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I II , , UNICEF , WHO : Invitations for Expressions of Interest (EOIs): - EOI HIV/AIDS - EOI Tub , - EOI Mal - EOI Reproductive 100 ., , ( . )

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ADMINISTRATIVE SCREENING TEMPLATE (To be done on receipt of the application by WHO officer) 1. Product information (entered into a logbook) 2. (C = Critical) C Is the FPP included in the current EoI? Applicant Product reference number Name of FPP [Name (INN), strength and pharmaceutical form]

(Project Technical Officer):

Administrative screening template: = =

Number of binders (Q + E) Date of covering letter Date of receipt Date unpacked Date of acknowledgement of receipt by e-mail

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2. Dossier information (C = Critical) DOSSIER (Q and E) Is the Quality part of dossier included Is Efficacy part dossier included? Is an index provided? Quality part Efficacy part Are the pages numbered satisfactorily? Quality part Efficacy part Does the submission follow the recommended format? Have SmPC and PIL been included? Is a CPP included? Is APIMF / DMF referred to? If yes, has a letter of access been provided? C C C YES NO

PQIF and BTIF Is it presented as a Word file? 1. PQIF 2. BTIF Is hard copy available? Are all sections filled out by applicant? FPP sample (s) Are samples provided for all pack types? C

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Project Technical Officer : /

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1 : - CTD CD/DVD) ( PDF

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Guideline on Submission of Documentation for Prequalification of Multi-Source (Generic) Finished Pharmaceutical Products (FPPs) Used in the Treatment of HIV/AIDS, Malaria and Tuberculosis [GuideGeneric] Guideline on Active Substance Master File Procedure [CPMP/QWP/227/02 Rev 1] Guideline on Summary of Requirements for Active Substances in the Quality Part of the Dossier [CPMP/QWP/297/97 Rev 1 corr] ICH Q3A [R] Impurities Testing Guideline: Impurities in New Drug Substances [CPMP/ICH/2737/99] ICH Q6A Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products: Chemical Substances [CPMP/ICH/367/96 corr] ICH Q2A Validation of Analytical Procedures: Definitions and Terminology [CPMP/ICH/381/95] ICH Q2B Validation of Analytical Procedures: Methodology [CPMP/ICH/281/95]

IV ( . (http://healthtech.who.int/pq/) / CRO GMP , . , , ) ( ) ( )

IV QUALITY ASSESSMENT REPORT Date Therapeutic area of finished pharmaceutical product (FPP)
HIV/AIDS MALARIA REPRODUCTIVE HEALTH CARE TUBERCULOSIS Please delete option which does not apply QUALITY NEW Name Name Name Signature Signature Signature

Part of dossier Type of submission First assessor Second assessor Bioequivalence assessor (when applicable) Reference number Date of submission Number of binders Proprietary product name International non-proprietary name (INN) of the Active Pharmaceutical
Ingredient (API), strength, pharmaceutical form

Conclusion of assessment

ACCEPTED [no outstanding issues except letter(s) of commitment(s)] ADDITIONAL DATA REQUESTED REJECTED Please delete which does not apply

Name and complete address of Applicant of dossier Name(s) and complete address(es) of manufacturer(s) of FPP(s),
including the final product release if different from the manufacturer.

Name(s) and address(es) of manufacturer(s) of API(s).

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3.2 Body of Data 3.2.1 Details of FPP 3.2.1.1 Name, strength and dosage form of FPP 3.2.1.2 International non-proprietary name of FPP 3.2.1.3 Visual description of FPP 3.2.1.4 Visual description of packaging Primary packing materials Secondary packing 3.2.2 Sample The visual inspection of the sample confirms what is written under 3.2.1.3 and 3.2.1.4 above. 3.2.3 Regulatory situation in other countries

