Pharmaceutical manufacturing is entering a phase defined less by singular breakthroughs and more by systems-level maturity. Across development, manufacturing, quality, and outsourcing, the industry is being asked to scale complexity without sacrificing control, whether that means adapting to new modalities, tightening regulatory timelines, or managing an increasingly outsourced supply chain. The July/August 2026 issue’s contributors offer a snapshot of what that maturity looks like in practice.

Our cover story examines downstream purification in biologics, where resilience and adaptability are becoming as important as throughput itself; operations must be built to evolve alongside the industry, not just keep pace with it. That same tension between complexity and consistency runs through our development feature on personalized therapies, where raw-material variability remains one of the toughest obstacles to reliable CAR-T and cell therapy manufacturing. Strategies like batch qualification, robust data systems, and automation are moving beyond efficiency plays and becoming prerequisites for reproducibility at the patient level.

On the automation side, contract research organizations are confronting the limits of spreadsheet-driven operations. As experimentation scales, so does the cost of manual processes, not just in time, but in compliance risk, traceability, and auditability. It’s a reminder that digitization in contract research is becoming table stakes.

This issue’s regulatory feature turns to the shifting biosimilar landscape, where faster approval pathways are reshaping market access, but, as the author notes, faster doesn’t necessarily mean easier for development teams navigating the new requirements.

Finally, our outsourcing piece makes a case that documentation reliability across contract organizations can’t be an afterthought bolted on before an audit. It must be engineered into quality systems from the start.

Taken together, these articles reflect an industry maturing under pressure to be more personalized, more outsourced, more automated, and more scrutinized than ever. Building the technical, regulatory, and organizational systems that can hold up under that pressure is the throughline.

Articles

Pharmaceutical manufacturing is shifting from isolated innovations to systems-level maturity across development, manufacturing, quality, and outsourcing. Biologics downstream purification is prioritizing resilience and adaptability alongside throughput to support evolving modality demands. Personalized therapies, particularly CAR-T and cell therapies, remain constrained by raw-material variability, driving adoption of batch qualification, robust data architectures, and automation to enable patient-level reproducibility. CROs are moving beyond spreadsheets as scale amplifies compliance, traceability, and audit risk. Meanwhile, accelerated biosimilar pathways alter access dynamics without simplifying development, and documentation reliability must be designed into partner quality systems from inception.

From the Chairman

Across development, manufacturing, quality, and outsourcing, the pharma industry is being asked to scale complexity without sacrificing control. 

Scaling Complexity Without Losing Control

regulatory actions are coming together in an effort to move biologics, gene therapy, and the ATMP platform forward quickly, say Susan J. Schniepp, distinguished fellow at Nelson Labs, and Siegfried Schmitt, PhD, vice president, technical, Parexel Consulting.

Q. My company manufactures biologics, and we saw some recent actions by the FDA, USP, and the EU. How do these regulatory actions impact us as a biologics manufacturer?

A. The US Pharmacopeia (USP) has released methods for biologics, without specifications, in an effort to help biologic manufacturers, because this is a rapidly growing field. So, this should help people So, this should help people in terms of their chemistry, manufacturing, and controls (CMC) sections, with methods, and then they can set the specifications depending on the product they're developing.

The European Medicines Agency (EMA) announced an agreement for its Critical Medicines Act that came out in 2025.

 This act addresses controlling drug shortages and eliminating some of those roadblocks, such as suppliers, because there may be critical elements a company needs to manufacture a biologic that are available from only one source; if that supplier has a problem, everybody has a problem.

The other recent action is from the FDA. The agency issued a draft guidance on leveraging prior knowledge in the development of human gene therapy products incorporating genome editing.

 The guidance says that, instead of establishing your own holistic platform, you can reference studies and information that have been published to enhance your CMC section or your filing.

These regulatory documents are open to public comment, and companies should consider submitting their comments and/or concerns, including the USP standards.

Let’s discuss the potential intentions of the regulators in taking these actions. These products are typically lifesaving products when we look at biologics. These are products that not only patients want to see urgently, but regulators are also supporting the industry in getting them to market.

But not only that, there is a supply chain behind it because you cannot make everything in-house. You need suppliers. And it may be for some of these raw materials and excipients, they may be very difficult to get hold of. And some may be very difficult to transport. So, there are many different aspects to this. And some of the technical ideas are to perhaps manufacture close to where your patients are.

Because the knowledge of these products may be limited to a few people or a few firms, the FDA draft guidance is trying to expand that knowledge by allowing companies to use information that's previously been published for their product, to be able to expedite approval of these lifesaving methods.

And coming back perhaps also to the manufacturing; you could, for example, traditionally file for a product in the United States, and then you file in Europe and maybe other jurisdictions. And you may typically have a product that you start making in the US, and then you ship it over to other markets. That's not always an option with biologics, especially because cell and gene therapy products may not be conducive to such shipments.

And something that all the regulators like to see now is to have manufacture much more within the market where they are regulating, which may mean, with this distributed manufacturing, that we are probably getting away more and more from the centralized large production facilities to more smaller, closer to the patient facilities where we have shorter supply chains.

