1 / 28

Impact of European Legislation on Indian API Manufacturers

9 th APIC/CEFIC European Conference on Active Pharmaceutical Ingredients. Impact of European Legislation on Indian API Manufacturers. Nandkumar Chodankar (Ph D) Sekhsaria Chemicals Ltd. Mumbai, India. 10 th October2006 (09.00-09.45). European New Legislation.

paul2
Download Presentation

Impact of European Legislation on Indian API Manufacturers

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. 9th APIC/CEFIC European Conference on Active Pharmaceutical Ingredients Impact of European Legislation on Indian API Manufacturers Nandkumar Chodankar (Ph D) Sekhsaria Chemicals Ltd. Mumbai, India 10th October2006 (09.00-09.45)

  2. Nandkumar Chodankar

  3. European New Legislation • The pharmaceutical manufacturer is responsible for ensuring that the APIs have been manufactured in accordance with the EU Guidelines to Good Manufacturing Practice for Active Substances, Volume 4, Part II. • After 17th December 2005, pharmaceutical manufacturer’s QP certifies by his or her signature to the register for release of medicinal products that also the API has been manufactured in accordance with GMP • This means that after that date the signature of the QP implies a greater responsibility. No separate signature is required in the register to certify that APIs have been manufactured in accordance with GMP. Nandkumar Chodankar

  4. Document to substantiate that APIs have been manufactured in accordance to GMP • The pharmaceutical manufacturer must have evidence of appropriate audit being performed on all its API manufacturers (in respect of manufacturing, packaging, repackaging, mixing, labeling, re-labeling, and supplementary labeling). Audit reports will become an issue for future inspections at the premises of pharmaceutical manufacturers. Nandkumar Chodankar

  5. Are third party inspection reports acceptable? • Most of the EU accepts third party inspections reports with following conditions, that: • The auditor is a QP • The auditor is independent of the company to be audited. • The auditor is acquainted with the rules of the governing medicinal products in the European Union, Volume 4, Part II • The audit report has been reviewed by the pharmaceutical manufacturer • The audit report is adequate . • Third party audit report must be in detail not just a summary. Nandkumar Chodankar

  6. Today’s Situation • From 17th December 2005 onwards the medicinal products of an API manufacturer who is not audited are quarantined on inspection until the API manufacturer has been audited. • Exception to the rule is there are some medicinal products that are not comprised by the rules on APIs. • Medicinal products dispensed by a special compassionate-use- permit in EU (Denmark) • Medicinal products prepared in accordance with a magisterial formula • Medicinal products for clinical studies for which a marketing authorization has not been granted GMP Requirement for API questions & Answers) http;//www.dkma.dk/1024/visUKLSArtikel.asp Nandkumar Chodankar

  7. Definition of API Manufacturer • An API manufacturer is defined in Executive Order No. 1242 of 12 December 2005, which briefly states that the API manufacturer is: • The manufacturer of API • The company in charge of packaging the APIs • The company in charge of repackaging / un-packaging, mixing the APIs • The company in charge of labeling or relabeling or providing supplementary labels for API. Nandkumar Chodankar

  8. Are Regular Inspections in the offing? • As a general rule, API manufacturers will not be inspected at regular intervals unless the manufacture concerned requires an authorization pursuant to EU Medicinal Act • API manufacturer who wish to receive GMP certificate must request an authority inspection. Nandkumar Chodankar

  9. Evolution of Indian Pharmaceutical Industry

  10. Indian Pharma Industry: Historical Background Nandkumar Chodankar

  11. Indian Pharma Industry: Historical Background1980-1990 Nandkumar Chodankar

  12. Indian Pharma Industry: Historical Background1990-2000 Nandkumar Chodankar

  13. Indian Historical Background • Approximately 11,000 registered units, engaged in the manufacture of drug substances and drug products. Among these around 300 are Large scale • More than 300 units have approval from International Agencies • All units licensed for export (300) are inspected by domestic Regulatory (Central & State) team, for WHO certification • 150- have received Approvals from: MHRA, TGA, etc. • 65 are US FDA Inspected & accepted. Nandkumar Chodankar

