WHO guidelines ON Technology TRANSFER ip

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1. Technology Development and Transfer Dr Sunil Kanvinde 10 August 2023 privileged and confidential - Dr Sunil Kanvinde

2. Technology Development and Transfer privileged and confidential - Dr Sunil Kanvinde Index Slide number Dosage Forms 3 - 5 Development of Tablets 5 - 11 Transfer of Technology Concept 12 - 14 WHO Guidelines - Principles Transfer of Technology 17 - 24 Summary 25 Reference World Health Organization WHO Technical Report Series, No. 961, 2011 Annex 7 WHO guidelines on transfer of technology in pharmaceutical manufacturing

3. Dosage Forms privileged and confidential - Dr Sunil Kanvinde Dosage forms  (also called unit doses) are  pharmaceutical drug   products - in the form in which they are marketed for use, - with a specific mixture of  active ingredients  (API) and inactive components ( excipients ), - in a particular configuration, and - apportioned into a particular  dose .

4. Dosage Forms and Uses privileged and confidential - Dr Sunil Kanvinde Dosage forms  (also called unit doses) are  pharmaceutical drug   products Example – Each Tablet contains 500mg of Paracetamol. Tablet weight is 800mg but it contains 500mg Paracetamol Therefore 300 mg is excipient Applicable to all similar units from same brand name from same manufacturer in the form in which they are marketed for use Tablets, Capsules, Injections, Liquid Orals, Eye drops with a specific mixture of  active ingredients  (API) and inactive components ( excipients ), Master formula in which API is mixed with excipients like lactose, MCC, Talc, Magnesium stearate for Tablets, Capsules in a particular configuration Quantities are defined in composition apportioned into a particular  dose Each unit has same configuration or content of API and excipients

5. Dosage Forms Dosage Forms Uses Tablets Oral administration Capsules Oral administration Liquid – Syrup, Suspension Oral administration Injection – Liquid, Dry Powder Parenteral route Ointment External application privileged and confidential - Dr Sunil Kanvinde

6. Development of Tablets Development is the first step where the Tablets are finalized Appearance, Shape, Embossing, Color, Coating Type of Tablets – Immediate release, SR, Chewable, Enteric coated etc privileged and confidential - Dr Sunil Kanvinde

7. Development of Tablets Development is the first step where the Tablets are finalized Appearance, Shape, Embossing, Color, Flavor Trade Dress is commonly used term in Global context Development is driven by Content of active, active/ excipient ratio Bench marking with innovator QBD concept Marketing expectations Patient compliance privileged and confidential - Dr Sunil Kanvinde

8. Development of Tablets Development experiments are small lots size experiments In development laboratory using manual or semi automatic machines privileged and confidential - Dr Sunil Kanvinde

9. Development of Tablets Development experiments are small lots size experiments In development laboratory using manual or semi automatic machines privileged and confidential - Dr Sunil Kanvinde

10. Development of Tablets Purpose of development is to achieve progressive end point of supply safe and effective medication to patient with consistent quality Outcome of various small experiments and testing Selection of successful experiments by evaluation Experiments with various processes privileged and confidential - Dr Sunil Kanvinde Tablet mass preparation by dry mixing Tablet mass preparation by dry mixing Tablet mass preparation by dry mixing and wet granulation Properties of powder Properties of granules Properties of granules Content evaluation Content evaluation Content evaluation Tablet preparation and evaluation Tablet preparation and evaluation Tablet preparation and evaluation Rating/ Evaluation for further experiments

11. Development of Tablets Purpose of development is to achieve progressive end point of supply safe and effective medication to patient with consistent quality Outcome of various small experiments and testing Selection of successful experiments by evaluation Development knowledge is therefore important database for future life cycle It is a starting point of successful commercial product available in market. privileged and confidential - Dr Sunil Kanvinde

12. Technology Transfer of Tablets - Connecting the DOTS privileged and confidential - Dr Sunil Kanvinde Development of Product Manufacturing of Product Research and Development Large scale manufacture for commerce

13. Technology Transfer of Tablets - Connecting the DOTS privileged and confidential - Dr Sunil Kanvinde Development of Product Manufacturing of Product Research and Development Large scale manufacture for commerce How to connect small experiments carried out in Development laboratory using small equipment, manual processes and end points with large size equipment, equipment have auto controls and where large batch size is required due to commercial needs

