INTRODUCTION

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 transfer technology, to the satisfaction of all parties and any applicable regulatory bodies. Transfer of technology requires a documented, planned approach using trained and knowledgeable personnel working within a quality system, with documentation of data Covering all aspects of development, production and quality control. Usually there is a Sending unit (SU), a receiving unit (RU) and the unit managing the process, this may or may not be a separate entity. Technology transfer is both integral and critical to the drug discovery and development process for new medicinal products. This process is important to elucidated necessary information for technology transfer from R and D (Research & Development) to PDL (Product development laboratory) and for development dosage forms in various ways Like it provides efficiency in process, help to maintain quality of products, helps to achieves standardized process, which in turn facilitates timely and cost effective production. Technology transfer in pharmaceuticals industry In the pharmaceuticals 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 are the process by which a developer of technology makes its technology available to commercial partner that will exploit technology. In pharmaceuticals industry preparation of dosage form needs scale up in Several stages, such as small scale laboratory development from 0.5-2kg batch can be Scaled up to 5-10 kg and then to 20-100kg on a pilot scale. Production scale can typically Range from 200kg to greater than 1000kg. Technology transfer involves manufacturing of drug product with increasing batch sizes on large equipment or using continuous processing on pilot plant 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 product and process. Principles to be followed for successful technology transfer Robust information exchange, providing the receiving Party with all information that is relevant to the processes and associated assays. Careful front-end planning and project management, with the designation of point people for specific positions of the projects. Ensuring that analytical assays are transferred ahead of the process. Performing small-scale verification at receiving sites. This provides confirmation that the information exchange was successful and allows the receiving party to be more self sufficient going forward. Always perform pre-GMP engineering runs. GMP runs are the end game. Put your technology transfer project in context by defining GMP success and failure and dont dismantle your team until success here has been verified. Reasons for Technology Transfer There may be many reasons why a developer of the technology might consider making its technology available to another person to exploit, instead of exploiting the technology itself. Some of these are: 1. Forming alliances with partners that can progress the development of the technology to take it to market. The developer of the technology might have the resources to take the technology to particular state of development, such as upto animal studies and toxicology studies, but does not have the resources to take the technology through its clinical and regulatory phases, and must collaborate with another organization to take it through these phases, and into the market. 2. Forming alliances with partners with manufacturing capability. The developer of the technology may have taken the technology to a state of development so that it is near market ready, but does not have the clean room

manufacturing capability or resources to manufacture the product, and must partner with another organization that dose have that capability.

3. Forming alliances with partners with marketing and distribution capability. The developer of the technology may have fully developed the technology and even have obtained regulatory approvals and product registrations for the product to be sold, but it lacks the marketing and distribution channels to give it a marking capability and must collaborate with another organization that doses have that capability. 4. Exploitation in a different field of application. 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 applications. By transferring the technology for the use in another field of application to another person, the developer of the technology creates another income stream from the exploitation that takes place on that takes place in that other field. 5. No Commercial capability. The developer of the technology may be research institute of a university, which doses not have the capability to exploit commercially at all, and need to collaborate with another organization that does have that capability. In the exploitation of pharmaceutical products, technology transfer by collaborating with this way to bring a pharmaceutical product to market is common feature of the industry. Importance of Technology Transfer to Pharmaceutical Industry The importance of technology transfer are: To elucidate necessary information to transfer technology from R&D to actual manufacturing by sorting out various information obtained during R&D; To elucidate necessary information to transfer technology of existing products between various manufacturing places; and 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 is applies to the technology transfer through R&D and production of drug

(chemically synthesized drug substances and drug products) and the technology transfer related to post-marketing changes in manufacturing places.

Technology Transfer Process The quality of design will be almost completed in phase II clinical study. Various standards for manufacturing and test will be established in process of reviewing factory production and phase III study to realized the quality of design, and the quality if design will be verified in various validation studies, and will be upgraded to be the quality of product and the actual production will be started. Technology transfer consists of action taken in these flows of development to realize through the quality as designed during the manufacture. Even if the production starts, the technology transfer will take place in process such as changes in manufacturing places. The processes are classified into the three categories. 1. Research Phase 2. Development Phase 3. Production Phase

1. Research Phase 1.1. Quality Design: For Drug Products, the quality design corresponds to so called pharmaceuticals design-todesign properties and functions such as elimination of adverse reactions, improvement of efficacy, assurance of stability during distribution, and adding usefulness based on various data such as chemical and physical properties, efficacy, safety and stability obtained form preclinical studies. For drug substance, the quality design is to determine starting materials and their reaction paths, and basic specification of the drug. 2. Development Phase 2.1. Research for Factory Production:

