Key Takeaways
The Visudyne shortage began in May 2020 amid reduced manufacturing capacity and dependence on a single U.S.-based active-substance manufacturing site, while full EU supply restoration is now expected in 2027.
Adding pharmaceutical manufacturing capacity can require technology transfer, gap assessment, analytical transfer, qualification, validation, training, documentation, and demonstration that the receiving site can reproducibly perform the transferred process.
Manufacturing-site changes must also move through the appropriate regulatory pathway, with requirements that can include dossier updates, GMP evidence, method-transfer data, batch information, validation, and regulatory approval.
Regulatory flexibility can help accelerate shortage remediation, but it does not replace the technical, quality, manufacturing, and regulatory work required to establish usable alternative capacity.
Pharmaceutical second sourcing and manufacturing redundancy are most effective when treated as life cycle—management capabilities developed before the primary source becomes a critical supply constraint.
The Long Path Back to Full Supply
When shortages expose a pharmaceutical supply chain vulnerability, the obvious remedy can sound deceptively simple: find another place to make the product. The prolonged shortage of Visudyne (verteporfin) — a photodynamic therapy used to treat certain forms of wet age-related macular degeneration and choroidal neovascularisation associated with pathological myopia — shows how much work can sit behind that solution. The medicine entered shortage in May 2020 because of reduced manufacturing capacity, and its active substance depended on a single U.S.-based manufacturing site. Some supply subsequently returned, but it remained insufficient to meet demand.1,2
On September 4, 2026, the European Medicines Agency (EMA) announced that approval of new supply arrangements, including registration of additional manufacturing sites, had been finalized. Full restoration of supply across the European Union is nevertheless expected only in 2027.2 In 2025, regulators were still supporting the variations required for a new EU supply chain, while reduced, controlled supply was expected to continue through the end of 2026.1,3
That chronology captures the central problem. Identifying a supply chain weakness can happen quickly. Replacing it with approved, operational manufacturing capacity can take years. Technology transfer may involve production processes, analytical procedures, documentation, personnel, quality systems, qualification, and validation, while manufacturing changes must also be incorporated into the product’s regulatory authorization through the appropriate variation pathway.4,5 For supply resilience, the relevant alternative is not simply another facility or supplier on paper. It is capacity that can actually support the approved medicine.
Single-Site Dependence Is More Than a Procurement Risk
The Visudyne shortage began with a particularly concentrated manufacturing arrangement. Before the new supply chain was established, production of the active substance depended on a single site in the United States. The EMA now explicitly includes overreliance on single manufacturing sites among the vulnerabilities considered in its work on medicine availability.2
That concern extends beyond one product. Current European policy aims to broaden supply chains and reduce dependencies on single suppliers, while the Critical Medicines Alliance has identified geographic concentration in the sourcing of active pharmaceutical ingredients (APIs) and raw materials as an industrial vulnerability.6,7 Its recommendations include measures intended to support investment and greater diversification.
For pharmaceuticals, however, redundancy cannot be reduced to a purchasing decision. Another manufacturer may have the equipment or nominal capacity to make a product, but that does not mean the site can immediately enter the authorized supply chain. Manufacturing processes, analytical methods, and quality systems may have to be transferred or established, while the supporting regulatory documentation must also be updated before that capacity becomes usable.
The Visudyne case illustrates the consequence of that distinction. Some availability returned after the original disruption, but supply remained inadequate. The longer-term response therefore required additional manufacturing sites to be established and registered as part of a new supply arrangement.
Adding a Site Is a Manufacturing Program
Technology transfer provides a clearer view of what can sit behind the phrase “add another manufacturing site.” World Health Organization (WHO) guidance describes pharmaceutical technology transfer as the transfer of products, processes, and knowledge supported by documentation and professional expertise. The process can span development, manufacturing, and testing functions rather than amounting to a simple handoff of operating instructions.4
A receiving site must be able to reproduce the transferred process or procedure successfully. WHO guidance calls for a planned approach involving trained personnel, appropriate quality systems, documentation and data, and consideration of regulatory requirements. It also identifies project planning, quality risk management, technical, quality, and regulatory gap analysis, assessment of differences between sending and receiving units, knowledge management, training, and communication as elements of a structured transfer.4
Those site-to-site differences matter because transferring a pharmaceutical process does not make two facilities interchangeable. The WHO describes successful transfer as resulting in documented evidence that the receiving unit can routinely reproduce the transferred product, process, or procedure against predefined specifications.4
The broader transfer framework can encompass production and analytical procedures, premises and equipment, documentation, qualification, validation, change management, and personnel training. The objective is to turn nominal capacity into manufacturing capability that can reliably support the product.
