Phases of a Technology Transfer Project in Pharmaceutical Industry

The technology transfer project plan can be divided into four different phases. These include:

• Phase I: Project initiation;
• Phase II: Project planning;
• Phase III: Project transfer execution; and
• Phase IV: Project review and closeout.

Phase I: Project initiation

During the initiation phase of the project, a unit normally identifies the need for the technology transfer. This may be due to a lack of capacity, a transfer from development to commercial site or a transfer from one company to another.

During an initial discussion, it should be identified whether or not a RU (Receiver Unit) has any interest in such a project.

• The RU should be able to accommodate the intended activity.
• The RU should have the necessary technical expertise, technology and capability.

A sufficient level and depth of detail in order to support the activity, and any further development and optimization at the RU, should be transferred.

Phase II: Project planning

The marketing authorization holder and the Sender Unit (SU) and Receiver Unit (RU) should jointly establish a team in order to coordinate activities and execute the technology transfer exercise. Where the technology transfer involves a site that has limited manufacturing experience or if the process being transferred is complicated, the SU should consider providing extensive training and onsite support before the project execution phase begins.

• The team should perform a gap analysis and risk assessment based on the available data, information and knowledge of the premises, equipment, materials, products, procedures and other related information.
• The team should prepare the technology transfer document such as the Master Plan (or Technology Transfer Protocol).
• The team should develop a control strategy which includes, for example: risks; raw, starting and packaging material attributes; analytical and microbiological test procedures; sampling plans, and release and stability specifications; critical quality attributes (CQAs), critical process parameters (CPPs) and in-process controls; and acceptance criteria and limits.

The specifications and critical material attributes of the starting materials (APIs and excipients) to be used at the RU should be consistent with those materials used at the SU, unless there is a planned change associated with these materials as part of the transfer and regulatory approval is obtained as applicable. Documentation to support compliance with transmissible animal spongiform encephalopathy certification requirements or other regulatory requirements should be available at the RU, where applicable.

The SU should provide the RU with the open part of the Drug Master File (DMF), API Master File (APIMF), as applicable, or equivalent information, as well as any relevant additional information on the API of importance for the manufacture of the pharmaceutical product.

The SU should provide the product information including its qualitative and quantitative composition, physical description, method of manufacture, in-process controls, control method and specifications, packaging components and configurations, and any safety and handling considerations to the RU.

The marketing authorization holder or SU should provide any information on the history of process development, as well as any historical process changes which may be required to enable the RU to perform any further development and/or process optimization after a successful transfer.

The SU should provide to the RU information on any health, safety and environmental issues associated with the manufacturing processes to be transferred and the implications thereof (i.e. a need for gowning or protective clothing).

The SU should provide information on current processing and testing to the RU, including but not limited to:

• a detailed description of facility requirements and equipment;
• information on starting materials, applicable Material Safety Data Sheet (MSDS) where required, storage and distribution requirements for raw materials, intermediates and finished products;
• a description of manufacturing steps (narrative and process maps or flow charts, and/or master batch records), including the qualification of in-processing hold times and conditions, the order and method of raw material addition and bulk transfers between processing steps;
• a description of analytical procedures;
• the identification and justification of control strategy (e.g. identification of critical performance aspects for specific dosage forms, identification of process control points, product quality attributes and qualification of critical processing parameter ranges, sampling plans, statistical process control {SPC} charts);
• design space, in cases where this has been defined;
• validation information (e.g. validation plans and reports);
• annual product quality reviews;
• stability information;
• an authorized set of protocols and work instructions for manufacturing; and
• environmental conditions or any special requirement needed for the facility or equipment, depending on the nature of the product to be transferred.

Information on packaging to be transferred from the SU to the RU should include specifications for a suitable container and closure system, as well as any relevant additional information on design, packing, processing or labelling requirements and tamper-evident and anti-counterfeiting measures.

For QC and microbiological testing of packaging components, specifications should be provided, including drawings, artwork and material and reference to relevant pharmacopoeias, where applicable.

Phase III: Project transfer execution

The team should execute the project in accordance with the procedures and agreed upon plan.

Production

During the transfer process, the RU should identify any differences in facilities, systems and capabilities and discuss these with the SU. The SU should cooperate with the RU in order to understand the potential impact and satisfactorily address this to assure an equivalent product quality. Based upon the information received from the SU, the RU should consider its own capability to manufacture and pack the product to the required standards and should develop the relevant site operating procedures and documentation prior to the start of routine production.