To manufacture drugs with qualities as designed, it is required to establish appropriate quality control method and manufacturing method, after detecting variability factors to secure stable quality in the scale-up validation that is performed to realize factory production of drug designed on the basis of result from small-scale experiments. 2.2. Consistency between Quality and Specification: When product specification is established on the basis of the quality of product determined in the above, it is required to verify that the specification adequately specifies the product quality. In short, the consistency between quality and specification is to ensure in the products specification that the quality predetermined in the quality design is assured as the manufacture quality, and the product satisfies the quality of design. 2.3. Assurance of consistency through development and manufacturing: To make developed product have indications as predetermined in clinical phases, the quality of design should be reproducible as the quality of product (assurance of consistency). For this purpose, the transferring party in charge of development should fully understand what kind of technical information is required by the transferred party in charge of manufacturing, and should establish an appropriate evaluation method to determine whether a drug to be manufactured meets the quality of design. 2.4. Technology Transfer from R&D to Production: Transfer of the technical information is necessary to realize manufacturing formula established in the above in the actual production facility. Technical information to be transfer should be compiled as R&D report. 3. Production Phase 3.1. Validation & Production: Production is implemented after various validation studies verify that it is able to stably product based on transferred manufacturing formula. While the manufacturing facility accepting technology is responsible for validation, the research and development department transferring technology should take responsibility for validation such as

performance qualification, cleaning validation, and process validation unique to subject drugs. 3.2. Feedback from Production and Technology Transfer of Marketed Products: Technical information of developed products are obtained from data of a limited amount of batches, various standards have been established from the limited data, and quality evaluation method established in development phase in not always sufficient for factory production, it is highly desired to feedback and accumulate technical information obtained from repeated production, if necessary. In addition, it is important to appropriately modify various standards established before based on this information, and accountability and responsibility for design and manufacturing should be executed. Technology Transfer Documentation Technology transfer documentation are generally interpreted as documents indicating contents of technology transfer for transferring and transferred parties. The raw data of the documents should be prepared and compiles according to purposed, and should be always readily available and traceable. For successful technology transfer, task assignments and responsibilities should be clarified, and acceptance criteria for the completion of technology transfer concerning individual technology to be transferred. Quality assurance department should established conformation process for all kinds of technology transfer documentation, and should check and approve the documentation. Technology transfer documentation are indicated as follows. 1. Organization for Technology Transfer: One of the most significant elements for successful technology transfer is closed communication between transferring and transferred parties. Therefore, organization for technology transfer should be established and composed of both party members, roles, scope of responsibilities of each party should be clarified and adequate communication, and feedback of information should be ensured. It is desirable that this organization complies with GMP. 2. Research and Development Report: To realize quality assurance at all stages from drug development to manufacturing, transfer to manufacturing, transfer of technical documents concerning product development or corresponding documents should be considered. The research and

development report (development report) is a file of technical development, and the research and development department is in charge of its documentation. This report is an important file to indicate rationale for the quality design of drug substances and drug specifications and test methods. The development report before the approval inspection. Although the development report is not prerequisite for the application for approval, it can be used at the pre-approval inspection as valid document for the quality design of new drug. In addition, this report can be used as raw data in case of post-marketing technology transfer.

The following exemplifies information to be contained in the development report. 1. Historical data of pharmaceutical development of new drug substances and drug products at stages from early development phase to final application of approval 2. Raw materials and components 3. Synthetic route 4. Rational for dosage form & formula designs and design of manufacturing methods 5. Rational and change histories of important processes and control parameters 6. Quality Profiles of manufacturing batches ( including stability data) 7. Specifications and test methods of drug substances, intermediates, drug products, raw materials, and components, and their rationale( validity of specification range of important tests such as contents impurities and dissolution, rational for selection of test methods, reagents and, columns, and traceability of raw data of those information) 3. Product Specification File: The product specification is to compile information, which enables the manufacture of the product, and to define specification, manufacturing and evaluations method of the product and its quality, and the transferring party is responsible for documenting the file. The product specification file should be reviewed at regular intervals, and incorporate various information obtained after the start of production of the product, and be revised as appropriate.

For new products, the development report can be used as a part of product specification file.

4. 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, and 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. 5. Technology Transfer Report: It is to report the completion of technology transfer after data of action taken according to the technology plan is evaluated and the data is confirmed pursuant to the predetermined judgment criteria. Both transferring and transferred parties can document the technology transfer report; however, they should reach an agreement on its contents. 6. Verification of Results of Technology Transfer: After the completion of technology transfer and before the start of manufacturing of the product, the transferring party should verify with appropriate methods such as product testing and audit that the product manufactured after the technology transfer meets the predetermined quality and should maintain records of the results. Introduction Technology transfer is the mechanism by which societies try to ensure that publicly funded research discoveries are transferred to companies so that they can be developed and commercialized as products that benefit the public. Technology transfer can occur by publication of information, transfers of personnel, and other avenues. However technology transfer of biomedical technologies to companies

