WHO Technical Report Series, No. 981 - World Health Organization

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WHO Expert Committee on Specifications for Pharmaceutical Preparations Forty-seventh report Table continued Conditions to be fulfilled 1. Specifications for the FPP are updated only with respect to dimensions of the FPP. 2. Multipoint in vitro dissolution profiles of the current and proposed versions of the product (determined in the routine release medium, on at least one batch of pilotor production-scale), are comparable. Documentation required 1. For gastro-resistant, modified or prolonged release FPPs, justification for not submitting a new bioequivalence study according to the current WHO guidelines on bioequivalence. For scored tablets where the scoring is intended to divide the FPP into equal doses, demonstration of the uniformity of the tablet portions. 2. Sample of the FPP. 3. (P.2) Discussion on the differences in manufacturing process(es) between the currently accepted and proposed products and the potential impact on product performance. 4. (P.2) Comparative multipoint in vitro dissolution profiles in the routine release medium, on at least one batch of pilot- or production-scale of the current and proposed products. 5. (P.5) Copies of revised FPP release and shelf-life specifications. 6. (R.1) Copies of relevant sections of blank master production documents with changes highlighted as well as relevant pages of executed production documentation for one batch and confirmation that there are no changes to the production documents other than those highlighted. 3.2. P.3 Manufacture Description of change Conditions to be fulfilled Documentation required Reporting type WHO Technical Report Series No. 981, 2013 134 28 Addition or replacement of a manufacturing site for part or all of the manufacturing process for an FPP involving: 28a 28b secondary packaging of all types of FPPs primary packaging site of: 28b.1 solid FPPs (e.g. tablets, capsules), semi-solid FPPs (e.g. ointments, creams) and solution liquid FPPs 28b.2 other liquid FPPs (suspensions, emulsions) 2–3 1 IN 2–4 1, 8 IN 2–5 1, 5, 8 IN continues
Annex 3 Table continued Description of change Conditions to be fulfilled Documentation required Reporting type 28c all other manufacturing operations except batch control and/or release testing 1–3, 5 1–9 Vmin Conditions to be fulfilled 1. No change in the batch formula, description of manufacturing process and process controls, equipment class and process controls, controls of critical steps and intermediates, or FPP specifications. 2. Satisfactory inspection in the last three years either by WHO or an SRA. 3. Site appropriately authorized by an NMRA (to manufacture the pharmaceutical form and the product concerned). 4. The change does not concern a sterile FPP. 5. Validation protocol is available or validation of the manufacturing process at the new site has been successfully carried out on at least three production-scale batches in accordance with the current protocol. Documentation required 1. Evidence that the proposed site has been appropriately authorized in the last three years, for the pharmaceutical form and the product concerned: • a copy of the current manufacturing authorization, a GMP certificate or equivalent document issued by the NMRA; • a GMP statement or equivalent issued by WHO or an SRA; • date of the last satisfactory inspection concerning the packaging facilities by WHO or an SRA in the last three years. 2. Date and scope (with indication as to whether scope was e.g. product-specific or related to a specific pharmaceutical form) of the last satisfactory inspection. 3. (P.2) Where applicable, for semisolid and liquid formulations in which the API is present in non-dissolved form, appropriate validation data including microscopic imaging of particle size distribution and morphology. 4. (P.2) For solid dosage forms, data on comparative dissolution tests in the routine release medium, with demonstration of similarity of dissolution profiles with those of the biobatch, performed on one production-scale batch each from current and proposed manufacturing sites and comparison with the biobatch results, with commitment to generate dissolution profiles on two more production-scale batches. 5. (P.3.5) Process validation reports or validation protocol (scheme) for three batches of the proposed batch size, which includes comparative dissolution against the biobatch results with f2 calculation as necessary. 6. (P.5.1) Copies of release and shelf-life specifications. 7. (P.5.4) Batch analysis data on one production-scale batch from the proposed site and comparative data on the last three batches from the previous site. continues 135
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The Expert Committee on Specificati
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W H O T e c h n i c a l R e p o r t
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Contents WHO Expert Committee on Sp
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12.4 Proposal for a procedure on sa
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WHO Expert Committee on Specificati
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2. General policy 2.1 Cross-cutting
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4. Quality control - International
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7. Quality assurance - new approach
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9. Prequalification of priority ess
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11. Prequalification of quality con
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14. Miscellaneous 14.1 Quality assu
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WHO Technical Report Series, No. 98
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Annex 1 Release procedure for Inter
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Annex 2 WHO guidelines on quality r
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Annex 2 While the choice of the too
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Annex 2 ■■ The level of effort,
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Annex 2 within companies and, where
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Annex 2 risk analysis The estimatio
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Annex 2 3.3 Knowledge of the produc
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Annex 2 During risk control activit
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Annex 2 diagrams and appropriate re
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Annex 2 Similarly, contract staff m
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Annex 2 4.5 QRM application during
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Annex 2 Among others, QRM methodolo
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Page 105 and 106: Annex 2 Table 3 continued Risk mana
Page 107 and 108: Annex 3 WHO guidelines on variation
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Page 113 and 114: Annex 3 WHO/PQP should be notified
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Page 117 and 118: Annex 3 active pharmaceutical ingre
Page 119 and 120: Annex 3 Table continued Description
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Page 165 and 166: Annex 3 3.2. P.8 Stability Descript
Page 167 and 168: Annex 3 Appendix 1 Examples of chan
Page 169 and 170: Annex 4 Collaborative procedure bet
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Annex 4 Date of prequalification (d
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Annex 4 Appendix 4 Report on post-r
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WHO Technical Report Series, No. 981 - World Health Organization

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