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ANALYTICAL METHOD VALIDATION -A PREDICAMENT OF SERVICE PROVIDER
 

ANALYTICAL METHOD VALIDATION -A PREDICAMENT OF SERVICE PROVIDER

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Presentation describes problems encountered by a service provider while defining requirements for analytical method validation as part of contract manufacturing effort in drug development

Presentation describes problems encountered by a service provider while defining requirements for analytical method validation as part of contract manufacturing effort in drug development

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    ANALYTICAL METHOD VALIDATION -A PREDICAMENT OF SERVICE PROVIDER ANALYTICAL METHOD VALIDATION -A PREDICAMENT OF SERVICE PROVIDER Presentation Transcript

    • ANALYTICAL METHOD VALIDATION - A PREDICAMENT OF SERVICE PROVIDER Sasha Nezlin VP Analytical Laboratories Nextar Ltd.
    • ??? WHY VALIDATE ??? What are the benefits of validating analytical methods? It allows for accurate assessment of sample information UNDERSTAND LIMITS AND LIMITATIONS OF THE METHOD:  Essential part of successful drug development and characterization  Proof that the method provides accurate data within the scope of its intended use  Ensure safety of product 2 ANALYTICAL METHOD VALIDATION – A PREDICAMENT OF SERVICE PROVIDER
    • ??? WHY OUTSOURCE ??? What are the benefits of outsourcing laboratory services? It saves total cost, investment and manpower Outsourcing allows companies:  to free resources from non-core competencies  adopt best practices to ensure quality of their products  to leverage internal resources more effectively  to turn toward core strengths, therefore further enhancing competitive position. 3 ANALYTICAL METHOD VALIDATION – A PREDICAMENT OF SERVICE PROVIDER
    • A key question regarding validation at various stages of drug development: How much validation is (really) needed and how much is sufficient  Needed – business point of view  Sufficient – regulatory point of view 4 ANALYTICAL METHOD VALIDATION – A PREDICAMENT OF SERVICE PROVIDER
    • Types of tests and parameters to be validated for full development From M.Bloch in “Method Validation in Pharmaceutical Analysis” Wiley [2005] 5 ANALYTICAL METHOD VALIDATION – A PREDICAMENT OF SERVICE PROVIDER
    • How can we reduce the effort? Depending on the test considered, some information on linearity, accuracy, specificity, precision / repeatability, reporting level / limit of quantification and limit of detection, is crucial for any analytics, also during development. But! this encompasses much of what is needed for a full validation according to ICH ! Thus the question remains: What simplifications may be permissible? Where / how can the validation load be reduced? 6 ANALYTICAL METHOD VALIDATION – A PREDICAMENT OF SERVICE PROVIDER
    • How can we reduce the effort? (cont.-1)  Adjust validation scope according to stage of development - e.g. perform qualification (for example: wider acceptance criteria, reduce number of replications, reduce extent of testing, short report, etc.)  Execute method feasibility during development – determine performance characteristics of the method – thus ensuring that the method will be able to meet validation acceptance criteria later on  Employ risk-based approach to prove method suitability to intended use 7 ANALYTICAL METHOD VALIDATION – A PREDICAMENT OF SERVICE PROVIDER
    • How can we reduce the effort? (cont.-2) Parameter Discovery Phase I Phase II Phase III / Registration 1. Linearity V V V V 2. Range V V V V 3. Accuracy --- V V V 4. Specificity / Stress Study --- V V V 5. Precision - Repeatability V V V V - Intermediate Precision (API) --- V V V - Intermediate Precision (RS) --- --- V V 6. Robustness --- --- V V 7. Solutions stability --- V V V 8. Limit of Detection --- --- V V 9. Limit of Quantitation --- V V V Abbreviations: V : Validated --- : Not Validated RS : Related Substances API : Active Pharmaceutical Ingredient 8 ANALYTICAL METHOD VALIDATION – A PREDICAMENT OF SERVICE PROVIDER
    • Regarding Validation of Analytical Methods the Sponsors could be roughly separated in 3 groups: 1) Know exactly what their regulatory/validation requirements are 2) Require CRO input regarding business/regulatory requirements 3) Are not aware of any business/regulatory requirements except for low costs and GMP certificate in the end 9 ANALYTICAL METHOD VALIDATION – A PREDICAMENT OF SERVICE PROVIDER
    • Real life questions - from projects performed at Nextar  Short term stability study (1-3 months) is performed as part of formulation development – why does the Assay method has to be developed/qualified as Stability Indicating Method (SIM)?  Material for Clinical trial Stage I is manufactured and released under cGMP requirements – why the analytical methods have to be verified? Why do they have to be SIM in order to perform stability study to establish shelf-life for the duration of clinical study?  Methods are transferred from Sponsor to support GMP manufacturing of Clinical Trial Material at Nextar, why analytical method transfer has to be performed? 10 ANALYTICAL METHOD VALIDATION – A PREDICAMENT OF SERVICE PROVIDER
    • PREDICAMENT  QUANDARY Definition from the Merriam-Webster Dictionary a difficult, perplexing, or trying situation 11 ANALYTICAL METHOD VALIDATION – A PREDICAMENT OF SERVICE PROVIDER
