Changes to an Approved Product

Save this PDF as:
 WORD  PNG  TXT  JPG

Size: px
Start display at page:

Download "Changes to an Approved Product"

Transcription

1 Changes to an Approved Product Chemistry, Manufacturing and Controls By Khandan Baradaran, PhD and Peggy Berry, MBA, RAC It is a huge achievement for any company to obtain licensing rights to an approved pharmaceutical product. Postapproval challenges are inherent in the marketing and distribution process. Of these, foreseen and unforeseen changes to the manufacturing process top the list. Sponsors of newly licensed products may encounter issues that were not fully realized during development, such as long-term stability issues, which only come to light within the first two years postapproval. Such unforeseen issues require corrective actions that usually impact the approved manufacturing process in one or more ways. At the same time, there are likely to be foreseen, legitimate needs to make changes to the approved product or production process. Postapproval changes can be relatively minor, such as like-for-like changes to manufacturing equipment; or they can be more critical, such as a change to the drug product container closure. The latter is common for products that undergo lifecycle management. For example, the company may, develop and obtain approval for the drug supplied in a vial, then plan to obtain approval for a prefilled syringe presentation for ease of patient use. Certain changes must be reported to regulatory authorities, and in some instances, the 30 April 2008

2 sponsor may be prevented from distributing the drug manufactured with a particular change until the regulatory authority has reviewed and approved the change. In the US, manufacturing changes can be reported to FDA in supplements to the marketing/license application and in annual reports. The four reporting categories are: prior-approval supplement (PAS), changes being effected (CBE), changes being effected in 30 days (CBE-30) and annual report (AR) (Table 1). Some changes are transparent to the license 1 and do not need to be reported. It is the regulatory professional s job to determine whether a change needs to be reported, and whether the regulatory agency needs to approve the change before distribution. This can be a complex task, involving extensive oversight, reporting and control within a company to identify a change, assess the impact to the drug product, tag out the impacted drug product lots until approval is obtained, and report the change to the relevant authorities. The complexity increases with more products in the manufacturing plant that may require changes, and marketing rights in multiple countries. In the US, licensed pharmaceutical drug manufacturers pay a postmarketing user fee to market the drug (see Prescription Drug User Fee Regulatory Focus 31

3 Table 1. Impact Assessment and Reporting of CMC Changes Degree of Change Impact Assessment Reporting Category Major change substantial potential to have an adverse effect prior-approval supplement (PAS) Moderate change moderate potential to have an adverse event changes being effected in 30 days (CBE-30) Certain moderate changes moderate potential to have an adverse event and FDA concurrence obtained for product distribution changes being effected (CBE or CBE-0) when supplement received Minor change minimal potential to have an adverse event annual report Act (PDUFA)). 2 Fees are collected from licensed pharmaceutical companies on a per-product (each approved dosage form) basis. Annual establishment fees and fees required for supplements with clinical information also apply. In return, FDA is required to review certain supplements within a specified time frame (four months for most PAS, 30 days for CBE-30); some supplements have no time constraints. Impact Assessment Each change must be assessed to determine whether it needs to be reported. Changes that must be reported include changes to the product, production process, quality controls, equipment or facilities established in the approved license application. 3,4 To assess a change, the regulatory professional must determine what potential adverse effects it could have on the product s identity, strength, quality, purity or potency as related to the product s safety or effectiveness. Which of the four reporting categories applies depends upon this product impact assessment. In addition to determining which submission type to file (based upon potential effect on product quality attributes), the impact assessment must include any repercussions for validation; equipment, the manufacturing process step, analytical methods or any combination Table 2. Major Changes (Substantial Potential of AE) Requiring Prior-approval Supplement Filing Process Changes change to validated sterilization process (sterile products) new/revised recovery procedures new/revised purification process, including column change change in process solution chemistry or formulation change in processing step sequence or processing step addition, deletion or substitution reprocessing a product without a previously approved protocol scale-up requiring larger fermenter, bioreactor or purification equipment (biologics) Changes to Analytical Methods Other Major Changes Triggers for Additional Clinical or Nonclinical Studies replacing an existing analytical method with a new one (e.g., RP-HPLC to replace ELISA) establishing wider specification limits deleting a specification or analytical method eliminating tests from the stability protocol assay transfer to another QC laboratory change in product composition or dosage form or ancillary components expiration dating period extension or change in storage temperature container/closure change change in manufacturing site conversion from single- to multi-product manufacturing area(s) culture growth time extension resulting in significant increase in cell doublings beyond validated parameters (biologics) cell line change or new MCB (biologics) formulation or excipient changes multiple simultaneous changes (e.g., scale-up, media components impacting titer, change in purification resin type, container closure) any change resulting in an observed change in activity assay (e.g., out-of-specification or trend regarding licensed specifications and manufacturing history) significant impurity profile increase 32 April 2008

