Zachary Zubulake

BioPhorum formed a group aimed at accelerating innovation across small molecule manufacturing

BioPhorum, a global forum for biopharmaceutical industry collaboration, has formed a new working group aimed at accelerating innovation across small molecule manufacturing.

 The Synthetic Molecule Process Innovation Phorum brings together 20 organizations spanning global pharmaceutical companies, specialist CDMOs, technology providers, and regulatory bodies, with the goal of aligning the broader ecosystem around faster, more coordinated adoption of new manufacturing approaches.

Participants include major pharmaceutical manufacturers alongside regulatory and standards bodies, such as the UK's Medicines and Healthcare products Regulatory Agency, the British Pharmacopoeia, and the US Pharmacopeia.

 Their involvement signals an intent to make the group a direct channel between industry practice and regulatory expectations, rather than a forum limited to internal industry discussion.

Why Is Small Molecule Manufacturing Under Pressure?

The initiative responds to a shift already underway in drug development pipelines.

 Small molecule therapies, once associated largely with niche or high-potency compounds, are increasingly central to high-volume treatments in oncology, neurology, obesity, and immunology. That shift is placing new demands on manufacturing infrastructure, which must scale efficiently while maintaining supply chain resilience. “As pipelines fill with complex small molecules, from next‑generation obesity treatments to breakthrough therapies in oncology and immunology, the question is no longer whether science can deliver, but whether manufacturing can keep up,” stated Andrea Johnston, senior director, BioPhorum, in a press release.

 “By bringing global pharma and specialist CDMOs around one table, the BioPhorum Synthetic Molecule Process Innovation is designed to turn market momentum into robust, efficient, and sustainable ways of making these products at scale.”

This framing matters because it reflects a broader industry pattern: therapeutic innovation is outrunning the operational systems meant to support it.

 Facilities built around older production assumptions may struggle to accommodate the complexity and scale of newer synthetic molecule pipelines without coordinated updates to process design, regulatory guidance, and data infrastructure.

Following a two-day planning session in Cork, Ireland, the collaboration identified four initial focus areas.

 The first addresses peptide manufacturing, specifically capacity constraints and raw material availability, which have become recurring bottlenecks as peptide-based therapies expand. The second targets regulatory alignment, including global acceptance of solvent reuse practices and clearer chemistry, manufacturing, and controls guidance for synthetic peptide production under biologics license applications. The third focuses on model-based predictive control, aiming to develop frameworks for robust, end-to-end control strategies across manufacturing processes. The fourth centers on knowledge lifecycle management, an effort to standardize how data are shared and interpreted across a product's development and manufacturing lifecycle.

Each of these areas touches a persistent operational challenge in the sector: fragmented regulatory expectations across regions, inconsistent data practices between organizations, and supply constraints that can delay production timelines even when clinical development proceeds smoothly.

 A coordinated, cross-industry approach to these issues could reduce duplicated effort among individual companies working through similar problems independently.

The launch also reflects a wider consolidation trend among industry organizations that support manufacturing best practices, as groups expand their scope to address adjacent operational challenges rather than operating within narrower technical silos.

The formation of this group is worth monitoring less for what it announces today than for what it may produce over time: potential shifts in regulatory guidance, emerging standards for predictive control systems, and clearer expectations around peptide manufacturing that could influence facility planning and compliance strategy in the coming years.

What Does Market Growth Show About the Urgency Behind This Collaboration?

Recent figures reinforce the timing of BioPhorum's initiative.

 The global small molecule API contract development and manufacturing market was valued at $46.6 billion in 2025 and is projected to grow to $80.7 billion by 2033, expanding at a compound annual rate of 7.3%. Analysts attribute this growth partly to rising demand for complex APIs, supply chain resilience initiatives amid shifting geopolitics, and increasing digitalization and regulatory evolution. Phorum's four work streams aim to address these same pressures collectively rather than company by company.

BioPhorum. BioPhorum unites regulators, big pharma and CDMOs to accelerate synthetic molecule innovation. Press release. July 1, 2026.