The EMA has not disclosed the detailed technical program used to establish the additional Visudyne sites, so these general technology-transfer requirements should not be treated as a description of that specific project. What the EMA has confirmed is that additional manufacturing sites ultimately had to be registered before the new supply arrangements were approved.
The Regulatory Authorization Has to Follow the Manufacturing Process
Manufacturing capability alone does not determine whether an additional site can supply an approved medicine. Post-authorization manufacturing changes must also be handled within the regulatory framework governing the marketing authorization.
Under the EU variations framework applicable from January 2026, manufacturing-site changes can fall into different regulatory categories depending on the nature of the proposed change and whether specified conditions are met.5 Adding a site is therefore not treated as the same regulatory event in every circumstance.
For active-substance manufacturing, certain additions can qualify as a Type IA variation requiring immediate notification when specified requirements are satisfied, while more consequential changes can require Type II assessment. Major Type II variations require regulatory approval before they can be implemented.5
The supporting package can reach deeply into manufacturing operations. Depending on the change, the EU framework can call for dossier amendments, evidence of successful analytical-method transfer, comparative batch information, Qualified Person declarations, evidence of good manufacturing practice compliance, validation information, and other technical data.
Finished-product manufacturing-site changes likewise follow different pathways according to the activity and risk involved. Applicable changes can require manufacturing validation, batch-analysis information, GMP documentation, dossier updates, and validation of transportation and bulk-storage conditions. In specified circumstances, validation at a new site can include production-scale batches.
The operational significance is straightforward: a new manufacturing site has to become part of the authorized supply chain. Regulatory affairs is not merely documenting a business decision after the manufacturing work is finished. The evidence generated during transfer, qualification, validation, analytical transfer, and testing may also be needed to support the regulatory change.
That linkage supports planning technical, quality, and regulatory workstreams together. A transfer program establishes whether the receiving operation can reproduce the required process and analytical performance, while the regulatory pathway determines what evidence must be submitted before the revised manufacturing arrangement can be implemented.
Why Supply Restoration Can Take Years
The most consequential fact in the Visudyne case may be the elapsed time. A shortage that began in May 2020 is not expected to be fully resolved across the EU until 2027.
The supply picture improved somewhat after the original disruption, but remained inadequate. In 2025, the EMA reported that regulatory support was continuing to accelerate the variations required for a new EU supply chain.3 As late as September of that year, reduced and controlled supply was still expected through the end of 2026.1
In September 2026, the EMA announced completion of approval for the new supply arrangements and registration of additional manufacturing sites, but full restoration of supply is not expected until 2027.2
The EMA has not published a detailed breakdown assigning portions of that timeline to technology transfer, validation, regulatory review, capacity ramp-up, or other individual activities. The broader manufacturing and regulatory frameworks do, however, show why establishing additional capacity can involve multiple forms of technical and regulatory work. Technology transfer can require gap assessment, equipment and facility evaluation, training, analytical and production transfer, qualification, validation, documentation, and demonstration of reproducibility. Manufacturing-site changes can also require formal regulatory variations supported by technical evidence.
The case also helps define what regulatory flexibility can and cannot accomplish. The EMA has stated that regulators provided regulatory flexibilities and support during the shortage and worked to accelerate the variations required for the new supply chain. Yet the additional sites still had to be registered, and the new arrangements still required approval.
Regulatory flexibility can help reduce avoidable procedural delay, but it cannot substitute for a receiving site’s ability to manufacture successfully, the evidence needed to demonstrate that capability, or the physical capacity required to supply the market. Establishing alternative capacity requires lead time that cannot always be compressed once supply is already constrained.
If diversification begins only after a shortage has developed, transfer, qualification, validation, regulatory change, and supply restoration may all have to proceed while product remains limited. If an alternative has been prepared earlier, more of that work can already be complete before the original site becomes a critical failure point.
Managing Scarcity While Capacity Is Being Rebuilt
New manufacturing capacity does not solve the immediate problem for patients while that capacity is still being established. During the Visudyne shortage, the European medicines regulatory network also had to manage the limited supply that remained available.