4 Table 3. Moderate Change Examples (moderate potential of AE) Requiring CBE Supplement Filing Changes Being Effected in 30 Days (CBE-30) Changes Being Effected (CBE-0) addition of duplicated process change (e.g., fermentation) or unit process (e.g., purification column) with no change in process parameters manufacture of an additional product in previously approved multiple-product manufacturing area with same equipment/personnel if no changes in validated cleaning and changeover procedures additional release tests and/or tightening of specifications changing from one compendial test method to another replacing an in-house reference standard of quality systems may need to be revalidated. Validation data may need to be included in the submission package with the data that demonstrate comparability before and after the change. Submissions In the US, the waiting period when reporting can be reduced if a protocol for assessing and determining comparability is submitted and approved prior to any changes being made. The comparability protocol should describe the change or possible changes, planned testing and revalidation studies and conformance to prespecified acceptance criteria. This, in effect, allows a sponsor to obtain FDA agreement on what studies are expected when certain changes are made, and acceptable comparability outcomes. A comparability protocol should be filed with the initial marketing application or as a PAS. It allows FDA and the sponsor to agree on methods to be used to demonstrate comparability between the old and new manufacturing process, including: analytical methods and acceptance criteria stability data requirements 5 statistical tools nonclinical studies, if needed clinical studies, if needed Table 2 gives examples of major changes. Significant process changes, formulation changes, widening acceptance criteria, replacing analytical methods, scale-up and container closure changes typically require PAS. Triggers for additional clinical or nonclinical studies may include formulation changes or new excipients, significant changes to activity or impurity levels and, for biologics, cell line changes. Regulators are especially concerned about the potential immunogenicity impact of formulation or cell line changes for biologics. Certain moderate changes can be reported as CBEs. Sponsors may submit a CBE-0 or CBE-30, depending in part upon the impact assessment as well as discussions with FDA in advance of the submission to obtain concurrence on the filing strategy and timing of the change (Table 3). Some examples are the addition of a duplicate process chain or operation unit that does not impact licensed/approved process parameters, the addition of new products in the licensed manufacturing areas, changes to compendial test methods and the replacement of reference standards. CBE reporting is a rather gray area, and the reporting category may change depending upon the availability (or lack thereof) of agreements with FDA and internal strategic needs. Changes with the least potential for impacting product quality attributes should be submitted in the Annual Report (Table 4). These can include additional or morestringent release or stability specifications, more-stringent stability test parameters or time points, and modifications to analytical test procedures that do not change the basic test methodology or acceptance criteria. Drug substance and drug product stability trends and data are also included in the AR. Summary Postapproval changes to manufacturing processes and quality controls present unique challenges to licensed drug companies and must be assessed for their potential impact. The regulatory professional plays a pivotal role in assessing the change, obtaining feedback from regulatory authorities, and acting as the liaison between Table 4. Minor Change Examples (Minimal Potential for AEs) to File in Annual Report Annually reportable modification in analytical procedures with no change in basic test methodology or release specifications additional release tests and/or tightening of specifications replacing an in-house reference standard more-stringent stability test parameters or time points report of drug substance and drug product trend analyses (release and stability data) Regulatory Focus 33

5 the regulatory agencies and the in-house quality, manufacturing and supply chain groups. F REFERENCES 1. Sufficiently described in the license, such as a like-forlike equipment change. 2. For more information and to see the updated PDUFA Accessed 4 January Labeling change reporting requirements are beyond the scope of this article and are not discussed herein CFR and 21 CFR Stability data may be required for both API/drug substance and final drug product, depending upon the potential impact of the change to either. Additional Bibliographic Material 1. International Conference on Harmonization (ICH) Q5E: Comparability of Biotechnological Products Subject to Changes in their Manufacturing Process November CFR (New Drug) CFR (Biologic) 4. Changes to an Approved NDA or ANDA. FDA CBER/ CDER, April Changes to an Approved Application for Specified Biotechnology and Specified Synthetic Biological Products. FDA CBER/CDER, July Comparability Protocols Protein Drug Products and Biological Products. FDA CBER/CDER, Draft September Demonstration of Comparability of Human Biological Products, Including Therapeutic Biotechnology Derived Products. FDA CBER/CDER, April AUTHORS Khandan Baradaran, PhD, is a Senior Manager of Regulatory Affairs at Dyax Corp. Prior to joining Dyax, she held management positions in analytical development, quality control, quality assurance and regulatory affairs at Biogen Idec. Peggy J. Berry, MBA, RAC, is Senior Vice President, Quality and Regulatory Affairs at Dyax Corp., responsible for the strategic management and oversight of the quality and regulatory affairs departments. Previously she was director of regulatory affairs at AstraZeneca and managed the regulatory and clinical departments at Dey Laboratories. Berry also has worked for ILEX Oncology and Cato Research Ltd.) and in FDA review divisions. 34 April 2008

Reporting Changes to an Approved NDA or ANDA

Reporting Changes to an Approved NDA or ANDA Coalition for PET Drug Approval Radiopharmaceutical Sciences Council Reporting Changes to an Approved NDA or ANDA SNMMI Annual Meeting - June 8, 2015 Michael Nazerias Sr. Director RA/QA PETNET Solutions,

More information

Guidance on CMC for Phase 1 and Phases 2/3 Investigational New Drug Applications

Guidance on CMC for Phase 1 and Phases 2/3 Investigational New Drug Applications Guidance on CMC for Phase 1 and Phases 2/3 Investigational New Drug Applications Charles P. Hoiberg, Ph.D. Executive Director, Pfizer Board Member, FDA Alumni Association DIA China, Beijing, China May

More information

Post-Approval Change Management: Challenges and Opportunities An FDA Perspective

Post-Approval Change Management: Challenges and Opportunities An FDA Perspective CMC Workshop From Drug Development to Global Supply to Patients April 15-17, 2013, Washington, DC Post-Approval Change Management: Challenges and Opportunities An FDA Perspective Christine M. V. Moore,

More information

Overview of Drug Development: the Regulatory Process

Overview of Drug Development: the Regulatory Process Overview of Drug Development: the Regulatory Process Roger D. Nolan, PhD Director, Project Operations Calvert Research Institute November, 2006 Adapted from course taught by Cato Research Background: Roger