Grand View Research. Small molecule CDMO market size | industry report, 2026. July 1, 2026. 

https://www.grandviewresearch.com/industry-analysis/small-molecule-cdmo-market-report

Articles

BioPhorum has launched the Synthetic Molecule Process Innovation Phorum to coordinate faster adoption of advanced small-molecule manufacturing practices across 20 stakeholders, including large pharma, CDMOs, technology vendors, and MHRA/BP/USP. The effort reflects mounting scale and complexity demands from oncology, immunology, neurology, and obesity pipelines, where operational capability increasingly constrains product delivery. Initial workstreams target peptide capacity and raw-material bottlenecks, global regulatory alignment (eg, solvent reuse and CMC for peptides under BLAs), model-based predictive control, and standardized knowledge lifecycle management.

BioPhorum launches a 20-member collaboration uniting pharma, CDMOs, and regulators to address manufacturing challenges in small molecule drug production.

BioPhorum Unites 20 Organizations to Modernize Small Molecule Production

Oxylanthanum carbonate was rejected for the 2nd time by the FDA

Oxylanthanum carbonate, an investigational phosphate binder developed by Unicycive Therapeutics for hyperphosphatemia in patients with chronic kidney disease on dialysis, has received a second Complete Response Letter (CRL) from the FDA.

 The agency raised no concerns about clinical efficacy or safety and requested no additional data. Instead, the rejection rests entirely on unresolved compliance deficiencies at the third-party manufacturing vendor responsible for producing the drug substance, the same deficiencies cited in the original CRL issued in June 2025.

Between the two decisions, the company had pursued a now-familiar regulatory sequence: a Type A meeting with the agency in September 2025, an EU inspection of the same vendor that found no deficiencies, and a resubmission of the New Drug Application built on the vendor's reported progress toward inspection readiness.

 Despite that progress, the FDA had not completed its own inspection of the facility by the time of the second decision, leaving the compliance question unresolved and the application unapprovable on chemistry, manufacturing, and controls grounds alone.

What Types of Deficiencies Trigger CRL for a Third-Party Manufacturer?

CRLs tied solely to chemistry, manufacturing, and controls (CMC issues generally stem from facility-level compliance findings rather than problems with the drug product itself.

 Common triggers include unresolved findings from a pre-approval inspection, data integrity concerns, deviations from current good manufacturing practice, or failure to demonstrate inspection readiness within the review cycle. In this case, the company has stated that the citations at the vendor were not specific to oxylanthanum carbonate production, underscoring a recurring theme in CMC rejections: a facility's broader compliance status can stall an otherwise clean application, independent of how the investigational product itself performs. This distinction shifts the resolution pathway away from additional clinical work and toward facility remediation, an inspection, and confirmation of compliance, none of which the sponsor directly controls.

How Should Sponsors Avoid Resubmission Delays?

The case illustrates the value and the limits of contingency planning around contract manufacturing.

 The company identified and qualified a second manufacturing vendor that had already produced drug product following the first rejection, yet the resubmission still relied on the original vendor's compliance status, and the second rejection again hinged on that same facility. The lesson for sponsors managing third-party manufacturing relationships is that qualifying a backup vendor is necessary but not sufficient; the qualification timeline, validation batches, and any required inspections need to run far enough ahead of a Prescription Drug User Fee Act target date that switching vendors does not itself become the source of delay. Sponsors that wait until a CRL arrives to activate a secondary supply path risk repeating the same compliance dependency that triggered the original rejection, since regulatory timelines for vendor transitions rarely compress to match a resubmission cycle already in progress.

What Does This Mean for Novel Oral Solid Dosage Forms?

Oxylanthanum carbonate is formulated using proprietary nanoparticle technology intended to increase phosphate-binding potency and reduce pill burden compared with existing binders, a formulation approach gaining traction across oral solid dosage development as sponsors seek to improve adherence in chronic disease populations.

 This case is a reminder that novel particle-engineering platforms often depend on specialized contract manufacturers with the equipment and process expertise to produce them at scale, narrowing the pool of qualified vendors and concentrating regulatory risk at the facility level. As more oral solid dosage candidates rely on nanoparticle-based drug delivery, sponsors and their manufacturing partners should expect facility compliance history and inspection readiness to weigh as heavily on approval timelines as the underlying formulation science, particularly when specialized production capacity is limited and difficult to replicate quickly across alternate sites.

