WHO Guidance on Technology Transfers
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The document provides guidance on technology transfer between pharmaceutical manufacturing sites. It discusses that technology transfer requires a documented, planned approach with trained personnel and quality systems. A successful transfer involves the sending unit providing documentation to the receiving unit, conducting training, and jointly executing a transfer protocol. The receiving unit must demonstrate it can routinely reproduce the product or process to specifications. The guidance addresses general principles, planning, information to be transferred for active pharmaceutical ingredients and excipients, process validation, and assessing a successful transfer.
WHO Guidance on Technology Transfers
- 1. This presentation is compiled by “ Drug Regulations” a Not for Profit organization from publicly available material on the world wide web. Visit www.drugregulations.org www.drugregulations.org 1
- 2. These guidelines are guiding principles Intended to serve as a flexible framework Focus on the quality aspects in line with WHO’s mandate. 2 Prepared by Drug Regulations a Not for Profit Organization
- 3. Transfer of processes to an alternative site occurs at some stage in the life cycle ◦ Development ◦ Scale-up ◦ Manufacturing ◦ Production and launch ◦ Post-approval phase 3 Prepared by Drug Regulations a Not for Profit Organization
- 4. 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”. 4 Prepared by Drug Regulations a Not for Profit Organization
- 5. Systematic procedure Passes documented knowledge and experience Experience gained during development and or commercialization Passes to an appropriate, responsible and authorized party. 5 Prepared by Drug Regulations a Not for Profit Organization
- 6. Technology transfer embodies ◦ Transfer of documentation ◦ Demonstrated ability of the receiving unit (RU) to effectively perform the critical elements of the transferred technology This should be to the satisfaction of all parties and any applicable regulatory bodies. 6 Prepared by Drug Regulations a Not for Profit Organization
- 7. Literature Little information available from national or regional regulatory bodies. Guidance available from ISPE 7 Prepared by Drug Regulations a Not for Profit Organization
- 8. Business strategies of pharmaceutical companies involves intra- and intercompany transfers of technology for ◦ Additional capacity, ◦ Relocation of operations ◦ Consolidations ◦ Mergers 8 Prepared by Drug Regulations a Not for Profit Organization
- 9. WHO Expert Committee on Specifications for Pharmaceutical Preparations recommended in its forty second report that WHO address this issue through preparation of WHO guidelines. The guidance was issued in the year 2011 in TRS 961 Annex 7. 9 Prepared by Drug Regulations a Not for Profit Organization
- 10. Transfer of technology requires ◦ Documented, planned approach ◦ Trained and knowledgeable personnel ◦ Compliant quality system, ◦ Documentation of data: Development, Production and Quality Control. Usually there is a ◦ Sending unit (SU), ◦ A receiving unit and ◦ Unit managing the process, which may or may not be a separate entity. 10 Prepared by Drug Regulations a Not for Profit Organization
- 11. For the transfer to be successful, the following general principles and requirements should be met: ◦ The project plan should encompass the quality aspects of the project Transfer ◦ Should be based on the principles of quality risk management; ◦ The capabilities of the SU and at the RU should be similar, but not necessarily identical 11 Prepared by Drug Regulations a Not for Profit Organization
- 12. For the transfer to be successful, the following general principles and requirements should be met: ◦ Facilities and equipment should operate according to similar operating principles; ◦ A comprehensive technical gap analysis between the SU and RU should be performed ( Technical , Quality , Regulatory) ◦ Adequately trained staff should be available or should be trained at the RU: 12 Prepared by Drug Regulations a Not for Profit Organization
- 13. For the transfer to be successful, the following general principles and requirements should be met: ◦ Regulatory requirements in the countries of the SU and the RU, should be considered. ◦ Regulatory requirements where product is intended to be supplied, should also be considered. ◦ There should be effective process and product knowledge transfer. 13 Prepared by Drug Regulations a Not for Profit Organization
- 14. Technology transfer can be considered successful ◦ Documented evidence ◦ RU can routinely reproduce the transferred product, process or method against a predefined set of specifications 14 Prepared by Drug Regulations a Not for Profit Organization
- 15. In the event that the RU identifies particular problems , the RU should communicate them back to the SU to ensure continuing knowledge management. 15 Prepared by Drug Regulations a Not for Profit Organization