More information

Overview of Pre-Approval Inspections

Overview of Pre-Approval Inspections Overview of Pre-Approval Inspections Presented by: Kelli F. Dobilas NWJ-DO Pre-Approval Manager Pre-Approval Drug Inspections What are Pre-Approval Inspections? One of the last reviews of the drug approval

More information

February 2006 Procedural

February 2006 Procedural Guidance for Industry Reports on the Status of Postmarketing Study Commitments Implementation of Section 130 of the Food and Drug Administration Modernization Act of 1997 U.S. Department of Health and

More information

Opinions expressed in this presentation are those of the speaker and do not necessarily reflect the views or policies of the FDA

Opinions expressed in this presentation are those of the speaker and do not necessarily reflect the views or policies of the FDA Opinions expressed in this presentation are those of the speaker and do not necessarily reflect the views or policies of the FDA Generic Drugs Application and Regulatory Review Naiqi Ya, Ph.D. Deputy Director

More information

Guidance for Industry

Guidance for Industry Guidance for Industry Changes to an Approved NDA or ANDA U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) April 2004 CMC Revision

More information

Generic Drug Review.

Generic Drug Review. Generic Drug Review Hanan Kakish Medical Research Scientist, M.Sc. Pharm. Middle East and North Africa Post Office of International Programs U.S. Food and Drug Administration Hanan.kakish@fda.hhs.gov Kakishh@state.gov

More information

Content and Format of Chemistry, Manufacturing, and Controls (CMC) in a New Drug Application (NDA)

Content and Format of Chemistry, Manufacturing, and Controls (CMC) in a New Drug Application (NDA) Content and Format of Chemistry, Manufacturing, and Controls (CMC) in a New Drug Application (NDA) - -PET Drug Products- Ravindra K Kasliwal, Ph.D. Office of New Drug Quality Assessment Center for Drug

More information

LIBRARY GUIDE: Pharmaceutical GMPs

LIBRARY GUIDE: Pharmaceutical GMPs LIBRARY GUIDE: Pharmaceutical GMPs Table of Contents Overview............................................................................ 3 Courses Listed by Functional Area....................................................

More information

Guidance for Industry

Guidance for Industry Guidance for Industry Content and Format of Investigational New Drug Applications (INDs) for Phase 1 Studies of Drugs, Including Well-Characterized, Therapeutic, Biotechnology-derived Products Center for

More information

Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: quality issues (revision 1)

Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: quality issues (revision 1) 22 May 2014 EMA/CHMP/BWP/247713/2012 Committee for Medicinal Products for Human Use (CHMP) Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance:

More information

Raw materials in the manufacture of biotechnology products: Regulatory considerations

Raw materials in the manufacture of biotechnology products: Regulatory considerations Raw materials in the manufacture of biotechnology products: Regulatory considerations Ruth Cordoba-Rodriguez, Ph.D. Division of Monoclonal Antibodies Office of Biotechnology Products 2009 CMC Strategy

More information

Guideline for Industry

Guideline for Industry Guideline for Industry Quality of Biotechnological Products: Stability Testing of Biotechnological/Biological Products July 1996 ICH Q5C Table of Contents I. INTRODUCTION (1)... 1 II. SCOPE OF THE ANNEX

More information

Guidance for Industry. Q10 Pharmaceutical Quality System

Guidance for Industry. Q10 Pharmaceutical Quality System Guidance for Industry Q10 Pharmaceutical Quality System U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center for Biologics Evaluation

More information

Analytical Procedures and Methods Validation for Drugs and Biologics

Analytical Procedures and Methods Validation for Drugs and Biologics Analytical Procedures and Methods Validation for Drugs and Biologics Guidance for Industry U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research

More information

Combination Products Regulation in the United States

Combination Products Regulation in the United States Combination Products Regulation in the United States Presenter: Scott Sardeson RAC US/EU 3M Health Care St. Paul, MN USA 1 Presentation Outline Combination products Definitions and Regulations Jurisdiction

More information

Valentina Gualato, Ph.D. Process Development Scientist

Valentina Gualato, Ph.D. Process Development Scientist COMPANY PRESENTATION Quality and Innovation Valentina Gualato, Ph.D. Process Development Scientist MISSION areta international is a biotech company dedicated to the contract development and manufacturing

More information

CATEGORY Advertising. CATEGORY Biopharmaceutics. CATEGORY Biosimilarity

CATEGORY Advertising. CATEGORY Biopharmaceutics. CATEGORY Biosimilarity CATEGORY Advertising Guidance Agenda: New & Guidances CDER is Planning to Publish During Calendar Year 2016 (See the Good Guidance Practices (GGPs) regulation on this Web page or 21 CFR 10.115 for details

More information

ANDA Submissions Refuse to Receive for Lack of Proper Justification of Impurity Limits Guidance for Industry

ANDA Submissions Refuse to Receive for Lack of Proper Justification of Impurity Limits Guidance for Industry Reprinted from FDA s website by EAS Consulting Group, LLC ANDA Submissions Refuse to Receive for Lack of Proper Justification of Impurity Limits Guidance for Industry DRAFT GUIDANCE This guidance document

More information

BIOTECHNOLOGY OPERATIONS

BIOTECHNOLOGY OPERATIONS BIOTECHNOLOGY OPERATIONS Principles and Practices Michael J. Roy TECHNISCHE INFORMATION SBIBLIOTHEK UNIVERSITATSBIBLIOTHEK HANNOVER CRC Press TaylorStFrancis Croup Boca Raton London New York CRC Press