    • Responsibility of Service Provider As analytical chemists we should be aware of multiple sources of error that could influence the measurement and therefore the trustworthiness of results. Analytical result reported without at least evaluation of its reliability (sensitivity, accuracy and precision) cannot be very meaningful or of help in making informed decisions. ICH and FDA state that while methods employed for various stages of development may not be yet fully validated – they should be “scientifically sound”. 12 ANALYTICAL METHOD VALIDATION – A PREDICAMENT OF SERVICE PROVIDER
    • Outsourcing Validation  One Size Never Fits All  Define Quality Expectations  Spend time on the Quality Agreement  Choose a service provider whose quality philosophy is aligned with yours  Stay involved (regular discussions)  Technical review using your own analytical and regulatory expertise  Ultimate responsibility for product quality remains with the Sponsor 13 ANALYTICAL METHOD VALIDATION – A PREDICAMENT OF SERVICE PROVIDER
    • QA Policy of Nextar Ltd. SOP 00S011 “QUALITY ASSURANCE POLICY” APPENDIX I FOR SUMMARY OF QA REQUIREMENTS Based on cGMP for Phase 1 Investigational Drugs (Guidance for Industry), FDA, 2008 Manufacture of IMP (Vol. 4, Annex 13, July 2003) Guideline on the preparation new IMP (Guidance for Industry), FDA, 1992 PIC/S GMP GUIDE (PE 009-08, Jan 2009) 14 ANALYTICAL METHOD VALIDATION – A PREDICAMENT OF SERVICE PROVIDER
    • QA Policy of Nextar Ltd. (cont. – 1) Step Formulation Clinical Clinical Production Tasks Pre-clinical Clinical phase I / R&D Phase II Phase III for marketing 8. Testing Testing Laboratory testing Appropriate SOP Appropriate SOP, validation protocol & methods for methods for should be carried (including verification report (relevant to the intended use) RM. PM , IPC and out to evaluate procedure) Laboratory testing to evaluate quality IPC and Finished quality attributes: Laboratory testing attributes: identification, strength, Finished goods identification, should be carried out potency, purity as appropriate. The goods release strength, purity as to evaluate quality manufacturer should establish release should be appropriate. attributes: acceptance criteria for testing and Laboratory controls should be scientifically The manufacturer identification, release on a base of relevant scientifically sound, should establish strength, potency information and on a base of scientific sound, suitable and acceptance purity as appropriate. knowledge and experience suitable and reliable for criteria for testing The manufacturer reliable for the specific and release on a should establish the specific purpose. basis of relevant acceptance criteria purpose. information and for testing and on a basis of release on a basis of scientific relevant information knowledge and and on a basis of experience scientific knowledge provided by and experience Sponsor 15 ANALYTICAL METHOD VALIDATION – A PREDICAMENT OF SERVICE PROVIDER
    • QA Policy of Nextar Ltd. (cont. – 2) Step Formulation / Clinical Clinical Production Tasks Pre-clinical Clinical phase I R&D Phase II Phase III for marketing 9. Testing Optionally Optionally: Appropriate SOPs Appropriate SOPs, including for SIM methods for including Stability (stability indicating method), stability Stability testing Stability testing Stability protocol and validation protocol validation protocol & report (as using using studies report (as suitable for suitable for the intended use) representative representative should be the intended use) samples to samples to The manufacturer should perform scientifically monitor the monitor the Stability testing using Stability testing using representative sound, stability and stability and representative samples samples to monitor the stability and suitable and quality of quality at least to monitor the stability quality of product in appropriate stability reliable for formulation for duration of and quality of phase 1 chambers and storage conditions. the specific Stability developed animal study. IMD at least for duration Establish acceptance criteria for purpose. product of human study in Stability testing on a basis of relevant appropriate stability information and scientific knowledge chambers and storage and experience. conditions. Establish acceptance criteria for Stability testing on a basis of relevant information and scientific knowledge and experience. 16 ANALYTICAL METHOD VALIDATION – A PREDICAMENT OF SERVICE PROVIDER
    • SERVICE PROVIDER PROFILE Nextar chempharma solutions Ltd. represents Israel's first fully integrated one-stop-shop contract development and manufacturing services company.  Located at the Weizmann Science Park in Ness Ziona  35 experienced highly skilled professionals  Over 1200 m2 state-of-the-art facilities & equipment  cGMP and GLP accreditation from regulatory agencies:  GLP recognition by ISRAC (07/2008); re-inspection December 2009  GMP Inspection by District Pharmacy, Ministry of Health (12/2008)  GMP Certificate from Ministry of Health Institute for Standardization and Control of Pharmaceuticals: granted for contract manufacturing of IMP and contract Quality Control analytical testing (11/2009) 17 ANALYTICAL METHOD VALIDATION – A PREDICAMENT OF SERVICE PROVIDER
    • NEXTAR Service Spectrum for Development of Your BioPharmaceuticals Method Development Bioanalytical Raw material and Validation Services testing & release GMP PK/ADME Production profiling Contract Formulation manufacturing development & packaging Custom chemical QA/QC synthesis services 18 ANALYTICAL METHOD VALIDATION – A PREDICAMENT OF SERVICE PROVIDER
    • As we have demonstrated above – requirements of ICH / FDA / GMP, business drivers and yes … common sense – all of those go hand in hand and stipulate that analytical methods should be “scientifically sound” 19 ANALYTICAL METHOD VALIDATION – A PREDICAMENT OF SERVICE PROVIDER
    • Thank you! Questions? 20 ANALYTICAL METHOD VALIDATION – A PREDICAMENT OF SERVICE PROVIDER