14. Technology Transfer of Tablets - Connecting the DOTS privileged and confidential - Dr Sunil Kanvinde Development of Product Manufacturing of Product Research and Development Large scale manufacture for commerce Transfer the process from R&D Technology Transfer

15. WHO guidelines - Principles 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” “a systematic procedure that is followed in order to pass the documented knowledge and experience gained during development and or commercialization to an appropriate, responsible and authorized party” privileged and confidential - Dr Sunil Kanvinde

16. WHO guidelines - Principles Transfer of technology is from Development lab to manufacturing site OR One manufacturing site to other manufacturing site It can happen during life cycle Planned activity driven by documentation, GMP, Quality system, skilled teams Risk based approach is adopted privileged and confidential - Dr Sunil Kanvinde

17. WHO guidelines – Principles of Transfer of Technology Principle explanation The Transfer of technology project should encompass the quality aspects of the project Quality defined for Product based on process developed. Quality – Physical parameters Appearance, Thickness, Friability, DT, Dissolution In process quality parameters - Bulk Density, Moisture content, Sieve analysis Process – Mixing speed, Time, end point measurement Drying – Temperature, Time Compression parameters Chemical test parameters assay, content uniformity, impurity, RS Stability evaluation privileged and confidential - Dr Sunil Kanvinde

18. WHO guidelines – Principles of Transfer of Technology Principle explanation Transfer of technology should be based upon the principles of quality risk management Mixing – mixing time is defied as 10 -15 min. During experimentation it is observed that if mixing time is less than 10 min uniformity is not obtained, granules are not formed properly Risk – Severity, Probability and Detectability If mixing time is more than 15 min granules are hard and difficult Equipment used for drying FBD/ Tray drier Effect on granules, temperature Time effect in two drying operations Risk analysis of area used for mixing for temperature, humidity Risk analysis for light sensitive product privileged and confidential - Dr Sunil Kanvinde

19. WHO guidelines – Principles of Transfer of Technology Principle explanation facilities and equipment in SU and RU should operate according to similar operating principles FBD vs Tray drier SU – sending unit Milling equipment at two sites RU – receiving unit Compression machines used for tablet compression Development facility has smaller machines whereas manufacturing facilities have high speed machines, similarity in operating principles Analytical equipment are also important privileged and confidential - Dr Sunil Kanvinde

20. WHO guidelines – Principles of Transfer of Technology Principle explanation a comprehensive technical gap analysis between the SU and RU including technical risk assessment and potential regulatory gaps, should be performed as needed In product transfer it is observed that equipment is similar but required setting parameters are not achievable Roll compactor pressure setting, screen size Coating machine temperature setting range Process parameters need critical analysis privileged and confidential - Dr Sunil Kanvinde

21. WHO guidelines – Principles of Transfer of Technology Principle explanation adequately trained staff should be available or should be trained at the RU Knowledge transfer is important part of Transfer of technology SU documents are reviewed, evaluated for any queries, more information need, sample evaluation Critical evaluation is possible only with adequate training and experience privileged and confidential - Dr Sunil Kanvinde

22. WHO guidelines – Principles of Transfer of Technology Principle explanation RU should reproduce the documented evidence of transferred product, process or manufacturing method against the predetermined specifications of SU. VALIDATION Experimentation for the product is very critical. Continuous manufacturing is possible only is validation is executed properly. there should be effective process and product knowledge transfer. Clarity of transfer process privileged and confidential - Dr Sunil Kanvinde

23. WHO guidelines – Principles of Transfer of Technology Principle explanation Reporting of out of specifications results and errors by the RU to SU. Analysis of results is very important. OOS results indicate process control and product parameters control Example – DT results variation during compression stage Cause analysis Hardness values Analytical OOS privileged and confidential - Dr Sunil Kanvinde

24. WHO guidelines –Transfer of Technology privileged and confidential - Dr Sunil Kanvinde Scope – Applies to API – Manufacturing and packaging Applies to all dosage forms - Manufacturing and packaging Risk based approach – should be applied GMP compliance during transfer Documentation, Qualification, Validation, People training

25. Summary Transfer of Technology is important intermediate step connecting development and manufacturing site or one manufacturing site with other It is knowledge based approach supported by documentation and Risk based evaluation of processes People play important role in knowledge creation and sharing Guidelines help to formulate Transfer of Technology process by providing Principles and practices to define systems and evaluation criteria privileged and confidential - Dr Sunil Kanvinde