More information

Roles & Responsibilities of the Sponsor

Roles & Responsibilities of the Sponsor Roles & Responsibilities of the Sponsor Developed by Center for Cancer Research, National Cancer Institute, NIH Endorsed by the CTN SIG Leadership Group Objectives Funding for clinical research comes from

More information

ABBREVIATED NEW DRUG APPLICATION (ANDA)

ABBREVIATED NEW DRUG APPLICATION (ANDA) CHAPTER-II ABBREVIATED NEW DRUG APPLICATION (ANDA) by: j. jayasutha lecturer department of pharmacy practice Srm college of pharmacy srm university ABBREVIATED NEW DRUG APPLICATION INTRODUCTION ANDA is

More information

Risk-Based Change Management Using QbD Principles

Risk-Based Change Management Using QbD Principles Risk-Based Change Management Using QbD Principles Lynne Krummen, Ph.D. VP, Global Head, Technical Regulatory Biologics Genentech, a member of the Roche Group CMC Forum 2013 Tokyo, Japan Presentation Outline

More information

Guidance for Industry

Guidance for Industry Guidance for Industry Major, Minor, and Telephone Amendments to Abbreviated New Drug Applications Comments and suggestions regarding this document should be submitted within 90 days of publication in the

More information

Technology Transfer of CMC Activities for MAb Manufacturing. 2010 ge healthcare (www.gelifesciences.com)

Technology Transfer of CMC Activities for MAb Manufacturing. 2010 ge healthcare (www.gelifesciences.com) M a n u f a c t u r i n g OPERATIONS Technology Transfer of CMC Activities for MAb Manufacturing by Patricia Seymour, Susan Dana Jones, Howard L. Levine With combined 2009 revenues estimated to be over

More information

Biologic License Application (BLA) Checklist

Biologic License Application (BLA) Checklist Biologic License Application (BLA) Checklist Under the Public Health Services Act, the Federal Food and Drug Administration (FDA) has been given the authority, concurrent with its authority under the Food

More information

Library Guide: Pharmaceutical GMPs

Library Guide: Pharmaceutical GMPs Library Guide: Pharmaceutical GMPs Table of Contents Overview...3 Courses Listed by Functional Area... 4 Course Descriptions: A Step-by-Step Approach to Process Validation (PHDV79)... 7 A Tour of the FDA

More information

Guidance for Industry

Guidance for Industry Guidance for Industry Container and Closure System Integrity Testing in Lieu of Sterility Testing as a Component of the Stability Protocol for Sterile Products For questions on the content of the guidance,

More information

Analytical Method Validation in Early Drug Development US FDA Perspective

Analytical Method Validation in Early Drug Development US FDA Perspective Analytical Method Validation in Early Drug Development US FDA Perspective Linda Ng, Ph.D. Office of Manufacturing & Product Quality, Office of Compliance Best Practices and Application of GMPs for Small

More information

Change Management Protocols: Overview and Comparison of Regulatory Procedures in US and EU. Dr Teresa Pepper May 2013

Change Management Protocols: Overview and Comparison of Regulatory Procedures in US and EU. Dr Teresa Pepper May 2013 Change Management Protocols: Overview and Comparison of Regulatory Procedures in US and EU Dr Teresa Pepper May 2013 Agenda US and EU Overview of Change Management Protocols When might a CP be useful for

More information

Risk Evaluation and Mitigation Strategies: Modifications and Revisions Guidance for Industry

Risk Evaluation and Mitigation Strategies: Modifications and Revisions Guidance for Industry Risk Evaluation and Mitigation Strategies: Modifications and Revisions Guidance for Industry The portion of this guidance document setting forth the submission procedures for risk evaluation and mitigation

More information

An FDA Perspective on Post- Approval Change Management for PAT and RTRT

An FDA Perspective on Post- Approval Change Management for PAT and RTRT An FDA Perspective on Post- Approval Change Management for PAT and RTRT IFPAC 2015 January 26, 2015 Christine M. V. Moore, Ph.D. Acting Director, Process and Facilities FDA/CDER/OPQ Post-Approval Changes

More information

Question-based Review for ANDAs

Question-based Review for ANDAs Question-based Review for ANDAs Chi-wan Chen, Ph.D. Executive Director, Pfizer Member, FDA Alumni Association DIA China, Beijing, China May 15-18, 2011 Disclosures I am currently an employee of Pfizer,

More information

New Drug Application (NDA) Checklist

New Drug Application (NDA) Checklist New Drug Application (NDA) Checklist New Drug Applications (NDA) are very complex and detailed. It is difficult to know whether a company has included all of the information that is required by the applicable

More information

May 18, 2011 Beijing, China. SHAO Jun, Ph.D.