- 16. Technology transfer projects have legal and economic implications. ◦ Intellectual property rights ◦ Royalties ◦ Pricing ◦ Conflict of interest ◦ Confidentiality These should be addressed before and during planning and execution of the transfer. Any lack of transparency may lead to ineffective transfer of technology. 16 Prepared by Drug Regulations a Not for Profit Organization
- 17. Some of the principles outlined here may also be applicable to manufacturing investigational pharmaceutical products Some of the responsibilities outlined here for the SU may also be considered to be part of the management unit responsibilities. 17 Prepared by Drug Regulations a Not for Profit Organization
- 18. This guidance provides for transfer of QC methods to RU QC laboratory where Technical Agreement exists between SU & RU. Such technical agreements may not exist ◦ e.g. testing by national laboratories or testing for procurement agencies Number of points listed in next slides may not be workable, and alternative approaches may be required. 18 Prepared by Drug Regulations a Not for Profit Organization
- 19. This guidance provides ◦ Principles for transfers ◦ General recommendations on the activities necessary to conduct a successful intra or inter site transfer ◦ Basic considerations needed for a successful transfer in order to satisfy the regulatory authority 19 Prepared by Drug Regulations a Not for Profit Organization
- 20. The guidelines will be applied to ◦ Manufacturing active pharmaceutical ingredients (APIs), ◦ Manufacturing and packaging of bulk materials, ◦ Manufacturing and packaging of finished pharmaceutical products (FPPs) ◦ Performing analytical testing. 20 Prepared by Drug Regulations a Not for Profit Organization
- 21. The recommendations provided in these guidelines apply to all dosage forms However they need to be adjusted on a case-by-case basis ◦ e.g. by using risk management principles Particularly close control of certain aspects will be required for certain formulations such as sterile products, and metered dose aerosols. WHO guidance on manufacture of specific pharmaceutical products will be useful in this regard. 21 Prepared by Drug Regulations a Not for Profit Organization
- 22. As each transfer project is unique these guidelines can not cover all possible situations. These guidelines do not provide guidance on any legal, financial or commercial considerations associated with technology transfer projects. 22 Prepared by Drug Regulations a Not for Profit Organization
- 23. Transfer comprises an SU and an RU. In some circumstances there may be an additional unit This unit may be responsible for directing, managing and approving the transfer. There is a formal agreement between the parties This specifies the responsibilities before, during and after transfer. 23 Prepared by Drug Regulations a Not for Profit Organization
- 24. A successful technology transfer need to ensure that the main steps have been executed and documented as described earlier in Introduction. There should be a project management plan This should identify and control all the necessary activities identified at the start of the undertaking. The transfer protocol should list the intended sequential stages of the transfer. 24 Prepared by Drug Regulations a Not for Profit Organization
- 25. The protocol should include: ◦ 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 points; 25 Prepared by Drug Regulations a Not for Profit Organization
- 26. The protocol should include: ◦ 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. 26 Prepared by Drug Regulations a Not for Profit Organization
- 27. The SU should provide the necessary validation documentation for the process and its support functions. Usually, an established process is transferred, and such documentation is already available. The SU should provide criteria and information on hazards and critical steps associated with the product, process or method to be transferred, This should serve as a basis for a quality risk management (QRM) exercise at the RU. 27 Prepared by Drug Regulations a Not for Profit Organization
- 28. The SU and the RU should jointly verify that the following, satisfactorily completed, validation protocols are available: ◦ Installation qualification (IQ) and operational qualification (OQ) data for Manufacturing equipment ◦ Packaging equipment ◦ Analytical equipment ◦ Qualification of the rooms for both manufacture and packaging 28 Prepared by Drug Regulations a Not for Profit Organization
- 29. The SU and the RU should jointly implement any training programmes that may be required specific to the product, process or method to be transferred, ◦ e.g. on analytical methods or equipment usage, and assess training outcomes. 29 Prepared by Drug Regulations a Not for Profit Organization