But how do we get all our suppliers to supply us to these locations rather than to just one? So, there are many aspects that need to be considered. It's important that companies provide their input to the regulators because they want to hear what is feasible and what is practical.

USP publishes product-specific emerging biologics standards for public comment. News release. USP. June 1, 2026. Accessed July 9, 2026. 

https://www.usp.org/news/usp-publishes-product-specific-emerging-biologics-standards-for-public-comment

 welcomes political agreement on Critical Medicines Act

. News release. European Commission. May 11, 2026. Accessed July 9, 2026. 

https://ec.europa.eu/commission/presscorner/detail/en/ip_26_1017

FDA issues draft guidance to help accelerate cell and gene therapies for patients. News release. FDA. June 2, 2026. Accessed July 9, 2026. 

https://www.fda.gov/news-events/press-announcements/fda-issues-draft-guidance-help-accelerate-cell-and-gene-therapies-patients

USP has issued product-specific analytical methods for emerging biologics without predefined specifications, enabling sponsors to tailor acceptance criteria while strengthening CMC packages. In Europe, the EMA-backed Critical Medicines Act targets shortage prevention and supply-chain resilience, particularly where single-source inputs create systemic vulnerability. FDA’s draft guidance on genome-edited gene therapies encourages leveraging published prior knowledge to expedite CMC development and regulatory review. Collectively, these actions support faster patient access and push manufacturing toward more distributed, in-market models. Public comment is actively solicited.

Three regulatory actions are converging to move biologics, gene therapy, and the ATMP platform forward quickly, say Susan J. Schniepp, distinguished fellow at Nelson Labs, and Siegfried Schmitt, PhD, vice president, technical, Parexel.

Regulatory Actions Impacting Biologics

While scientific excellence within contract research organizations (CROs) and contract development and manufacturing organizations (CDMOs) is crucial, it’s now a commodity.

Competition is now operational. Margins are increasingly tied to efficiency; manual steps and disconnected systems directly impact cost and delivery.

CROs must deliver results faster at the highest levels of quality, accuracy, and repeatability at the lowest possible operating costs, all while elevating the client experience. CROs need fully predictable processes, moving samples through the lab efficiently and delivering data quickly. The CROs that can scale volume while simultaneously increasing speed without compromising quality are the ones that stand out.

Clients want to be secure in the knowledge that timelines will be met, with consistent outcomes, and full transparency and reporting. Clients want to understand what's happening with their samples and studies without having to chase the CRO for updates.

Long-term CRO success requires a focus on strengthening the following 3 operational aspects and building an organization that is fast, reliable, and trusted:

Efficiency and automation, which encompass speed and scale. It’s about how quickly the CRO can move samples, execute workflows, and deliver results without increasing risk. Manual steps, disparate spreadsheets, and workarounds work at low volumes, but they quickly become bottlenecks as demand grows.

Data integrity and compliance must be a given. Clients and regulators primarily care about whether data are complete, accurate, traceable, and trustworthy, with integrity and authenticity.

 This translates into standardized workflows, structured data captured at the source, and built-in readiness for audits and inspections.

Client experience has become a key differentiator. Clients are demanding more real-time visibility into what is happening. The CRO needs to proactively communicate with the client, keeping them abreast of all activities. It should not fall to the client to request status updates.

The catalyst driving lab digitization is simple: the CRO has outgrown spreadsheets and homegrown systems, and execution is difficult to manage. Furthermore, the dependency on manual operations has increased risks in compliance, auditability, traceability, and repeatability of experimentation.

The larger the CRO, the more manual processes and workflows cause significant bottlenecks and errors. Every time a sample comes in, is stored, moved, or processed, it needs to be tracked. The process needs to work just as well for 10,000 samples as for 10.

The key is going from survival-mode operations to operations built to scale. In survival mode, samples are tracked by hand, inventory systems work fine until volume increases, and information is passed around in different files and emails. The result is reactive work.

Automation reduces the effort per sample. An organization operating at scale has standardized, automated workflows with no compromise in data quality, so the system can handle volume spikes. Their technologies are designed for growth, systems are connected end to end, and teams have real-time visibility into what is happening.

Strengthening Data Integrity and Compliance

As a CRO grows, data becomes more complex, with ever-increasing volumes. More studies are done, results need to be communicated to more clients, and all activities must comply with the latest regulatory requirements.

The adoption and application of FAIR principles: findable, accessible, interoperable, and reusable, can add value to CROs in the management of their clients’ data.

 If data are not structured properly from the beginning, management is a major challenge, especially if it’s siloed among hardware and software. With the volume of data generated by individual AI tools, data management becomes an even greater bottleneck. Properly managed data integrity results in standardized experimental design and protocols with structured, machine-readable results.

Once data management is out of the way, end-to-end sample traceability must be addressed. CROs need to know exactly where every sample has been, what has been done to it, and by whom. Barcoded samples combined with a comprehensive sample management system can be used to ensure this happens.

Everything needs to support built-in regulatory readiness. Instead of scrambling for audits or inspections, compliance is a natural outcome of well-designed workflows and connected systems.

Driving the Client Experience Toward Excellence

A strong client experience is a competitive advantage. When the CRO delivers clients visibility, transparency, and predictable delivery, client confidence increases significantly. Creating the infrastructure to fulfill those requirements takes a measured approach.

