CBER Expectations Regarding Contract Manufacturing

Size: px
Start display at page:

Download "CBER Expectations Regarding Contract Manufacturing"

Transcription

1 CBER Expectations Regarding Contract Manufacturing LCDR Qiao Bobo, Ph.D. FDA/CBER/OCBQ/DMPQ CASSS CMC Strategy Forum Summer 2014

2 Outline 2 Types of Cooperative Manufacturing Arrangements CBER Expectations Licensed Manufacturer Responsibilities Contract Manufacturer Responsibilities Case Studies Quality Agreements Quizzes

3 Guidance for Industry November Guidances/General/ucm pdf

4 Types of Cooperative Manufacturing Arrangements 4 Divided Manufacturing - two or more manufacturers, each registered with FDA in accordance with 21 CFR Parts 207, 607, or 807 as applicable, and licensed to manufacture a specific biological product in its entirety, participate jointly in the manufacture of that product.

5 Types of Cooperative Manufacturing Arrangements 5 Shared Manufacturing - two or more manufacturers are licensed and responsible for specific aspects of the manufacture of a product but none is licensed for all aspects of the manufacture of the product. Company A is licensed to manufacture the bulk drug substance and Company B is licensed to manufacture the final drug product.

6 Types of Cooperative Manufacturing Arrangements 6 Contract Manufacturing - a licensed manufacturer establishes a contract with another entity(ies) to perform some or all of the manufacture of a product as a service to the licensed manufacturer. A contract facility that is engaged in significant manufacturing is not required to be separately licensed, as is the case in a Shared Manufacturing Arrangement.

7 Contract Manufacturing Facilities 7 Contract Manufacturing Facilities (21 CFR ) Bulk Drug Substance Manufacturers Drug Product Manufacturers Testing Laboratories Labeling Packaging Warehouse

8 Responsibilities of Licensed Manufacturer 8 The licensed manufacturer must have a procedure in place for receiving information from the contract facility on all deviations, complaints, and adverse events (21 CFR (a)). Final approval or rejection of drug product to the market (211.22(a)).

9 WL to Product Owner: Disposition 9 Your firm is the owner of this drug product, but did not adequately evaluate whether the CMO, which is an extension of your operations, can consistently produce product that is suitable for distribution. For example, your quality unit did not evaluate the quality of each batch of drug product produced by the CMO in order to make an appropriate disposition decision (approval or rejection). Your finished product, XXXX, was not tested for conformance to the labeled amount of active ingredients. Your firm contracted out the XXXX product. Your firm accepted and relied on the Certificate of Analysis (COA) from your contract manufacturer (CMO) and failed to verify the accuracy and completeness of testing results in the COA. For example, XXXX contains six active ingredients. The COA for this lot showed that only identity testing for two of the six active ingredients was conducted. No assay testing was conducted.

10 Responsibilities of Licensed Manufacturer 10 The licensed manufacturer should be aware that all contract manufacturing locations must be in compliance with CGMP regulations and are subject to inspection from the time of the submission. The FDA regards these locations as an extension of the licensed manufacturer s own facility (21 CFR ).

11 Issuance and Denial of License (601.4) 11 A license will not be issued unless the product and establishment(s) meet the applicable standards. Such an issuance is for the relevant establishments and applicable standards.

12 . Responsibilities of Product Owner - Scenario 1 12 Pre-approval inspection of a BLA owner revealed that the fill volume size as stated in the BLA was filled at a contract facility. The contract facility was located in a different country, was not registered and had never been inspected before. Outcome - The review clock was stopped in the form of a CR letter stating outstanding compliance issues with regard to your contract filling facility, as this facility has no compliance history. End result is no product to the market at that time.

13 Responsibilities of Product Owner - Scenario 2 13 The product owner submitted a PAS for an alternative contract facility to manufacture a bulk drug substance. The FDA compliance check revealed that the contract facility was under an OAI (Official Action Indicated) for another product. Outcome A CR letter was issued due to outstanding compliance issues based on the inspection conducted on XXXX date..

14 Responsibilities of Contract Manufacturer 14 Contract facilities are subject to FDA inspection under section 351(c) of the PHS Act and section 704(a) of the FD&C Act. Facilities performing contract operations for biological products must register with FDA in accordance with registration and listing provisions in 21 CFR Parts 207, 607 and 807.

15 Expectations of Contract Manufacturer 15 Ensure full compliance to CGMP to the operations being performed. Allow the licensed manufacturer to regularly assess the contract manufacturing facility s compliance. This may include, but is not limited to, review of records and manufacturing deviations and defects, and performance of periodic audits.

16 WL to Contracted Facilities: CGMP Violation 16 you state that you have informed your clients on the importance of validating the methods, but they have chosen not to validate the methods. In addition, you state that you will inform them again in writing. Your response, however, is inadequate because you do not provide your firm's planned corrective actions for this CGMP violation. You are responsible for ensuring that the test methods used by your firm are validated. Data generated by an unvalidated method(s) should not be used for establishment of expiration dates, commercial batch release, or other CGMP decisions.

17 Expectations of Contract Manufacturer 17 Should ensure the notification to the licensed manufacturer of any FDA list of inspectional observations related to the contracted product. Fully inform the licensed manufacturer of the results of all tests and investigations regarding or possibly having an impact on the product. Notify the licensed manufacturer of any changes.

18 WL to Contracted Facilities: Data Integrity and Notification 18 Please note that as a contract testing laboratory, it is your responsibility to ensure the integrity of the data generated and that all test results be properly documented, maintained and reported. Failure to investigate OOS: Please indicate if all your customers were notified of these failures and date of notification.

19 Expectations of Contract Manufacturer 19 Allow the licensed manufacturer access to floor plans, equipment validation, and other production information. Note that this information will be submitted to FDA by the applicant as part of the submission

20 21 CFR The FDA does not consider results of validation studies of analytical and assay methods and control procedures to be trade secrets that may be withheld from the drug manufacturer by the contract facility.