May 18, 2011 Beijing, China. SHAO Jun, Ph.D. Development & The US FDA Approval of Generic Drugs May 18, 2011 Beijing, China SHAO Jun, Ph.D. Agenda About Generic Drugs Business Strategy for Generic Drugs Generic Drug Product Development Generic Drug

More information

Best Practices In Ensuring Quality Standards When Outsourcing To Contract Manufacturers, Licensees And Consultants

Best Practices In Ensuring Quality Standards When Outsourcing To Contract Manufacturers, Licensees And Consultants Best Practices In Ensuring Quality Standards When Outsourcing To Contract Manufacturers, Licensees And Consultants Alex D. Kanarek, PhD BioProcess Technology Consultants, Inc. Strategic Institute Quality

More information

Preparing for the Pre-Approval Inspection What to do Before the FDA Arrives. Barry A. Friedman, Ph.D. Consultant

Preparing for the Pre-Approval Inspection What to do Before the FDA Arrives. Barry A. Friedman, Ph.D. Consultant Preparing for the Pre-Approval Inspection What to do Before the FDA Arrives Barry A. Friedman, Ph.D. Consultant FDA Overview FDA is a consumer protection agency within the Department of Health & Human

More information

FDA s Question-based Review (QbR): A Risk-based Pharmaceutical Quality Assessment Tool

FDA s Question-based Review (QbR): A Risk-based Pharmaceutical Quality Assessment Tool FDA s Question-based Review (QbR): A Risk-based Pharmaceutical Quality Assessment Tool Jennifer A. Maguire, Ph.D., OGD Sharmista Chatterjee, Ph.D., ONDQA CDER, FDA ASQ509 Biomed/Biotech SIG December 5,

More information

Career Opportunities at FDA From a regulatory scientist perspective. Ke Zhang, Ph.D. U.S. Food and Drug Administration Silver Spring, MD

Career Opportunities at FDA From a regulatory scientist perspective. Ke Zhang, Ph.D. U.S. Food and Drug Administration Silver Spring, MD Career Opportunities at FDA From a regulatory scientist perspective Ke Zhang, Ph.D. U.S. Food and Drug Administration Silver Spring, MD Disclaimers 1. The views expressed in this presentation are those

More information

Excipients Facing Increased Scrutiny How to Use Secondary Reference Standards to Help Maintain Regulatory Compliance

Excipients Facing Increased Scrutiny How to Use Secondary Reference Standards to Help Maintain Regulatory Compliance Excipients Facing Increased Scrutiny How to Use Secondary Reference Standards to Help Maintain Regulatory Compliance by Tom Savage, NSF International Since 2008, when patient deaths were first linked to

More information

POLICY AND PROCEDURES OFFICE OF NEW DRUGS. Good Review Practice: Management of Breakthrough Therapy-Designated Drugs and Biologics.

POLICY AND PROCEDURES OFFICE OF NEW DRUGS. Good Review Practice: Management of Breakthrough Therapy-Designated Drugs and Biologics. POLICY AND PROCEDURES OFFICE OF NEW DRUGS Good Review Practice: Management of Breakthrough Therapy-Designated Drugs and Biologics Table of Contents PURPOSE...1 BACKGROUND...2 POLICY...3 ROLES AND RESPONSIBILITIES...4

More information

Guidance for Industry Classifying Resubmissions in Response to Action Letters

Guidance for Industry Classifying Resubmissions in Response to Action Letters Guidance for Industry Classifying Resubmissions in Response to Action Letters U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center

More information

Guidance for Industry

Guidance for Industry Guidance for Industry Q8, Q9, and Q10 Questions and Answers(R4) U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center for Biologics

More information

Extemporaneously Prepared Early Phase Clinical Trial Materials

Extemporaneously Prepared Early Phase Clinical Trial Materials Extemporaneously Prepared Early Phase Clinical Trial Materials Richard Hoffman, MS, RAC Eli Lilly & Co. Regulatory Advisor International Consortium for Innovation & Quality in Pharmaceutical Development

More information

A Risk Assessment of Pre-Licensure Manufacturing Changes

A Risk Assessment of Pre-Licensure Manufacturing Changes A Risk Assessment of Pre-Licensure Manufacturing Changes Patrick G. Swann, Ph.D. Deputy Director Division of Monoclonal Antibodies Office of Biotechnology Products Office of Pharmaceutical Science FDA-CDER

More information

INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE

INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE ICH HARMONISED TRIPARTITE GUIDELINE THE COMMON TECHNICAL DOCUMENT FOR THE REGISTRATION

More information

ANDA CHECKLIST FOR CTD or ectd FORMAT FOR COMPLETENESS and ACCEPTABILITY of an APPLICATION FOR FILING

ANDA CHECKLIST FOR CTD or ectd FORMAT FOR COMPLETENESS and ACCEPTABILITY of an APPLICATION FOR FILING ANDA CHECKLIST FOR CTD or ectd FORMAT FOR COMPLETENESS and ACCEPTABILITY of an APPLICATION FOR FILING For More Information on Submission of an ANDA in Electronic Common Technical Document (ectd) Format

More information

Although not specifically

Although not specifically Change Control: Seven Pharmaceutical Manufacturers Share Their Experiences Individuals from seven different pharmaceutical companies met to discuss change in the pharmaceutical industry, what a change

More information

Regulatory Strategy 101

Regulatory Strategy 101 Regulatory Strategy 101 By Meredith Brown-Tuttle, RAC What is regulatory strategy? As a regulatory associate you hear the word strategy bandied about without any real definition. You know that is what

More information

Data Standards Strategy. Version: 1.0

Data Standards Strategy. Version: 1.0 Data Standards Strategy Version: 1.0 Document Date: December 5, 2012 Version Number REVISION HISTORY Implemented By Revision Date Description of Change 1.0 CDER DSPB December 5, 2012 Initial Document The

More information

Guidance for Industry

Guidance for Industry Guidance for Industry INDs for Phase 2 and Phase 3 Studies Chemistry, Manufacturing, and Controls Information U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation

More information

Introduction to Drug Naming. Angela G. Long, M.S. Senior Vice President, Global Alliances and Organizational Affairs

Introduction to Drug Naming. Angela G. Long, M.S. Senior Vice President, Global Alliances and Organizational Affairs Introduction to Drug Naming Angela G. Long, M.S. Senior Vice President, Global Alliances and Organizational Affairs What s in a Name? International Nonproprietary Names (INN) Sponsored by World Health