In many CROs, this is how it works today: requests come in by email, phone, or chat. They ask:

Clients don't just want results; they want confidence in how those results were generated, stored, and reused. If systems don't talk to each other, information is scattered. No single place connects customers and the lab through the entire process. Every step becomes a bottleneck in the communications process. Clients must constantly ask for updates as each team handles a different aspect of the project, and no one can give them the big picture. All this creates extra work that adds no scientific value but does significantly add time and expense.

The goal is to create a seamless, transparent partnership with clients. Instead of numerous of messages back and forth and the time spent tracking everything from both sides, the ideal is a single, 2-way communications channel, with secure, segregated access that provides real-time visibility into sample status, inventory availability, and more.

Many vendors of laboratory information management systems or electronic lab notebooks offer CRO-client portals; a dedicated portal makes it easy to share data, results, and samples with clients, customers, partners, and other external collaborators. Each client should have a separate dashboard that shows the results of each phase of their project. Both the FDA and the European Union have specific regulations affecting data sharing, including the 21 CFR Part 11 (FDA)

 which require authenticated, authorized, and audit-trailed access to electronic records.

All this results in faster communication, fewer errors, and a smoother operational experience for both sides. If the client is using the same platform within its laboratory environment, the platforms can be connected, allowing access to the information critical to both parties.

Simultaneously, the aggregated dashboard infrastructure gives CRO management real-time insights into customer status, turnaround times, samples in progress, hours spent per client, instrument usage, and other activities that streamline corporate decision-making. When the data are also available on a granular level, such as reagent usage, it streamlines resource allocation as well.

CRO success is not about replacing what already works; it’s driven by connectivity. A strong scientific foundation is a given. Success or failure depends on whether disconnected systems and manual handoffs can be replaced by a digitized lab. The key is integrating lab automation, orchestration, data management, and AI technology. When workflows, data, and client interactions are connected, visibility improves, delays disappear, and everything flows more smoothly. The more connectivity, the more scalable CRO operations become.

When a CRO has embraced efficiency and automation, strengthened data integrity and compliance, and driven the client experience toward excellence, it are on the path to long-term success. It will deliver faster results, reliable data, and a professional experience that clients want to come back to—again and again.

21 CFR PART 11, electronic records; electronic signatures. US Code of Federal Regulations. Accessed July 8, 2026. 

https://www.ecfr.gov/current/title-21/chapter-I/subchapter-A/part-11/subpart-B

Practical considerations for CROs to play FAIR. FAIR Cookbook. Accessed July 8, 2026. 

https://faircookbook.elixir-europe.org/content/recipes/introduction/fair-cro.html

EudraLex The Rules Governing Medicinal Products in the European Union

, Volume 4 Good Manufacturing Practice Medicinal Products for Human and Veterinary Use. European Commission. Accessed July 8, 2026 

https://health.ec.europa.eu/system/files/2016-11/annex11_01-2011_en_0.pdf

Tim Stroud is an experienced life sciences professional with more than 20 years in the pharmaceutical drug discovery industry. Prior to joining Cenevo, he worked as a scientist and lab automation specialist in the pharmaceutical industry at Pfizer and AstraZeneca. He leads Cenevo's team of solutions consultants, who deliver expert support to the sales teams in providing laboratory automation and software solutions to clients in the academic, biotech, pharma, hospital, and agriscience sectors. www.cenevo.com

Scientific capability is no longer differentiating for CROs/CDMOs; operational excellence is. Competitive advantage now depends on digitized, connected workflows that increase throughput, reduce manual handoffs, and maintain quality while lowering cost. Scalable automation enables predictable sample movement and faster data delivery. Data integrity requires structured capture at source, FAIR-aligned management, end-to-end traceability (e.g., barcoding), and audit-ready compliance with 21 CFR Part 11 and EU Annex 11. Connectivity across automation, orchestration, data, and AI unlocks scale.

Outsourcing

To drive long-term success, CROs need to strengthen their focus on efficiency, automation, data integrity, and compliance to generate higher ROI for clients.

It’s Time to Build a More Scalable, Connected CRO

Control of process and product quality is essential to ensuring the development and manufacture of safe and effective medicines. For autologous adoptive cell therapies, establishing control can be challenging due to significant variability in raw materials. The quality of patient cells, media formulations containing serum, and viral vectors used for gene delivery depends on numerous factors, not all of which can be easily controlled. Understanding the potential variabilities and how they may impact the cell therapy process and product quality is therefore essential.

Adopting a risk-based, phase‑appropriate control strategy that identifies critical raw materials, qualifies suppliers, defines functional specs and testing (including safety), and predefines adaptive controls is essential to minimize negative impacts on product identity, purity, potency, and safety, according to Chy-Anh Tran, head of science and technology with FUJIFILM Biotechnologies in California. Establishing, to the extent possible, standardized manufacturing practices that are still sufficiently flexible to accommodate raw material variability is equally important.

Starting material variability arises from several factors. The most consequential source, observes Cellares COO Ossama Eissa, is the starting material itself. “Patient apheresis quality is shaped by disease state, prior treatments, and collection method, and you simply cannot standardize it away,” he states.

