Semisolid Tech Transfer to a European CDMO in 2026: A Step-by-Step Guide for CMC Leaders

Transferring semisolid drug product manufacturing to a European Contract Development and Manufacturing Organisation requires structured planning across six distinct workstreams: scope definition, contract development and manufacturing organisation selection, Chemistry, Manufacturing and Controls package assembly, analytical method transfer, process characterisation and equipment qualification, and process validation with scale-up controls. When each workstream is managed with discipline and documented to European Union Good Manufacturing Practice standards, the transfer reaches manufacturing readiness predictably, without regulatory delay or batch failure at scale.

This guide is written for Chemistry, Manufacturing and Controls and technical operations leaders responsible for directing or overseeing outsourced semisolid manufacturing. It covers creams, gels, ointments and healing pastes and is structured to align with European Union Good Manufacturing Practice Annex 15 (Qualification and Validation) and ICH Q10 (Pharmaceutical Quality System).

Workstream	Key Activities	EU GMP Reference	Documentation Output
1. Scope Definition and Governance	Transfer charter, joint team formation, milestone planning	EU GMP Chapter 4	Transfer project plan; governance matrix
2. European CDMO Selection	Equipment pre-qualification, GMP certification review, controlled substance authorisation check	EU GMP Chapter 3	Technical pre-qualification report
3. CMC Package Assembly	Formulation report, master batch record, risk assessment, stability data compilation	ICH Q10; ICH Q9	Chemistry, Manufacturing and Controls transfer dossier
4. Analytical Method Transfer	Transfer protocol, suitability experiments, acceptance criteria assessment	EU GMP Chapter 6	Method transfer report
5. Equipment Qualification and Process Characterisation	Installation Qualification, Operational Qualification and Performance Qualification; critical process parameter mapping; cleaning validation	EU GMP Annex 15	Qualification protocols and reports
6. Process Validation and Scale-Up	Three consecutive validation batches; continued process verification programme establishment	EU GMP Annex 15; ICH Q10	Process validation protocol and report
7. Regulatory and Documentation	Variation submission strategy, site master file update, Qualified Person batch release	EU GMP Chapter 4	Variation dossier; updated site master file

Step 1: Define the Transfer Scope and Establish Governance

The first action in any pharmaceutical technology transfer to a contract development and manufacturing organisation is to define, in writing, exactly what is being transferred. For semisolid drug product, this includes the formulation, the manufacturing process, the in-process control specifications, the analytical methods, the packaging configuration and the stability programme.

Governance must be established before any technical work begins. A joint transfer team, comprising representatives from the sending site and the receiving contract development and manufacturing organisation, should be formed and assigned clear accountabilities. A transfer charter or project plan should document:

• The scope of dosage forms and batch sizes in scope
• Milestones for each workstream with target dates
• The roles of the Qualified Person at each site
• Escalation routes for technical and regulatory risks
• The version-controlled documentation set that will govern the transfer

Ambiguity at this stage is the most common root cause of delays later in the programme. Define the scope tightly before technical activities begin.

Step 2: Select the Right European CDMO for Semisolid Manufacturing

European Contract Development and Manufacturing Organisation selection for semisolid drug manufacturing is not equivalent to selecting a fill-finish partner. Semisolid manufacturing demands specific equipment configurations, controlled thermal processing capability and validated cleaning procedures for high-viscosity products. A receiving site that lacks any of these cannot be remediated quickly.

When evaluating European contract development and manufacturing organisations for semisolid manufacturing, assess the following:

Equipment Compatibility and Batch Size Range

The receiving site must operate manufacturing equipment that is compatible with your formulation type. Heated and cooled mixing vessels, homogenisers and deaeration systems must be available at batch scales that span your development and commercial requirements. A site that can accommodate batch sizes from 15 litres through to 1,250 litres or higher provides the flexibility required to run pilot, validation and commercial batches on the same platform, which simplifies comparability documentation.