- 30. The SU and the RU should jointly execute the transfer protocol according to a checklist A flow diagram may also be used showing the sequence of steps to be carried out to effect an efficient transfer. Any changes and adaptations made during the course of the technology transfer should be fully documented. The SU and the RU should jointly document the execution of the transfer protocol in a transfer of technology summary in a report. 30 Prepared by Drug Regulations a Not for Profit Organization
- 31. Any transfer project will be managed by a team comprising members with clearly defined key responsibilities. The team should be drawn from members of relevant disciplines from both the SU and RU sites. The team members should have the necessary qualifications and experience to manage their particular aspect of the transfer. 31 Prepared by Drug Regulations a Not for Profit Organization
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- 33. The RU should be able to accommodate the intended production capacity. Establish if single-batch manufacture, continuous production or campaigns is required. Consideration should be given to ◦ The level and depth of detail to be transferred to support production and ◦ Any further process development and optimization at the RU as intended under the transfer project plan. 33 Prepared by Drug Regulations a Not for Profit Organization
- 34. Consideration should be given to the ◦ Technical expertise ◦ Site technology ◦ Site capabilities for the RU. Any process robustness issues should be identified Put in place plans at the RU to resolve these. 34 Prepared by Drug Regulations a Not for Profit Organization
- 35. The SU and the RU should jointly develop a protocol for ◦ The transfer of relevant information related to the process under consideration from the SU to the RU, as well as ◦ The development of a comparable process at the RU. 35 Prepared by Drug Regulations a Not for Profit Organization
- 36. The specifications and relevant functional characteristics of the starting materials: ◦ APIs and excipients to be used at the RU should be consistent with materials used at the SU. Any properties, which are likely to influence the process or product, should be identified and characterized. 36 Prepared by Drug Regulations a Not for Profit Organization
- 37. The SU should provide the RU with the open part of the API master file ◦ (APIMF or drug master file (DMF) or ◦ active substance master file (ASMF)), or ◦ Equivalent information Any relevant additional information on the API of importance for the manufacture of the pharmaceutical product. The following are examples of the information which may typically be provided; However the information needed in each specific case should be assessed using the principles of QRM: 37 Prepared by Drug Regulations a Not for Profit Organization
- 38. Manufacturer and associated supply chain; Step of the API to be transferred; Flow chart of synthesis pathway, outlining the process, including entry points for raw materials, critical steps, process controls and intermediates; Where relevant, definitive physical form of the API (including photomicrographs and other relevant data) and any polymorphic and solvate forms; Solubility profile; If relevant, pH in solution; 38 Prepared by Drug Regulations a Not for Profit Organization
- 39. Partition coefficient, including the method of determination; Intrinsic dissolution rate, including the method of determination; Particle size and distribution, including the method of determination; Bulk physical properties, including data on bulk and tap density, surface Area and porosity as appropriate; Water content and determination of hygroscopicity, including water Activity data and special handling requirements; Microbiological considerations in accordance with national, regional or international pharmacopoeial requirements; 39 Prepared by Drug Regulations a Not for Profit Organization
- 40. Specifications and justification for release and end-of-life limits; Summary of stability studies conducted in conformity with current guidelines, including conclusions and recommendations on retest date; List of potential and observed synthetic impurities, with data to support proposed specifications and typically observed levels; Information on degradants, with a list of potential and observed degradation products and data to support proposed specifications and typically observed levels; 40 Prepared by Drug Regulations a Not for Profit Organization
- 41. Potency factor, indicating observed purity and justification for any recommended adjustment to the input quantity of API for product manufacturing, providing example calculations; and Special considerations with implications for storage and or handling, including but not limited to safety and environmental factors (e.g. as specified in material safety data sheets) and sensitivity to heat, light or moisture. 41 Prepared by Drug Regulations a Not for Profit Organization
