. This helps to stay compliant with the standard rules for data integrity.

Environmental monitoring data can help keep sterile environments sterile.

Microbe Monitoring

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On July 26, 2023, FDA released a guidance document on a program at FDA’s Center for Drug Evaluation and Research (CDER) to publicize a listing of accepted voluntary consensus standards that related to pharmaceutical quality. FDA wrote that its involvement in the development and use of technical consensus standards has been crucial to its mission. FDA has used its standards to “develop and/or evaluate performance characteristics of dosage forms, testing methodologies, manufacturing practices, product standards, scientific protocols, ingredient specifications, labeling of drug products, and other technical or policy criteria.”

The guidance document highlights the scope and purpose of the program, before going through the specific elements of the program, including openness, balance, due process, appeals process, and consensus. The document then addresses CDER’s policies and procedures for evaluating voluntary consensus standards, which are recognition request submission and communication with requestors, recognition request evaluation, and updating the CDER program’s recognized standards database. The document ends with a Q&A section, addressing queries such as where recognized standards are posted and how the CDER program will affect other FDA centers.

The CDER program aids submissions by external stakeholders and FDA staff who are proposing voluntary consensus standards that relate to pharmaceutical quality for recognition. In the document, FDA wrote, “CDER believes that this program will help promote beneficial innovation in pharmaceutical development and manufacturing and streamline the preparation and assessment of marketing applications for products regulated by CDER.”

If an industry stakeholder references one of CDER’s accepted voluntary consensus standards with a product regulated by CDER, FDA may still request additional information to show that the standard was observed and is correct for the intended purpose. FDA wrote that the stakeholder’s use of a recognized standard is strictly voluntary.

The program aims to aid submissions from external stakeholders and FDA staff.

FDA Releases Guidance on Standards Related to Pharmaceutical Quality

Biogen announced that it had entered into a definitive agreement to acquire Reata Pharmaceuticals, a pharmaceutical company working in areas of high unmet need, on July 28, 2023. Biogen will acquire Reata for $172.50 per share in cash, an approximate valuation of $7.3 billion. According to a company press release, Reata owns the rights to the first and only FDA-approved treatment for Friedreich’s ataxia, an ultra-rare, genetic, life-shortening, debilitating, and degenerative neuromuscular disorder.

Reata’s Skyclarys (omaveloxolone), is an oral, once-daily medication indicated for the treatment of Friedreich’s ataxia in adults and adolescents aged 16 years and older in the U.S. Omaveloxolone was approved by FDA in February 2023 and is currently under European regulatory review. In addition to omaveloxolone, Reata is developing a portfolio of treatments for various neurological diseases.

“With extensive expertise in rare disease product development and global commercialization… we believe Biogen has the foundation in place to accelerate the delivery of [omaveloxolone] to patients around the world,” said Christopher Viehbacher, president and CEO, Biogen, in the release. “This is a unique opportunity for Biogen to bolster our near-term growth trajectory, and [omaveloxolone] is an excellent complement to our global portfolio of treatments for neuromuscular and rare disease.”

“Biogen’s expertise and commercial footprint make it the optimal choice to help [omaveloxolone] realize its full potential,” said Warren Huff, chairman and ChEO, Reata, in the release. “With its clear understanding of the rare disease patient journey and existing commercial infrastructure, we believe Biogen will establish [omaveloxolone] as the standard of care in the treatment of this devastating genetic disease.”

Biogen’s acquisition of Reata will grant them access to Reata’s FDA-approved treatment for Friedreich’s ataxia.

Biogen to Acquire Reata Pharmaceuticals for $7.3 Billion 

Alexion Pharmaceuticals, a subsidiary of AstraZeneca focusing on rare disease management, announced a definitive purchase agreement with Pfizer on July 28, 2023. Alexion will acquire a portfolio of preclinical rare disease gene therapies from Pfizer for a total consideration of up to $1 billion.

