Technology Transfer and Development.pdf

Subject: Industrial Pharmacy 2 Unit: 2 TECHNOLOGY DEVELOPMENT AND TRANSFER INTRODUCTION Transfer of technology is de...

Subject: Industrial Pharmacy 2 Unit: 2 TECHNOLOGY DEVELOPMENT AND TRANSFER INTRODUCTION Transfer of technology 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 manufacture sites”. Transfer of technology requires: Documented, planned approach Trained and knowledgeable personnel Complaint quality system 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, which may or may not be a separate entity. Invention Financial Invention return Disclosure TECHNOLOGY TRANSFER PROCESS Licensing Assessment Marketing Protection Barriers of TT Lack of awareness, knowledge and efficiency Lack of government focus and low market share Web access and scientific publications Cost of prequalification National security issues and restrictions Inadequate funding and possible treaties Labour issues 1  Practical aspects of TT Mindset of researchers Implementation of policies Lack of platforms and disconnect from the markets Project type Finding and retaining expertise Finding the resources Clarity and transparency Fear to technology risk Ecosystem promoting tech innovation Institutional mechanisms Research ideas WHO GUIDELINES FOR TECHNOLOGY TRANSFER Guiding principles that provides flexible framework as guidance. The major intention: To place special attention on the quality aspects of a pharmaceutical products as per WHO’s mandate. The transfer of process/es or technology/ies to an alternative site occurs at some stage in the lift cycle of most products. Transfer sequence: development, scale up, manufacturing, production and launch, to the post-approval phase. Transfer of technology is a logical procedure that controls the transfer of any process together with its documentation and professional expertise between development and manufacture or between manufacture sites. TOT is a systematic procedure It is followed to pass on documented knowledge and experience gained during development and/or commercialization to an authorized agency. TOT involves transfer of documentation as well as the ability of the Receiving Unit (RU) to effectively perform the critical procedures of the transferred technology, to the satisfaction of all parties and any applicable regulatory bodies. The International Society for Pharmaceutical Engineering (ISPE) has prepared the guidelines for the intracompany transfers. why intra- and inter-company transfers of technology? For the need of additional capacity, relocation of operations or consolidations and mergers etc. 2  The WHO Expert Committee on Specifications for Pharmaceutical Preparations (WHO ECSPP), in its 42nd report recommended that WHO address this issue through preparation of WHO guidelines for TOT. TOT requires a documented and planned approach. A Sending Unit (SU), a RU and the unit managing the process. Scope of Guidelines: WHO guidelines for TOT specifically provides guidance for transfer of QC methods, if a technical agreement exists for SU manufacturer to RU manufacturer or SU manufacturer to RU QC laboratory. If no such technical agreements exist, for example, for testing by national laboratories or for testing of procurement agencies, issues listed in point (iv) below may not work, and in such cases an alternative approaches may be required. (1) General recommendations (2) Guidelines for materials (3) Guidelines for specific products (4) The guidelines for SU and RU: (a) Transfer of development and production (processing, packaging and cleaning). (b) Transfer of analytical methods for QA and QC. (c) Skills assessment and training of personnel. (d) Organization and management of the transfer. (e) Assessment of premises and equipment. (f) Documentation, qualification and validation TECHNOLOGY TRANSFER PROTOCOL Transfer comprises an SU and an RU. There may be an additional unit which will be responsible for directing, managing and approving the transfer. There is a formal agreement between the parties, which specifies the responsibilities before, during and after transfer. Organization and management of a successful technology transfer need to ensure that the main steps have been executed and documented. The transfer protocol should list the intended sequential stages of the transfer. The protocol should include: 3  Objective Scope Key personnel and their responsibilities A parallel comparison of materials, methods and equipment The transfer stages with documented evidence that each critical stage has been satisfactorily accomplished before the next commences Identification of critical control point Experimental design and acceptance criteria for analytical methods Information on trial production batches, qualification batches and process validation Change control for any process deviations encountered Assessment of end-product Arrangements for keeping retention samples of active ingredients, intermediates and finished products, and information on reference substances where applicable Conclusion, including signed off approval by project manager The SU and the RU should jointly verify that the following, satisfactorily completed, validation protocols are available: (i) IQ and OQ data for manufacturing and packaging equipment at the RU site and analytical equipment (ii) Qualification of the rooms for both manufacture and packaging at the RU site 4 QUALITY RISK MANAGEMENT The quality risk management is a systematic process for the assessment, control communication and review of risks to the quality of the drug product throughout the