21 Contract Manufacturing Facilities 21 Contract Manufacturing Facilities (21 CFR ) Bulk Drug Substance Manufacturers Drug Product Manufacturers Testing Laboratories Labeling Packaging Warehouse

22 21 CFR In accordance with 21 CFR , FDA may disclose any information obtained during the inspection of a contract facility having a specific bearing on compliance with the FD&C Act to the licensed manufacturer. The FDA s position is that by accepting contract work, the contract facility authorizes such disclosures.

23 WL to Contracted Facility: CC Your Customers! 23 Your firm does not have adequate written procedures for production and process controls [under (a)] You conducted validation activities for only products X and Y, which you deemed to be the worst case products you have not provided a scientific rationale to demonstrate that the mixing studies for X and Y are adequate and fully representative for the other 118 products Unless you are able to demonstrate that your matrix approach is scientifically sound, all products must be individually validated. Copies of WL to CEOs of five of Contracted Facility s customers.

24 Draft Guidance - May

25 Quality Agreement 25 The CGMP regulations don t explicitly require a written quality agreement, but 21 CFR (a): QU responsible for approving or rejecting drug products manufactured, processed, packed, or held under contract by another company 21 CFR (d): QU procedures & responsibilities must be in writing 21 CFR : contract manufacturers are an extension of the manufacturer s own facility Quality Agreement can be a tool that is used to ensure all establishment standards and applicable regulations are followed.

26 Scope of Draft Guidance 26 What is covered: human drugs, veterinary drugs, biological and biotechnology products, finished products, active pharmaceutical ingredients (APIs or drug substances, or their intermediates), and drug constituents of combination drug/device products manufacturing includes processing, packing, holding, labeling operations, testing, and operations of quality unit What is not: Type A medicated articles and medicated feed, medical devices, dietary supplements, or HCT/Ps qualification activities, auditing, or disqualification of contracted facilities controls related to qualification, auditing, monitoring, or disqualification of suppliers of raw materials or ingredients, including recommendations for Quality Agreements with vendors/suppliers distributors

27 Purpose 27 Outlines critical roles played by both Product Owners and Contracted Facilities Explains how manufacturers should use Quality Agreements to define, establish, and document their responsibilities Emphasizes that Quality Agreements should: Promote communication between the parties Clearly delineate the parties responsibilities, especially with respect to quality issues Assure coverage of all CGMP requirements Provide for change management

28 Basic Sections and Elements 28 Basic Sections: Purpose/Scope Terms (including effective date and renewal/extension) Dispute Resolution how will disagreements be elevated to decisionmakers in each company (not ADR or arbitration, etc.) Responsibilities, including communication mechanisms & contacts Change control and revisions Critical Elements from cgmp Perspective Responsibilities: Quality Unit, Facilities and Equipment, Material Management, Product Specific Terms, Laboratory Controls, Documentation Change Control

29 Change Control 29 Changes can be initiated by either party Contract Facility should notify the Owner of the changes, including but not limited to: Raw materials Establishment locations Manufacturing processes Additional product brought in Changes in equipment, shipping methods, container closures Owner in turn must then submit the changes based upon 21 CRF , and or Expectation that there will be documentation to support the change.

30 Quizzes - So who is responsible? 30

31 Quiz 1 - Change Control 31 A Contract Facility informed the Owner about obvious powder segregation issues. Correction of the issues involved major changes that would require re-designing the process, changing raw material specifications and submission of a PAS to the FDA The Contract Facility could not make changes without the Owner s approval. The Owner refused to approve the change. The Contract Facility continued manufacturing the product using the flawed process.

32 Quiz 2 Equipment Maintenance and Upkeep 32 FDA inspection revealed deficient maintenance of the facilities and equipment such as defective or partially broken equipment, visibly tarnished piping, leaking seals, etc. In addition, facility design is inadequate to prevent contamination. This Contract Facility has a Quality Agreement specifying the Owner s responsibility for upgrades and maintenance of the facilities and equipment. The Owner fails to provide the requisite resources or carry out the necessary upgrades and maintenance, but the Contract Facility continues to manufacture the product under non-cgmp conditions that could result in product contamination.

33 Quiz 3 Documenting Steps in the Manufacturing Process 33 Inspection of Contract Facility revealed that batch records do not accurately reflect the actual manufacturing process. The Contract Facility claims that this practice of incomplete batch records was in accordance with the wishes of the Owner.

34 Bottom Line 34 A Quality Agreement Can be used as a tool to help ensure that all responsibilities and expectations are met. A Quality Agreement is not a substitute for compliance with CGMP requirements by either party The Contract Facility cannot essentially agree to manufacture under non-cgmp conditions The Owner is not relieved of its responsibility to ensure the quality and safety of the product introduced into interstate commerce FDA could also inspect the Owner and if necessary take regulatory action based on oversight failures in monitoring the activities of the contract facility.

35 References 35 Guidance for Industry - Cooperative Manufacturing Arrangements for Licensed Biologics November 2008 Draft Guidance for Industry - Contract Manufacturing Arrangements for Drugs: Quality Agreements May 2013

36 Acknowledgements 36 Paula Katz - Acing Branch Chief, FDA/CDER/OC/OMPQ Nancy Waites - Consumer Safety Officer, FDA/CBER/OCBQ/DMPQ Marion Michaelis - Branch Chief FDA/CBER/OCBQ/DMPQ Laurie Norwood Deputy Division Director FDA/CBER/OCBQ/DMPQ John Eltermann - Division Director FDA/CBER/OCBQ/DMPQ Mary Malarkey - Director, Office of Compliance FDA/CBER/OCBQ

Subpart B Organization and Personnel, 21 CFR Responsibilities of the quality control unit.

