Technology transfer is helpful to develop dosage forms in various ways as it provides efficiency in process, maintains quality of product, helps to achieve standardized process which facilitates cost effective production. It is the process by which an original innovator of technology makes its technology available to commercial partner that will exploit the technology.
Technology transfer is both integral and critical to drug discovery and development for new medicinal products. The cost of product development raises during pilot scale-up and initial production batch i.e. the critical path for success is dependent on completion of technology transfer to the production site at an affordable cost.
Technology transfer is defined as “The processes that are needed for successful progress from drug discovery to product development to clinical trials to full-scale commercialization.”
Importance of Technology Transfer
To elucidate necessary information to transfer technology of existing products between various manufacturing places and to exemplify specific procedures and points of concern for smooth technology transfer. The ultimate goal for successful technology transfer is to have documented evidence that the manufacturing process for drug substance and drug products are robust and effective in producing the drug and drug products complying with the registered specifications and Good Manufacturing Practice requirement.
Reasons for Technology Transfer
1) Lack of manufacturing capacity – The developer of technology may only have manufacturing equipment which is suitable for small scale operation, and must collaborate with another organization to do large scale manufacturing.
2) Lack of resources to launch product commercially – The original inventor of technology may only have the resources to conduct early-stage research such as animal studies and toxicology study, 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 partner for the exploitation of therapeutics application.
Constituents of Technology Transfer Process
Factors Influencing Technology Transfer
(A) Drivers for Technology Transfer –
- Good business and manufacturing practices – The company’s success is primarily the result of its adoption of good business and manufacturing practices, particularly in the areas of product identification and formulation technology.
- Potential for competitive pricing – Balance cost to remain competitive by having higher private sector prices and very low public sector prices.
- Strategic planning – Create an enabling environment for vertical integration, with prospects for higher capacity utilization and eventual lowering of production costs.
- Strong economy and environment – For technology transfer to be successful there needs to be supportive business and scientific environment in the recipient country, and that environment should include skilled workers, economic and political stability, supportive regulatory environment, market size and potential and a well developed national infrastructure of natural resources and transport.
- Transparent and efficient regulation – Pharmaceuticals are necessarily a high regulated industry, the regulatory function must be efficient and transparent for technology transfer to be economically viable.
- Opportunities for contingency supply – Multinational pharmaceutical companies are inclined to transfer technology to local manufacturers with the potential to receive when they foresee an inability to meet time scales and volume demand from large procurers.
- Access to new machinery, training, know-how and business partnership – This makes the prospect of technology transfer very desirable to local pharmaceutical manufacturers since the technology, equipment, etc. could be applied profitably beyond the initial purpose.
(B) Barriers of Technology Transfer –
- Lack of efficiency – Automation of production processes to improve efficiency and lower costs.
- Low market share – Local producers face significant challenges in meeting International Quality Standards and capturing a critical market share. Greater market share would increase profitability.
- Cost of prequalification – There is benefit in meeting International Standards since it opens up the opportunity for trading across the entire world.
- Labour issues – The pharmaceutical sector demands relatively skilled labour. High labour turn over and absenteeism owing to unattractive conditions of service is negative contributors.
Steps in Technology Transfer
During development of a formulation, it is important to understand the procedure of operations used, critical and non-critical parameters of each operation, production environment, equipment and excipient availability should be taken into account during the early phases of development of formulation so that successful scale up can be carried out. The steps involved in technology transfer are as follows –
(A) Development of technology by R&D. (Research Phase)
- Design of procedure and selection of excipients by R&D – Selection of materials and design of procedures is developed by R&D on the basis of innovator product characteristics.
- Identification of specifications and quality by R&D – Quality of product should meet the specifications of an innovator product.
(B) Technology transfer from R&D to production (Development Phase) – R&D provides technology transfer dossier (TTD) document to product development laboratory, which contains all information of formulation and drug product as follows -
- Master Formula Card (MFC) – Includes product name along with its strength, generic name, MFC number, page number, effective date, shelf life and market.
- Master Packing Card – Gives information about packaging type, material used for packaging, stability profile and shelf life of packaging.
- Master Formula – Describes formulation order and manufacturing instructions. (Process order and environment conditions)
- Specifications and Standard Test Procedures (STP’S) – Helps to know active ingredients and excipients profile, in-process parameters, product release specifications and finished product details.
(C) Optimization and Production. (Production Phase)
- Validation Studies – Production is implemented after validation studies that can verify that process is able to stabilize the product based on transferred manufacturing formula. Manufacturing department accepting technology is responsible for validation and the R&D department transferring technology should take responsibility for validation such as performance qualification, cleaning and process validation.
- Scale up for production – Involves the transfer of technology during small scale development of the product and processes. It is essential to consider the production environment and system during development of process. Operators should concentrate on keeping their segment of the production process running smoothly.