product lifecycle. A project risk is reduced by use of technical skills, planning, multitasking organization flexibility, troubleshooting, and negotiation and by being goal oriented etc. Risk management is an integral part of any type of technology transfer in industrial manufacturing. Table 1: Types of Risks Associated with Technology Transfer Type of risk Description of risk Comparability Leads to non-comparability of process or product between SU and RU. Manufacturing process Risks to routine manufacturing, for example microbial contamination risks, operator error etc. Equipment, utilities, and facility Risks associated with equipment, utilities, or facilities failure etc. Project Leads to delay in project timeline which is often related to planning, resources etc. 5  Fig.: SYSTEMATIC PROCESS FOR QRM 1. Types of Changes: a. Known changes (i) Assessment of known changes (ii) Assessment of individual changes (iii) Assessment of aggregated changes b. Unanticipated changes Assessment of unanticipated changes 2. Risk Management Structure and Organization: A critical aspect of risk management in technology transfer is appropriate organization of people and documentation. An integrated technology transfer team structure allows all relevant functions to address and resolve change in a timely manner and to escalate issues quickly. As changes are not always predictable, the availability of cross-functional teams on a continuous basis is needed. 3. Risk Assessment and Mitigation Approach (RAMA): The RAMA is part of company DNA. It has application in all technology transfers and during the whole project lifecycle. 6  In line with the current regulatory guidance, GMP and must be based on scientific principles. It is managed by appropriate flexible, robust and efficient tools. TRANSFER FROM R & D TO PRODUCTION (PROCESS, PACKAGING AND CLEANING) Technology transfer The process by which the manufacturing process, packaging and cleaning and analytical methods are transferred from one manufacturing unit to another unit or from R&D to manufacturing unit. Technology transfer from R&D to manufacturing site: critical A typical technology transfer process can be divided into production part including packaging, quality control part including analytical methods, cleaning and documentation part. RU and SU both develops product transfer protocol jointly to transfer the product related information. The necessary information is transferred according to technical expertise of the staff and the capabilities of manufacturing site to run the transfer process. Cleaning is very crucial parameter if plant is processing different products. During the manufacturing process, pharmaceutical products and APIs may be contaminated by residual materials left behind of the other pharmaceutical products. Adequate cleaning procedures: minimize the risk of contamination, cross- contamination, operator exposure and environmental effects. Cleaning In order to define cleaning strategy at the RU, the SU should provide information related to cleaning at the SU to minimize cross-contamination. This information usually includes: 1. Information on solubility of active ingredients, excipients and vehicles. 2. Minimum therapeutic doses of active ingredients. 3. Therapeutic category and toxicological assessment. 4. Existing cleaning procedures etc. Additional information 1. Cleaning validation reports (for example, chemical and microbiological). 2. Information on cleaning agents used (including efficacy, documentary evidence that these agents do not interfere or hamper analytical testing for residues of APIs and removal of residual cleaning agents). 3. Reports of recovery studies to validate the sampling methodology. Once process capability established at the RU, assuring that the product, process or method at the RU meets the predefined and justified specifications at SU, the process validation and cleaning validation is carried out. 7 GRANULARITY OF TECHNOLOGY TRANSFER PROCESS The granularity is level of details considered in a transfer model or decision making process. The greater the granularity, the deeper is the level of details about the transfers. Granularity: used to characterize the scale or level of detail in a set of data. Process models vary in depth depending on the needs they have to satisfy. Different depths result in process models with different granularity, It depends on the needs the transfer process model should fulfil. To present a large overview of certain activities enclosed in a transfer process model, a large-grained process model is preferred. It is used by top-level managers and business analysts who want to have a general overview of the time and resources needed to accomplish the transfer process. A fine-grained process model: a detailed model describing not only transfer activities but also different roles and dependencies is needed. Starting Materials Any properties which are likely to influence the process or product should be identified and well characterized. 