Subpart B Organization and Personnel, 21 CFR Responsibilities of the quality control unit. FDA inspections continue to focus on CGMP violations related to basic GMP controls. A survey of Warning Letters issued in 2013 on CMC (Chemistry / Manufacturing / Controls) violations reveals an emphasis

More information

Supply Chain Supplier Quality Management. Nicholas Violand, Investigator/Drug Specialist US FDA, New Jersey District

Supply Chain Supplier Quality Management. Nicholas Violand, Investigator/Drug Specialist US FDA, New Jersey District Supply Chain Supplier Quality Management Nicholas Violand, Investigator/Drug Specialist US FDA, New Jersey District 1 Overview Product Life Cycle Maintaining Quality in Supply Chain FDA and ICH Guidances

More information

CGMP for Phase 1 INDs

CGMP for Phase 1 INDs CGMP for Phase 1 INDs Laurie P. Norwood Deputy Director Division of Manufacturing and Product Quality Office of Compliance and Biologics Quality Center for Biologics Evaluation and Research 1 Overview

More information

Quality Agreements with CMO s. Presented at ASQ Orange Empire Meeting May 13, 2014 By Luke Foo Sr. Director QA/QC Spectrum Pharmaceuticals

Quality Agreements with CMO s. Presented at ASQ Orange Empire Meeting May 13, 2014 By Luke Foo Sr. Director QA/QC Spectrum Pharmaceuticals Quality Agreements with CMO s Presented at ASQ Orange Empire Meeting May 13, 2014 By Luke Foo Sr. Director QA/QC Spectrum Pharmaceuticals FDA Guidance Contract Manufacturing Arrangements for Drugs: Quality

More information

Guidance for Industry

Guidance for Industry Guidance for Industry Cooperative Manufacturing Arrangements for Licensed Biologics DRAFT GUIDANCE This guidance document is being distributed for comment purposes only. Comments and suggestions regarding

More information

Guidance for Industry

Guidance for Industry Guidance for Industry Cooperative Manufacturing Arrangements for Licensed Biologics Additional copies of this guidance are available from the Office of Communication, Training and Manufacturers Assistance

More information

Inspections, Compliance, Enforcement, and Criminal Investigations

Inspections, Compliance, Enforcement, and Criminal Investigations Page 1 of 8 Inspections, Compliance, Enforcement, and Criminal Investigations Lupin Limited 5/7/09 Department of Health and Human Services Public Health Service Food and Drug Administration CENTER FOR

More information

QUALITY AGREEMENT. The following Agreement has been concluded between

QUALITY AGREEMENT. The following Agreement has been concluded between QUALITY AGREEMENT The following Agreement has been concluded between LLC LABORATORIES The contract laboratory and service provider 1625 Trinity Dr., Unit 11 Mississauga, Ontario Canada L5T 1W9 Hereinafter

More information

Quality Agreement. by and between. Supplier Name. Address: and. Client Name: Address:

Quality Agreement. by and between. Supplier Name. Address: and. Client Name: Address: NOTE TO USERS This Quality Agreement template was developed by the Bulk Pharmaceutical Task Force (BPTF), an affiliate organization of the Society of Chemical Manufacturers and Affiliates (SOCMA), as a

More information

While the recognition

While the recognition Designing the Perfect Change Control System Change control systems today are expected to be designed in a way that provides a system to not only document and approve changes, but also to anticipate change

More information

Inspections, Compliance, Enforcement, and Criminal Investigations

Inspections, Compliance, Enforcement, and Criminal Investigations Page 1 of 5 Home Inspections, Compliance, Enforcement, and Criminal Investigations Enforcement Actions Warning Letters Inspections, Compliance, Enforcement, and Criminal Investigations Thomas E. Young,

More information

IDT Australia Ltd. 5/23/18

IDT Australia Ltd. 5/23/18 IDT Australia Ltd. 5/23/18 10903 New Hampshire Avenue Silver Spring, MD 20993 Via UPS Warning Letter 320-18-55 Return Receipt Requested May 23, 2018 Dr. Graeme R. Kaufman CEO, Acting, and Chairman of the

More information

Compliance Trends Paula Katz

Compliance Trends Paula Katz Compliance Trends Paula Katz Director, Manufacturing Quality Guidance and Policy Staff Office of Manufacturing Quality Office of Compliance Center for Drug Evaluation and Research India Pharmaceutical

More information

Inspections, Compliance, Enforcement, and Criminal Investigations

Inspections, Compliance, Enforcement, and Criminal Investigations Home > Inspections, Compliance, Enforcement, and Criminal Investigations > Enforcement Actions > Warning Letters Inspections, Compliance, Enforcement, and Criminal Investigations Apotex Inc. 3/29/10 Warning

More information

Porton Biopharma Limited 1/17/17

Porton Biopharma Limited 1/17/17 Porton Biopharma Limited 1/17/17 10903 New Hampshire Avenue Silver Spring, MD 20993 Via UPS Warning Letter 320 17 19 Return Receipt Requested January 19, 2017 Dr. Roger J. Hinton Managing Director Porton

More information

Continental Manufacturing Chemist, Inc. 12/21/17

Continental Manufacturing Chemist, Inc. 12/21/17 Continental Manufacturing Chemist, Inc. 12/21/17 Division of Pharmaceutical Quality Operations III 300 River Place, Suite 5900 Detroit, MI 48207 Telephone: (313) 393-8100 Fax: (313) 393-8139 December 21,

More information

Inspections, Compliance, Enforcement, and Criminal Investigations

Inspections, Compliance, Enforcement, and Criminal Investigations Inspections, Compliance, Enforcement, and Criminal Investigations Nostrum Laboratories Inc 4/27/09 Department of Health and Human Services Public Health Service Food and Drug Administration Kansas City

More information

Inspections, Compliance, Enforcement, and Criminal Investigations

Inspections, Compliance, Enforcement, and Criminal Investigations Page 1 of 5 Home Inspections, Compliance, Enforcement, and Criminal Investigations Compliance Actions and Activities Warning Letters 2014 Inspections, Compliance, Enforcement, and Criminal Investigations

More information

Cell Therapy Product Manufacturing Considerations. July 17, 2017 CMC Strategy Forum Mo Heidaran, Ph.D.