More information

PHARMACEUTICAL QUALITY SYSTEM Q10

PHARMACEUTICAL QUALITY SYSTEM Q10 INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE ICH HARMONISED TRIPARTITE GUIDELINE PHARMACEUTICAL QUALITY SYSTEM Q10 Current Step

More information

Data Standards Program Action Plan

Data Standards Program Action Plan Data Standards Program Action Plan Version: 2.2 Document Date: May 25, 2016 REVISION HISTORY Version Number Implemented By Revision Date Description of Change 1.0 CDER DSPB February 21, 2013 Initial Document

More information

Manufacturing process of biologics

Manufacturing process of biologics Manufacturing process of biologics K. Ho Afssaps, France 2011 ICH International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use 2011 ICH 1 Disclaimer:

More information

Step-by-Step Analytical Methods Validation and Protocol in the Quality System Compliance Industry

Step-by-Step Analytical Methods Validation and Protocol in the Quality System Compliance Industry Step-by-Step Analytical Methods Validation and Protocol in the Quality System Compliance Industry BY GHULAM A. SHABIR Introduction Methods Validation: Establishing documented evidence that provides a high

More information

Guidance for Industry

Guidance for Industry Guidance for Industry Q2B Validation of Analytical Procedures: Methodology November 1996 ICH Guidance for Industry Q2B Validation of Analytical Procedures: Methodology Additional copies are available from:

More information

Current Good Manufacturing Practice for PET Drugs - CGMP 21 CFR 212

Current Good Manufacturing Practice for PET Drugs - CGMP 21 CFR 212 Current Good Manufacturing Practice for PET Drugs - CGMP 21 CFR 212 CDER Office of Regulatory Policy Jane Axelrad, JD CDER Office of Compliance Brenda Uratani, Ph.D. CDER ONDQA Ravindra Kasliwal, Ph.D.

More information

Elemental Impurities in APIs and Excipients - GMP Expectations

Elemental Impurities in APIs and Excipients - GMP Expectations Elemental Impurity Requirements in a Global Environment PQRI/USP Workshop, USP, Rockville, Maryland March 31 April 1, 2015 Elemental Impurities in APIs and Excipients - GMP Expectations Vibhakar Shah,

More information

Guidance for Industry

Guidance for Industry Guidance for Industry Scientific Considerations in Demonstrating Biosimilarity to a Reference Product DRAFT GUIDANCE This guidance document is being distributed for comment purposes only. Comments and

More information

Guidance for Industry ANDAs: Stability Testing of Drug Substances and Products

Guidance for Industry ANDAs: Stability Testing of Drug Substances and Products Guidance for Industry ANDAs: Stability Testing of Drug Substances and Products Questions and Answers U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation

More information

Combination Products: A Regulatory Perspective. Kathy Lee, M.S. Associate Chief, Laboratory of Biochemistry DTP/OPB/OPS/CDER/FDA WCBP 2012

Combination Products: A Regulatory Perspective. Kathy Lee, M.S. Associate Chief, Laboratory of Biochemistry DTP/OPB/OPS/CDER/FDA WCBP 2012 Combination Products: A Regulatory Perspective Kathy Lee, M.S. Associate Chief, Laboratory of Biochemistry DTP/OPB/OPS/CDER/FDA WCBP 2012 1 Outline Combination Products Jurisdiction Regulatory Challenges

More information

Breakthrough Therapy CMC Challenges. Ganapathy Mohan, PhD Merck & Company FDA/PQRI Conference October 2015

Breakthrough Therapy CMC Challenges. Ganapathy Mohan, PhD Merck & Company FDA/PQRI Conference October 2015 Breakthrough Therapy CMC Challenges Ganapathy Mohan, PhD Merck & Company FDA/PQRI Conference October 2015 1 Topics Current state of Breakthrough Therapy Designation Merck s experience Closing thoughts

More information

POLICY AND PROCEDURES OFFICE OF NEW DRUGS. NDAs and BLAs: Communication to Applicants of Planned Review Timelines.

POLICY AND PROCEDURES OFFICE OF NEW DRUGS. NDAs and BLAs: Communication to Applicants of Planned Review Timelines. CENTER FOR DRUG EVALUATION AND RESEARCH MAPP 6010.8 Rev. 1 POLICY AND PROCEDURES OFFICE OF NEW DRUGS NDAs and BLAs: Communication to Applicants of Planned Review Timelines Table of Contents PURPOSE...1

More information

The Ever-increasing Complexity of Biotech Changes - A Pledge for Global Convergence

The Ever-increasing Complexity of Biotech Changes - A Pledge for Global Convergence The Ever-increasing Complexity of Biotech Changes - A Pledge for Global Convergence CMC Strategy Forum, Sorrento, May 7th, 2014 Susanne Ausborn, Pharma Technical Regulatory Policy F. Hoffmann-La Roche,

More information

Guidance for Industry

Guidance for Industry Guidance for Industry Process Validation: General Principles and Practices U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center

More information

ASEAN GUIDELINE ON SUBMISSION OF MANUFACTURING PROCESS VALIDATION DATA FOR DRUG REGISTRATION

ASEAN GUIDELINE ON SUBMISSION OF MANUFACTURING PROCESS VALIDATION DATA FOR DRUG REGISTRATION ASEAN GUIDELINE ON SUBMISSION OF MANUFACTURING PROCESS VALIDATION DATA FOR DRUG REGISTRATION TABLE OF CONTENTS 1. INTRODUCTION... 2 2. SCOPE... 2 3. DATA SUBMISSION REQUIREMENTS... 2 4. CONTENT OF DEVELOPMENT