Prior systemic therapies to which patients have been exposed significantly impact T cell fitness and functionality, adds Chantale Bernatchez, senior director of cell therapy process development at CTMC. “This consideration applies equally to hematologic malignancies and solid tumors, therefore influencing the performance of multiple T cell–based therapeutic modalities, including chimeric antigen receptor (CAR)-T, T-cell receptor (TCR)-engineered T cells, and tumor-infiltrating lymphocyte (TIL) therapies,” she says.

The collection method, encompassing the device, protocol settings, anticoagulant type, operator technique, timing relative to the last treatment, and the use of mobilization agents, can also introduce variability, Tran says. Handling conditions for patient-derived cellular raw materials, including transport temperature and time, fresh vs cryopreserved workflows, and storage duration, can compound the variabilities, according to Tran.

Variability in viral vectors and media components, especially if media are uncharacterized or not chemically defined, further compounds the challenge, notes Eissa. Downstream manipulations can also magnify raw material variabilities.

 “All these factors combined make a flexible, data-rich manufacturing system essential,” he concludes.

Creating Numerous Process Development and Manufacturing Challenges

The consequences of failing to effectively manage raw material variability in autologous adoptive cell therapies can be severe. Failure to incorporate clinically representative starting material during process development introduces substantial risk to manufacturing robustness. “This gap frequently manifests as unanticipated variability or elevated batch failure rates during clinical production, ultimately necessitating reactive process redesign and delaying program progression,” says Bernatchez. In the worst-case scenario, failure of a production batch means the patient, who has been waiting for perhaps several weeks, does not receive what is likely a last-line treatment.

 The drugmaker also experiences lost revenues.

During process development, differences in raw materials make it hard to assess true process effects, so assay results can be highly variable, Tran notes. “For instance, healthy donor data may not always predict patient cells. As a result, teams have to adjust on the fly, which makes runs harder to compare and adds time, effort, and cost,” she comments.

For good manufacturing practice (GMP) compliance, Tran notes that variability drives unreliable yields and cycle times, elevating out-of-specification rates and deviations. “Here again, operators must make more real-time adjustments, straining scheduling, capacity, and logistics,” she says.

Eissa agrees: “Compounding the inherent, unavoidable variability of patient cells during early development stages with avoidable variability from manufacturing processes makes it nearly impossible to distinguish true process signals from noise, leading to parameters that don't hold in GMP and ultimately driving batch failures.”

In addition, supplier lot differences require prequalification/bridging and widen critical quality attribute (CQA) spread, challenging release and regulatory justification, according to Tran.

It is therefore imperative, emphasizes Eissa, to eliminate avoidable variability through chemically defined media and well-characterized processes, so that the unavoidable biological variability from patient material can be isolated and managed on its own terms. “Equally important,” he observes, “is to systematically and progressively characterize patient material variability through GMP manufacturing and across clinical phases, building the knowledge needed to predict its impact at commercial scale and design a process robust enough to succeed across most or the full spectrum of patients it will serve.”

Use a Multipronged Approach to Enhance Control of Cellular Variability

To accommodate the variability inherent to patient-derived raw materials, it is necessary to enhance overall process robustness. That can be achieved by using patient-derived material during process development instead of donor cells, according to Bernatchez. “This approach enables early characterization of variability across key process parameters under conditions that reflect the intended clinical starting material,” she explains.

In addition, because not all unit operations are equally sensitive to variability in starting materials, Bernatchez notes that it is also important to systematically identify those most affected by patient-to-patient heterogeneity so that optimization efforts can be targeted. She highlights optimization of ex vivo T-cell expansion processes because it can partially mitigate deficits in T-cell function that otherwise limit viral transduction efficiency and proliferative capacity.

In this context, Bernatchez says longitudinal data trending from development studies through clinical manufacturing are critical, particularly in cases where development activities relied predominantly on healthy donor material. “Continuity in data analysis enables the early detection of out-of-trend performance and supports timely implementation of corrective process adjustments,” she observes.

More specific steps noted by Eissa that can be taken include the following:

Use of automated manufacturing and quality control testing, chemically defined media, standardized apheresis handling (collection, transport, timing), and well-characterized unit operations to eliminate avoidable variability and remove confounding factors so patient biology can be studied clearly.

Profile incoming apheresis material and collate the information as a database progressively across clinical phases, spanning diverse patient populations, disease states, and treatment histories to thoroughly characterize patient material and identify which starting material attributes predict process performance and product quality.

Integrate electronic batch records and laboratory information management systems for real-time data capture and analysis to further connect process data to starting material attributes and product outcomes.

Apply multivariate modeling and statistical process control to predict batch performance from incoming material profiles and use a design-of-experiment approach during development to separate patient-driven signals from process noise.

Collaborate with clinical sites and apheresis centers to create a structured apheresis checklist that captures all relevant starting material attributes at the point of collection and educates clinical staff on what matters and why, flags patients whose material may not meet ideal criteria before manufacturing begins, and provides critical context when process or testing issues arise downstream.