- 42. The excipients to be used have a potential impact on the final product. Their specifications and relevant functional characteristics should, therefore, be made available by the SU for transfer to the RU site. The following are examples of the information, which may typically be provided; However, the information needed in each specific case should be assessed using the principles of QRM: Manufacturer and associated supply chain; 42 Prepared by Drug Regulations a Not for Profit Organization
- 43. Description of functionality, with justification for inclusion of any antioxidant, preservative or any excipient; Definitive form (particularly for solid and inhaled dosage forms); Solubility profile (particularly for inhaled and transdermal dosage forms); Partition coefficient, including the method of determination (for transdermal dosage forms); Intrinsic dissolution rate, including the method of determination (for transdermal dosage forms); Particle size and distribution, including the method of determination (for solid, inhaled and transdermal dosage forms); 43 Prepared by Drug Regulations a Not for Profit Organization
- 44. Bulk physical properties, including data on bulk and tap density, surface area and porosity as appropriate (for solid and inhaled dosage forms); Compaction properties (for solid dosage forms); Melting point range (for semi-solid or topical dosage forms); pH range (for parenteral, semi-solid or topical, liquid and transdermal dosage forms); Ionic strength (for parenteral dosage forms); Specific density or gravity (for parenteral, semi-solid or topical, liquid and transdermal dosage forms); 44 Prepared by Drug Regulations a Not for Profit Organization
- 45. Viscosity and or viscoelasticity ◦ (for parenteral, semi-solid or topical, liquid and transdermal dosage forms); Osmolality (for parenteral dosage forms); Water content and determination of hygroscopicity, including water activity data and special handling requirements ◦ (for solid and inhaled dosage forms); Moisture content range ◦ (for parenteral, semisolid or topical, liquid and transdermal dosage forms); Microbiological considerations (including sterility, bacterial endotoxins Bio burden levels where the excipient supports microbiological growth ◦ in accordance with national, regional or international pharmacopoeial requirements, as applicable (for general and specific monographs); 45 Prepared by Drug Regulations a Not for Profit Organization
- 46. Specifications and justification for release and end-of-life limits; Information on adhesives supporting compliance with peel, sheer and adhesion design criteria (for transdermal dosage forms); Special considerations with implications for storage and or handling, including but not limited to safety and environmental factors ◦ (e.g. as specified in material safety data sheets (MSDS)) and sensitivity to heat, light or moisture; and Regulatory considerations, ◦ e.g. documentation to support compliance with transmissible animal spongiform encephalopathy certification requirements (where applicable). 46 Prepared by Drug Regulations a Not for Profit Organization
- 47. The SU should provide a detailed characterization of the product, including its qualitative and quantitative composition, Physical description, Method of manufacture, In-process controls, Control method and specifications, Packaging components and configurations, and any safety and handling considerations. 47 Prepared by Drug Regulations a Not for Profit Organization
- 48. The SU should provide any information on the history of process development, Such information may include the following: Information on clinical development, ◦ e.g. information on the rationale for the synthesis, route and form selection, technology selection, equipment, clinical tests, and product composition; Information on scale-up activities: ◦ Process optimization, ◦ Statistical optimization of critical process parameters, ◦ Critical quality attributes, ◦ Pilot report and or information on pilot-scale development activities indicating the number and disposition of batches manufactured; 48 Prepared by Drug Regulations a Not for Profit Organization
- 49. Information or report on full-scale development activities, indicating ◦ the number and disposition of batches manufactured, and ◦ deviation and change control (sometimes referred to as change management) reports which led to the current manufacturing process; The change history and reasons, ◦ e.g. a change control log, indicating any changes to the process or primary packaging or analytical methods as a part of process optimization or improvement; and Information on investigations of problems and the outcomes of the investigations. 49 Prepared by Drug Regulations a Not for Profit Organization
- 50. The SU should provide to the RU information on any health, safety and environmental issues associated with the manufacturing processes to be transferred, and the implications, e.g. need for gowning or protective clothing. 50 Prepared by Drug Regulations a Not for Profit Organization