Tube and Container Format Capability

For semisolid drug products, container compatibility is critical. Confirm that the receiving site can fill the formats required by your registered dossier or target markets, whether aluminium tubes, laminate tubes or plastic tubes, and that secondary packaging is integrated within the same facility.

European Union Good Manufacturing Practice Certification Scope

Verify that the European Union Good Manufacturing Practice certificate explicitly covers the intended dosage forms. For organisations supplying human and veterinary pharmaceutical markets, confirm that both scopes are held where relevant.

Controlled Substance Handling

If the product is a controlled drug, the receiving site must hold the appropriate national and European authorisations. Not all semisolid contract development and manufacturing organisations are licensed to handle narcotics or psychotropic substances. Establish this before progressing to due diligence.

Quality Systems and Analytical Infrastructure

The site’s quality management system must be capable of supporting method transfer, stability programme execution under International Conference on Harmonisation conditions and batch release by a Qualified Person. Analytical infrastructure should cover high-performance liquid chromatography, gas chromatography and stability chamber capacity for International Conference on Harmonisation climate zones relevant to your target markets.

Where transfers commonly fail at selection stage: Many pharmaceutical companies select a contract development and manufacturing organisation based on price or geographic convenience, without confirming equipment fit at the formulation level. Discovering that a site’s homogeniser cannot reproduce the shear rate profile of the sending site’s process is a significant setback that no project plan can easily absorb. Technical pre-qualification, not just an audit questionnaire, is essential.

Step 3: Assemble and Qualify the Chemistry, Manufacturing and Controls Package

A complete Chemistry, Manufacturing and Controls transfer package is the single most important enabler of a smooth pharmaceutical technology transfer to a contract development and manufacturing organisation. Incomplete documentation extends timelines, increases batch failure risk and generates regulatory queries during post-transfer variation submissions.

The Chemistry, Manufacturing and Controls package for a semisolid product should include:

• The formulation development report, including rationale for excipient selection and concentrations
• The master batch record from the sending site, with all in-process control limits and action limits defined
• The process description, with critical process parameters and their proven acceptable ranges documented
• The analytical methods package (see Step 4)
• A stability data package that covers at least accelerated and intermediate conditions per the applicable International Conference on Harmonisation guideline, with supporting data from relevant climate zones
• A risk assessment for the transfer, identifying critical quality attributes and the process steps at which they are controlled
• A cleaning validation report or cleaning characterisation data from the sending site

The risk assessment should follow a structured quality risk management methodology consistent with International Conference on Harmonisation Q9, assigning likelihood and severity scores to each identified risk and defining mitigation actions that the receiving site can implement.

Step 4: Analytical Method Transfer

Analytical method transfer is a workstream that is frequently underestimated in scope and timeline, particularly for semisolid drug products where matrix complexity can affect method performance.

A formal method transfer protocol must be drafted prior to any transfer experiments. The protocol should define:

• The analytical methods in scope for transfer
• Acceptance criteria for each method, expressed as measurable comparability limits
• The experimental design, including the number of analysts, instruments and sample preparations involved
• The process for handling out-of-specification results during transfer experiments
• The documentation required to close the transfer and authorise routine use

For semisolid products, the methods most commonly transferred include identity and assay by high-performance liquid chromatography, impurity profiles, viscosity measurement, pH, microbiological limit testing and, where applicable, in vitro release testing. Gas chromatography methods for residual solvents may also be in scope depending on the manufacturing process.

Where transfers commonly fail at this stage: Sending sites that have not maintained complete method validation documentation will encounter delays when the receiving site requests the full validation report as part of method suitability qualification. Ensure that all method validation records are current and retrievable before initiating the transfer.

Step 5: Process Characterisation and Equipment Qualification

Before the first Good Manufacturing Practice-compliant batch is manufactured at the receiving site, the equipment must be qualified and the process must be characterised at the receiving site’s scale.