Cell Therapy Product Manufacturing Considerations. July 17, 2017 CMC Strategy Forum Mo Heidaran, Ph.D. Cell Therapy Product Manufacturing Considerations July 17, 2017 CMC Strategy Forum Mo Heidaran, Ph.D. Office of Tissues and Advanced Therapies FDA/CBER Overview Establishing Manufacturing Control Applying

More information

August 11, 2005 VIA FEDERAL EXPRESS

August 11, 2005 VIA FEDERAL EXPRESS DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Atlanta District Offke _ G 5 (/ k r) r.;%~ 6fl Sth Street, N.E. Atlsntx, Georgla 30304 August 11, 2005 VIA FEDERAL EXPRESS Dushyant

More information

An FDA Perspective on Atypical Active Ingredients

An FDA Perspective on Atypical Active Ingredients An FDA Perspective on Atypical Active Ingredients Presented by Steven Wolfgang, Ph.D. Center for Drug Evaluation and Research Office of Compliance Office of Drug Security, Integrity and Response steven.wolfgang@fda.hhs.gov

More information

Inspections, Compliance, Enforcement, and Criminal Investigations

Inspections, Compliance, Enforcement, and Criminal Investigations Seite 1 von 10 Inspections, Compliance, Enforcement, and Criminal Investigations Laboratoire Atlas Inc. 6/25/09 hhsbluebird Department of Health and Human Services Public Health Service Food and Drug Administration

More information

Inspections, Compliance, Enforcement, and Criminal Investigations

Inspections, Compliance, Enforcement, and Criminal Investigations Home Inspections, Compliance, Enforcement, and Criminal Investigations Enforcement Actions Warning Letters Inspections, Compliance, Enforcement, and Criminal Investigations Celltex Therapeutics Corporation

More information

Registration and renewal of the credential certificate for registration

Registration and renewal of the credential certificate for registration Registration and renewal of the credential certificate for registration 1. Qualification of the applicant: 1.1 Must be a holder of the license to manufacture or import the psychotropic substances of category

More information

"Regulatory challenges and trends in finished dosage manufacturing: A CMO perspective"

Regulatory challenges and trends in finished dosage manufacturing: A CMO perspective "Regulatory challenges and trends in finished dosage manufacturing: A CMO perspective" Presented by Milton Boyer CEO SCA Pharmaceuticals PDA NE Chapter November 2017 1 Overview At Informex 2013 I presented

More information

WARNING LETTER AUG 3, 2016

WARNING LETTER AUG 3, 2016 Ropack, Inc. 8/3/16 Department of Health and Human Services Public Health Service Food and Drug Administration 10903 New Hampshire Avenue White Oak Building 66 Silver Spring, MD 20993 WARNING LETTER AUG

More information

CGMP Requirements for Investigational Products

CGMP Requirements for Investigational Products PREP #6 CGMP Requirements for Investigational Products Ji-Eun Kim, RPh, PhD Research Pharmacist Regulatory Affairs Office of Research Compliance December 6, 2016 1 CME Disclosure Statement Northwell Health

More information

Hot Topics in Drug Product Process Validation: A Reviewer s Perspective

Hot Topics in Drug Product Process Validation: A Reviewer s Perspective Hot Topics in Drug Product Process Validation: A Reviewer s Perspective Colleen Thomas, Ph.D. Quality Assessment Lead (Acting) FDA/CDER/OPQ/OPF Division of Microbiology Assessment CASSS CMC Strategy Forum

More information

Quality Assurance in Pharmaceutical and Biotech Industries as Per Regulatory Guidelines

Quality Assurance in Pharmaceutical and Biotech Industries as Per Regulatory Guidelines Human Journals Review Article January 2017 Vol.:8, Issue:2 All rights are reserved by Chagi Venkatesh et al. Quality Assurance in Pharmaceutical Biotech Industries as Per Regulatory Guidelines Keywords:

More information

Navigating an FDA GMP and Validation Inspection- Best Practices and Pitfalls

Navigating an FDA GMP and Validation Inspection- Best Practices and Pitfalls Navigating an FDA GMP and Validation Inspection- Best Practices and Pitfalls Sonali P. Gunawardhana FDA Practice Group Wiley Rein LLP 1776 K Street NW Washington, DC (202) 719-7454 sgunawardhana@wileyrein.com

More information

Interpharm Praha A.S. 10/18/16

Interpharm Praha A.S. 10/18/16 Interpharm Praha A.S. 10/18/16 Department of Health and Human Services Public Health Service Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993 Via UPS Return Receipt Requested

More information

Pre-Approval Inspections for Drug Products

Pre-Approval Inspections for Drug Products Pre-Approval Inspections for Drug Products FDA Small Business Regulatory Education for Industry Conference June 20, 2013 H.L. Jamillah Selby Consumer Safety Officer FDA, Dallas District Office Presentation

More information

Good Manufacturing Practice ( GMP ) Compliance: GMPs EXPLAINED

Good Manufacturing Practice ( GMP ) Compliance: GMPs EXPLAINED Good Manufacturing Practice ( GMP ) Compliance: GMPs EXPLAINED Presented by Raymond A. Bonner Nathan C. Sheers SIDLEY AUSTIN BROWN & WOOD, LLP Washington, D.C. (202) 736-8000 To The Fourth Annual Pharmaceutical

More information

Facility and Operational Issues for Cord Blood Banks: FDA Draft Guidance

Facility and Operational Issues for Cord Blood Banks: FDA Draft Guidance Facility and Operational Issues for Cord Blood Banks: FDA Draft Guidance Mary Malarkey, Director Office of Compliance and Biologics Quality ISCT 7 th Annual Somatic Cell Therapy Symposium, September 26-28,

More information

RECOMMENDATIONS FOR DIETARY INGREDIENT PROCESSORS

RECOMMENDATIONS FOR DIETARY INGREDIENT PROCESSORS RECOMMENDATIONS FOR DIETARY INGREDIENT PROCESSORS Facilities that manufacture 117, pack, or hold dietary supplements are subject to the regulations in 21 CFR Part 111, while those that manufacture, pack,