On the latter point, Eissa observes that “even when collection proceeds outside ideal parameters, the checklist creates an early indicator of where the process may struggle, turning what would otherwise be an unexpected deviation into an anticipated and manageable variable.”

With respect to patient material characterization, Eissa believes it should be treated as a core development deliverable. “The knowledge built through clinical phases should make the commercial process predictably robust across the full patient population, not just ideal donors,” he notes.

Minimize Variability in Media and Viral-Vector Raw Materials

Although variability in patient-derived cellular starting materials often dominates the discussion of raw material variability in the development of autologous cell therapies, use of serum-containing media formulations and, for adoptive cell therapies that require genetic modification, batch-to-batch variability of viral vectors can exacerbate the challenges posed by the variability of cellular starting materials. Using well-characterized and defined reagents can help minimize these issues.

For media formulations, variability can, according to Bernatchez, be reduced through the use of chemically defined media supplemented with serum replacement components. “The increasing availability of GMP-grade, chemically defined media may enable greater control and consistency in cell therapy manufacturing processes,” she comments.

When it comes to viral vectors, a key issue can be variable potency due to different concentrations of functional infectious particles from batch to batch. A key objective of process development is, therefore, to define the optimal ratio of viral particles to T cells required to achieve a target transduction efficiency, according to Bernatchez. “Once established using a reference viral-vector lot, it is generally assumed that maintaining a constant particle-to-cell ratio across subsequent lots of the same construct will yield comparable T-cell engineering outcomes,” she explains.

This assumption does not consistently hold, however, because variability introduced during viral vector production and purification can significantly affect particle infectivity and functional potency. “As such,” says Bernatchez, “reliance solely on particle counts or nominal multiplicity of infection may be insufficient to ensure process consistency.”

The development and implementation of advanced analytical methods to more accurately characterize viral vector quality and infectivity are therefore essential. “These approaches enable more robust definition of CQAs and support improved standardization of viral-vector manufacturing processes, ultimately ensuring consistent production of T-cell therapy products that meet predefined specifications,” she concludes.

Decentralized Manufacturing Can Make a Difference

A big change with significant potential to help reduce and manage raw material variability for autologous adoptive cell therapies is to switch from a centralized to a decentralized manufacturing strategy. “Decentralized and point-of-care manufacturing approaches offer the possibility to mitigate risks associated with logistical delays during the transport of patient-derived materials, including starting material (eg, apheresis products or tumor tissue) and final drug product, that have the potential to adversely affect cell viability and functional quality,” notes Bernatchez.

Cold-chain and logistics variability are real and underappreciated sources of risk, agrees Eissa. However, he emphasizes that decentralized manufacturing only reduces these risks at scale if it involves deployment of a standardized, automated platform consistently across sites. “It is essential to achieve decentralized manufacturing without sacrificing the process consistency that patient outcomes depend on,” he states.

Collaboration With Vendors Is Essential to Success

Vendors have an important role to play in helping to minimize raw material variability. Developers and manufacturers of autologous, adoptive cell therapies therefore have the best chance of managing raw material variability by collaborating closely with vendors, including media suppliers, viral-vector producers, and hospitals and apheresis centers.

In fact, Eissa believes the latter group should be considered as key participants in the first step of the manufacturing process. That means engaging clinical sites early and working to help them understand how apheresis quality impacts manufacturing success and patient outcomes; codeveloping the apheresis checklist mentioned above; providing guidance on patient selection and preapheresis conditioning, especially timing relative to prior treatment; and qualifying and auditing apheresis centers as supply chain partners, with periodic retraining and performance trending across sites.

“The earlier clinical sites [and suppliers of media and viral vectors] are engaged as partners with shared accountability, the more predictable and manageable starting material variability becomes,” Eissa concludes.

Regalo G. From research to reality: how raw materials, media composition and process decisions shape T-cell therapies. RegMedNet

 January 13, 2026. Accessed July 7, 2026. 

https://www.regmednet.com/from-research-to-reality-how-raw-materials-media-composition-and-process-decisions-shape-t-cell-therapies_fujifilm/

Life Science Connect Editorial Staff. How to promote batch-to-batch consistency in CAR-T therapies. Cell & Gene. March 18, 2024. Accessed July 7, 2026. 

https://www.cellandgene.com/doc/how-to-promote-batch-to-batch-consistency-in-car-t-therapies-0001

Challener CA. Managing raw material variability for autologous cell therapies. 

https://www.biopharminternational.com/view/managing-raw-material-variability-for-autologous-cell-therapies

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

Raw material variability is a central constraint in autologous adoptive cell therapy manufacturing, driven primarily by heterogeneous patient apheresis shaped by disease, prior therapies, and collection/handling logistics. Additional variability from serum-containing media and viral vectors can obscure true process effects, elevate deviations, and increase batch failure risk with direct patient and commercial consequences. A risk-based, phase-appropriate control strategy emphasizes supplier qualification, functional specifications, standardized yet flexible practices, and data-rich manufacturing to separate unavoidable biology from avoidable process noise and improve robustness.

Development

It is essential to understand how raw material variability can create challenges in process control for autologous adoptive cell therapies. 