According to a company press release, the transaction features various novel adeno-associated virus (AAV) capsids, which are used for delivering therapeutic gene cargos for both gene therapy and gene editing. In addition to the portfolio, Alexion will welcome talent from Pfizer associated with the portfolio.

In the release, Alexion indicated that the deal is designed to further the combined capabilities of both it and AstraZeneca in genomic medicines. It follows a move from last October, where the company 

, a genetic medicines company, with the objective of developing new genetic therapies with improved safety and efficacy profiles.

“Today’s announcement represents another major step forward in Alexion and AstraZeneca’s ambition to be an industry leader in genomic medicine, which has potential to be transformative and even curative for patients with devastating diseases,” said Marc Dunoyer, CEO, Alexion, AstraZeneca Rare Disease, in the release. “We look forward to continuing our work to develop enhanced platforms and technologies with broad therapeutic application while integrating best-in-class expertise to accelerate promising therapeutics into the clinic.”

AstraZeneca, via its subsidiary Alexion Pharmaceuticals, will purchase a portfolio of preclinical rare disease gene therapies from Pfizer in a deal worth up to $1 billion.

AstraZeneca and Pfizer Ink $1 Billion Rare Disease Deal

FDA announced a final guidance for industry on July 25, 2023, 

titled M7(R2) Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk

 (M7(R2) Guidance). Two additional documents, 

M7(R2) Addendum: Application of the Principles of the ICH M7 Guidance to Calculation of Compound-Specific Acceptable Intakes

M7(R2) Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk, Questions and Answers,

The M7 (R2) guidance emphasizes the importance of safety and risk management in creating levels of mutagenic impurities that are anticipated to not pose significant carcinogenic risk. It outlines recommendations for assessment and control of mutagenic impurities that live in (or are anticipated to live in) final drug substance or product, with consideration for the planned conditions of human use.

The guidance highlights considerations for marketed products, including post-approval changes to the drug substance chemistry, manufacturing, and controls, and changes to the clinical use of marketed products. It also contains a drug substance and drug product impurity assessment, touching on synthetic impurities, degradation products, and considerations for clinical development. Then it goes over hazard assessment elements and risk characterization, with sections for threshold of toxicological concern (TTC)-based acceptable intakes and acceptable intakes based on compound-specific risk assessments, less-than-lifetime (LTL) exposure, and multiple mutagenic impurities. Finally, the document outlines control of process-related impurities and degradation products, lifecycle management, and considerations for control approaches, periodic testing, and clinical development.

FDA stated, “This document is intended to provide guidance for new drug substances and new drug products during their clinical development and subsequent applications for marketing.” The focus of the guidance is on DNA-reactive substances that could cause direct DNA damage when present at low levels, which could lead to mutations and potentially cause cancer. The agency clarified that assessment is not intended for these drug substances and drug products: biological/biotechnological, peptide, oligonucleotide, radiopharmaceutical, fermentation products, herbal products, and crude products of animal or plant origin. It is also not intended to be used with certain advanced cancer indications, excipients used in existing marketed products, perfumes, colorants, or flavoring agents. A more detailed description of applications for this guidance can be found under section II: Scope of Guidance.

The guidance document outlines recommendations to limit potential carcinogenic risk.

FDA Guidance on Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals

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

In this episode of the Drug Solutions podcast, Felicity Thomas, European/Senior Editor, talks to David Tisi, technical director at Senopsys LLC, and Reenal Gandhi, global business development director for the Prescription Division of 

. In the first segment of the episode, David chats about some of the key challenges impacting oral dosage forms and the approaches and solutions available that are helping developers overcome these hurdles. After, Reenal details the intricacies of intranasal drug dosage forms, such as the convenience and the growth of this route of administration, challenges of development, and the possibilities of repositioning drug products.