More information

Regulatory Perspective on Assuring Ingredient Quality

Regulatory Perspective on Assuring Ingredient Quality Regulatory Perspective on Assuring Ingredient Quality PQRI Conference December 15, 2009 Rockville, MD Steven M. Wolfgang, Ph.D., Acting Associate Director, Regulatory Science US Food and Drug Administration

More information

GMP On Site Series. GMP Essentials

GMP On Site Series. GMP Essentials GMP On Site Series GMP Essentials GMP Basics Objectives 1. State the critical definitions of the pharmaceutical industry. 2. Describe the law as it applies to various critical functions. 3. State the history

More information

Inspections, Compliance, Enforcement, and Criminal Investigations

Inspections, Compliance, Enforcement, and Criminal Investigations Page 1 of 6 Home Inspections, Compliance, Enforcement, and Criminal Investigations Enforcement Actions Warning Letters Inspections, Compliance, Enforcement, and Criminal Investigations Lloyd Inc. of Iowa

More information

Inspections, Compliance, Enforcement, and Criminal Investigations

Inspections, Compliance, Enforcement, and Criminal Investigations Seite 1 von 10 Inspections, Compliance, Enforcement, and Criminal Investigations Dabur Oncology PLC hhsbluebird Department of Health and Human Services Warning Letter Public Health Service Food and Drug

More information

A Life Cycle Approach to Raw Material Qualification for Cell and Gene Therapy Products

A Life Cycle Approach to Raw Material Qualification for Cell and Gene Therapy Products A Life Cycle Approach to Raw Material Qualification for Cell and Gene Therapy Products Angela Whatley, Ph.D. Office of Tissues and Advanced Therapies CBER/FDA CMC Strategy Forum on Cell & Gene Therapies

More information

April 12, 2010 WARNING LETTER (10-ATL-12)

April 12, 2010 WARNING LETTER (10-ATL-12) Hospira, Inc. Department of Health and Human Services Public Health Service Food and Drug Administration Atlanta District Office 60 8th Street, N.E. Atlanta, Georgia 30309 April 12, 2010 VIA FEDERAL EXPRESS

More information

Documenta tion and Records

Documenta tion and Records Documenta tion and Records Page 1 of 30 Training Outcome of the Module: After completing this module, you will be able to: Recognize the importance of procedures Recognize the importance of record keeping

More information

Inspections, Compliance, Enforcement, and Criminal Investigations

Inspections, Compliance, Enforcement, and Criminal Investigations Page 1 of 8 HomeInspections, Compliance, Enforcement, and Criminal InvestigationsEnforcement ActionsWarning Letters Inspections, Compliance, Enforcement, and Criminal Investigations Capco Custom Packaging

More information

Inspections, Compliance, Enforcement, and Criminal Investigations

Inspections, Compliance, Enforcement, and Criminal Investigations Page 1 of 5 Inspections, Compliance, Enforcement, and Criminal Investigations Hill Dermaceuticals, Inc. Department of Health and Human Services Public Health Service Food and Drug Administration Food and

More information

FOREIGN DRUG INSPECTION/AUDITS FROM THE FDA PERSPECTIVE

FOREIGN DRUG INSPECTION/AUDITS FROM THE FDA PERSPECTIVE FOREIGN DRUG INSPECTION/AUDITS FROM THE FDA PERSPECTIVE Robert C. Fish EAS Consulting Group, LLC. Statistics About 80% of world supply of APIs from India and China Some API produced in Korea, but little

More information

21 CFR Ch. I ( Edition) Personnel Design controls Identification Traceability.

21 CFR Ch. I ( Edition) Personnel Design controls Identification Traceability. Pt. 820 device together with an explanation of the basis for the estimate; (iv) Information describing the applicant s clinical experience with the device since the HDE was initially approved. This information

More information

Pharmaceutical Reference Standards: Overview and Role in Global Harmonization

Pharmaceutical Reference Standards: Overview and Role in Global Harmonization Matthew Borer, Ph.D., Advisor Pharmaceutical Reference Standards: Overview and Role in Global Harmonization 3rd DIA China Annual Meeting Beijing, China, 16-18 May, 2011 What is a Pharmaceutical Reference

More information

The FDA Just Arrived... Are You Ready? Presented By Sandra Lueken Sr. Director, Quality AstraZeneca Biologics

The FDA Just Arrived... Are You Ready? Presented By Sandra Lueken Sr. Director, Quality AstraZeneca Biologics The FDA Just Arrived... Are You Ready? Presented By Sandra Lueken Sr. Director, Quality AstraZeneca Biologics Objectives Review Quality Systems Audit Approach and cgmp fundamentals Logistical Audit Preparation

More information

Drug Quality Assurance: Systems at ChemCon Author: Dr. Peter Gockel

Drug Quality Assurance: Systems at ChemCon Author: Dr. Peter Gockel Drug Quality Assurance: Systems at ChemCon Author: Dr. Peter Gockel On February 13th, 2006, the FOOD AND DRUG ADMINISTRATION (FDA) implemented a revision to the Compliance Program Guidance Manual for active

More information

Divi's Laboratories Ltd. (Unit II) 4/13/17

Divi's Laboratories Ltd. (Unit II) 4/13/17 Divi's Laboratories Ltd. (Unit II) 4/13/17 10903 New Hampshire Avenue Silver Spring, MD 20993 Via UPS Warning Letter 320 17 34 April 13, 2017 Mr. Kiran S. Divi Director and President of Operations Divi

More information

Divi's Laboratories Ltd. (Unit II) 4/13/17

Divi's Laboratories Ltd. (Unit II) 4/13/17 Divi's Laboratories Ltd. (Unit II) 4/13/17 10903 New Hampshire Avenue Silver Spring, MD 20993 Via UPS Warning Letter 320 17 34 April 13, 2017 Mr. Kiran S. Divi Director and President of Operations Divi

More information

The APIC Audit Programme Version 5, July 2017

The APIC Audit Programme Version 5, July 2017 The APIC Audit Programme Version 5, July 2017 Table of contents 1 General 2. APIC Audit Programme 3 The Auditors 3.1 Educational Background and Experience 3.2 Auditor Training Courses for Certification

More information

ABB Industries PAT Validation

ABB Industries PAT Validation Alison Harrington ABB Industries PAT Validation ABB Industries - 1 - Topics PAT disciplines and framework FDA evolution PAT Regulatory Process Quality System Comparability Protocol Submission example Validation

More information

ORC Sponsor-Investigator IDE Checklist

ORC Sponsor-Investigator IDE Checklist A sponsor-investigator assumes BOTH investigator and sponsor responsibilities as outlined in the FDA Code of Federal Regulations 21CFR812. This means that such investigators have additional responsibilities.