Reuters. US FDA declines to approve Unicycive’s drug for dialysis patients. Press Release. June 30, 2026. 

https://www.reuters.com/legal/litigation/us-fda-declines-approve-unicycives-drug-dialysis-patients-2026-06-30/

Unicycive Therapeutics, Inc. Unicycive Therapeutics Receives Complete Response Letter from FDA Regarding Resubmitted Oxylanthanum Carbonate (OLC) New Drug Application (NDA). Press Release. June 30, 2026. 

https://ir.unicycive.com/news/detail/123/unicycive-therapeutics-receives-complete-response-letter

Oxylanthanum carbonate, Unicycive’s investigational phosphate binder for dialysis-dependent CKD, received a second FDA Complete Response Letter driven solely by third-party manufacturing compliance deficiencies. No new clinical efficacy or safety issues were raised, and no additional data were requested. Despite a Type A meeting, an EU inspection finding no deficiencies, and an NDA resubmission citing vendor remediation progress, FDA had not completed its own facility inspection, leaving CMC approvability unresolved. The situation highlights how facility-level GMP status can dominate timelines for specialized nanoparticle-enabled oral solids.

The FDA again rejected Unicycive's oxylanthanum carbonate over third-party manufacturing compliance, not safety, spotlighting CMC risk in nanoparticle drug development.

Manufacturing Deficiencies Behind FDA's Oxylanthanum Carbonate Rejection

AI is reshaping GMP documentation and quality workflows, but human accountability remains non-negotiable and the regulatory consequences for over-relying on AI are real.

PharmTech Explained: Human Accountability with AI in GMP

, featuring industry experts Brian Drapeau and Richard Jaenisch, examines how AI is already reshaping pharmaceutical manufacturing and where the risks of getting it wrong are emerging.

AI is no longer a future consideration for pharmaceutical manufacturers; it is an operational reality. Regulatory submissions containing AI and machine learning components are rising sharply, and the pressure to deploy these tools across GMP environments continues to grow. But as adoption accelerates, a foundational question confronts every quality organization: where exactly does algorithmic decision support end and human accountability begin?

Deviation management has become the leading early use case, offering a clear proof of concept: if a process can be reduced to a fillable form, generative AI can enhance and accelerate it. Beyond time savings, the more consequential benefit is cognitive reallocation, freeing qualified professionals from administrative burden so their expertise can be directed toward investigation, root cause analysis, and risk-based decision-making that no algorithm can perform.

But accountability structures in GMP settings remain unchanged. As Drapeau illustrates with a recent FDA 483 observation, among the first issued specifically over AI use, manufacturers cannot delegate quality unit responsibility to a tool. The AI doesn't get cited. The human does.

The more systemic threat, Drapeau argues, is the slow, unnoticed drift toward autonomy. When AI outputs are consistently reliable, human verification tends to erode over time, an incremental shift that can embed unvalidated process changes into controlled manufacturing operations before anyone recognizes what has occurred.

To govern AI effectively, Drapeau identifies four emerging roles quality organizations should consider essential: AI-literate quality reviewers, a dedicated AI validation lead, a computational pharmaceutical scientist, and an IT and cybersecurity liaison embedded within quality.

The organizations best positioned for the next decade of AI integration, the episode concludes, will be those that invest in human capability with the same rigor they apply to the technology itself.

Videos

AI is reshaping GMP documentation and quality workflows, but human accountability remains non-negotiable, and the regulatory consequences for over-relying on AI are real.

The pace of life sciences M&A has slowed in 2026, but Kristin Ciriello Pothier, life sciences sector leader, KPMG US, says lower deal volume doesn't mean lower value. It means companies are finally doing the work.

Watch the 3-part video interview with Pothier:

What's Driving Biopharma M&A Strategy in 2026

How to Maximize Value in Platform Technology Deals

Why Pharma Dealmaking Slowed in Q1 2026 and What Is Coming Next

PharmTech: How Would You Characterize the State of Life Sciences M&A In Q1 2026?