Equipment Qualification

European Union Good Manufacturing Practice Annex 15 requires that equipment is qualified through Installation Qualification, Operational Qualification and Performance Qualification activities. For semisolid manufacturing, the equipment subject to qualification typically includes:

• Heated and cooled manufacturing vessels with temperature mapping
• Homogenisers and high-shear mixers, with qualification of speed ranges and shear profiles
• Filling equipment for tube formats
• In-process control instruments, including viscometers and pH meters

Installation Qualification confirms that equipment is installed according to specification. Operational Qualification confirms that equipment operates within defined parameters across its operating range. Performance Qualification confirms that the process, when run on the qualified equipment, consistently produces product meeting specification.

Process Characterisation

Critical process parameters for semisolid drug product typically include mixing temperature, mixing time, homogenisation speed, cooling rate and filling temperature. Where these parameters interact, a structured process characterisation study should map the relationships and establish the proven acceptable ranges that will underpin the validation protocol.

For heat-sensitive excipients or emulsion systems, the temperature profile during cooling is a particularly critical parameter and must be reproducible across batches.

Cleaning Validation

Semisolid formulations present specific challenges for cleaning validation due to product viscosity and the potential for residue adherence to vessel surfaces. The cleaning validation programme must demonstrate removal of the product to below the calculated safe carry-over limit, as well as removal of cleaning agents. This workstream should be initiated early, as cleaning validation data are required before the process validation batches are manufactured.

Step 6: Process Validation and Scale-Up Controls

Process validation for semisolid drug manufacturing in Europe must be conducted in accordance with European Union Good Manufacturing Practice Annex 15, which requires a lifecycle approach to validation covering process design, process qualification and continued process verification.

Scale-Up Considerations

When transferring from a pilot or development scale to a larger commercial batch size, scale-up must be managed systematically. Key scale-up parameters for semisolid products include:

• The ratio of mixing vessel surface area to batch volume, which affects heat transfer rates
• The tip speed and power input of homogenisers and mixers, which must be maintained or adjusted to achieve equivalent shear
• The fill rate and temperature at the point of filling, which affect container fill accuracy and product appearance

Where batch size increases are significant, intermediate scale batches may be appropriate to confirm that the critical quality attributes are maintained before committing to full commercial scale validation.

Process Validation Protocol and Report

The process validation protocol must define the number of validation batches (typically a minimum of three consecutive batches is expected under European Union Good Manufacturing Practice), the critical quality attributes to be measured, the acceptance criteria and the sampling plan. The process validation report must document actual results against acceptance criteria and provide a clear conclusion regarding validation status.

Continued Process Verification

Following successful process validation, a continued process verification programme must be established to monitor process performance and detect undesired variation during routine commercial manufacturing. Statistical process control tools are used to trend critical quality attributes and critical process parameters over time.

Step 7: Regulatory and Documentation Requirements

A pharmaceutical technology transfer to a contract development and manufacturing organisation in Europe will typically require a regulatory variation to the existing Marketing Authorisation, unless the transfer is part of an initial Marketing Authorisation application.

The variation type depends on the nature of the change. Adding a new manufacturing site for the finished product typically requires at minimum a Type IB variation, with Type II variation required where major changes to the manufacturing process accompany the site change. Early engagement with your regulatory affairs team is essential to plan the variation strategy and align it with the transfer timeline.

European Union Good Manufacturing Practice Chapter 4 documentation requirements apply throughout the transfer. All master batch records, standard operating procedures, validation protocols and reports, and change control records must be version-controlled and approved by authorised personnel. The receiving site’s Site Master File must be updated to reflect the new product scope.

Batch certification by a Qualified Person at the receiving site is required before any transferred batches can be released to the European market. The Qualified Person must have access to the complete batch record, all in-process control results, the finished product release test results and confirmation that the batch was manufactured in accordance with the authorised process.

