Keys to Successful Technology Transfer

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Technology transfer is a sophisticated and complex undertaking that requires careful planning to ensure successful transition and regulatory compliance. The biopharmaceutical industry is concerned with two main types of technology transfer: scale-up and transfer to a different site (1, 2). Scale-up technology transfer often occurs within an organization or facility and involves moving a technology or process from a laboratory or pilot-scale environment to a larger manufacturing scale. Such work can help to increase production capacity, improve efficiency, and optimize technology for commercialization.

Transfer to a different site involves relocating a technology or process from one location or organization to another. This type of transfer often is undertaken when a company wants to replicate or implement a technology at a new facility, either within the same organization or internationally. This article focuses primarily on the considerations that organizations should make when conducting technology transfer to another site.

Technology transfer begins when an organization evaluates a process to ensure its scalability, robustness, and efficiency. The organization also should consider the characteristics of the initial equipment and production environment; the quality assurance (QA) and control (QC) measures necessary to maintain product consistency and meet regulatory requirements; and the training and support needed for operating personnel. It is important to ensure that the supply-chain network is reliable and that scale up or transfer to a different site is financially viable.

Evaluating Site Suitability

Companies should evaluate a number of key aspects before deeming a site suitable for technology transfer. They must consider site infrastructure, compliance with local laws and regulations, availability of skilled labor, market proximity, and logistics. An organization should conduct prequalification assessment of the new site and define qualification criteria according to specific needs the requirements of the technology being transferred. Qualification helps to ensure that a proposed site has the capabilities, infrastructure, and quality systems needed to implement a transferred technology effectively.

A site evaluation should include assessment of manufacturing operations, infrastructure, quality systems, and overall regulatory compliance. Evaluators should note whether a nominated facility will require modifications to accommodate a transferred technology. Such modifications might include equipment installation, infrastructure upgrades, and operational changes to ensure compliance with safety and environmental standards.

Necessary Documentation: Next, organizations should establish a quality or technical agreement that defines roles, responsibilities, and expectations related to quality management, regulatory compliance, change control, risk management, and communication between the organization and the new site. Such information informs the development of a step-by-step technical-transfer plan that includes timelines, milestones, documentation requirements, and testing and validation protocols.

It’s important to ensure that the personnel involved in the technology-transfer process are appropriately trained and that they can undertake skills development when necessary. Companies should conduct periodic audits and compliance checks of their site and keep comprehensive records of all qualification activities and ongoing monitoring, including reviews, feedback sessions, and key performance indicators.

Navigating the Regulatory Landscape

When organizations conduct a technology transfer to a different region or country, they must identify the regulatory authority responsible for overseeing their product’s manufacture and marketing in that location. Only then can they develop an understanding of local good manufacturing practice (GMP) guidelines. Such guidelines outline the requirements and standards for compliance as described in 21 CFR Parts 210/211 from the US Food and Drug Administration (FDA), or the EudraLex Volume 4 in the European Union (EU) (3, 4). Assessing the manufacturing facility and processes at a new site ensures compliance with GMP requirements. Then, companies can prepare for an inspection and audit by establishing comprehensive documentation and record-keeping systems that show compliance.

To implement a quality management system (QMS) that aligns with GMP principles, companies must establish standard operating procedures (SOPs) and a robust change control process. Sponsors that outsource should conduct regular audits and ensure the continuous improvement of manufacturing processes. Ongoing compliance with GMP standards must be maintained through periodic inspections, reporting, and regulatory submissions. Regulators follow agreed-upon submission timelines and check procedures for technology transfer. It is important to develop relevant procedures that include validation and risk analysis.

The Need for Validation

Validation demonstrates repeatability by showing that processes, methods, and equipment work as designed and consistently lead to expected results (5). Almost every regulatory authority requires validation. Therefore, technology-transfer plans should contain a number of validation-related tasks and milestones.