David Tisi, technical director at Senopsys LLC

David is founding member of the scientific team at Senopsys LLC, a specialty services firm dedicated to the development of palatable drug products. He has over 15 years of experience in taste assessment and taste masking novel drug formulations for children and adults, leveraging his background in sensory science and food chemistry. David received his Masters in Food Science from Cornell University and began his career in product innovation at PepsiCo and Nestle.

Reenal Gandhi, global business development director for the Prescription Division of 

Reenal has more than 15 years’ experience within the drug delivery and pharmaceutical industries, involved in the development and commercialization of wide-ranging drug delivery solutions. Over the course of her career, Reenal has actively worked on business development related to nasal and injectable devices, such as prefilled syringes and autoinjectors. Since December 2020, Reenal has been working for Aptar Pharma, driving the assessment of new opportunities and focusing on new technologies in particular.

 presents the Drug Solutions podcast, where the editors will chat with industry experts from across the pharmaceutical and biopharmaceutical supply chain. Join us as experts share insights into your biggest questions—from the technologies, to strategies, to regulations related to the development and manufacture of drug products.

Podcasts

In this episode, David Tisi and Reenal Gandhi provide expert insights into advances and innovations changing the drug dosage form landscape.

Drug Solutions Podcast: Innovations and Advances in Drug Dosage Forms

SCG Therapy opened its new cell therapy manufacturing facility and research and development center in Singapore, the company announced on July 20, 2023, to pioneer Singapore’s Manufacturing 2030 Vision, according to a company press release.

The new facility is set to utilize and extend SCG's capabilities in advanced cell therapy manufacturing and off-the-shelf human-induced Pluripotent Stem Cell (iPSC) technology. Further, the facility will supply cell therapy products to partner hospitals in Asia Pacific, North America, and Europe, according to the release.

"Cell therapy has demonstrated the potential to revolutionize treatment for cancers and other life-threatening diseases. However, the high manufacturing costs and supply limitation are limiting patient access to the treatment,” said Christy Ma, chief strategy officer of SCG Cell Therapy, in a press release.

Low Yen Ling, minister of state at the Ministry of Trade and Industry, described that Singapore’s Manufacturing 2030 vision aims to position Singapore as a global business, innovation, and talent hub for advanced manufacturing. “The biotechnology sector is an important flank of our strategy. Today, we have a thriving ecosystem comprising both local and global companies pursuing their ambitions in biotechnology from Singapore,” Ling said in a press release. “SCG Cell Therapy is one of our promising local startups, developed its first cell therapy product, SCG101, with the support of agencies like the Health Sciences Authority (HSA) and the Agency for Science, Technology and Research (A*STAR). Headquartered in Singapore, and with teams in China and Germany, SCG Cell Therapy offers the entire drug development cycle—from research and development (R&D), GMP manufacturing, and clinical development to commercialization. The cGMP [current good manufacturing practice] facility will enable SCG Cell Therapy to further scale its operations. Its development augurs well for the growth of our biotech sector.”

The new facility is set to utilize and extend SCG's capabilities in advanced cell therapy manufacturing and off-the-shelf human-induced Pluripotent Stem Cell (iPSC) technology.

SCG Therapy Opens Cell Therapy Manufacturing Facility in Singapore

Jill Wechsler is Pharmaceutical Technology's Washington Editor, jillwechsler7@gmail.com.

The legislators departed Washington, D.C. in late July for a six-week summer recess without passing a host of critical budget bills, including key measures involving health care and drug regulation. At the top of the legislative to-do list are multiple appropriation bills to continue funding the federal government past Sept. 30, 2023. Another important measure on hold would reauthorize programs to prepare the nation for the next pandemic. And policies to rein in pharmacy benefit managers (PBMs) gained approval from some committees, but not a final vote.

Demands to radically cut spending and to further limit access to abortion erected major roadblocks to agreement on important funding bills, as conservatives in the House demanded spending cuts unacceptable to Democrats and moderate Republicans. Only the Department of Veterans Affairs saw its budget approved, enabling members of Congress to claim support for military veterans when engaging with constituents back home.

