Question-based Review (QbR)

Transcription

1 Question-based Review (QbR) Rebecca L. Owen, Ph.D. Team Leader, Feed/Topical Team Division of Manufacturing Technologies ONADE/CVM/FDA Outline Background on CMC Filing Requirements What is QbR? QbR at CVM Advantages of QbR Background CMC Filing Information The goal of the chemistry, manufacturing and controls (CMC) review is to ensure that the product is appropriately designed and that sponsors have methods and controls in place for the manufacture, processing, and packaging of a drug that are adequate for assuring and preserving the identity, strength, quality, and purity of the drug product. 1

2 Federal Food, Drug, and Cosmetic Act Per Section 512(b)(1) of the Federal Food, Drug, and Cosmetic (FFD&C) Act Applicants must identify all of the components of the drug Applicants must provide the composition or formulation of the drug Applicants must provide a full description of the methods, facilities, and controls used in the manufacture, processing and packing of the drug Code of Federal Regulations The Code of Federal Regulations (CFR) Title 21, Part 514.1(b) provides more information on CMC filing requirements. Many sponsors use 21 CFR 514.1(b)(4) and (5) as a template to format CMC submissions. 21 CFR 514.1(b)(4) Applicants shall provide a complete list of all articles used for production of a new animal drug, including the composition of each article. (i) A full list of the components of the new animal drug (ii) A full statement of the composition of the new animal drug (iii) Additional composition information for new animal drugs produced by fermentation 2

3 21 CFR 514.1(b)(5) Applicants shall provide full information in sufficient detail to permit the evaluation of the adequacy of the CMC information as it pertains to the identity, strength, quality and purity of the drug. (i) Outside Firms (ii) Personnel (iii) Facilities and Equipment (iv) New Drug Substance Synthesis (v) Raw Material Controls (vi) Manufacturing Instructions (vii) Analytical Controls (viii) Batch Control Numbering (ix) Container/Closure (x) Stability (xi) Additional Procedures Guidance Documents To further assist applicants in addressing CMC filing issues, guidance documents are available. CVM guidance VICH guidance Applicable human drug guidance from FDA and ICH Guidance Documents - CVM CVM GFI #5: Stability Guidelines CVM GFI #23: Medicated Free Choice Feeds Manufacturing Controls CVM GFI #42: Animal Drug Manufacturing Guidelines CVM GFI #48: Submission Documentation for Sterilization Process Validation in Applications for Human and Veterinary Drug Products CVM GFI #50:Target Animal Safety and Human Food Safety, Drug Efficacy, Environmental and Manufacturing Studies for Teat Antiseptic Products CVM GFI #135: Validation of Analytical Procedures for Type C Medicated Feeds CVM GFI #136: Method Transfer Studies for Type C Medicated Feed Assay Methods CVM GFI #137: Analytical Methods Description for Type C Medicated d Feeds CVM GFI #145: Bioanalytical Method Validation CVM GFI #164: PAT A Framework for Innovative Pharmaceutical Development, Manufacturing and Quality Assurance CVM GFI #169: Drug Substance Chemistry, Manufacturing and Controls Information CVM GFI #190: Container and Closure System Integrity Testing in Lieu of Sterility Testing and a Component of the Stability Protocol for Sterile Products CVM GFI #196: Process Validation: General Principles and Practices ces CVM GFI #211: Residual Solvents Q&A 3

4 Guidance Documents - VICH VICH GL1 & 2: Validation of Analytical Procedures VICH GL3(R): Stability Testing of New Veterinary Drug Substances VICH GL4: Stability Testing of New Veterinary Dosage Forms VICH GL5: Stability Testing Photostability Testing of New Veterinary Drug Substances and Medicinal Products VICH GL8: Stability Testing for Medicated Premixes VICH GL10(R): Impurities in New Veterinary Drug Substances VICH GL11(R): Impurities in New Veterinary Medicinal Products VICH GL17: Testing of New Biotechnological/Biological Products VICH GL18: Residual Solvents in New Veterinary Medicinal Products VICH GL45: Bracketing and Matrixing Designs for Stability Testing of New Veterinary Drug Substances and Medicinal Products VICH GL176: Specifications Test Procedures and Acceptance Criteria for New Veterinary Drug Substances and New Medicinal Products: Chemical Substances Guidance Documents - Other CDER GFI: Validation of Chromatographic Methods CDER GFI: Pharmaceutical Solid Polymorphism ICH Q1E: Evaluation of Stability Data ICH Q7A: Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients The FFD&C Act and the CFR require full descriptions and sufficient detail, but it is not always clear to sponsors and reviewers what specific information should be submitted to meet these requirements. CMC guidance documents are useful, but sponsors and reviewers must refer to many different documents and not all aspects of the CMC section are addressed in guidance. 4

5 What is QbR? A series of questions that focus on the critical information needed to evaluate product quality. Acceptable responses to the questions will satisfy the CMC filing requirements in the FFD&C Act and the CFR. QbR addresses CVM s current CMC filing expectations QbR at FDA A Brief History The QbR concept was pioneered at FDA by CDER s Office of Generic Drugs (OGD) January 2005: OGD drafted a QbR for CMC submissions to Abbreviated New Drug Applications July 2005: OGD solicited comments from staff and stakeholders Fall 2005: Start of pilot QbR program January 2007: Full implementation of QbR for CMC submissions Development of QbR at CVM CVM is adapting the QbR concept for CMC information filed in generic and pioneer animal drug submissions. QbR at CVM is being developed based on: OGD QbR Current filing requirements for (A)NADAs( Current CVM guidance documents Input from CVM reviewers Input from regulated industry 5

6 QbR Format QbR is based on the Common Technical Document - Quality (CTD-Q) format. CVM currently accepts the CTD format for quality (CMC) submissions only. Module 2: 2.3.S (drug substance) and 2.3.P (drug product) Module 3: 3.2.S (drug substance) and 3.2.P (drug product) QbR Format CVM QbR documents will cover the submission of information that should be included in Module 2. Quality Overall Summary (QOS) The QOS provides a summary of the critical information needed for approval of a new animal drug. Supporting documents and data provided in Module 3 QbR Format The QbR format includes high level questions and detail questions under each CTD-Q heading. The high level questions are the critical questions that should be answered to address product quality. The detail questions are intended to clarify what information is needed to address the high level question. The QbR format may also include Questions commonly asked by the applicant, which provide additional explanation about the questions and suggestions for formatting the responses. 6

7 QbR Format High-level question Detailed question Questions commonly asked by the sponsor Stability QbR Example What stability studies support the retest or expiry period and the storage conditions? What are the conditions and tests for the stability program? What is the proposed commercial packaging and how does it compare with the packaging chosen for the stability program? QbR at CVM CVM s QbR document will cover the submission of CMC information for Drug Substance, Drug Product and Sterile Process Validation. CVM s QbR document can be used by contract drug substance manufacturers drug product applicants who manufacture their own drug substances drug product applicants who reference master files for the manufacture of drug substances 7

8 QbR at CVM CVM has presented webinars to share the QbR concept with the regulated industry and the public. Drug Substance, March 2010 Drug Product, July 2010 Sterile Process Validation, February 2011 QbR is the basis of the esubmitter template for the CMC Technical Section. Advantages of QbR Provides more transparency to applicants Provides focus for CVM reviewers Potential increase in one cycle reviews Flexible process that provides the opportunity for focused guidance to address common deficiencies or evolving regulatory and manufacturing science Rebecca Owen Team Leader, Feed/Topical Team (HFV-141) Division of Manufacturing Technologies Office of New Animal Drug Evaluation 8