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3.2.S Active Pharmaceutical Ingredient (API) 3.2.S.1 General information 3.2.S.1.1 Nomenclature International Nonproprietary Name (INN) http://www.who.int/medicines/publications/EssMedList15.pdf Compendial name if relevant Ph. Int. ( Ph. Eur. and USP) Chemical name(s) Ph. Int. ( Ph. Eur. and USP) Chemical Abstracts Service (CAS) registry number Ph. Int. (Ph. Eur., USP or Merck Index) 3.2.S.1.2 Structure 3.2.S.1.3 General properties

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3.2.S.2 Manufacture 3.2.S.2.1 Manufacturer(s) 3.2.S.2.2 Description of Manufacturing Process and Process Controls 3.2.S.2.3 Control of Materials 3.2.S.2.4 Controls of Critical Steps and Intermediates 3.2.S.2.5 Process Validation and/or Evaluation 3.2.S.2.6 Manufacturing Process Development 3.2.S.3 Characterization 3.2.S.3.1 Elucidation of Structure and other Characteristics (Polymorphism, BCS) 3.2.S.3.2 Impurities (stereochemistry, isomerization)

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3.2.S.4 Control of API 3.2.S.4.1 Specification 3.2.S.4.2 Analytical Procedures 3.2.S.4.3 Validation of Analytical Procedures If the submitted dossier does not contain information regarding the validation of the method used to determine the assay and impurities of the active ingredient or the drug product, the assessment of this application should be terminated. In preparing the notice to terminate the assessment, a justification which is supported by the appropriate WHO guidelines, should be communicated internally and externally to the Applicant. 3.2.S.4.4 Batch Analyses 3.2.S.4.5 Justification of Specification a) Establishing limits for impurities: i) Impurities in the Drug Substance: b) Residual solvents

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3.2.S.5 Reference Standards or Materials 3.2.S.6 Container closure system 3.2.S.7 Stability testing 3.2.S.7.1 Stability Summary and Conclusions 3.2.S.7.2 Post-approval Stability Protocol and Stability Commitment 3.2.S.7.3 Stability Data If the Compendia such the IP, USP or EP, states in the monograph for the active pharmaceutical ingredient or drug product, "Protect from light", there is no need to request photostability data or testing.

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3.2.P Finished Pharmaceutical Product(s) [FPP(s)] 3.2.P.1 Description and Composition of FPP 3.2.P.2.1.2 Excipients 3.2.P.2.2 Finished Pharmaceutical Product 3.2.P.2.2.1 Formulation Development
a) Characterization of the Innovator drug product. b) Particle size c) Score line of tablets d) Comparative in vitro dissolution study: format of report The report on a comparative dissolution study should include at least: 1. Purpose of study 2. Products / batches information Batch numbers, manufacturing/expiry date, and packaging of the two batches used in the study Batch manufacturing record (s), batch size (s), manufacturing sites and CoAs for the batch(es) of the multisource product (s) used in the comparative dissolution study. 3. Full dissolution conditions and method, as well as the number of units (tablets, capsules, etc) per study. It should be indicated how and when the samples were filtered. Any problems with pH related stability of samples should be indicated and discussed in terms of preventative handling measures, analysis and interpretation of data. 4. Analytical method (validated) or reference to part of dossier 5. Results (% API dissolved) Tabulated (individual results, mean and %CV) Graphically Similarity determination / f2 calculation if necessary 6. Conclusion/recommendation

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3.2.P.2.2.2 Overages (ICH Guideline Pharmaceutical Development Q8 (Step 2)) 3.2.P.2.2.3 Physicochemical and Biological Properties 3.2.P.2.3 Manufacturing Process Development Manufacturing processes are the same for innovator and multisource (generic) pharmaceutical products. The selection and optimization of the process described under Manufacturing process, in particular its critical aspects, should be explained. It is a good strategy to use the innovators manufacturing process. 3.2.P.2.4 Container Closure System It is a good strategy to use the innovators primary packaging materials. 3.2.P.2.5 Microbiological Attributes 3.2.P.2.6 Compatibility If the Generic Drug Product Manufacturer does not use the approach of Qualitative and Quantitative, then complete compatibility studies should be submitted. These studies should examine the interaction of the API/excipient and for the cases of Fixed Dose Combination products, the Applicant must examine the interactions of API/API in combination with each excipient. It should be noted that colour tests (visual examination) are considered to be insufficient and testing should consist of chromatographic methods.