Overcoming Raw Material Variability Challenges for Autologous Adoptive Cell Therapies 

Contractor-supported execution is now routine in pharmaceutical development and manufacturing. Sponsors may rely on contract development and manufacturing organizations, contract research organizations, analytical laboratories, packaging vendors, logistics providers, and technical consultants across the product life cycle. This operating model can improve flexibility and access to specialized capacity, but it also increases the number of handoffs in which documentation can weaken.

In many programs, the problem is not a complete absence of documentation. The harder problem is that documentation exists but is not reliable enough to support an efficient technical, quality, or regulatory review. A batch record may be available but not reconciled with deviations. A method-transfer report may be final but disconnected from change-control rationale. A stability package may contain the expected files but lack a clear chain linking protocol, execution, data review, investigation, and final conclusion. A contractor may send a deliverable on time, but the receiving team may still need to reconstruct context before the record can be used.

That distinction matters. FDA data-integrity guidance states that current Good Manufacturing Practice (cGMP) data must be reliable and accurate and that firms should use meaningful, effective strategies to manage data-integrity risk.

FDA guidance on electronic systems, records, and signatures in clinical investigations similarly describes the expectation that electronic records be trustworthy, reliable, and generally equivalent to paper records.

 International Council for Harmonisation (ICH) Q9(R1) emphasizes quality risk management, and ICH Q10 describes the pharmaceutical quality system as a framework for process performance, product quality, corrective action, change management, and continual improvement.

 European Union GMP Chapter 7 also makes clear that outsourced activities should be defined, agreed, and controlled to avoid misunderstandings that could result in work or products of unsatisfactory quality.

For contractor-supported execution, those principles point to a practical conclusion: Documentation reliability is a quality-system output. It should be designed into contractor interfaces before work starts, monitored during work in progress, and tested before the record is needed for submission, transfer, audit, or inspection.

Why Documentation Breaks Across Contractor Interfaces

Documentation reliability often weakens at boundaries rather than within a single function. A sponsor may define the intended quality expectation, the contractor may execute the work, another vendor may generate testing or data outputs, and a quality or regulatory group may later need to defend the result. Each group may complete its assigned task, yet the total evidence chain may remain incomplete.

Three recurring issues are common. First, deliverable ownership is often defined at a high level, whereas record-level accountability remains unclear. A statement of work may say that a contractor will provide a report, but it may not define who owns source-data reconciliation, deviation linkage, review of supporting attachments, or version control. Second, handoffs often focus on transmission rather than usability. A file can be sent, uploaded, or marked complete before the receiving team can use it without additional explanation. Third, late review frequently identifies issues that should have been visible earlier: missing attachments, inconsistent dates, unresolved deviations, undocumented rationale, or terminology differences across contractor and sponsor records.

These issues pose practical risks because review timelines rarely extend when documentation gaps are discovered. Once a regulatory submission, process validation review, technology-transfer milestone, or inspection-readiness activity is close, teams may have to repair evidence under pressure. That reactive approach can produce more rework, more clarification cycles, and less confidence in the record.

A quality systems approach treats documentation reliability as a controlled process rather than a final document check. The question is not only whether the document exists. The question is whether the evidence can be traced, interpreted, and defended by someone who was not part of the day-to-day execution.

 summarizes common failure modes that appear in contractor-supported execution. The failure modes are intentionally operational: They are the types of issues that surface during quality review, technology transfer, regulatory-response preparation, or inspection-readiness work.

Table 1. Common Documentation Reliability Failure Modes Across Contractors

The approach begins by defining which documents and data are critical to the program. Not every record needs the same level of control. A risk-based model should focus on records that support product quality, patient safety, regulatory commitments, validated processes, release or stability decisions, method transfers, deviations, change controls, investigations, and batch or site readiness. ICH Q9(R1) supports the use of risk management principles that are proportionate to the level of risk.

Once critical records are identified, organizations can apply a contractor documentation control plan. The plan should be short, practical, and embedded in execution. It does not need to become a separate bureaucracy. It should define the expected artifact, the owner, the reviewer, the required source evidence, the timing of review, and the escalation threshold if the record does not meet expectations.

Control Point 1: Define the Record Before the Work Starts

Documentation problems often begin before execution. If a sponsor and contractor do not agree on what a complete record should contain, the final deliverable is likely to reflect local assumptions. For example, a contractor may consider a technical report complete when summary results are included, whereas the sponsor may need traceability to raw data, deviations, method conditions, equipment history, analyst review, and change-control rationale.

A record definition should include more than the document title. It should specify the data sources, attachments, required approvals, naming conventions, version expectations, and links to related quality records. This definition is especially important for batch documentation, analytical method transfer, stability packages, validation work, comparability assessments, and outsourced testing.

Control Point 2: Assign Ownership at the Artifact Level

Contractor governance often defines organizational responsibility, but documentation reliability depends on artifact-level ownership. Each critical record should have an accountable owner for creation, technical review, quality review, reconciliation, and final acceptance. The same person does not need to own every step, but the ownership model should be visible.

This prevents a familiar late-stage problem: Each party believes another party is responsible for final usability. The contractor may believe the deliverable was complete once transmitted. The sponsor function may assume quality will resolve gaps during review. Quality may expect the technical team to provide rationale. Regulatory may later need a clean story but receive a fragmented evidence trail.

