Transfer. Technology. Part 2. Annex 7. TRS 961, Module 14 Slide 1 of

Transcription

1 Basic Principles of GMP Transfer Of Technology Part 2 Annex 7. TRS 961, 2011 Module 14 Slide 1 of

2 Production: Processing, packaging and cleaning Module 14 Slide 2 of

3 Production - Processing, packaging and cleaning Principles: RU able to accommodate the intended production capacity Single-batch manufacture, continuous production or campaigns. Identify technical expertise, site technology and site capabilities of RU Module 14 Slide 3 of

4 Processing Starting materials Same specifications / relevant functional characteristics SU and RU Ensure properties the same where these may influence the process or product 5.5 Module 14 Slide 4 of

5 Active pharmaceutical ingredients (API) open (applicant s) part of APIMF/DMF or equivalent information 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 Information on physical form e.g. photomicrographs, polymorphic and solvate forms solubility profile; ph in solution /2 5.6 Module 14 Slide 5 of

6 intrinsic dissolution rate particle size and distribution bulk physical properties (e.g. bulk and tap density) water content microbiological considerations (including sterility, bacterial endotoxins and bioburden) specifications and justification for release and end-of-life limits summary of stability studies and retest date /3 5.6 Module 14 Slide 6 of

7 observed synthetic impurities information on degradants potency factor storage and or handling (e.g. sensitivity to heat, light or moisture) 5.6 Module 14 Slide 7 of

8 Excipients manufacturer and associated supply chain description of functionality 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) dissolution rate 5.7 Module 14 Slide 8 of

9 particle size and distribution bulk physical properties; 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) microbiological considerations specifications and justification for release and end-of-life limits; storage and or handling 5.7 Module 14 Slide 9 of

10 ionic strength (for parenteral dosage forms) specific density or gravity (for parenteral, semi-solid or topical, liquid and transdermal dosage forms) viscosity and or viscoelasticity (for parenteral, semi-solid or topical, liquid and transdermal dosage forms) osmolarity (for parenteral dosage forms) water content (for solid and inhaled dosage forms) moisture content range (for parenteral, semisolid or topical, liquid and transdermal dosage forms) 5.7 Module 14 Slide 10 of

11 Provide detailed characterization of the product Qualitative and quantitative composition Physical description Method of manufacture In-process controls Control method and specifications 5.8 Module 14 Slide 11 of

12 Provide detailed characterization of the product Packaging components and configurations Safety and handling considerations History of process development helps with further development and or process optimization after successful transfer 5.8 Module 14 Slide 12 of

13 Development information Clinical development route and form selection, technology selection, equipment, clinical tests, and product composition; Scale-up activities process optimization, statistical optimization of critical process parameters, critical quality attributes Pilot report and pilot-scale development activities 5.9 Module 14 Slide 13 of

14 Development information (2) Full-scale development activities number and disposition of batches manufactured deviation and change control Change history and reasons Investigations of problems and the outcomes of the investigations 5.9 Module 14 Slide 14 of

15 Current processing and testing information to be provided by the SU Health, safety and environmental issues Detailed description of facility requirements and equipment Information on starting materials, applicable MSDS Storage requirements for raw materials and finished products Description of manufacturing steps and analytical methods narrative and process maps or flow charts, and or master batch records, in-process hold times and conditions, order and method of raw material addition and bulk transfers between processing steps Module 14 Slide 15 of

16 Current processing and testing information to be provided by the SU Identification and justification of control strategy critical performance aspects process control points product quality attributes statistical process control (SPC) charts Validation plans and reports PQR; stability information; environmental conditions 5.11 Module 14 Slide 16 of

17 Location of all equipment considered process maps or flow charts Flows of personnel and material Impact of introducing a new product Modification of existing equipment documented in the transfer project plan RU compare own with that of SU - including qualification Gap analysis 5.11 Must be able to reproduce the process (volumes and batch sizes) Module 14 Slide 17 of

18 During transfer process Identify and understand any differences in facilities, systems and capabilities Actions may include: comparison and assessment of suitability and qualification of facility and equipment; description of manufacturing process and flow of personnel and of materials 5.12 Module 14 Slide 18 of

19 Actions may include (2): determination of critical steps in manufacture also hold times, endpoints, sampling points and sampling techniques writing and approval of SOPs evaluation of stability information Generate site-specific stability data compliance with regulatory requirements for any changes made, e.g. in terms of batch size 5.12 Module 14 Slide 19 of

20 Packaging Same procedure/principles as those of the production and include: specifications for a suitable container or closure system additional information on design, packing, processing or labelling requirements tamper-evident and anti-counterfeiting measures specifications for QC testing also drawings, artwork and material (e.g. glass, card) Module 14 Slide 20 of

21 Based on the information provided, the RU should perform a suitability study for initial qualification of the packaging components. Other considerations in packaging: to provide adequate protection (preventing degradation of the medicine due to environmental influences) Should be safe (absence of undesirable substances released into the product) Compatibility (absence of interaction possibly affecting medicine quality) Performance (functionality in terms of drug delivery) 5.16 Module 14 Slide 21 of

22 Cleaning Module 14 Slide 22 of

23 Cleaning - Key messages Prevention of contamination and cross contamination essential Manufacturing process, operator exposure, environmental effects Limits for product residues Rationale for limit selection Site SOPs developed and validated based on e.g.: potency, toxicity, solubility, corrosiveness, temperature sensitivity, manufacturing equipment design and configuration, cleaning agent and product residue Module 14 Slide 23 of

24 Adequate cleaning procedures are essential Cleaning procedures and their validation are site-specific Know: information on solubility of active ingredients, excipients and vehicles minimum therapeutic doses of active ingredients therapeutic category and toxicological assessment existing cleaning procedures 5.18 Module 14 Slide 24 of

25 Adequate cleaning procedures SU to provide cleaning validation reports chemical and microbiological Information on cleaning agents used Efficacy Not interfere with analytical testing for residues of APIs Information on recovery studies to validate the sampling methodology 5.18 Module 14 Slide 25 of

26 Documentation Wide range of documents needed to support transfer Documented evidence for successful transfer Technology transfer summary report: the scope of the transfer, the critical parameters as obtained in the SU and RU (tabulated) final conclusions Discrepancies and actions taken listed Module 14 Slide 26 of

27 Examples Key Task Document from SU Transfer document Equipment selection and transfer List of equipment, systems, makes and models, qualification Drawings, manuals Side by side comparison Gap analysis Qualification Module 14 Slide 27 of

28 Examples Key Task Process transfer: Production and packaging Document from SU Transfer document Reference batches Development reports Specifications Validation DMF BMRs BPRs Stability Deviations PQR History of development Experiences Provisional BMD Provisional BPD Process validation Module 14 Slide 28 of

29 Key Task Examples Document from SU Transfer document Cleaning SOPs and Validation SOPs Cleaning validation protocol and report Module 14 Slide 29 of

30 Summary SU and RU - responsibilities Regulatory requirements Transfer: Organized and managed Premises, Equipment, Materials, Documentation, Personnel Data and information protocols and reports Production and Quality control Include qualification and validation Module 14 Slide 30 of

31 Case study and/or assessment Module 14 Slide 31 of