Common Pitfalls to Avoid

The following issues are consistently identified as causes of delays and additional cost in semisolid pharmaceutical technology transfers to contract development and manufacturing organisations:

• Equipment mismatch at selection stage: Failing to technically pre-qualify the receiving site’s equipment against the formulation’s critical process parameter requirements
• Incomplete method transfer documentation: Proceeding without full method validation records from the sending site, which delays the receiving site’s method suitability qualification
• Underestimating cleaning validation scope: Treating semisolid cleaning validation as equivalent in complexity to simple liquid products, which it is not
• Insufficient stability data at the point of transfer: Attempting to initiate validation before adequate stability data are available to anchor the formulation at the receiving site’s scale
• Poorly defined change control governance: Allowing informal technical changes to occur during transfer activities without formal change control, which compromises the comparability of validation data

Ready to Transfer Your Semisolid Manufacturing?

Our team at Adragos Leipzig is experienced in managing end-to-end technology transfer programmes for semisolid drug products. Speak with us to discuss your formulation requirements and transfer readiness.

Contact Our Leipzig Team

Adragos Leipzig: Semisolid Contract Manufacturing in Germany

For companies seeking a European contract development and manufacturing organisation with a long-established semisolid manufacturing capability, Adragos Pharma’s Leipzig facility offers an integrated platform across the full range of semisolid dosage forms.

Located in eastern Germany, the Leipzig site carries 100 years of manufacturing heritage and operates under European Union Good Manufacturing Practice certification covering both human and veterinary pharmaceutical products. The team is long-established and stable, which is a material quality-risk consideration when selecting a receiving site for technology transfer.

Semisolid Manufacturing Capabilities at Adragos Leipzig

The site operates two production lines for semisolid products (Marchesini and Norden), with batch sizes ranging from 15 litres to 1,250 litres. This range is specifically suited to the progression from pilot and clinical batches through to commercial-scale validation and routine supply, without requiring equipment or facility changes between phases.

Products manufactured at Adragos Leipzig include creams, gels, ointments and healing pastes. Container formats span aluminium tubes (2 g to 150 g), laminate tubes and plastic tubes (25 g to 200 g), providing flexibility for different market presentations and dossier requirements.

Controlled Substance Handling

The Leipzig facility holds the capability to handle controlled drugs, which extends the accessible product portfolio for Chemistry, Manufacturing and Controls teams working with narcotics-containing formulations.

Integrated Transfer Support

Adragos Leipzig provides transfer management as a formal service, covering galenical development support, pilot batch manufacturing, analytical and batch release testing, method transfer, stability studies across International Conference on Harmonisation climate zones II, IVa and IVb, cleaning and process validation, and batch certification by a Qualified Person. Serialisation in accordance with the European Union Falsified Medicines Directive is also included.

Non-Sterile Liquid Manufacturing

For organisations managing a broader non-sterile portfolio alongside semisolids, the Leipzig site also operates three non-sterile liquid manufacturing lines (Dovema, Würschum and Groninger) with batch sizes up to 4,000 litres and plastic and glass bottle formats from 20 ml to 700 ml. Full capability and contact information are available at www.adragos-pharma.com.

Conclusion

A successful pharmaceutical technology transfer to a European contract development and manufacturing organisation for semisolid drug product depends on six sequential workstreams: governance and scope definition, evidence-based contract development and manufacturing organisation selection, a complete Chemistry, Manufacturing and Controls package, rigorous analytical method transfer, systematic equipment qualification and process characterisation, and prospective process validation aligned with European Union Good Manufacturing Practice Annex 15.

Organisations that invest adequately in the planning and documentation phases consistently reach process validation with fewer deviations and achieve regulatory approval on first submission. Those that compress the early phases in the interest of speed routinely encounter the delays they were attempting to avoid.

For Chemistry, Manufacturing and Controls leaders beginning or reviewing a semisolid technology transfer programme in 2026, the structured approach described in this guide provides a reliable framework for managing risk, protecting timelines and achieving durable manufacturing performance at the receiving site.

FAQs About Semisolid Technology Transfer