1. Active Pharmaceutical Ingredients: API Master File (APIMF) or Drug Master File (DMF) or Active Substance Master File (ASMF), or equivalent information and any relevant additional information on the API of importance for the manufacturing of the pharmaceutical product. a) Manufacturer and associated supply chain, b) Step of the API to be transferred, c) Flow chart of synthesis pathway d) Definitive physical form of the API (including photomicrographs and other relevant data and any polymorphic and solvate forms), e) Solubility profile of API f) If relevant, pH in solution, g) Partition coefficient (including the method of determination), h) Intrinsic dissolution rate (including the method of determination), i) Particle size and distribution (including the method of determination), j) Bulk physical properties k) Water content and determination of hygroscopicity (including water activity data and special handling requirements), l) Microbiological considerations in accordance with regional, national or international pharmacopoeial requirements m) Specifications and justification for release and expiry limits, n) Summary of stability studies o) List of potential and observed synthetic impurities p) Information on degradants q) Potency factor r) Special considerations 8 Excipients The excipients to be used may have a potential impact on the final product. Therefore, their specifications and relevant functional characteristics should be made available by the SU for transfer to the RU site. The following are examples of the information which may typically be provided: a) Manufacturer and associated supply chain, b) Description of functionality, c) Definitive form d) Solubility e) Partition coefficient f) Intrinsic dissolution rate g) Particle size and distribution h) Bulk physical properties i) Compaction properties j) Melting point range k) The pH range l) Ionic strength m) Specific density n) Viscosity and or viscoelasticity o) Osmolarity p) Water content and determination of hygroscopicity q) Moisture content range r) Microbiological considerations s) Specifications and justification for release and end-of life limits, t) Information on adhesives supporting compliance with peel, sheer and adhesion design criteria (for transdermal dosage forms), u) Special considerations with implications for storage and/or handling, v) Regulatory considerations Finished Products The SU provides detailed characterization information (qualitative and quantitative composition, physical description, method of manufacture, in-process controls, control method and specifications, packaging components with configurations and specifications, and any safety precautions and handling methods ) of the finished product. Additionally the SU also provides any information generated during process development which is required to enable the RU to perform further development, if any, and or for process optimization after successful transfer Such historical information may include the following: 1. Information on clinical development, for example, information on the rationale for the synthesis, route and form selection, technology selection, equipment, clinical tests, and product composition. 2. Information on scale-up activities, for example, process optimization, statistical optimization o critical process parameters, critical quality attributes, pilot report and or information on pilot-scale development activities indicating the number of batches manufactured. 9 3. Information on full-scale development activities, indicating the number and disposition of batches manufactured, and deviation and change control (change management) reports which led to the current manufacturing process. 4. The change history and reasons, for example, a change control log, indicating any changes to the process, primary packaging and analytical methods, if any, as a part of process optimization or improvement. 5. Information about investigations of critical issues and problems and the outcomes of these investigations. The SU also provide to the RU information on current processing and testing, that includes: A detailed description of facility Validation information such as validation requirements and equipment. plans and reports. Information of starting materials, Annual product quality reviews and stability applicable material safety data sheet information. (MSDS) and storage requirements for raw materials and finished products. Description of manufacturing steps An authorized set of protocols and (process maps, flow charts, and master operative instructions for manufacturing. batch records), including qualification of in processing hold times and conditions, order and method of raw material addition and bulk transfers between processing steps. Description of analytical methods. Environmental conditions during manufacturing. Identification and justification of control Any special requirement needed for the strategy, for example, identification of facilities or equipments for specific product critical performance aspects for specific to be transferred. dosage forms, identification of PCP, PQA and qualification of critical processing parameter ranges, statistical process control (SPC) charts. Design space, if defined. Packaging and Packaging materials: Similar to production transfer, the transfer of packaging operations also follow similar procedural patterns. The information about packaging to be transferred from the SU to the RU includes: 1. Specifications for a suitable container or closure system. 2. Any relevant additional information on design, packing, processing or labeling requirements. 3. Tamper-evident and anti-counterfeiting measures needed for qualification of packaging components. For QC testing of packaging components, specifications should be provided for drawings, artwork and material (for example, glass, card or fibre board). Based on the formation provided, the RU performs a suitability check for initial qualification of the packaging components. Packaging is considered to be suitable if it provides: 10 1. Adequate protection against degradation of the formulation components due to environmental influences. 