Technology Transfer in Pharmaceutical Industry

Technology Transfer is defined as “a logical procedure that controls the transfer of any process together with its documentation and professional expertise between development and manufacture or between manufacturing sites”.

A proper technology transfer (TT) is both essential and important to drug discovery and development for new medicinal products. It is also required to upgrade drug quality planned during research development and to the final product during manufacturing as well as to guarantee that stable quality is transferred.

• It is a systematic procedure that is followed in order to pass the documented knowledge and experience gained during the development and or commercialization to an appropriate, responsible and authorized party. Technology transfer embodies both the transfer of documentation and the demonstrated ability of the receiving unit (RU) to effectively perform the critical elements of the transferred technology, to the satisfaction of all parties and any applicable regulatory bodies.
• The transfer of technology is considered both fundamental and significant to the drug discovery and development process for any new medicinal entity. This process is important for elucidating necessary information for technology transfer from R & D (Research & Development) to PDL (product development laboratory).

Why technology transfer is required in the Pharmaceutical Industry?

• Technology transfer refers to the processes that are needed for successful progress from drug discovery to product development, to clinical trials to full-scale commercialization or it is the process by which a developer of technology makes its technology available to commercial partners that will exploit technology.
• Technology transfer involves manufacturing drug products with increasing batch sizes on larger equipment or using continuous processing on pilot-scale equipment. Generally, scale-up involves the transfer of technology and the transfer of knowledge that has been accumulated during the small-scale development of products and processes.
• In the pharmaceutical industry, technology transfer by collaborating with other departments and other organizations to commercialize a pharmaceutical product is a common process.

Importance of Technology Transfer in the Pharmaceutical Industry

1. To elucidate necessary information to transfer technology from R&D to actual manufacturing by sorting out various information obtained during R&D.
2. To elucidate necessary information to transfer the technology of existing products between various manufacturing places.
3. To exemplify specific procedures and points of concern for the two types of technology transfer in the above to contribute to smooth technology transfer. This applies to the technology transfer through R&D and production of drug substances or drug products and the technology transfer related to post-marketing changes in manufacturing places.

Reasons for Technology Transfer

1. Lack of manufacturing capacity: The developer of technology may only have manufacturing equipment that is suitable for a small-scale operation, and must collaborate with another organization to do large-scale manufacturing.
2. Lack of resources to launch the product commercially: The original inventor of technology may only have the resources to conduct early-stage research such as animal studies and toxicology studies, but doesn’t have the resources to take technology through its clinical and regulatory phases.
3. Lack of marketing and distribution capability: The developer of technology may have fully developed the technology and even have obtained regulatory approvals and product registrations, but it may not have the marketing and distribution channels.
4. Exploitation in a different field of application: Each partner may have only half of the solution i.e. the developer of the technology might be capable of exploiting the technology itself in the field of diagnostic applications and may grant exploitation right to commercial partners for the exploitation of therapeutics applications.

Technology Transfer in the Pharmaceutical Industry

• Technology transfer is the process by which the manufacturing process and analytical method are transferred from one manufacturing unit to another unit or from R&D to the manufacturing unit.
• Technology transfer from R&D to the manufacturing site is critical because of the scale-up of the product from pilot batch to large-scale commercial batch. A typical technology transfer process can be divided into production part, quality control part, and documentation part.

A.  Production: Technology Transfer

• The receiving unit and sending unit both should develop the product transfer protocol jointly to transfer the product-related information. Information should be transferred according to the technical expertise of the staff and the manufacturing site capabilities to run the process smoothly.

1. Raw Materials:

• The material used for manufacturing on the receiving unit should be consistent with the material used at the sending unit. The properties of the raw material that can alter the quality of the product should be identified.

i.  Active Pharmaceutical Ingredients (API):

The sending unit should provide the drug master file (DMF) and other related information on the active materials. It may include the following information:

• Flowchart of the manufacturing process of the drug material
• Physical properties including bulk and tap density
• Moisture content including water activity
• Bioburden, endotoxin, and sterility as required
• Solubility and pH of the solution
• Particle size distribution and its dissolution profile
• Manufacturer and the supply chain of the material
• Other information like heat, light, and moisture sensitivity

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ii.  Excipients:

Excipients also have a considerable effect on the final product so their detailed information should also be provided by the sending unit to the receiving unit. It may include the following information:

• Viscosity of material
• Flowchart of the manufacturing process of the drug material
• Physical properties including bulk and tap density
• Moisture content range
• Melting range
• Bioburden, endotoxin, and sterility as required
• The ion strength of the material
• Solubility and pH of the solution
• Specific gravity
• Particle size distribution and its dissolution profile
• Manufacturer and the supply chain of the material
• Compliance with
• TSE and BSE requirements
• MSDS and heat, light, and moisture sensitivity

2. In-process Materials

The sending unit should provide detailed information about the manufacturing process, physical description, specification, and in-process controls.

3. Finished Products

• History of the development of the product should also be provided for further development or process optimization after the successful technology transfer.
• Information regarding the environment, health, and safety should also be provided to the receiving unit. It should also include information on product quality review, validation, stability, and environmental conditions for manufacturing.
• Generally, trial batches are taken at the receiving unit to test the manufacturing parameters and capability of the manufacturing process before running the validation batch.

4. Packing Process

All the information regarding the packing should be transferred to the manufacturing process. It includes the specification of foils or containers and closures, and other related information such as design labeling, artwork, and drawings.

5. Cleaning Process

• To prevent contamination in pharmaceutical products, it is essential they follow an adequate cleaning procedure. It can minimize the risk of cross-contamination during manufacturing. 
• The receiving unit should validate the cleaning procedure and the sending unit should provide the required information such as the existing cleaning procedure, the solubility of all materials, therapeutic dose, the toxicity of the API, cleaning agents, and recovery studies.

6. Manufacturing Facility

The sending unit should provide the information related to the facility design.

i.  Premises

• It should include the layout of the facility, buildings, utility services, fire risk, health and safety requirements for operators, and environmental issues.

ii.  Equipment

• A list of required equipment with their make and models should be provided by the sending unit. It should include the manuals, drawings, and cleaning, operating, and maintenance procedures. IQ, OQ, and PQ of the equipment should be done by the receiving unit.

B.  Quality Control: Analytical Method Transfer

• The analytical method has its own importance because the manufactured product shall be tested by the developed analytical method and accuracy in the analytical method can save time. The receiving unit should implement the method of analysis for the finished product, raw materials, packing materials, and cleaning residues before the starting of the process validation.

• Analytical method transfer protocol should be prepared including responsibilities of both the sanding unit and receiving unit, the specification of the product, acceptance criteria, interpretation of results, report formats, reference standards, and deviations during analysis. Training should be provided to the analysts and should be documented in the training record.

C.  Documentation

• Every step followed during the technology transfer process should be documented and a summary report should be prepared to contain the conclusion of the technology transfer.
• Discrepancies found during the process should be listed and should be resolved by taking the appropriate action. 
• The following documents should be prepared during the successful tech transfer.

1. Technology transfer protocol
2. Facility qualification protocol and report
3. Equipment qualification protocol and report
4. Process validation protocol and report
5. Cleaning validation protocol and report

Annex 7 - WHO guidelines on transfer of technology in pharmaceutical manufacturing

 

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