Validation is required whenever a company makes a new product or performs a technology transfer. The process might include installation qualification/operational qualification (IQ/OQ), performance qualification (PQ), or process performance qualification (PPQ). Other elements such as cleaning validation and transport/shipping validation will apply in certain circumstances. The sequential activities validate manufacturing facilities, equipment, and with different requirements can differ depending on the industry, technology, and regions involved in a transfer (6). It is important to identify regulatory approvals, certifications, and licenses that may be required for technology transfer.

Usually, validation is first required during the commercial phase, but there are two exceptions to that rule. The first is analytical-method validation, which regulators expect to occur in late clinical stages. Some regulators also enforce validation as part of quality-system implementation during clinical stages to assess intrabatch variability and show repeatability of results.

The FDA, however, expects sponsors to include process validation — whereby the agency considers an entire process, including early development work — as part of overall validation (7). And the European Medicines Agency (EMA) refers to process validation as PPQ (8). Although the agencies differ in terms of nomenclature and emphasis, they are aligned for most expectations and requirements. During late clinical stages, regulators enforce validation requirements for dosage forms. The EMA is explicit in its requirements for sterile dosage forms, as outlined in Annex 1 (9).

Risk management is integral to the validation life cycle (8, 10, 11). Although regulators generally do not expect companies to document early stages of commissioning in a corrective and preventative action (CAPA) or investigative system, such measures should be described as part of a validation master plan. On reaching the PQ or PPQ phase of development, companies should document unexpected results that deviate from the validation plan in an official investigation or CAPA system. Companies that take a holistic approach to their quality systems during early development can help to ensure compliance by determining the root causes of unexpected events and apply that knowledge in preventing recurrences.

When phase 2 results are successful, companies should review their quality systems and ensure that their procedures address process validation in its entirety. Procedures can be modified over time, but it’s important to have a fundamental policy documented and connected with other quality systems. It is also important to understand best industry practices for both validation and technology transfer.

Assembling the Right Team

Technology transfer unites specialists from diverse fields, including analysts who focus on method transfer, engineers who navigate the complexities of equipment considerations, and financial departments that seek to maximize profitability. But it is essential to go beyond individual perspectives and develop a comprehensive understanding of an entire business process. Companies should have dedicated technology-transfer teams that foster collaboration and communication among sites.

An experienced project manager should oversee the technology-transfer process, identify optimum resources, coordinate team members, establish and manage timelines and milestones, collaborate with stakeholders, and ensure effective communication within the team. The team also should include technology and analytical experts; regulatory and compliance specialists; legal and intellectual property experts; operations, facility, and manufacturing specialists; QA/QC experts; training and knowledge-transfer specialists; and communication and stakeholder engagement professionals.

A chemistry, manufacturing, and controls (CMC) team can support technology transfer. This is done by making required updates and modifications to a regulatory-submission dossier, working with the regulatory-affairs team, and providing comprehensive information about changes in manufacturing processes, equipment, analytical methods, specifications, and controls.

Dossier submissions to regulatory agencies are important during technology transfer, especially when a product, manufacturing process, or site location has changed. Regulators review submitted changes to assess their effects on the safety, efficacy, and quality of a product (12). After a successful review, regulators grant approval or authorization for the proposed changes, enabling a company to implement the transferred technology at a new site and ensure the validity of the associated marketing authorization.

Posttransfer Monitoring

Once a technology transfer is complete, a marketing-authorization holder can take steps to ensure its correct implementation and that products meet the required quality, safety, and efficacy standards (13). The manufacturing process at the new site must align with the approved process described in a marketing authorization dossier. Making that happen might involve on-site inspections, audits, or quality assessments to ensure that the technology transfer has been implemented accurately.

Companies should conduct a batch-record review of their first commercial batches manufactured at new sites. Doing so verifies that all critical steps and parameters have been followed and that batch records are accurately documented. Similarly, it is best practice to collect representative samples of those batches and perform comprehensive analysis and testing to verify quality, consistency, and compliance with specifications.

