Technology transfer from Research and development to production

Technology transfer process from R&D to production, Granularity,Complete process from raw materials to finished products, analytical method transfer,Transfer protocol, responsibilities

1. Technology transfer from R&D TO PRODUCTION Archana.k

2. Objective Manufacturing process, packing, cleaning methods are transferred from one manufacturing unit to another or from R&D to manufacturing unit. RU and SU both develops the protocol for the successful transfer RU should be able to accommodate the production capacity Consideration should be given to technical expertise, site specifications, site capabilities.

3. GRANULARITY OF TECHNOLOGY TRANSFER PROCESS The granularity is a level of details considered in a transfer model or decision process. The greater the granularity the greater the level of details of transfer Granularity depends on the needs the transfer model should fulfil. It was often used by the top-level managers, business analysts who want to have a general over view and time and resources needed to accomplish the transfer.

4. process Technology transfer Production part (starting materials, excipients) Quality control ( Analytical test, Finished product) Cleaning and documentation

5. STARTING MATERIALS(API, EXCIPIENTS) Specifications and considerations should be consistent with the API , Excipients that are to be used by the RU in all aspects with the SU. API - SU should provide RU with the following details Drug master file which includes the specifications as follows: Manufacture associated supply chain API Transfer Flow chart of synthesis Pathways, Physical properties of API ( physical form, particle size, particle shape, polymorphism etc) Solubility studies, microbiological studies, pH, partition coefficient, dissolution tare, water content, stability studies, degradants, potency factor, expiry limits, storage conditions. All the factors should be assessed for QRM.

6. EXCIPIENTS- Excipients may have potential impacts on the final products. Following details should be provided- Manufacture associated supply chain Description of functionality (e.g. Antioxidant, binder, preservative) Flow chart of synthesis Pathways, Physical properties of API ( physical form, particle size, particle shape, polymorphism etc) Compaction property Solubility studies, microbiological studies, pH, partition coefficient, dissolution tare, water content, stability studies, degradants, potency factor, expiry limits, storage conditions. Melting point, Ionic strength, viscosity studies, osmolarity, specific density Information of expiry limits, regulatory considerations for proper applications. All the factors should be assessed for QRM.

7. Finished products SU should provide following details: Quantitative and qualitative composition, physical description, In-process controls, Handling methods, Packing, storing conditions. Any information generated during process development, process optimization should be provided Historical data: Clinical development ( route of administration selection, clinical tests) Scale-up activities: Process optimization, critical parameters, pilot scale reports along with the pilot batches details. Full scale manufacturing activities : number of batches, any change controls Change control log: Changes to particular process, Analytical methods, process optimization, Improvements Investigations about the critical issues and their outcomes of these investigations.

8. The SU should provide details of the Healthy, safety, environmental, parameters to be considered during the manufacturing process ( protective clothing, precautions for certain procedures) SU should provide information about current processing's and testing's information: Details of facility requirements MSDS –Material safety data sheet ( Information of starting materials and storage requirements) Manufacturing steps-(flow charts, master batch records, qualification of equipment, holding times, bulk transfer between steps) Description of analytical methods Design space Validation records Annual product quality review Authorized protocols Environmental conditions, any special requirements of equipment for specific product transfer .

9. The Ru should consider to do the tasks of the following , If any changes or differences collaborate with the SU. Qualification of facilities and equipment. Description of manufacturing process, flow charts, procedure at the RU. Determining of critical steps in manufacturing. Preparation of SOP’S. Stability information evaluation along with site specific stability evaluation. Compliance with the regulatory requirements.

10. PACKING AND PACKING MATERIALS Details from SU should include: Specifications of suitable container system, closure system. Any information on design, packing, processing, labelling. QC testing- details should include: Protection against degradation of formulation of products due to environmental influences. Safety of formulation Compatibility Drug delivery

11. CLEANING Cleaning is very crucial parameter to prevent contamination between API and other residual materials. Cleaning and validation is site specific because of different arrangement of equipment and design space. SU should provide the information to minimize the cross contamination in all the procedures. Solubility information of all ingredients Minimum therapeutic doses of API Toxicological assessment Existing cleaning procedures Cleaning validation reports Information on cleaning agents

12. DOCUMENTATION Document that indicates the contents of technology transfer for transferring. Raw documents always readily available and traceable Technology transfer document contains “know how” and “know why” with information, the team can evaluate, can work more and distinguish critical to incidental. The document should provide information for smooth transfer of technology. Huge document is required for the transfer which consists of the scope of transfer, critical parameters observed in SU.

13. PREMISES SU should provide information to RU about the plant layout, building and its construction as well as specifications of the building and facilities such as heating, Air conditioning HVAC, temperature, relative humidity, water, power and other services. Inherent risks of manufacture such as chemical hazards, exposure limits , fire etc Health safety environment- for contamination, pharmaceutical dust Emergency planning- Gas or dust release, spillage, fire Waste streams- Recycling, Re-use, Disposal.

14. EQUIPMENT SU should provide list of equipment models for manufacturing such as filling, packing or control of product. Qualification and validation documentation. Drawings, Manuals, Maintenance logs, Calibration logs, set to step procedures, cleaning and maintenance. RU should review the information by SU and compare the comparison of equipment at site should be done with their functionalities , models, capacities. Perform gap analysis , If require acquisition of new equipment or adjustment to existing equipment should be done. GMP requirements should be satisfied. The impact of manufacturing new product with the existing equipment should be considered.

15. QUALITY CONTROL : ANALYTICAL METHOD TRANSFER Is the documented process that qualifies a laboratory (the receiving unit) to use an analytical test procedure that originated in another laboratory (the transferring unit), thus ensuring that the receiving unit has the procedural knowledge and ability to perform the transferred analytical procedure as intended. Is the verification that a method or test procedure works in an equivalent fashion at two or more different sites or laboratories and meets all acceptance criteria. In short, analytical method transfer qualifies a laboratory to use a test procedure .

16. TRANSFER PROTOCOL Objective, scope, responsibilities of SU and RU Specifications of methods and materials Experimental design and acceptance criteria Documentation Procedure for handling deviations References Signed approvals Reference sample details (starting materials, intermediates, finished products)

17. RESPONSIBILITIES

18. Assay for potency: Bracketing may be appropriate. Each site 2x analysts 3x lots –total 18 per site Difference should not be more than ≤2%, 95% confidence. Content uniformity : Assay method Each site 2x analysts 1x lot SD should not be ±3%, 95% confidence. Dissolution : Bracketing method 6 units for extended release. Mean ±5% with SU

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