More information

Jilin Shulan Synthetic Pharmaceutical Co. Ltd. 5/13/10

Jilin Shulan Synthetic Pharmaceutical Co. Ltd. 5/13/10 Jilin Shulan Synthetic Pharmaceutical Co. Ltd. 5/13/10 Department of Health and Human Services Public Health Service Food and Drug Administration Silver Spring MD 20993 Warning Letter VIA UPS MAIL WL:

More information

Guidance for Industry

Guidance for Industry Guidance for Industry Formal Dispute Resolution: Scientific and Technical Issues Related to Pharmaceutical CGMP DRAFT GUIDANCE This guidance document is being distributed for comment purposes only. Comments

More information

Guidance for Industry

Guidance for Industry Guidance for Industry Formal Dispute Resolution: Scientific and Technical Issues Related to Pharmaceutical CGMP DRAFT GUIDANCE This guidance document is being distributed for comment purposes only. Comments

More information

Validation/Verification of Test Methods An FDA Perspective. Laure H. Kairawicz, Ph.D. Senior Scientist Expert Witness

Validation/Verification of Test Methods An FDA Perspective. Laure H. Kairawicz, Ph.D. Senior Scientist Expert Witness Validation/Verification of Test Methods An FDA Perspective Laure H. Kairawicz, Ph.D. Senior Scientist Expert Witness FD & C Act Overview Definition of drugs What cgmps are Finished Pharmaceuticals cgmp

More information

San Jose, California, USA

San Jose, California, USA Glisland, Inc. San Jose, California, USA http://www.glisland.com Welcome to the Drug GMP World Current Good Manufacturing Practice cgmp ICH Q10 Pharmaceutical Quality System PQS GMP QSR Quality System

More information

GOOD MANUFACTURING PRACTICES - AUDIT REPORT FORM AKA GMP Standards Program

GOOD MANUFACTURING PRACTICES - AUDIT REPORT FORM AKA GMP Standards Program GOOD MANUFACTURING PRACTICES - AUDIT REPORT FORM AKA GMP Standards Program HC USE ONLY File Number Date/Time of Receipt To be completed by an Independent 3 rd Party Auditor. GENERAL INFORMATION A. Submission

More information

GMP GUIDELINES. GMP Guides from Industry Organisations. FDA cgmp WHO GMP. cgmp Guide Drugs 21 CFR 210 GAMP. ISPE Technical Guides

GMP GUIDELINES. GMP Guides from Industry Organisations. FDA cgmp WHO GMP. cgmp Guide Drugs 21 CFR 210 GAMP. ISPE Technical Guides FDA cgmp cgmp Guide Drugs 21 CFR 210 cgmp Guide Drugs 21 CFR 211 cgmp Guide Medical Device 21 CFR 808, 812, 820 cgmp Guide Biologics 21 CFR 600, 606, 610 Guideline List Human Drugs Guideline List Biologics

More information

BBT Biotech Gmbh 5/16/16

BBT Biotech Gmbh 5/16/16 U.S. Food and Drug Administration Search FDA Home Inspections, Compliance, Enforcement, and Criminal Investigations Compliance Actions and Activities Warning Letters 2016 BBT Biotech Gmbh 5/16/16 SHARE

More information

Library Guide: Active Pharmaceutical

Library Guide: Active Pharmaceutical Library Guide: Active Pharmaceutical Ingredients (API) Table of Contents Overview...3 Sample Curriculum...5 Course Descriptions: A Step-by-Step Approach to Process Validation (PHDV79)...7 A Tour of the

More information

SUPPLIER FOOD SAFETY ASSURANCE

SUPPLIER FOOD SAFETY ASSURANCE Chapter 12 SUPPLIER FOOD SAFETY ASSURANCE 1.0 PARTS OF A SUPPLIER FOOD SAFETY ASSURANCE PROGRAM 2.0 CHOOSING SUPPLIERS 2.1 Supplier Approval 2.2 Approved Supplier List 3.0 PRODUCT SPECIFICATIONS AND CONTROLS

More information

WARNING LETTER CMS #

WARNING LETTER CMS # U.S. Food and Drug Administration Division of Pharmaceutical Quality Operations I 10 Waterview Blvd 3rd FL, Parsippany NJ 07054 Telephone: (973) 331-4900 Fax: (973) 331-4969 www.fda.gov Via UPS Next Day

More information

Mahendra Chemicals 7/13/15

Mahendra Chemicals 7/13/15 Mahendra Chemicals 7/13/15 Department of Health and Human Services Public Health Service Food and Drug Administration Silver Spring, MD 20993 CERTIFIED MAIL RETURN RECEIPT REQUESTED July 13, 2015 Mr. Rajnibhai

More information

National Animal Supplement Council

National Animal Supplement Council NASC established a Preferred Supplier Program for companies who wish to provide products and services to NASC member companies, including raw materials (ingredients), contract manufacturing (dosage form

More information

Auditing Your Laboratory for Compliance with the FDA Dietary Supplement GMP s

Auditing Your Laboratory for Compliance with the FDA Dietary Supplement GMP s Tech Tip 0020 With the advent of the cgmp s, the majority of companies are increasing the frequency of their outsourced analytical testing. But the GMPs are just that, Good Manufacturing Practices, and

More information

Synopsis: FDA Process Validation Guidance

Synopsis: FDA Process Validation Guidance Synopsis: FDA Process Validation Guidance This synopsis is a comparison of the draft version 2008 and the final version 2011 of the U.S. FDA Guidance Process Validation: General Principles and Practices.