Implementing a robust QA/QC system at a new site is critical to monitoring a manufacturing process. It’s also important to maintain documents of all postauthorization activities related to a site’s first commercial batches. Those include records of inspections, audits, testing results, stability data, and all corrective actions taken. Such postauthorization steps provide confidence in the quality, safety, and efficacy of a product after technology has been transferred to a new site.

The Keys to Success

Due diligence, careful planning, and robust oversight are key to successful technology transfer, whether scaling up within the same organization or transferring to a new site in another region. But it is just as critical to maintain open and effective communication throughout a transfer process, starting among the team members who will interact with internal and external stakeholders and the new manufacturing site to ensure that constructive feedback is implemented when required. The path to successful technology transfer is much smoother with quality procedures underpinning each step of the process.

References

1 Annex 7: WHO Guidelines on Transfer of Technology in Pharmaceutical Manufacturing. World Health Organization: Geneva, Switzerland, 2011; https://extranet.who.int/prequal/sites/default/files/document_files/TRS_961_Annex7_2011.pdf.

2 TRS 1044 — Annex 4: WHO Guidelines on Technology Transfer in Pharmaceutical Manufacturing. World Health Organization: Geneva, Switzerland, 2022; https://www.who.int/publications/m/item/trs1044-annex4.

3 21 CFR 210-211. US Food and Drug Administration: Rockville, MD, 2023; https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=211.

4 EudraLex — Volume 4 — Good Manufacturing Practice (GMP) Guidelines. European Commission: Brussels, Belgium, 2024; https://health.ec.europa.eu/medicinal-products/eudralex/eudralex-volume-4_en.

5 Annex 3: Good Manufacturing Practices: Guidelines on Validation. World Health Organization: Geneva, Switzerland, 2019; https://www.who.int/docs/default-source/medicines/norms-and-standards/guidelines/production/trs1019-annex3-gmp-validation.pdf.

6 Validation Master Plan Installation and Operational Qualification Non-Sterile Process Validation Cleaning Validation. PIC/S, Geneva, Switzerland, 2007; https://picscheme.org/docview/3447.

7 Process Validation: General Principles and Practices. US Food and Drug Administration: Rockville, MD, 2011; https://www.fda.gov/files/drugs/published/Process-Validation--General-Principles-and-Practices.pdf.

8 Guideline on Process Validation for Finished Products — Information and Data To Be Provided in Regulatory Submissions. European Medicines Agency: Amsterdam, the Netherlands, 2016; https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-process-validation-finished-products-information-and-data-be-provided-regulatory-submissions-revision-1_en.pdf.

9 Annex 1: Manufacture of Sterile Medicinal Products. European Commission: Brussels, Belgium, 2022; https://health.ec.europa.eu/system/files/2022-08/20220825_gmpan1_en_0.pdf.

10 ICH Q9(R1): Quality Risk Management. International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use: Geneva, Switzerland, 2023; https://database.ich.org/sites/default/files/ICH_Q9%28R1%29_Guideline_Step4_2023_0126_0.pdf.

11 Annex 15: Qualification and Validation. European Commission: Brussels, Belgium, 2015; https://health.ec.europa.eu/system/files/2016-11/2015-10_annex15_0.pdf.

12 EC No 1234/2008 Concerning the Examination of Variations to the Terms of Marketing Authorisations for Medicinal Products for Human Use and Veterinary Medicinal Products. Off. J. Eur. Union: Mercier, Luxembourg, 2008; https://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2008:334:0007:0024:en:PDF.

13 ICH Guideline Q10 on Pharmaceutical Quality System. European Medicines Agency: Amsterdam, the Netherlands , 2015; https://www.ema.europa.eu/en/documents/scientific-guideline/international-conference-harmonisation-technical-requirements-registration-pharmaceuticals-human-guideline-q10-pharmaceutical-quality-system-step-5_en.pdf.

Corresponding author Olena Chervonenko is associate director of quality management and compliance (QMC) at Cencora PharmaLex; [email protected]. Now at Moderna, Gerardo Gomez is the former director of QMC, United States at Cencora PharmaLex.