- 51. The SU should provide to the RU information on current processing and testing, including but not limited to: A detailed description of facility requirements and equipment; Information on starting materials, applicable MSDS and storage requirements for raw materials and finished products; Description of manufacturing steps ◦ (narrative and process maps or flow charts, and or master batch records) 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; 51 Prepared by Drug Regulations a Not for Profit Organization
- 52. Identification and justification of control strategy ◦ identification of critical performance aspects for specific dosage forms, ◦ identification of process control points, ◦ Product quality attributes and ◦ Qualification of critical processing parameter ranges, statistical process control (SPC) charts Design space, in cases where this has been defined; Validation information, e.g. validation plans and reports; Annual product quality reviews; Stability information; 52 Prepared by Drug Regulations a Not for Profit Organization
- 53. An authorized set of protocols and work instructions for manufacturing; and Environmental conditions or any special requirement needed for the facility or equipment depending on the nature of the product to be transferred. During the transfer process, the RU should identify any differences in facilities, systems and capabilities Communicate the same with the SU about these differences Understand the potential impact on ability to run the process to deliver good product quality. 53 Prepared by Drug Regulations a Not for Profit Organization
- 54. Differences should be understood and satisfactorily addressed to assure equivalent product quality. Based on the information received from the SU, the RU should consider its own capability to manufacture and pack the product to the required standards SU should develop relevant plant operating procedures and documentation before the start of production. Process development at the RU should address the following tasks: 54 Prepared by Drug Regulations a Not for Profit Organization
- 55. Comparison and assessment of suitability and qualification of facility and equipment; Description of manufacturing process and flow of personnel and of materials at the RU (narrative and or process maps or flow charts); Determination of critical steps in manufacture, including hold times, endpoints, sampling points and sampling techniques. Writing and approval of SOPs for all production operations ◦ Dispensing, ◦ Granulation or blending or solution preparation, ◦ Tablet compression, ◦ Tablet coating, encapsulation, liquid filling, primary and secondary packaging and in-process quality control), packaging, cleaning, testing and storage; 55 Prepared by Drug Regulations a Not for Profit Organization
- 56. Evaluation of stability information, with generation of site-specific stability data if required and Compliance with regulatory requirements for any changes made, e.g. in terms of batch size. 56 Prepared by Drug Regulations a Not for Profit Organization
- 57. The transfer of packaging operations should follow the same procedural patterns as those of the production transfer. Information on packaging to be transferred from the SU to the RU includes ◦ Specifications for a suitable container or closure system, ◦ Any relevant additional information on design, packing, processing or labeling requirements ◦ Tamper-evident and anti-counterfeiting measures needed for qualification of packaging components at the RU. For QC testing of packaging components, specifications should be provided for drawings, artwork and material (for example, glass, card or fibre board). 57 Prepared by Drug Regulations a Not for Profit Organization
- 58. Based on the information provided, the RU should perform a suitability study for initial qualification of the packaging components. Packaging is considered suitable if it provides ◦ Adequate protection (preventing degradation of the medicine due to environmental influences), ◦ Safety (absence of undesirable substances released into the product), compatibility (absence of interaction possibly affecting medicine quality) and ◦ Performance (functionality in terms of drug delivery) 58 Prepared by Drug Regulations a Not for Profit Organization
- 59. During the manufacturing process, pharmaceutical products and APIs can be contaminated by other pharmaceutical products or APIs if the plant is processing different products. To minimize the risk of contamination and cross-contamination, operator exposure and environmental effects, adequate cleaning procedures are essential. Cleaning procedures and their validation are site-specific. 59 Prepared by Drug Regulations a Not for Profit Organization
- 60. In order for the RU to define its cleaning strategy the SU should provide information on cleaning at the SU to minimize cross-contamination due to ◦ Residues from previous manufacturing steps, ◦ Operator exposure and ◦ Environmental impact, including: Information on solubility of active ingredients, excipients and vehicles; Minimum therapeutic doses of active ingredients; Therapeutic category and toxicological assessment; and Existing cleaning procedures. 60 Prepared by Drug Regulations a Not for Profit Organization