The RU should address the following tasks:

• the comparison and assessment of suitability and qualification of facility and equipment;
• a description of the manufacturing process and flow of personnel and/of materials at the RU (a narrative and/or process map or flow chart);
• the determination of critical manufacturing steps, including hold times, endpoints, sampling points and sampling techniques;
• the writing and approval of a training plan, SOPs for all production operations (e.g. dispensing, granulation or blending or solution preparation, tablet compression, tablet coating, encapsulation, liquid filling, primary and secondary packaging and in-process QC and microbiology), packaging, cleaning, testing and storage;
• the evaluation of stability information with generation of site-specific stability data if required; and
• compliance with regulatory requirements for any changes made (e.g. in terms of batch size).

The transfer of packaging operations should follow the same procedural principles as those of the product processing and the RU should determine the need for qualification and validation for the packaging process.

Quality Control

Analytical procedures used to test pharmaceutical products, starting materials, packaging components and cleaning (residue) samples, if applicable, should be implemented at the testing laboratory before the testing of samples for process validation studies is performed by the RU. The transfer of the analytical procedure may be accomplished by several approaches such as confirmation testing, comparability testing between SU and RU results, co-validation between laboratories, or through a “paper-based knowledge” transfer. The chosen strategy should be risk-based and scientifically justifiable.

A protocol and Test Transfer Plan defining the steps should be prepared for transfer of analytical procedures. The analytical procedures transfer protocol should include:

• a description of the objective, scope and respective responsibilities of the SU and RU;
• a specification of materials and methods;
• the experimental design and acceptance criteria;
• documentation (including information to be supplied with the results and report forms to be used, if any);
• the procedure for the handling of deviations; and
• details of test samples (i.e. starting materials, intermediates and finished products).

The SU’s responsibilities for the transfer of analytical procedures are typically to:

• provide method-specific training for analysts and other QC and microbiology staff, if required;
• assist in the analysis of QC and microbiology testing results;
• define all procedures to be transferred for testing a given product, starting material or cleaning sample;
• define experimental design, sampling methods and acceptance criteria;
• provide any validation reports for procedures under transfer, including proof of their robustness;
• provide details of the equipment used, as necessary (part of validation report, if available) and any standard test samples;
• provide approved procedures used in testing; and
• review and approve transfer reports.

The RU should exercise its responsibility to:

• review analytical procedures provided by the SU and formally agree on acceptance criteria before execution of the transfer protocol;
• ensure that the necessary equipment for QC is available and qualified at the RU site; the equipment used by the RU during the analytical transfer should meet the appropriate specifications in order to ensure the requirements of the procedure or specification are met;
• ensure that adequately trained and experienced personnel are in place for analytical testing;
• provide a documentation system capable of recording the receipt and testing of samples to the required specification using approved test procedures, and reporting, recording and collating data and designation of status (i.e. approved, rejected, quarantine);
• execute the transfer protocol;
• perform the appropriate level of validation or verification to support the
• implementation of the procedures; and
• generate and obtain the approval of transfer reports.

Cleaning

In order to minimize the risk of contamination and cross-contamination, adequate cleaning procedures should be followed.

Cleaning procedures and their validation should normally be site-specific. In order for the RU to define its cleaning strategy, the SU should provide information on cleaning at the SU to minimize cross-contamination due to residues from previous manufacturing steps, operator exposure and environmental impact, including:

• information on cleanability;
• information on solubility of active ingredients, excipients and vehicles;
• toxicological assessment including Health Based Exposure Limits; and
• existing cleaning procedures.

Phase IV: Project review and closeout

The progress and success of the technology transfer should be monitored and reviewed during and after completion of the project. The review should further ensure that, as appropriate, stability studies are started and continued; post-marketing commitments are monitored; and new material suppliers are integrated into the quality management system.

Compliance with the procedures and protocols should be verified. Deviations and changes should be documented and investigated, where appropriate.

Where possible, data and results should be subjected to the appropriate statistical calculation and evaluation in order to determine trends, compliance with control limits and capability studies.

A document such as a technology transfer report should be prepared, based on the data and information obtained during the project. The supportive data should be kept and be accessible at all times.

The document, which should include an assessment of the data and information and a conclusion, should be authorized by the appropriate, responsible person(s). It should further state whether or not the team has achieved the completion of the technical transfer. Any deviations and changes from the Master Plan should additionally be assessed and evaluated before closeout of the project.

Read also:

• Technology Transfer in Pharmaceutical Industry
• Major Documents for Technology Transfer in Pharma Industry
• Good Practices for Research and Development (R&D) Facilities

Reference: WHO Guidelines on Technology Transfer in Pharmaceutical Manufacturing