2. Safety of formulation as absence of undesirable substances released into the product. 3. Compatibility as absence of interaction possibly affecting medicine quality, 4. Performance through functionality in terms of drug delivery. DOCUMENTATION, PREMISES AND EQUIPMENTS (a) Documentation: o Technology transfer documentation is a document that indicates contents of technology transfer for transferring and transferred parties. o The raw data of the documents should be prepared and compiled accordingly and should be always readily available and traceable. o For successful technology transfer, task assignment and responsibilities are usually clarified. o The acceptance criteria for the completion of technology transfer concerning respective technology to be transferred are prepared. o Quality assurance department establishes confirmation process for all kinds of technology transfer documentation and check and approve the documentation. o A successful technology transfer document contains both "know how" and "know why". o With antecedent and peripheral information, members of the technology transfer team have more to work with, can better evaluate options and can distinguish the critical from the incidental. o A huge documentation is required for the transfer project. o The examples of documentation commonly required for various transfers are Table. Examples Technology Transfer Documentation Sr.No. Key tasks Documentation provided by SU Transfer 1 Project definition Project plan and quality plan (where Project implementation separate documents), protocol, risk plan (TOT protocol). assessments, gap analysis. 2 Facility assessment Plans and layout of facility, buildings Qualification protocol (construction, finish), qualification and report: Side-by-side status (design qualification, comparison with RU installation qualification, operational facility and buildings; Qualification and reports gap analysis. o The documented evidence of successful technology transfer is formalized and stated in a technology transfer summary report. o This report comprises summary of scope of the transfer, the critical parameters observed in the SU and RU in a tabulated format and the final concluding remarks of the transfer. o Possible discrepancies too are listed and appropriate actions, where needed, taken to resolve them are also included. (b) Premises: The SU provides information to the RU about the plant layout, building and its construction as well as finishing specifications of the buildings, facilities such as Heating, 11 Ventilation and Air Conditioning (HVAC), temperature, relative humidity, water, power and compressed air and other services, Because these may affect product, process or method to be transferred. In addition, SU provides following information about relevant health, safety and environmental issues: 1. Inherent risks of the manufacturing processes, for example, reactive chemical hazards, exposure limits, and fire and explosion risks. 2. Health and safety requirements to minimize operator exposure, for example, atmospheric containment of pharmaceutical dust. 3. Emergency planning considerations, for example, gas or dust release, spillage, fire and firewater run-offs. 4. Identification of waste streams and provisions for recycling, re-use, and/or disposal. (c) Equipments: The SU should provide a list of equipments, makes and models involved in the manufacture, filling, packing and or control of the product, process or method to be transferred, together with existing qualification and validation documentation. Relevant documentation includes drawings, manuals, maintenance logs, calibration logs, and procedures regarding equipment set-up, operation, cleaning, maintenance, calibration and storage. The RU should review the information provided by the SU together with its own inventory list includes installation, operational and process qualification of all equipment and systems. Additionally, RU is supposed to perform a comparison of equipments at the two sites for their functionality, makes, models, capacity and qualification status. On the RU side, it is must to perform a gap analysis. Why so???????????? TO identify requirements for adaptation of existing equipment, or acquisition of new equipment, or a change in the process, to enable them to reproduce the process being transferred. Factors of comparison Critical Critical Minimum equipment quality Critical and Material of component, attributes operating maximum construction for example, and range of parameters capacity filters, intended screens, etc., use. The availability of facilities and specific locations of all equipment at the RU is considered at the time of designing manufacturing process maps or drawing up flow charts including flows of personnel and material to be transferred. The impact of manufacturing new products on products currently manufactured with the same equipment should be determined. Any modification of existing equipment that needs to be adapted to become capable of reproducing the process being transferred should be documented in the transfer project plan. 12 VALIDATION Quality of product cannot be ensured only by sampling, testing, and release of materials or products but the quality assurance techniques must be used to build the quality into the product at every step and not just tested for at the end. Validation of a process ensures production of drugs with reproducible quality. The concept of validation was first proposed by two USFDA officials, Ted Byers and Bud Loftus, in the mid 1970's in order to improve the quality of pharmaceuticals. In