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3.2.P.3 Manufacture 3.2.P.3.1 Manufacturers 3.2.P.3.2 Batch Formula 3.2.P.3.3 Description of Manufacturing Process and Process Controls 3.2.P.3.4 Controls of Critical Steps and Intermediates 3.2.P.3.5 Process Validation and/or Evaluation

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3.2.P.4 Control of Excipients 3.2.P.4.1 Specification a) Though the FPP in total should be in compliance for residual solvents (including excipients) however assessors should not ask the applicant to control excipients for compliance with ICH note for guidance on residual solvents Q3C. b) Opadry Colorants: - assessing this class of excipient - certificate of analysis - the FPP must have a specification for this exicipient which includes a test for identification 3.2.P.4.2 Analytical Procedures 3.2.P.4.3 Validation of Analytical Procedures 3.2.P.4.4 Justification of Specifications 3.2.P.4.5 Excipients of Human or Animal Origin Declarations with respect to the BSE/TSE risk are required - stearic acid, magnesium stearat and other stearats - Gelatin (www.edqm.eu/Databases-10.html) 3.2.P.4.6 Novel Excipients not described in Ph. Int., Ph. Int. or USP

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3.2.P. 5 Control of FPP 3.2.P.5.1 Specifications for the FPP a) If there is a reaction product between an active pharmaceutical ingredient and excipient including API/API/excipient, a specification should be established for the FPP. b) Specifications at release and at the end of shelf - Should be assessed in detail before acceptance. - The specifications proposed should be justified by the applicant. - Attention to the critical parameters: = Assay of the API in the FPP at release should be 100 5% (of the label claim) = Shelf life, the limits for the assay of API can be widened to 100 10% only in 2 cases: The applicant refers to a specific monographic in the Ph. Int. which describes the above limits The applicant does not refer to a Ph. Int. monograph however the stability data and degradation obtained justify the above limits.

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3.2.P.5.2 Analytical procedures 3.2.P.5.3 Validation of analytical procedures It was agreed for Compendial drug products that the method verification consists of the following parameters; specificity, accuracy and precision. 3.2.P.5.4 Batch analyses 3.2.P.5.5 Characterization of Impurities 3.2.P.5.6 Justification of Specifications a) Establishing limits for degradation products: Degradation Products in the Drug Product: A degradation product not described in a compendial monograph but, present in a generic drug product can be qualified by comparing the analytical profiles of the innovative drug product using the same validated, stability-indicating analytical procedure (e.g., comparative HPLC studies). It is recommended that the studies be conducted on comparable samples (e.g., age of samples) to get a meaningful comparison of the degradation product profiles. Levels of degradation products generated from studies under accelerated of the innovative drug product are not considered qualified.

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3.2.P.6 Reference Standards or Materials See Section 3.2.S.5. 3.2.P.7 Container/closure system 3.2.P.8 Stability 3.2.P.8.1 Stability Summary and Conclusion See 3.2.P.8.3 for further details. AMN 3.2.P.8.2 Post approval Stability Protocol and Stability Commitment 3.2.P.8.3 Stability Data If the Compendia such the IP, USP or EP, states in the monograph for the drug product, "Protect from light", there is no need to request photostability data or testing. 3.2.P.9 Container labeling 3.2.P.9.1 Outer packaging or, where there is no outer packaging, on the immediate packaging 3.2.P.9.2 Blisters and strips 3.2.P.9.3 Product information for health professionals 3.2.P.9.4 Patient information and package inserts Recommendations for inspection (advices)

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, FDA(USA), EMEA (EU/EEA), )

(Guideline on Submission of Documentation for Prequalification of Multisource (Generic) Finished Pharmaceutical Product (FPP) )

WHO-

V, VI

VII

V : ) (WHO GMP) ) (WHO GCP/GLP) (WHOPAR)

VI (WHOPIR)

VII

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