- 61. Additional information should be provided, as appropriate and where available, e.g.: Cleaning validation reports (chemical and microbiological); Information on cleaning agents used ◦ (efficacy, evidence that they do not interfere with analytical testing for residues of APIs, removal of residual cleaning agents); and Recovery studies to validate the sampling methodology. 61 Prepared by Drug Regulations a Not for Profit Organization
- 62. Before the transfer, the SU should provide information on limits for product residues, and the rationale for limit selection. Based on the information provided by the SU, cleaning procedures should be designed at the RU, taking into account ◦ Relevant characteristics of the starting materials (e.g. potency, toxicity, solubility, corrosiveness and temperature sensitivity), ◦ Manufacturing equipment design and configuration, ◦ Cleaning agent and products residue. Implementation of processing, packaging and cleaning systems 62 Prepared by Drug Regulations a Not for Profit Organization
- 63. Trial batch(es) (“demonstration batches”) are normally produced to confirm process capability before initiating formal validation. Where trial batches are produced, at a minimum, all critical processing parameters and finished product specifications should be assessed. Once process capability has been established at the RU, assuring that the product, process or method at the RU meets predefined and justified specifications, process validation and cleaning validation can be carried out. 63 Prepared by Drug Regulations a Not for Profit Organization
- 64. Transfer of analytical methods should accommodate all the analytical testing This should demonstrate compliance of the product to be transferred with the registered specification Analytical methods used to test pharmaceutical products, starting materials, packaging components and cleaning (residue) samples, if applicable, should be implemented at the testing laboratory before testing of samples for process validation studies is performed by the RU. Process validation samples may be tested at the RU, the SU or a third laboratory. 64 Prepared by Drug Regulations a Not for Profit Organization
- 65. A protocol defining the steps should be prepared for transfer of analytical methods. The analytical methods transfer protocol should include a description of the objective, scope and responsibilities of the SU and the RU; A specification of materials and methods; the experimental design and acceptance criteria; Documentation ◦ (including information to be supplied with the results, and report forms to be used, if any); Procedure for the handling of deviations; references; signed approval; And details of reference samples ◦ (starting materials, intermediates and finished products). 65 Prepared by Drug Regulations a Not for Profit Organization
- 66. The SU’s responsibilities for the transfer of analytical methods are to: Provide method-specific training for analysts and other quality control staff, if required; Assist in analysis of QC testing results; Define all methods to be transferred for testing a given product, starting material or cleaning sample; 66 Prepared by Drug Regulations a Not for Profit Organization
- 67. Define experimental design, sampling methods and acceptance criteria; Provide any validation reports for methods under transfer and demonstrate their robustness; Provide details of the equipment used, as necessary (part of validation report, if available) and any standard reference samples; Provide approved procedures used in testing; and Review and approve transfer reports. 67 Prepared by Drug Regulations a Not for Profit Organization
- 68. The RU’s responsibilities are to: Review analytical methods provided by the SU, and formally agree on acceptance criteria before execution of the transfer protocol; 68 Prepared by Drug Regulations a Not for Profit Organization
- 69. Ensure that the necessary equipment for QC is available and qualified at the RU site. The equipment used by the RU during the analytical transfer should meet appropriate specifications to ensure the requirements of the method or specification are met; Ensure that adequately trained and experienced personnel are in place for analytical testing; 69 Prepared by Drug Regulations a Not for Profit Organization
- 70. Provide a documentation system capable of recording receipt and testing of samples to the required specification using approved test methods, and of reporting, recording and collating data and designation of status (approved, rejected, quarantine); Execute the transfer protocol; Perform the appropriate level of validation to support the implementation of the methods; and Generate and obtain approval of transfer reports. 70 Prepared by Drug Regulations a Not for Profit Organization