We've stopped counting deals, and we've started making them count. Volume has continued to come down, but the assets in this space are very precious. Every company we're working with is diligencing each asset to determine whether it will be a prime in their portfolio, not just another layer on top of an already complex biopharma landscape. What we're also seeing is more pricing discipline: companies are paying what the data suggests is fair, not bloating deal values. It's a very disciplined approach to life sciences in the first half of this year.

Which Therapeutic Areas Are Generating the Most Deal Activity?

Oncology continues to be very hot. We just came back from ASCO 2026 in Chicago, and the excitement around combination therapies and modality complexity was extraordinary, the largest pharma companies each brought 50 to 100 people to work through assets and IP. Beyond oncology, we're seeing tremendous activity in chronic disease, particularly around GLP-1s [glucagon-like peptide-1] and everything surrounding them. GLP-1s are no longer just about diabetes or obesity management, their effects are expanding into cardiovascular health, oncology support, and holistic patient care. That broader view of what a GLP-1 ecosystem looks like is generating significant deal interest.

How Is Manufacturing Readiness Factoring into Deal Diligence?

For cell and gene therapy, manufacturing diligence is more intensive than for almost any other asset class, and the reason is straightforward, you cannot ship cell and gene therapy from one part of the globe to the other. It must follow a corridor-based strategy, dedicated strategies for the United States, the European Union, and in the Asia-Pacific region. So when acquirers are looking at these assets, one of the first questions is whether the manufacturing plants are included in the deal. We're seeing situations where buyers want those facilities and sellers won't give them up, and when that happens, the deal valuation changes completely. The acquirer must factor in where and how they'll manufacture in each region, and what it will cost to upskill or upscale a facility in any geography they're missing.

How are Tariffs Influencing Manufacturing Strategy Decisions?

What we're not seeing is a knee-jerk reaction. Rather than immediately committing to building a plant in the Americas or fully reshoring, companies are having very careful conversations about whether regional manufacturing investment pencils out, or whether the smarter move is to absorb tariff costs and adjust their P&L accordingly. The companies we work with are running rigorous analyses rather than making reactive decisions. That's a sign of maturity in how our sector handles geopolitical and trade pressures.

What Do You Expect to Drive Deal Momentum in the Second Half Of 2026?

We see 3 levers. The first is artificial intelligence (AI) and data, not through large M&A, but through partnerships and alliances, because the best-in-class AI capability isn't being built inside life sciences companies. The second is manufacturing sites and contract manufacturing acquisitions, particularly as platform technology complexity increases in oncology and other areas. And the third is therapeutic area M&A, anchored by oncology assets and the GLP-1 ecosystem, including adjacent services, diagnostics, consumer health, and functional nutrition. As earlier deals from this year come to fruition and unlock confidence, we expect both deal volume and deal value to rise as we move into 2027.

Life sciences M&A in early 2026 is marked by lower volume but higher selectivity, with acquirers emphasizing strategic fit, rigorous diligence, and pricing discipline aligned to data. Oncology remains the most active therapeutic area, fueled by combination regimens and modality complexity, while chronic disease dealmaking is expanding around GLP-1 ecosystems beyond diabetes and obesity. Manufacturing readiness—especially for cell and gene therapies—has become a valuation determinant. Tariff uncertainty is driving analytical, not reactive, manufacturing decisions. Second-half momentum is expected from AI alliances, manufacturing acquisitions, and oncology/GLP-1 transactions.

Kristin Ciriello Pothier, KPMG US, discusses deal discipline, manufacturing diligence, and why oncology and GLP-1s are driving biopharma M&A activity in 2026.

Q&A: Why Pharma Deal Volume Is Down but Value Is Up

Karianne Gelinas, Lehigh Valley Economic Development Corporation 

Karianne Gelinas, vice president of Talent Strategies at the Lehigh Valley Economic Development Corporation (LVEDC), discusses how Eli Lilly is moving forward with its $3.5B manufacturing investment in the Lehigh Valley of Pennsylvania, regional workforce developers are working to ensure the local talent base can meet the facility's technical demands.

Watch the 2-part video interview with Gelinas:

Why Eli Lilly Chose Pennsylvania for its $3.5B Facility

How the Lehigh Valley Is Building Lilly's Workforce

PharmTech: What Makes the Lehigh Valley Well-Positioned to Support a Pharmaceutical Manufacturer Like Lilly?