More information

NEW CHEMICAL ENTITIES

NEW CHEMICAL ENTITIES NEW CHEMICAL ENTITIES PIONEERING PARTNER FOR PEPTIDES With more than 40 years of expertise in peptide synthesis, a track record in process development, large-scale manufacturing and outstanding product

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

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

ICH Topic Q 5 E Comparability of Biotechnological/Biological Products

ICH Topic Q 5 E Comparability of Biotechnological/Biological Products European Medicines Agency June 2005 CPMP/ICH/5721/03 ICH Topic Q 5 E Comparability of Biotechnological/Biological Products Step 5 NOTE FOR GUIDANCE ON BIOTECHNOLOGICAL/BIOLOGICAL PRODUCTS SUBJECT TO CHANGES

More information

A FDA Perspective on Nanomedicine Current Initiatives in the US

A FDA Perspective on Nanomedicine Current Initiatives in the US A FDA Perspective on Nanomedicine Current Initiatives in the US Carlos Peña, PhD Office of the Commissioner FDA September 3, 2010 Outline Context Nanotechnology Task Force report summary Identification

More information

Topics for today. Issues: Regulatory Obligations Post-marketing Adverse Event Reporting; MDRs and Safety Reports. Post-marketing Submissions

Topics for today. Issues: Regulatory Obligations Post-marketing Adverse Event Reporting; MDRs and Safety Reports. Post-marketing Submissions Issues: Regulatory Obligations Post-marketing Adverse Event Reporting; MDRs and Safety Reports Martha A. Feldman, RAC Drug & Device Development Co., Inc. Topics for today Post-approval requirements for

More information

A Stability Program for the Distribution of Drug Products

A Stability Program for the Distribution of Drug Products A Stability Program for the Distribution of Drug Products Teresa I. Lucas*, Rafik H. Bishara, and Robert H. Seevers Drug products must be transported in a manner that ensures products will be maintained

More information

POLICY AND PROCEDURES OFFICE OF PHARMACEUTICAL SCIENCE

POLICY AND PROCEDURES OFFICE OF PHARMACEUTICAL SCIENCE POLICY AND PROCEDURES OFFICE OF PHARMACEUTICAL SCIENCE CLARIFICATION TELECONFERENCES BETWEEN SPONSORS, APPLICANTS, OR MASTER FILE HOLDERS AND THE ONDQA REVIEW TEAM Table of Contents PURPOSE...1 BACKGROUND...2

More information

2008 USPC Official 12/1/07-4/30/08 General Chapters: <1225> VALIDATION OF C...Page 1 of 10

2008 USPC Official 12/1/07-4/30/08 General Chapters: <1225> VALIDATION OF C...Page 1 of 10 2008 USPC Official 12/1/07-4/30/08 General Chapters: VALIDATION OF C...Page 1 of 10 1225 VALIDATION OF COMPENDIAL PROCEDURES Test procedures for assessment of the quality levels of pharmaceutical

More information

DEVELOPMENT AND MANUFACTURE OF DRUG SUBSTANCES (CHEMICAL ENTITIES AND BIOTECHNOLOGICAL/BIOLOGICAL ENTITIES) Q11

DEVELOPMENT AND MANUFACTURE OF DRUG SUBSTANCES (CHEMICAL ENTITIES AND BIOTECHNOLOGICAL/BIOLOGICAL ENTITIES) Q11 INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE ICH HARMONISED TRIPARTITE GUIDELINE DEVELOPMENT AND MANUFACTURE OF DRUG SUBSTANCES

More information

QUALITY BY DESIGN (QBD) : A COMPLETE REVIEW

QUALITY BY DESIGN (QBD) : A COMPLETE REVIEW Review Article QUALITY BY DESIGN (QBD) : A COMPLETE REVIEW Nishendu P. Nadpara*, Rakshit V. Thumar, Vidhi N. Kalola, Parula B. Patel Department of Quality Assurance, S. J. Thakkar Pharmacy College, Opp.

More information

Blood, Plasma, and Cellular Blood Components INTRODUCTION

Blood, Plasma, and Cellular Blood Components INTRODUCTION Blood, Plasma, and Cellular Blood Components INTRODUCTION This chapter of the Guideline provides recommendations to Sponsors of Requests for Revision for new monographs for blood, plasma, and cellular

More information

Ideas That Speed Pharma Products To Market

Ideas That Speed Pharma Products To Market Ideas That Speed Pharma Products To Market The increasing complexity of modern pharmaceutical product development poses many challenges when progressing lead compound opportunities. How companies leverage

More information

POST-MASTER S CERTIFICATES in ADVANCED QUALITY ASSURANCE or REGULATORY AFFAIRS

POST-MASTER S CERTIFICATES in ADVANCED QUALITY ASSURANCE or REGULATORY AFFAIRS Temple University - School of Pharmacy 425 Commerce Drive, Suite 175 Fort Washington, PA 19034 Phone: 267.468.8560 Fax: 267.468.8565 POST-MASTER S CERTIFICATES in ADVANCED QUALITY ASSURANCE or REGULATORY

More information

IND Process and Review Procedures (Including Clinical Holds) CONTENTS

IND Process and Review Procedures (Including Clinical Holds) CONTENTS MANUAL OF POLICIES AND PROCEDURES CENTER FOR DRUG EVALUATION AND RESEARCH MAPP 6030.1 REVIEW MANAGEMENT IND Process and Review Procedures (Including Clinical Holds) CONTENTS PURPOSE REFERENCES DEFINITIONS