- 71. Appropriate training should be provided and all training activities and outcomes should be documented. Reference to compendial monographs (e.g. The International Pharmacopoeia , European Pharmacopoeia, British Pharmacopoeia and United States Pharmacopeia), where available, is expected. 71 Prepared by Drug Regulations a Not for Profit Organization
- 72. Possible experimental designs and acceptance criteria for the main analytical testing methods are shown in Table 1. Note that this table represents high-level guidance to apply the general principle that method transfers should account for the variability and sensitivity of the method and the specifications for the quality parameter. Alternative procedures and acceptance criteria may be applied based on science and the characteristics of the analytical method and the analyte. 72 Prepared by Drug Regulations a Not for Profit Organization
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- 78. The SU should provide information to the RU on the layout, construction and finish of buildings and services, which have an impact on the product, process or method to be transferred. ◦ HVAC ◦ Temperature ◦ Relative humidity ◦ Water ◦ Power ◦ Compressed air 78 Prepared by Drug Regulations a Not for Profit Organization
- 79. The SU should provide information on relevant health, safety and environmental issues, including: Inherent risks of the manufacturing processes ◦ (e.g. reactive chemical hazards, exposure limits, fi re and explosion risks); Health and safety requirements to minimize operator exposure ◦ (e.g. atmospheric containment of pharmaceutical dust); Emergency planning considerations ◦ (e.g. in case of gas or dust release, spillage, fire and fire water run-off); Identification of waste streams and provisions for re-use, recycling and/ or disposal. 79 Prepared by Drug Regulations a Not for Profit Organization
- 80. The SU should provide a list of equipment, makes and models involved in the manufacture, filling, packing and or control of the product, process or method to be transferred, Should also provide existing qualification and validation documentation. Relevant documentation may include: ◦ Drawings; ◦ Manuals; ◦ Maintenance logs; ◦ Calibration logs; ◦ Procedures (e.g. regarding equipment set-up, operation, cleaning, maintenance, calibration and storage). 80 Prepared by Drug Regulations a Not for Profit Organization
- 81. The RU should review the information provided by the SU together with its own inventory list including the qualification status (IQ, OQ, PQ) of all equipment and systems Perform a side-by-side comparison of equipment at the two sites in terms of their functionality, makes, models and qualification status. 81 Prepared by Drug Regulations a Not for Profit Organization
- 82. The RU should perform a gap analysis to identify requirements for adaptation of existing equipment, or acquisition of new equipment, or a change in the process, to enable the RU to reproduce the process being transferred. GMP requirements should be satisfied and intended production volumes and batch sizes (e.g. same, scaled-up or campaign) should be considered. Factors to be compared include: ◦ Minimum and maximum capacity; ◦ Material of construction; ◦ Critical operating parameters; ◦ Critical equipment components ◦ (e.g. fi lters, screens, and temperature/ pressure sensors); ◦ Critical quality attribute; and ◦ Range of intended use. 82 Prepared by Drug Regulations a Not for Profit Organization
- 83. The facility- and building-specific location of all equipment at the RU should be considered at the time of drawing up process maps or flow charts of the manufacturing process to be transferred, including flows of personnel and material. 83 Prepared by Drug Regulations a Not for Profit Organization
- 84. 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. 84 Prepared by Drug Regulations a Not for Profit Organization
- 85. The documentation required for the transfer project itself is wide ranging. ◦ Examples of documentation commonly required are summarized in Table 2. The documented evidence that the transfer of technology has been considered successful should be formalized and stated in a technology transfer summary report. 85 Prepared by Drug Regulations a Not for Profit Organization
- 86. That report should summarize the scope of the transfer, the critical parameters as obtained in the SU and RU (preferably in a tabulated format) and the final conclusions of the transfer. Possible discrepancies should be listed and appropriate actions, where needed, taken to resolve them. 86 Prepared by Drug Regulations a Not for Profit Organization
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- 89. The extent of qualification and or validation to be performed should be determined on the basis of risk management principles. Qualification and validation should be documented. 89 Prepared by Drug Regulations a Not for Profit Organization
- 90. This presentation is compiled by “ Drug Regulations” a Not for Profit organization from publicly available material on the world wide web. Visit www.drugregulations.org www.drugregulations.org 90