While the Senate passed most fiscal 2024 spending measures, very partisan proposal in the House blocked any agreement on final measures. Funding for the Department of Defense was stymied by Republican opposition to a Biden administration policy to fund travel of armed forces members to obtain abortion services. House Republicans alienated Democrats with cuts in multiple agencies in the Department of Health and Human Services (HHS), including the National Institutes of Health (NIH) and the Centers for Disease Control and Prevention (CDC) and proposed to eliminate the Agency for Healthcare Research and Quality (AHRQ), a perennial target of conservatives.

Similarly, the House measure to fund the Department of Agriculture, including FDA programs, made significant cuts in food program such as foreign food aid and support for US food exports, outraging both Republicans and Democrats from rural states. Not only was FDA’s overall budget slashed, but the bill sought to ban mail order delivery of the abortion pill mifepristone, a proposal that drew a veto threat from the Biden administration. The Agriculture/FDA funding bill in the Senate provides a slight 1% budget increase for FDA, which means less severe but still significant program reductions.

House and Senate committees made some progress on legislation to support national preparedness and response to future pandemics, which has to be reauthorized before it expires Sept. 30, 2023. But that tight timeframe for passing the Pandemic All Hazards and Preparedness Act (PAHPA) is encouraging lawmakers to include various pet programs and policies in the measure. The Senate Health, Education, Labor and Pensions (HELP) committee approved PAHPA on July 20, 2023, readying the measure for a vote by the full Senate in September. HELP committee chairman Bernie Sanders added a number of provisions, including one requiring drug manufacturers to notify FDA in advance of product shortages and other shortage-related provisions. While the legislators generally back continued support for preparedness, House Republicans moved to slash funding for the program, setting up a partisan battle over the program’s future.

Also pending is legislation to boost transparency and revise fees from insurers to pharmacy benefit managers (PBMs). These drug plan middlemen have been under attack from manufacturers and policy makers for failing to pass on savings to consumers and limiting patient access to certain medicines, and both the House and Senate held hearings this past year to consider reforms. Continued Federal Trade Commission investigation of PBM practices has set the stage for legislative reform.

Despite this support for change, the policy reforms in current bills appear relatively tame. The Senate Finance Committee recently approved a legislative package aimed at boosting transparency of PBM practices affecting Medicare Part D plans. And the House Ways & Means Committee similarly agreed to give patients and employers more information to stimulate competition in the field. House Republicans approved a bill that Democrats opposed as too weak, raising the likelihood of differing bills from the House and Senate in the fall which may be hard to reconcile.

With the August recess extending through mid-September, Congress will have only a few days to approve 12 appropriations bills and other expiring measures before the September 30 deadline. Unless the feuding parties reach some agreement, that could mean a federal government shutdown in October and added difficulties in maintaining the nation’s health care system, along with a viable drug approval and regulatory program.

Pandemic, PBM, and other policies on hold during the summer recess.

Congress Leaves Town with Major Drug-Related Bills on Hold

Biovian Oy announced a major investment of over €50 million to expand its manufacturing facility in Turku, Finland on July 26, 2023. The new facility plans to include house cutting-edge equipment and advanced technologies to support Advanced Therapy Medicinal Products (ATMP), such as adenoviral and adeno-associated viral (AAV) therapies.

According to the press release, it will feature dedicated Class A to D cleanroom areas for bulk drug substances and final drug product manufacture. Additionally, the expanded facility will follow current good manufacturing practices (cGMP) and fulfill both EU and US GMP requirements.

The expansion project is aimed to be completed in December 2024 and the new facility will be fully operational by 2025. Further, the investment hopes to create 100 job opportunities in the region.

The expansion project is aimed to be completed in December 2024 and the new facility will be fully operational by 2025.

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