with the expectation that the recipients will actively exploit or develop the technology and share benefits with the academic inventors usually occurs under one of the following three types of arrangements: (a) Licenses or assignments of preexisting technologies; (b) Collaborative or sponsored research agreements to develop new information or technologies; (c) Formation of start-up companies, usually financed largely by private venture capital. Taken together, these methods constitute the technology transfer system between publicly supported research institutions and industry. Technology transfer under any of these three types of arrangements usually involves the transfer of IP rights, although sometimes corporate sponsors of research ask only for information. Transfers of IP rights involve either licenses or assignment (i.e., complete sale or transfer) of IP rights. Therefore understanding how IP rights are acquired and transferred is key to understanding any technology transfer system. INTRODUCTION The transfer of technology is fundamentally a matter of the flow of human knowledge from one human being to another. The classic view of a flow from basic to applied technology is a over simplification, for example problems or insights arising at the production level give rise to new idea that contribute to fundamental basic advantage. Technology transfer is helpful todevelop 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 theproduction 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 forsmall 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 doesnt 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 thetechnology 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.

FACTORS INFLUENCING TECHNOLOGY TRANSFER Drivers for Technology Transfer (B) Good business and manufacturing practices The companys 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. 1. Lack of efficiency Automation of production processes to improve efficiency and lower costs. 2. 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. 3. Cost of prequalification There is benefit in meeting International Standards since it opens up the opportunity for trading across the entire world. 4. Labour issues The pharmaceutical sector demands relatively skilled labour. High labour turn over and absenteeism owing to unattractive conditions of service is negative contributor. 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) (a) 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. (b) 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 (a) Master Formula Card (MFC) Includes product name along with its strength, generic name, MFC number, page number, effective date, shelf life and market. (b) Master Packing Card Gives information about packaging type, material used for packaging, stability profile and shelf life of packaging. (c) Master Formula Describes formulation order and manufacturing instructions. (Process order and environment conditions) (d) Specifications and Standard Test Procedures (STPS) Helps to know active ingredients and excipients profile, in-process parameters, product release specifications and finished product details. (C) Optimization and Production. (a) 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. (b) 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. (a) 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.

(b) 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. (c) 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.

POLICY APPROACHES THAT OVER COME BARRIERS IN TECHNOLOGY TRANSFER. (a) Commercializing publicly funded technologies The basic pattern envisioned is to give institutions receiving public research funds the right to obtain and exploit patents on inventions developed in the course of research. (b) Research tool patents and freedom to operate for the public sector Patents sometimes make it difficult for public researchers to carry out their research or to make the products of that research available. It is intensified by the tendency of some publicly funded research laboratories to avoid use of a patented technology without permission even in nations where no relevant patent is in force. (c) Web access and scientific publication Limited access to scientific journals led to enormous problems for developing nations scientists. (d) National security issues and restrictions on exports of particular technology International controls designed to protect national security and to prevent the proliferation of important technologies also restrict the flow of technologies. (e) Inadequate funding in important areas and possible treaties There are areas of research of importance to the developing world that are being funded inadequately. (f) Co-operative research agreements Global support for public sector research might be encouraged is through co-operative research agreements designed to meet specific goals. It would seem more feasible to focus efforts on

technologies of significant social benefit to the developing nations. (g) Possible treaty on scientific access There has also been a proposal for an international treaty on access to knowledge and technology negotiated on the basis of the type of reciprocity found in normal international trade negotiations. The concept is mean to be nonzero sum in the sense that, like free trade in goods, free trade in scientific ideas benefits all, and such arrangements could be made bilaterally as well as multilaterally. IF TECHNOLOGY TRANSFER ISNT 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 require effective technology transfer smoothly moving technical knowledge processes and analytical requirements between the different parties involved. The issues to be focused are (a) 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. (b) Lack of experience working with Contract Manufacturing Organizations

The key building blocks of this approach include i. ii. iii. iv. 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.

CONCLUSION 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. Provide strong support for scientific education and for basic research in areas that are important to the nation. It is important to remove barriers to the free flow of science and technology. Seeking global technological integration is far better for a world than political restrictions on the transfer of technology. REFERENCES 1. YUE Feifei and YUE Yingming. Research on Technology Transfer in the Pharmaceutical Industry.

2. Dr. John H. Amuasi (MBChB. MPH). Technology Transfer and Local manufacturing of Pharmaceuticals: The South African case. African Dialogue on Technology Transfer for Local Manufacturing Capacity on Drugs and Vaccines Cape Town, South Africa, 1011 December 2009. 3. Singh Amanjeet, Aggarwal Geeta. Technology Transfer In Pharmaceutical Industry: A Discussion. International Journal of Pharma and Bio Sciences. July-September 2009; 1, Issue-3. 4. Barton John H. New Trends in Technology Transfer Implications for National and International Policy. ICTSD Programme on IPRs and Sustainable Development 2007; 8:14-31. 5. YUE Feifei and YUE Yingming. Research on Technology Transfer in the Pharmaceutical Industry.