A simple responsibility map can reduce this ambiguity. The map should be tied to records, not only to functions or meetings. 

 provides an example of how control points can be translated into owner and evidence expectations.

Table 2. Contractor Documentation Control Points

Control Point 3: Treat Handoffs as Quality Events

A handoff should not be considered complete merely because a document has been sent. It should be considered complete when the receiving team can use the record for its intended purpose. That purpose may be technical assessment, quality disposition, regulatory authoring, process validation, stability review, inspection response, or transfer to another site or vendor.

Effective handoff criteria should answer 4 questions:

If those questions cannot be answered at the handoff, the receiving team is likely to spend time reconstructing context later. For outsourced activities, this is also a contract-quality issue. EU GMP Chapter 7 expects outsourced activities and related responsibilities to be clearly defined and controlled.

 In practice, that control should include the documentation handoff, not only the performance of the work.

Control Point 4: Reconcile Before the Deadline

Reconciliation is most effective when it occurs during execution, not at the end. Programs should define review points when critical records are checked against related evidence before the deadline is close. For example, a method-transfer report can be checked against protocol requirements, deviations, raw data, acceptance criteria, and change-control records before final approval. A batch package can be checked against deviations, investigations, environmental-monitoring records, material status, and release criteria before it becomes part of a larger readiness package.

Reconciliation should also include metadata and version checks. Dates, document numbers, study identifiers, batch numbers, product names, and sample identifiers should align across records. Inconsistent identifiers may look small, but they create friction during review and can require unnecessary clarification. FDA data-integrity guidance emphasizes reliable and accurate data, and that principle applies directly to the way documentation packages are assembled and reviewed.

Control Point 5: Escalate Documentation Risk Early

Documentation risk is often escalated only after a record becomes late. That is too narrow. A record may be on time but still unreliable. Escalation should occur when a documentation issue threatens downstream usability, regulatory traceability, quality disposition, or inspection response.

Useful triggers include repeated missed review cycles, unresolved discrepancies between contractor and sponsor records, late changes without rationale, missing source evidence, unclear ownership, or deliverables that require repeated clarification. These triggers should be visible in routine governance, not hidden in email threads or informal follow-up.

This is where the quality system and program governance need to meet. Quality functions can define expectations, but program and technical teams need to manage timing, dependencies, and follow-through. Documentation reliability is therefore not only a quality assurance task; it is a cross-functional execution control.

A practical implementation model can be built in 4 steps.

First, identify the critical records for the outsourced activity. These may include protocols, batch records, test methods, validation reports, deviation records, change controls, certificates of analysis, stability summaries, regulatory response inputs, technology transfer reports, and inspection readiness packages.

Second, define the evidence chain for each record. The evidence chain should show where the record originates, which data or records support it, who reviews it, what must be reconciled, and how the final version is accepted.

Third, place review gates before high-pressure milestones. These gates should not duplicate quality review. Instead, they should confirm whether the record is usable for the next step. If it is not usable, the issue should be corrected while options remain available.

Fourth, capture recurring documentation failures as quality-system learning. If the same documentation issue appears across multiple contractors, products, or sites, the solution is rarely more reminders. The organization may need better templates, clearer handoff criteria, stronger statement-of-work language, revised review checklists, or improved training. ICH Q10 emphasizes continual improvement within the pharmaceutical quality system, which makes recurring documentation failures a signal for system correction rather than isolated rework.

 presents a readiness check that organizations can adapt for contractor-supported records.

Table 3. Readiness Check for Contractor-Supported Records

Contractor-supported pharmaceutical execution depends on more than completing the work. It depends on producing evidence that can be used, reviewed, and defended across organizational boundaries. Documentation reliability should therefore be treated as part of the quality system, not as a late formatting or filing task.

The most useful test is straightforward: Can a reviewer follow the record without reconstructing the story from emails, meetings, or individual memory? If the answer is no, the record is not yet reliable enough for regulatory-ready execution.

Sponsors and contractors can reduce late-stage remediation by defining critical records early, assigning artifact-level ownership, treating handoffs as quality events, reconciling evidence before deadlines, and escalating documentation risk before it becomes a submission or inspection problem. These controls are not meant to add administrative burden. They are meant to make the evidence easier to trust when it matters.

Data Integrity and Compliance With Drug CGMP: Questions and Answers. Guidance for Industry. 