pharmaceutical industry, process validation performs this task to build the quality into the product. This is because, according to ISO 9000: 2000, it had proven to be an important tool for quality management of pharmaceuticals. Validation is an ongoing activity that covers development, operation, and maintenance. Reasons for Validation: 1. Quality assurance 2. Economics 3. Compliance QUALITY CONTROL: ANALYTICAL METHOD TRANSFER Manufactured product is tested by the developed analytical method. The accuracy in the analytical method saves time. RU develops 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: o responsibilities of both SU and RU the specification of product, o acceptance criteria, and o interpretation of results, o report formats, o reference standards o deviations during analysis. The transfer protocol of analytical methods includes: 1. Description of the objective, scope and responsibilities of the SU and the RU. 2. Specification of materials and methods. 3. Experimental design and acceptance criteria. 4. Documentation (including information to be supplied with the results, and report forms to be used, if any) 5. Procedure for the handling of deviations. 6. References. 7. Signed approval. 8. Details of reference samples (starting materials, intermediates and finished products). Responsibilities of SU 1. Provide method-specific training for analysts and other quality control staff, if required. 2. Assist in analysis of QC testing results. 3. Define all methods to be transferred for testing a given product, starting material or cleaning sample. 4. Define experimental design, sampling methods and acceptance criteria. 13 5. Provide any validation reports for methods under transfer and demonstrate their robustness. 6. Provide details of the equipment used, as necessary (part of validation report, if available) and any standard reference samples. 7. Provide approved procedures used in testing. 8. Review and approve transfer reports. Responsibilities of RU 1. Review analytical methods provided by the SU, and formally agree on acceptance criteria before execution of the transfer protocol. 2. Ensure that the necessary equipment for QC is available and qualified at the RU site. 3. Ensure that adequately trained and experienced personnel are in place for analytical testing. 4. Provide a documentation system capable of recording receipt and testing of samples to the required specification using approved test methods, 5. Execute the transfer protocol. 6. Perform the appropriate level of validation to support the implementation of the methods. 7. Generate and obtain approval of transfer reports. APPROVED REGULATORY BODIES AND AGENCIES There are many regulatory authorities with reference to the concept of technology transfer in their respective regulatory frameworks. 1. European Union's Guidelines for GMP for Medicinal Products for Human and Veterinary Use 2. USFDA 3. World Health Organization: The information for pharmaceutical technology transfer can also be found in the Guidelines published by World Health Organization (WHO) in 2011 and by the International Society for Pharmacoepidemiology (ISPE) in 2014. Following is the list of institutes in India assisting in Technology Transfer: (i) Asia Pacific Centre for Transfer of Technology (APCTT): C2, Qutab Institutional Area, New Delhi-110016. (ii) National Research and Development Corporation (NRDC) (iii) Technology Bureau for Small Enterprises (TBSE): Room no. 123, Udyog Bhawan, (iv) Foundation for Innovation & Technology Transfer (FITT): Indian Institute of Technology Hauzkhas, New Delhi-110016. Asian and Pacific Centre for Transfer of Technology (APCTT): Address: C2, Qutab Institutional Area, New Delhi-110016. Nodal Ministries: Department of Scientific and Industrial Research, Ministry of Science and Technology, India. APCTT publishes Asia-Pacific Tech Monitor (techmonitor.net) devoted to information on latest technology innovations and events. It also publishes Value-Added Technology Information Service (VATIS) periodicals in five thematic areas of biotechnology, food processing, non-conventional energy, ozone layer protection, waste management. 14 The National Research Development Corporation (NRDC): Address: 20-22, Zamroodhpur Community Center, Kailash colony, New Delhi-110048. Nodal Ministry: DSIR, Ministry of Science and Technology, India. The NRDC was a non- departmental government body established by the British Government for the transfer of technology from public sector to the private sector. It was established in India in 1953 to help develop, promote and commercialize technologies/ know-how inventions/ patents/processes emanating from various national R&D institutions/Universities. Technology Information, Forecasting and Assessment Council (TIFAC): Address: Room no, 123, Udyog Bhawan, Rafi Marg, New Delhi-110011 Nodal Ministry: Department of Science and Technology (DST), Ministry of Science and Technology, India. TIFAC is an autonomous organization set up in 1988 under the Department of Science & Technology (DST) to look ahead in technology domain, assess the technology trajectories, and support innovation by networked actions in selected areas of national importance. TIFAC works for formulating a Technology Vision for the country in various emerging technology areas. Under the leadership of Dr. APJ Abdul Kalam, Technology Vision 2020 exercise led to set of 17 documents (sixteen on technology areas and one on services). Biotech Consortium India Limited (BCIL): Address: V Floor, Anuvrat Bhawan, 210, Deen Dayal Upadhay Marg, New Delhi-110002. Nodal