The EMA’s Single Point of Contact Working Party and Executive Steering Group on Shortages and Safety of Medicinal Products coordinated controlled distribution among Member States to help direct limited supplies to patients in greatest need. The EMA has said that the shortage affected treatment planning, prioritization, and prescribing.2
Shortage remediation therefore has two parallel dimensions. One addresses the structural problem by establishing additional manufacturing capacity. The other manages scarcity until that capacity can support normal supply.
The Visudyne case shows both operating over a prolonged period. Controlled distribution remained necessary while the new supply arrangements were being developed, and the EMA expects the additional manufacturing sites eventually to allow that system to end.
Regulators are also expanding the European Shortages Monitoring Platform to support more consistent and data-driven exchange of information on potential shortages, including information related to supply, demand, and availability. Such visibility cannot produce additional supply, but it can support allocation and coordination while manufacturing remediation proceeds.
Restoring supply and managing shortage are related but different tasks. A new site addresses the structural weakness. Controlled distribution and cross-border coordination address the period before that solution is fully operational.
Alternative Capacity Has to Be Designed Before It Is Needed
The broader policy response in Europe increasingly emphasizes diversification. European Commission policy identifies reducing dependence on single suppliers and broadening supply chains as resilience objectives, while the Critical Medicines Alliance has highlighted concentrated sourcing of APIs and raw materials and called for measures supporting investment and diversification.
Visudyne should not be described as a verified example of independent second sourcing because EMA has disclosed additional manufacturing sites but not their ownership, supplier relationships, or locations. However, the case demonstrates the larger principle behind diversification: alternative manufacturing capacity has to be sufficiently prepared to enter the technical, quality, and regulatory architecture of the product before it can materially reduce vulnerability.
For some products, resilience may involve additional qualified manufacturing sites. For others, it may include independent suppliers, geographic diversification, or transfer strategies that make it possible to bring another manufacturing operation into the authorized supply chain.
Second sourcing therefore becomes less a procurement tactic and more a life cycle–management capability. Transfer planning, regulatory strategy, quality oversight, validation, and supply planning determine whether an alternative can actually be used when the primary source falters.
A contract, an identified facility, or nominal excess capacity may provide a fallback. It does not provide the same protection as an alternative that has progressed far enough through technical and regulatory preparation to support the product.
From Shortage Response to Supply chain Design
The Visudyne shortage began with dependence on a single active-substance manufacturing site and progressed into a multiyear effort to establish and register additional capacity. During that period, regulators also had to coordinate constrained distribution while the new supply arrangements advanced.
Pharmaceutical supply chain resilience depends on more than redundancy. Alternatives have to function within the requirements of the product itself. Technology transfer, qualification, validation, regulatory change management, and manufacturing readiness determine whether backup capacity is merely available in theory or capable of supporting supply in practice.
European policy is increasingly focused on reducing dependence on single suppliers and concentrated sources of medicines, APIs, and raw materials. For manufacturers, the implication is to treat alternative supply as something that must be engineered and maintained, not identified only after the primary source has failed.
The most resilient alternative manufacturing site is one that has been prepared far enough in advance to become operational before the original site turns from a concentration risk into a shortage.
References
1. Arzneimittelkommission der Deutschen Apotheker (AMK). “39/25: Information der Hersteller: Informationsschreiben zu Visudyne (Verteporfin): Lieferengpass bis voraussichtlich Ende des Jahres 2026.” Pharm. Ztg. 170: 150 (2025).
2. “New EU supply chain to end Visudyne shortage.” European Medicines Agency. 4 Sep. 2026.
3. “Facilitating the path to accessibility and strengthening the availability of medicines.” EMA Annual Report 2025. European Medicines Agency. Accessed 04 Sep. 2026.
4. “WHO guidelines on technology transfer in pharmaceutical manufacturing.” World Health Organization Technical Report Series. 1044: 197–224 (2022).
5. “Communication from the Commission – Guidelines on the details of the various categories of variation, on the operation of the procedures laid down in Chapters II, IIa, III and IV of Commission Regulation (EC) No 1234/2008 concerning the examination of variations to the terms of marketing authorisations for medicinal products for human use, and on the documentation to be submitted pursuant to those procedures.” Official Journal of the European Union. C/2025/5045. 22 Sep. 2025.
6. “Critical medicines Act.” European Commission. Directorate-General for Health and Food Safety. Accessed 04 Sep. 2026.
7. “Critical Medicines Alliance Report recommends priority actions to strengthen the supply of medicines in the EU and prevent shortages.” European Commission. Health Emergency Preparedness and Response Authority. 28 Feb. 2025.