Center for Drug Evaluation and Research, Office of Regulatory Policy; Center for Biologics Evaluation and Research; Center for Veterinary Medicine. December 2018. Accessed July 9, 2026 

https://www.fda.gov/regulatory-information/search-fda-guidance-documents/data-integrity-and-compliance-drug-cgmp-questions-and-answers

2. Electronic Records; Electronic Signatures. 62 Federal Register 13464 (1997). Accessed July 9, 2026 

https://www.ecfr.gov/current/title-21/chapter-I/subchapter-A/part-11

3. Electronic Systems, Electronic Records, and Electronic Signatures in Clinical Investigations: Questions and Answers. Guidance for Industry. Center for Drug Evaluation and Research, Office of the Commissioner, Office of Clinical Policies and Programs. October 2024. Accessed July 9, 2026 

https://www.fda.gov/regulatory-information/search-fda-guidance-documents/electronic-systems-electronic-records-and-electronic-signatures-clinical-investigations-questions

4. Q9(R1) Quality Risk Management. Step 4 version. International Council for Harmonisation. January 18, 2023. Accessed July 9, 2026 

https://www.ich.org/page/quality-guidelines

5. Q10 Pharmaceutical Quality System. Step 4 version. International Council for Harmonisation. June 4, 2008. Accessed July 9, 2026  

 Volume 4: EU Guidelines for Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use. Chapter 7: Outsourced Activities. European Commission. January 31, 2013. Accessed July 9, 2026 

https://health.ec.europa.eu/medicinal-products/eudralex/eudralex-volume-4_en

Contractor-enabled development and manufacturing expands specialized capacity but increases handoffs where evidence chains degrade. Documentation failures are typically about usability and traceability, not missing files, creating late-stage rework and inspection risk. Global expectations for trustworthy, reliable records (FDA data integrity, Part 11, ICH Q9/Q10, EU GMP Chapter 7) imply documentation reliability must be designed, governed, and tested as a quality-system output. A risk-based control plan should define critical records, assign artifact-level ownership, qualify handoffs, reconcile evidence early, and escalate documentation risk proactively.

Documentation reliability across CDMOs, CROs, and other contractors should be engineered into quality systems before, during, and after execution, not patched together at submission or inspection time.

Documentation Reliability Across Contractors: A Quality Systems Approach

Since 2024, new guidance from the FDA and the European Medicines Agency (EMA) has advanced efforts to streamline biosimilar development. Biosimilars—products created to closely emulate the mechanism of action, safety, and efficacy of reference biologic products whose patents have expired—encourage competition and lower prices in the biologics market. Because of this, they are critical to enhancing patient access to biologic therapies and decreasing pressure on health care budgets.

Although biosimilars typically cost less to develop than novel biologics, it has historically been challenging for developers to balance return on investment with the lower prices markets expect from biosimilars. As a result, changes to regulatory guidelines that reduce costs and expedite approval processes are invaluable in encouraging the continued development of biosimilars.

Although these changes to regulatory approaches will ultimately reduce the time and resources required to develop biosimilars, they also represent a fundamental shift in strategies for biosimilar submissions. Understanding the implications of the new regulatory guidance and publications, including their impact on data generation and the competitive landscape, will be crucial to future success in the biosimilar field.

What Are the Key Changes to EMA and FDA Regulations?

There is a considerable amount of new biosimilar regulatory information to review in the European Union and the United States. For the EMA, relevant documents include the recently released “Reflection Paper on a Tailored Clinical Approach in Biosimilar Development” and the “Workshop on a Tailored Clinical Approach in Biosimilar Development.”

One of the most important takeaways from these updates is the idea that, in certain cases, in which physiochemical and functional properties can be well characterized, such as with state-of-the-art analytical tools, comparative efficacy studies may not be required. Reducing the need for such studies, which typically assess a biosimilar’s efficacy and immunogenicity in humans, would give sponsors the means to eliminate a major time- and resource-consuming element of biosimilar development. However, it is important to note that comparative efficacy studies will still play an important role in biosimilars that are difficult to characterize or have a poorly understood mechanism of action.

The FDA also released multiple documents with guidance intended to encourage biosimilar development while reducing timelines and costs. These include the Biosimilars Action Plan, as well as the draft guidance documents 

Development of Therapeutic Protein Biosimilars: Comparative Analytical Assessment

Other Quality-Related Considerations and Scientific Considerations in Demonstrating Biosimilarity to a Reference Product: Updated Recommendations for Assessing the Need for Comparative Efficacy Studies

Similarly to the EMA, the FDA’s updates reexamine the clinical development pathway required for approval, placing greater weight on pharmacokinetic (PK) similarity studies and suggesting that clinical comparative efficacy studies may not be required. They also increase the emphasis on comparative analytical assessment, which includes a biosimilar’s structure, function, process, and product‐related attributes.

Regulatory evolution since 2024 is materially reshaping biosimilar development in the EU and US by shifting evidentiary weight from clinical comparative efficacy toward state-of-the-art analytics and PK similarity. Both EMA and FDA increasingly support tailored pathways where robust physicochemical and functional characterization can obviate confirmatory efficacy trials, while maintaining their role for complex or poorly characterized products. FDA’s 2026 Q&A revision enables greater reliance on non‑US comparators, lowering program costs and enabling global development strategies amid intensifying competition.

Changes in regulations are reducing costs, expediting approval, and increasing the market for biosimilars.

ParmTech July August 2026

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Regulatory Actions Impacting Biologics

It’s Time to Build a More Scalable, Connected CRO

Overcoming Raw Material Variability Challenges for Autologous Adoptive Cell Therapies

Documentation Reliability Across Contractors: A Quality Systems Approach

Faster Doesn’t Mean Easier: Development Impacts of a New Biosimilar Regulatory Landscape

Transforming Downstream Purification: Trends Shaping the Future of Biologics Manufacturing