More information

THE COMPLETE GUIDE TO FDA-REGULATED SUPPLIER QUALIFICATION & QUALITY MANAGEMENT

THE COMPLETE GUIDE TO FDA-REGULATED SUPPLIER QUALIFICATION & QUALITY MANAGEMENT THE COMPLETE GUIDE TO FDA-REGULATED SUPPLIER QUALIFICATION & QUALITY MANAGEMENT A risk-based approach to qualifying, managing and auditing third party providers TABLE OF CONTENTS 1 Outsourcing under greater

More information

Drug Good Manufacturing Practices Inspections

Drug Good Manufacturing Practices Inspections Drug Good Manufacturing Practices Inspections New England District Investigations Branch Parenteral Drug Association New England Chapter May 17, 2006 DRUG MANUFACTURING INSPECTIONS Inspections Include:

More information

Established Conditions: Reportable CMC Changes for Approved Drug and Biologic Products Guidance for Industry

Established Conditions: Reportable CMC Changes for Approved Drug and Biologic Products Guidance for Industry Established Conditions: Reportable CMC Changes for Approved Drug and Biologic Products Guidance for Industry DRAFT GUIDANCE This guidance document is being distributed for comment purposes only. Comments

More information

Correspondence Between ISO 13485:2016 and 21 CFR Part 820 QMS Requirements

Correspondence Between ISO 13485:2016 and 21 CFR Part 820 QMS Requirements Correspondence Between and 21 CFR Part 820 QMS Requirements 10411 Corporate Drive, Suite 102, Pleasant Prairie, WI 53158 262.842.1250 262.842.1240 info@rcainc.com rcainc.com 2 4 Quality Management System

More information

August 28, WARNING LETTER (07-ATL-1 0)

August 28, WARNING LETTER (07-ATL-1 0) DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Atlanta District Offic e 60 8th Street, N.E. Atlanta, Georgia 3030 9 August 28, 200 7 VIA FEDERAL EXPRESS WARNING LETTER (07-ATL-1 0)

More information

CERTIFIED MAIL RETURN RECEIPT REQUESTED

CERTIFIED MAIL RETURN RECEIPT REQUESTED Department of Health and Human Services Public Health Service Food and Drug Administration Warning Letter WL: 320-14-11 CERTIFIED MAIL RETURN RECEIPT REQUESTED June 16, 2014 Jeremy B. Desai, PhD President

More information

PART 820 QUALITY SYSTEM REGULATION. 21 CFR Ch. I ( Edition)

PART 820 QUALITY SYSTEM REGULATION. 21 CFR Ch. I ( Edition) 814.126 (b) Withdrawal of IRB approval. A holder of an approved HDE shall notify FDA of any withdrawal of approval for the use of a HUD by a reviewing IRB within 5 working days after being notified of

More information

HACCP audit checklist

HACCP audit checklist Requirement HACCP audit checklist Prerequisite Program Management Commitment 1. Senior management ensures that the responsibilities and authorities are defined and communicated within the company Internal

More information

Role of Industrial Engineer in Compliance with FDA Regulations

Role of Industrial Engineer in Compliance with FDA Regulations Role of Industrial Engineer in Compliance with FDA Regulations Wanda J. Torres Medical Device Specialist Libia M. Lugo Drug Specialist Simposio de Ingeniería Industrial Polytechnic University, San Juan

More information

Quality Agreements and Managing Contract Supplier Quality

Quality Agreements and Managing Contract Supplier Quality Quality Agreements and Managing Contract Supplier Quality American Society for Quality Lloyd Bailey November 3, 2005 Service Mark of The Dow Chemical Company TM Trademark of The Dow Chemical Company Abstract

More information

ICH Q8/Q8(R)

ICH Q8/Q8(R) Pharmaceutical Quality for the 21 st Century Temple University May 06, 2008 Joseph Famulare, Deputy Director FDA CDER Office of Compliance CDER Office of Compliance and the Critical Path Initiative Since

More information

Food and Drug Administration, HHS Pt Sec Scope Definitions Quality system.

Food and Drug Administration, HHS Pt Sec Scope Definitions Quality system. Food and Drug Administration, HHS Pt. 820 authorized designee. If, however, a physician in an emergency situation determines that approval from an IRB cannot be obtained in time to prevent serious harm

More information

Laboratory OOS Investigations The Missing Link

Laboratory OOS Investigations The Missing Link Laboratory OOS Investigations The Missing Link India Pharmaceutical Alliance Carmelo Rosa, Psy.D Director Division of Drug Quality I November 6-17, 2017 Indian Pharmaceutical Alliance DISCLAIMER: The views

More information

ISPE-FDA 3 rd Annual CGMP Conference 2 4 June 2014 Baltimore, MD. Detecting GMP Data Integrity Issues

ISPE-FDA 3 rd Annual CGMP Conference 2 4 June 2014 Baltimore, MD. Detecting GMP Data Integrity Issues Detecting GMP Data Integrity Issues Elaine Eborall Senior Director, GMP Compliance, Americas and Asia Pacific Compliance and External Collaboration ISPE-FDA cgmp Conference Baltimore, Maryland 2-4 June

More information

OOS: Back to Basics. Compliant, Effective, Efficient PATH

OOS: Back to Basics. Compliant, Effective, Efficient PATH OOS: Back to Basics Even with the number of trainings, seminars, online webinars and consultant guided investigations, companies are still seeing FDA 483 observations around how they are handling and investigating

More information

21CFR Ventilation, air filtration, air heating and cooling. 21CFR211 Details, Details. 21CFR Equipment Cleaning and Maintenance

21CFR Ventilation, air filtration, air heating and cooling. 21CFR211 Details, Details. 21CFR Equipment Cleaning and Maintenance 21CFR211 Details, Details Kirsten L. Vadheim, Ph.D., RAC 7710 196th Avenue N.E. Redmond WA 98053 Tel: 651.260.6560 Fax: 425.868.4302 klvadheim@hotmail.com 21CFR211.46 Ventilation, air filtration, air heating