The region has a long history as a manufacturing hub. Sixteen percent of the Lehigh Valley's gross regional product comes from manufacturing, compared to 11% at the national level, so building a workforce for a pharmaceutical manufacturer was an extension of what we already do. We have 11 colleges and universities in the region, including 2 community colleges and 3 career and technical schools, all of which already have curriculum oriented toward skilled and technical manufacturing roles.

How Did LVEDC Demonstrate That the Talent Pool Existed to Support Lilly's Needs?

We use a lot of data when responding to company inquiries. Within an hour's commute from where the Lilly operation is being built, we could document specific volumes of people already employed in engineering, quality control, and chemistry technician roles. We're also an hour from Philadelphia and two hours from New York City, within the biopharma and biotech belt. That geography gives us access to commuter populations, people who are currently commuting out of the region for biopharma roles could potentially be retained here with a position at Lilly.

What Role Did Community College Programming Play in Lilly's Decision?

A significant one. Lehigh Carbon Community College was planning and beginning the full renovation of its facilities and curriculum when Lilly was evaluating the region. The school had won an NSF [National Science Foundation] grant and was partnered with Wake Tech as its mentor institution. Lilly holds Wake Tech as a gold standard for workforce preparation, particularly its BioWork certificate and articulation agreements with four-year institutions. When Lilly heard about that partnership, it was very motivating. We weren't doing this reactively. Attracting pharmaceutical and life science companies has been a strategic priority at LVEDC for years.

Beyond Lehigh Carbon, What Other Workforce Development Infrastructure is Being Built?

Lehigh Career and Technical Institute, one of the premier career and technical schools in Pennsylvania, is developing a pre-apprenticeship program that stacks into the community college certificate programs. That, in turn, can feed into the Industrial Training and Education Consortium, or ITEC, a nonprofit apprenticeship program run by roughly a dozen manufacturing and industrial employers in the region. ITEC currently has five Commonwealth of Pennsylvania-approved apprenticeship programs, including chemistry lab technician, mechatronics, maintenance tech, and quality control tech, roles that translate directly to pharmaceutical manufacturing operations.

With More Than 850 Jobs Expected, Where Do the Gaps Lie?

Volume is the primary challenge right now. At least half of those positions will require a certificate or a 2-year degree. That means we need to build community awareness starting at the K-12 level, ensuring students know these careers exist before they choose their high school coursework. Having Lilly here is a real asset in that effort. We can now point to real jobs that will exist by 2031 and say, we want everyone to be part of this.

How is LVEDC Approaching the Potential Impact of AI On Technical Workforce Planning?

We're building advisory groups, convening conversations with AI leaders and consultants, and working with schools that have stood up AI curriculum and brought local industry onto their advisory boards. We're also asking our CIOs [chief information officers] directly what they're doing within their companies. What we haven't yet done is have those specific conversations with Lilly about how AI may shape their workforce needs , but we're ready to have them when they are.

Eli Lilly’s $3.5B Lehigh Valley manufacturing project is being supported by a region with above-average manufacturing intensity, proximate access to Philadelphia and New York talent, and a dense education ecosystem. Workforce readiness is anchored by data-driven talent mapping, community college modernization, and stackable credentials spanning pre-apprenticeships through state-approved apprenticeships aligned to pharma operations. The central constraint is scaling credentialed labor to fill >850 roles, prompting earlier K–12 career awareness initiatives. AI’s workforce implications are being explored via regional advisory structures, ahead of direct alignment with Lilly.

How the Lehigh Valley Economic Development Corporation is building a technical workforce pipeline to support Eli Lilly's 850-job pharmaceutical manufacturing expansion.

Q&A: The Reason Behind Lilly's Pennsylvania Facility

FDA's Revised Draft Guidance Updates Master Protocol

The FDA released a revised draft guidance on June 22, 2026 offering updated recommendations on the design, analysis, and regulatory submission of clinical trials conducted under master protocols.

The document is a revision of a December 2023 draft and reflects the FDA’s consideration of public comments received on that earlier version.