Ministry: Department of Biotechnology (DBT), Ministry of Science and Technology, India. BCIL was incorporated as public limited company in 1990 under The Companies Act, 1956. The consortium is promoted by the DBT, Government of India and financed by the All India Financial Institutions (AIFI) and some corporate sectors. BCIL's major functions include the development and transfer of technology for the commercialization of biotechnology products, project consultancy, biosafety awareness and human resource development. It has been successfully managing several Flagship schemes and Programmes of the DBT, Government of India which include: i. Biotechnology Industry Partnership Programme (BIPP) ii. Biotechnology Industrial Training Programme (BITP) iii. Small Business Innovation Research Initiative (SBIRI) The Technology Bureau for Small Enterprises (TBSE) /Small Industries Development Bank of India (SIDBI) Address: SIDBI: SIDBI Tower, 15, Ashok Marg, Lucknow - 226001, Uttar Pradesh. TBSE: MSME "A" Wing 7th Floor, Nirman Bhawan, New Delhi-110108, SIDBI was set up on 2nd April 1990 under an Act of Indian Parliament, acts as the principal financial institution for promotion, financing and development of the Micro, Small and Medium Enterprise (MSME) sector as well as for co-ordination of functions of institutions engaged in similar activities. 15 Foundation for Innovation and Technology Transfer (FITT): Address: Indian Institute of Technology Hauzkhas, New Delhi-110016. FITT is an industrial interface organization. Established at the Indian Institute of Technology Delhi (IIT Delhi) as a Registered Society on 9th July 1992. FITT aims to be an effective interface with the industry to foster, promote and sustain commercialization of science and technology in the institute for mutual benefits. TECHNOLOGY TRANSFER RELATED DOCUMENTATION (a) Confidentiality Agreement: Protects the rights of technology. Recently its role to protect technology has increased a lot due to the rising costs of patent protection; either by costs incurred in patent grant or solve patent litigation. In addition, confidentiality is must due to the short life of innovations with an industrial application. The draft confidentiality agreement should include: (i) All the necessary information about the parties and the people involved in the negotiations (ii) A brief description of the confidential technology. (iii) The means used for communications between the parties. (iv) Draft should be circulated between the parties and complemented with regard to any details which may be helpful, in particular concerning the group of people involved on each side. (v) The means for communications for the agreement. (b) Licensing: Technology Transfer and its licensing have played a crucial role in its all round development. A license is agreement whereby an owner of a technological IP (the licensor) allows another party (the licensee) to use, modify, and/or resell that property in exchange for compensation (consideration). Technology transfer involves more than a license to a patent; Moving the technology from the inventor's laboratory into the licensee's laboratory. (c) Memoranda of Understanding & Inter-Institutional Agreements: Whenever domestic and foreign firms discuss on technology transfer they preliminary agree on various legal issues previous to the operation that possibly will be held. The parties, at the time, establish confidentiality, non-competition, whether or not the possibility of exclusivity and many other topics relevant to the future structure of the transaction. This particular instrument is called memorandum of understanding (MOU) or letter of intent (U) or Inter-Institutional Agreements (IA). The collaborative research efforts with outside institutions/industries are defined in MOU or IIA before final agreements are executed. An MOU typically defines ways to share IP and the roles and responsibilities of the involved parties. In order to enter into a collaborative relationship with an outside party, it is important to 16 have a MOU. The general objects of MOU/IIA are to examine legally the instrument, as: (i)Scope (ii) Concept (iii) Legal nature and (iv) Different punctuation species. The especial aims of MOU/IIA are: (1) To understand if the absence of good faith in this treaty characterize the illegal practice or if it deals with abuse of right, and (2) To establish in which cases and how it will be attributed equity consequences arising from the breach of any of its provisions or of the covenant. (c) Legal Issues: The licensing of know-how or IP is governed by the contractual agreement signed between research laboratory and client. The legal agreement contains details such as name, address and activities being done by both the parties, it clearly states the purpose of the agreement, scope, financial conditions, royalty rate, valid term of the agreements, details for arbitration in case of dispute, confidentiality term, provision for amendment in the agreement etc. IP rights for patent are rights parallel to that of real estate rights. Unauthorized use of his/her IP. Infringement in IP Two types of infringements namely; product infringement and process or method infringement. Infringer Willful infringement, Alternate Dispute Resolution (ADR) is any mechanism for parties to resolve their dispute other than through traditional court litigation. ADR is based on mutual contract / agreement. It is recognized by United Nations Commission on International Trade Law (UNCITRAL1980) -Geneva Convention (1923/1961) and - New York Convention (1958). 17