More information

Control strategy and validation. Emanuela Lacana PhD Office of Biotechnology Products CDER/FDA

Control strategy and validation. Emanuela Lacana PhD Office of Biotechnology Products CDER/FDA Control strategy and validation Emanuela Lacana PhD Office of Biotechnology Products CDER/FDA 1 Disclaimer The views and opinions expressed in this presentation are those of the speaker and should not

More information

Vital Laboratories Pvt Ltd Plant II 10/10/17

Vital Laboratories Pvt Ltd Plant II 10/10/17 Vital Laboratories Pvt Ltd Plant II 10/10/17 10903 New Hampshire Avenue Silver Spring, MD 20993 Via UPS Warning Letter 320-18-01 October 10, 2017 Mr. Rajiv Bajaj Director Vital Laboratories Private Limited

More information

EU and FDA GMP Regulations: Overview and Comparison

EU and FDA GMP Regulations: Overview and Comparison THE QUALITY ASSURANCE JOURNAL, VOL. 2, 55 60 (1997) EU and FDA GMP Regulations: Overview and Comparison The increasing emphasis on global supply of drug products, as well as starting materials and investigational

More information

January 24, WARNING LETTER (08-ATL-04 )

January 24, WARNING LETTER (08-ATL-04 ) DEPARTMENT OF HEALTH AND HU N[ AIN SERVICES Food and Drug Administration Atlanta District Office 60 Eighth Street, NE Atlanta, GA 3030 9 Telephone : 404/253-1161 FAX: 404/253-120 1 VIA FEDERAL EXPRESS

More information

As discussed in Chapter 5, 21 CFR introduces the concept of and basic requirements for preventive controls. Recall that a preventive control

As discussed in Chapter 5, 21 CFR introduces the concept of and basic requirements for preventive controls. Recall that a preventive control (The supply chain program described in this chapter is not the same as a supply chain program typically thought of by the animal food industry. In fact, supplychain applied controls may have limited applicability

More information

Public Health Service Food and Drug Administration Silver Spring, MD WARNING LETTER VIA UPS WL:

Public Health Service Food and Drug Administration Silver Spring, MD WARNING LETTER VIA UPS WL: Department of Health and Human Services Public Health Service Food and Drug Administration Silver Spring, MD 20993 WARNING LETTER VIA UPS WL: 320-16-04 December 17, 2015 Mr. Avinash Joshi Quality Head

More information

BATCH DISPOSITION BATCH DISPOSITION REGULATION. Jakarta 14 DECEMBER Speaker: MIMI VIRLANY SYAHPUTRI, M.Sc., S.si., APT

BATCH DISPOSITION BATCH DISPOSITION REGULATION. Jakarta 14 DECEMBER Speaker: MIMI VIRLANY SYAHPUTRI, M.Sc., S.si., APT BATCH DISPOSITION REGULATION Jakarta 14 DECEMBER 2017 Speaker: MIMI VIRLANY SYAHPUTRI, M.Sc., S.si., APT Definition Batch disposition = product disposition = lot disposition The documented control, status

More information

Sun Pharmaceutical Industries Ltd. 12/17/15

Sun Pharmaceutical Industries Ltd. 12/17/15 1 of 7 02/18/2016 11:34 AM U.S. Food and Drug Administration Protecting and Promoting Your Health Sun Pharmaceutical Industries Ltd. 12/17/15 Department of Health and Human Services Public Health Service

More information

HOT TOPICS CURRENTLY IN FOCUS BY THE US-FDA. Roy T. Cherris - Managing Partner

HOT TOPICS CURRENTLY IN FOCUS BY THE US-FDA. Roy T. Cherris - Managing Partner HOT TOPICS CURRENTLY IN FOCUS BY THE US-FDA Roy T. Cherris - Managing Partner INTRODUCTION: DATA? Why is Data Important? Data is as important as the research and products we produce Everything we do in

More information

Request for Quality Metrics Guidance for Industry

Request for Quality Metrics Guidance for Industry Request for Quality Metrics Guidance for Industry DRAFT GUIDANCE This guidance document is being distributed for comment purposes only. Comments and suggestions regarding this draft document should be

More information

Ensuring An Effective Quality System. M. Kowolenko, Ph.D. SVP, Biopharmaceutical Operations & Technology

Ensuring An Effective Quality System. M. Kowolenko, Ph.D. SVP, Biopharmaceutical Operations & Technology Ensuring An Effective Quality System M. Kowolenko, Ph.D. SVP, Biopharmaceutical Operations & Technology Role of the Quality Unit Compliance with all relevant regulations and commitments made in license

More information

Supplier Quality Agreements

Supplier Quality Agreements Supplier Quality Agreements Dan O Leary CBA, CQA, CQE, CRE, SSBB, CIRM President Ombu Enterprises, LLC Dan@OmbuEnterprises.com www.ombuenterprises.com 603-209-0600 OMBU ENTERPRISES, LLC 1 Outline QSR Requirements

More information

The Application of Pharmaceutical cgmp to Live Bacterial Products. James Harris Business Development Manager

The Application of Pharmaceutical cgmp to Live Bacterial Products. James Harris Business Development Manager The Application of Pharmaceutical cgmp to Live Bacterial Products James Harris Business Development Manager The Objective CMC expectations of a cgmp live bacterial biopharmaceutical project Overview Define

More information

How to Select a Microbiology Contract Testing Laboratory? Tony Cundell, Ph. D. Microbiological Consulting, LLC Scarsdale, New York

How to Select a Microbiology Contract Testing Laboratory? Tony Cundell, Ph. D. Microbiological Consulting, LLC Scarsdale, New York How to Select a Microbiology Contract Testing Laboratory? Tony Cundell, Ph. D. Microbiological Consulting, LLC Scarsdale, New York June 13, 2017 IVT Microbiology Week 1 Presentation Overview Rationale

More information

Page 1 of 5 Home Inspections, Compliance, Enforcement, and Criminal Investigations Compliance Actions and Activities Warning Letters 2014 Inspections, Compliance, Enforcement, and Criminal Investigations

More information