(D) Technology Transfer Documentation – Generally interpreted as document indicating contents of technology transfer for transferring and transferred parties. Each step from R&D to production should be documented, task assignments and responsibilities should be clarified and acceptance criteria for completion of technology transfer concerning individual technology to be transferred. It is duty of Quality Assurance department to check and approve the documentation for all processes of technology transfer.
- Development Report – The R&D report is a file of technical development, and R&D department is in-charge of its documentation. This report is an important file to indicate rationale for the quality design of drug substances and its specifications and test methods. The development report is not prerequisite for the application for approval; it can be used at the pre approval an inspection as valid document for quality design of new drug. The development report contains – (1) Data of pharmaceutical development of new drug substances and drug products at stages from early development phase to final application of approval. (2) Information of raw materials and components. (3) Design of manufacturing methods. (4) Change in histories of important processes and control parameters. (5) Specifications and test methods of drug substances. (6) Validity of specification range of important tests such as contents impurities and dissolution. (7) Verifications of results.
- Technology Transfer Plan – The technology transfer plan is to describe items and contents of technology to be transferred and detailed procedures of individual transfer and transfer schedule, establish judgment criteria for the completion of the transfer. The transferring party should prepare the plan before the implementation of the transfer and reach an agreement on its contents with the transferred party.
- Report – Completion of technology transfer is to be made once data are taken accordingly to the technology plan and are evaluated to confirm that the predetermined judgment criteria are met. Both transferring and transferred parties should document the technology transfer report.
(E) Exhibit – After taking scale up batches of the product, manufacturing of exhibit batches takes place. In case of exhibit, batch sizes are increased along with equipments and their processes. This is done for filling purpose in regulatory agencies.
If Technology Transfer isn’t done right…
(1) Process Validation may be unsuccessful.
(2) Delayed regulatory approval and/or product launch.
(3) Flawed processing may result – high rate of batch rejections, costly schedule revisions and excessive labour requirements.
(4) Analytical methods cannot support production.
(5) Product does not perform as intended.
Issues in the Technology Transfer Process
Pharmaceutical and biotech industry is becoming increasingly competitive; many players are boosting their in-licensing activities, consolidating manufacturing networks and outsourcing production to less costly third-party manufacturers. All these strategic initiatives requires effective technology transfer – smoothly moving technical knowledge processes and analytical requirements between the different parties involved. The issues to be focused are –
- Lack of repeatable and scalable business processes – Many organizations manage transfers as isolated, non strategic events involving little more than a procedural exchange of process documents between sending and receiving parties. But without repeatable and scalable processes companies are forced to reinvent the wheel each time technology changes hands. This leads to variety of inefficiencies such as suboptimal allocation of resources, higher development costs, quality and compliance issues.
- Lack of experience working with Contract Manufacturing Organizations – The key building blocks of this approach include:
- Rigorous selection process of contract manufacturing partner.
- Clear and well documentation objectives and expectations.
- Leading-edge process guide-lines and project management tools.
- High-performance, dedicated cross-functional technology transfer teams.
Progressive pharmaceutical companies should pay more attention to streamlining and optimizing their technology transfer process to ensure the rapid and successful introduction of new medicinal products to market. Technology transfer can be considered successful if a receiving unit can routinely reproduce the transferred product, process or method against a predefined set of specifications as agreed with a sending unit and/or a development unit.
A dedicated technology transfer organization should set up to facilitate and execute the process. To achieve this end, its recommended that company should adopt a rigorous process to select its contract manufacturing partners to prevent issues in the future collaboration process.
- Technology Transfer In Pharmaceutical Industry: A Discussion by Amanjeet Singh and Geeta Aggarwal, Published in International Journal of Pharma and Bio Sciences. Vol.1/Issue-3/Jul-Sep. 2010.
- Facts of Technology Transfer: A Perspective of Pharmaceutical Industry by M. S. Janodia, D Shreedhar, V. S. Ligade, A. Pise and N. Udupa, Published in J. Intellectual Property Rights 13:28-34 Jan. 2008.
- Research on Technology Transfer in the Pharmaceutical Industry by YUE Feifei and YUE Yingming.
- Technology Transfer in Practice by Green S and Warren P, 2002, Sue Horwood Publishing Limited, Storrington, West Sussex, UK.
- African Dialogue on Technology Transfer for Local Manufacturing Capacity on Drugs and Vaccines by Dr. John H. Amuasi (MBChB. MPH), Cape Town, South Africa, 10-11 Dec. 2009.
- Effective and Efficient Knowledge Transfer from R&D to Manufacturing by F. Sexton, Purdue Pharma’s SMC Meeting, Mar. 2004.
- Technology Transfer: Manufacturing Perspective by G. Millili, Ph. D, Pharm Tech Conference 1996.
- Pharmaceutical Technology Transfer: Pre and Post NDA Submission by S. Liebowitz, Ph. D, Pharm Tech Conference 1995.
- ISPE Technology Transfer Giude, 2003.
Rajkumar P. Patil
Sr. Production Officer
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