  14. Journey: DMF to EDMF- COS –CTD Formats • UK companies took the lead and their Quality Assurance personnel started investing their time in Indian companies. • Grabbing of opportunity: Indians were quick to learn and grab the opportunity. • Introduction of COS and its declaration that the APIs are manufactured under GMP, • Introduction of ICH Guidelines and their implementation:. • The CTD format for DMF submission. Nandkumar Chodankar

  15. Current scenario: DMFs, COSs, Dossiers and ANDAs • DMF Filing by Indians: Largest number of DMFs & COSs from Indian Companies • About 132 ANDA in Partnerships have been submitted with US Generic companies. Similarly Dossiers have been submitted • A few have signed partnerships. • The acquisitions of pharmaceutical industries by Indians and vice versa. Indian Generic Products available at Indian cost with International standard for all Regulated Markets Nandkumar Chodankar

  16. The impact of CTD Formats for Document submission • The new legislation such as improved documentation/CTD is a positive move for all involved as it is moving to one common standard of documents and ultimately material and pharmacopoeia standards which has a very positive impact on the ability of companies to produce good documentation and quality product. Indians have taken a lead in this field. Nandkumar Chodankar

  17. The Impact: ICH Q 7 requirements for GMP Manufacturing • Implementation of ICH Q7 A guideline for manufacturing API and Intermediates. • Training of the staff to understand and to follow the requirements of the ICH guidelines • Realigning of the facilities to meet GMP & environmental requirements • Separation of the Final API purification step from the other synthetic steps, and manufacture it with precisely as per the ICH Q7 Requirements • Product isolation at each stage of manufacturing in a controlled environment. • Critical unit operations like Drying, Milling, Packaging, Labeling, etc., in controlled environment. Nandkumar Chodankar

  18. Continuous Improvement (At What Cost?) • Quality Management • Personnel selection and their education, apparels, etc. • Equipment design, finishes • Documentation & Records • Material Management & Sampling • Production & Process control, Contamination control, Blending to make large batch size & blending of Tailings • Laboratory Control • Stability monitoring & Storage conditions • Expiry and Retest Period (Reprocessed Material?) Nandkumar Chodankar

  19. Continuous Improvement (At What Cost?) • Qualification (URS, DQ, IQ, OQ, PQ) • Calibrations • Validations • Process Validation (Prospective, retrospective, concurrent) • Analytical method validation, • Cleaning process and analytical method validations • OOS, OOT, • Change Control, • Annual reports, • Reprocessing, Recovery, Reworking • Returns and Complaint handling, etc. • Agents, brokers, traders, distributors, re-packers & re-labelers Nandkumar Chodankar

  20. Impact of Increase in the audit frequency Nandkumar Chodankar

  21. Impact of Increase in the audit frequency Nandkumar Chodankar

  22. Impact of Increase in the audit frequency Nandkumar Chodankar

  23. Impact of Increase in the audit frequency Nandkumar Chodankar

  24. Every Audit is as Good as The Inspector

  25. Impact due to other factors • Overall documentation / Expectation and Paper work has increased. • Analytical work has increased, especially Validation of every method that is used. • QC, QA, Documentation staff has increased almost by two folds • Customer request for impurity reference standards has increased. Nandkumar Chodankar

  26. Summary • European Legislation is showing a positive effect on the Indian API manufacturers with long term benefits to the end customer • Among 11,000 Registered units (India), only 300 are large and medium scale Manufacturing units and have almost 70% market share • EDQM and US FDA inspections have brought in a change in the “Mind Set” • European customers have started Auditing the API Manufacturing Plants, which is leading to up-gradation of the facilities, documentation and Quality Assurance Systems • Domestic CGPM Guidelines “Schedule M” (almost equivalent to ICH Q7A) are being enforced on all manufacturing plants. • To meet CGMP New API Manufacturing plants are being installed using ISPE & ICH Guidelines. Nandkumar Chodankar

  27. I will like to thank the following individuals for making this presentation possible; • Laurie Cook • Lalit Sharma Nandkumar Chodankar

  28. Impact of European Legislation on Indian API manufacturers To Vacuum Crystallization Reactor Thank You Sifter U T I L I T Y Sifter To Recovery U T I L I T Y Utility U T I L I T Y S E K H S A R I A Multi Mill Multi Mill Blender Blender S E K H S A R I A Receiver Dissolution Reactor S E K H S A R I A Centrifuge Pump Mill Dryer Packaging Mother Liquor Tank Nandkumar Chodankar

More Related