 The update adds expanded recommendations on basket trials and clarifies guidance on randomization, choice of control, and informed consent. The guidance addresses practical challenges that have historically complicated master protocol adoption for many drug developers.

Master protocols are structured to evaluate drugs across one or more diseases within a single overarching study framework.

 The three primary trial types covered are umbrella trials, which test multiple drugs against a single disease; basket trials, which evaluate a single drug across multiple diseases or disease subtypes; and platform trials, which allow drugs to enter and exit an ongoing evaluation structure over time. Each presents distinct design challenges that the guidance attempts to address with greater specificity than prior versions.

What Does the Guidance Say About Control Groups and Randomization?

One of the more technically significant sections concerns how control group data should be used in platform trials, where participants randomized to a control arm early in a long-running study may not have been eligible for drugs that entered the platform later.

 The guidance recommends that primary comparisons for any given drug use only concurrently eligible control participants, those who met drug-specific eligibility criteria and could have been randomized to that drug at the time of enrollment.

The agency acknowledged that using nonconcurrent control data can increase statistical precision, particularly in rare disease settings with constrained enrollment, but cautioned that temporal shifts in patient characteristics or standard of care can introduce bias that statistical adjustments may not fully correct.

 Sponsors who believe nonconcurrent controls are warranted are advised to discuss that rationale with the FDA early in planning.

On randomization, the guidance recommends allocating a greater proportion of participants to the shared control arm than to any individual drug arm in multi-drug trials.

 The mathematical basis for this, derived from minimizing the variance of each drug-versus-control comparison for a fixed total sample size, favors a control-to-drug ratio of the square root of the number of drugs being evaluated.

How Should Sponsors Approach Blinding and Regulatory Submissions?

Blinding presents another layer of complexity in master protocols, particularly when drugs being evaluated have different routes or schedules of administration.

 The guidance describes a range of approaches from complete blinding via multiple-dummy designs to partial blinding strategies in which participants know their assigned sub study but not whether they are receiving an active drug or placebo. The FDA recommends complete blinding where feasible, and open-label designs only in narrow circumstances where endpoints are objective and blinding would be highly impractical.

From a regulatory submission standpoint, each master protocol must be filed under a new Investigational New Drug Application.

 Sponsors are advised to request pre-submission meetings well in advance, given the layered coordination required among the master protocol sponsor, individual drug sponsors, and the FDA review divisions. The guidance includes detailed procedures for protocol amendments, cross-referencing between applications, and safety reporting obligations, all areas where multi-sponsor arrangements can generate compliance complexity.

What Other FDA's Moves Are Affecting the Broader Development Landscape?

FDA approved the first generic version of baloxavir marboxil tablets in June 2026, clearing a single-dose treatment option for acute uncomplicated influenza and post-exposure prophylaxis in patients five years and older

 The approval, arrives ahead of the 2026–2027 flu season. Agency officials framed the decision around public health access, noting that influenza drives millions of illnesses annually in the United States. Generic drugs currently account for 9 out of 10 prescriptions filled domestically, and expanded generic availability is expected to introduce competitive pricing pressure on the existing market.

Master Protocols for Drug and Biological Product Development: Guidance for Industry. Draft Guidance

. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research; Center for Biologics Evaluation and Research. June 2026.

FDA approves first single-dose generic treatment for influenza. Press Release. FDA. June 16, 2026. 

https://www.fda.gov/news-events/press-announcements/fda-approves-first-single-dose-generic-treatment-influenza

FDA issued a revised June 2026 draft guidance refining expectations for master protocol trials, incorporating feedback to the 2023 draft. It expands basket-trial recommendations and provides sharper direction on randomization, control selection, blinding, and informed consent. For platform trials, primary drug comparisons should rely on concurrently eligible controls to mitigate temporal bias, with limited use of nonconcurrent controls via early FDA engagement. The guidance also outlines IND submission, amendment, cross-referencing, and safety-reporting logistics in multi-sponsor settings, alongside FDA’s approval of a first generic baloxavir tablet.

The FDA's revised draft guidance updates master protocol recommendations on randomization, control groups, blinding, and regulatory submissions for multi-drug trials.