More information

ectd Digital Handbook Table of Contents

ectd Digital Handbook Table of Contents ectd Digital Handbook Table of Contents Introduction by Emily Ethridge, Editor, FDAnews Part 1 Tutorial Section 1.0 ectd Tutorial Table of Contents. This FDA tutorial, consisting of seven PowerPoint presentations,

More information

Change Management in Development White Paper

Change Management in Development White Paper Change Management in Development White Paper Introduction/Background In 2008, the International Conference on Harmonization published the ICH tripartite guideline titled, Pharmaceutical Quality System:

More information

ICH guideline Q11 on development and manufacture of drug substances (chemical entities and biotechnological/biological entities)

ICH guideline Q11 on development and manufacture of drug substances (chemical entities and biotechnological/biological entities) May 2011 EMA/CHMP/ICH/425213/2011 ICH/ Committee for medicinal products for human use (CHMP) ICH guideline Q11 on development and manufacture of drug substances (chemical entities and biotechnological/biological

More information

CTD Dossier Preparation. Sr.Manager-Regulatory Affairs

CTD Dossier Preparation. Sr.Manager-Regulatory Affairs CTD Dossier Preparation K. Srikantha Reddy Sr.Manager-Regulatory Affairs Medreich Limited Srikanth.k@medreich.com CTD Dossier Preparation CTD (Common Technical Document) contains 5 modules Module 1 Module

More information

Industry Implications of Pharmaceutical Quality ICH Guidelines

Industry Implications of Pharmaceutical Quality ICH Guidelines EIPG General Assembly Industry Implications of Pharmaceutical Quality ICH Guidelines 20 th April 2008 Pharmaceutical Quality Develop a harmonised pharmaceutical quality system applicable across the lifecycle

More information

Pharmaceutical Quality Management System: Current Concept

Pharmaceutical Quality Management System: Current Concept Pharmaceutical Quality Management System: Current Concept Neetu Dubey 1, *, Himanshu Gupta 3, R.K. Sharma 2, Nitin Dubey 1, Nidhi Dubey 4 1. IPS Academy, Indore, Madhya Pradesh, India. 2. Prestige Institute

More information

Annex 6. Guidance on variations to a prequalified product dossier. Preface

Annex 6. Guidance on variations to a prequalified product dossier. Preface Annex 6 Guidance on variations to a prequalified product dossier Preface This guidance document was technically and structurally inspired by the Guideline on dossier requirements for type IA and IB notifi

More information

The 505(b)(2) Drug Development Pathway:

The 505(b)(2) Drug Development Pathway: The 505(b)(2) Drug Development Pathway: When and How to Take Advantage of a Unique American Regulatory Pathway By Mukesh Kumar, PhD, RAC and Hemant Jethwani, MS The 505(b)(2) regulation offers a less expensive

More information

Guideline for Industry

Guideline for Industry Guideline for Industry The Extent of Population Exposure to Assess Clinical Safety: For Drugs Intended for Longterm Treatment of Non-Life- Threatening Conditions ICH-E1A March 1995 GUIDELINE FOR INDUSTRY

More information

Guidance for Industry

Guidance for Industry Guidance for Industry CGMP for Phase 1 Investigational Drugs U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center for Biologics

More information

ICH guideline Q11 on development and manufacture of drug substances (chemical entities and biotechnological/ biological entities)

ICH guideline Q11 on development and manufacture of drug substances (chemical entities and biotechnological/ biological entities) November 2012 EMA/CHMP/ICH/425213/2011 ICH guideline Q11 on development and manufacture of drug substances (chemical entities and biotechnological/ biological entities) Step 5 Transmission to CHMP May

More information

ICH guideline Q10 on pharmaceutical quality system

ICH guideline Q10 on pharmaceutical quality system September 2015 EMA/CHMP/ICH/214732/2007 Committee for Human Medicinal Products Step 5 Transmission to CHMP May 2007 Transmission to interested parties May 2007 Deadline for comments November 2007 Final

More information

Annex 7 Guidelines on pre-approval inspections

Annex 7 Guidelines on pre-approval inspections World Health Organization WHO Technical Report Series, No. 902, 2002 Annex 7 Guidelines on pre-approval inspections 1. General 94 2. Glossary 94 3. Objectives 95 4. Priorities 96 5. Preparation for the

More information

Defining DITA for Pharmaceutical Documentation. an OASIS webinar

Defining DITA for Pharmaceutical Documentation. an OASIS webinar Defining DITA for Pharmaceutical Documentation an ASIS webinar Agenda Welcome & Introductions ASIS Content Challenges in the Pharma Industry James Averback Is DITA the Answer? Steffen Frederiksen The ASIS

More information

Host cell Protein Clearance and Detection: Critical issues for Biopharmaceutical development

Host cell Protein Clearance and Detection: Critical issues for Biopharmaceutical development Host cell Protein Clearance and Detection: Critical issues for Biopharmaceutical development Protein Quantification workshop, Waters: 13 th November 2012 Vincent Monchois, R&D and Pilot Services Manager,

More information

FDA-2012-D :

FDA-2012-D : October 11, 2013 Division of Dockets Management (HFA-305) Food and Drug Administration Department of Health and Human Services 5630 Fishers Lane Room 1061 Rockville, MD 20852 Comments of the Generic Pharmaceutical

More information