Drug Applications

Drug Application Regulatory Compliance

Introduction

FDA ensures the quality of drug products by carefully monitoring drug manufacturers' compliance with its Current Good Manufacturing Practice (CGMP) regulations.  The CGMP regulations for drugs contain minimum requirements for the methods, facilities, and controls used in manufacturing, processing, and packing of a drug product.  The regulations make sure that a product is safe for use, and that it has the ingredients and strength it claims to have.

The approval process for new drug and generic drug marketing applications includes a review of the manufacturer's compliance with the CGMP.  FDA inspectors determine whether the firm has the necessary facilities, equipment, and skills to manufacture the new drug for which it has applied for approval.   Decisions regarding compliance with CGMP regulations are based upon inspection of the facilities, sample analyses, and compliance history of the firm. This information is summarized in reports which represent several years of history of the firms.

FDA can issue a warning letter or initiate other regulatory actions against a company that fails to comply with Current Good Manufacturing Practice regulations.  Failure to comply can also lead to a decision by FDA not to approve an application to market a drug.

This web page provides links to resources to help drug manufacturers comply with the Current Good Manufacturing Practice regulations.

Federal Regulations

Code of Federal Regulations (CFR).  The final regulations published in the Federal Register (daily published record of proposed rules, final rules, meeting notices, etc.) are collected in the CFR.  The CFR is divided into 50 titles which represent broad areas subject to Federal regulations.  The FDA's portion of the CFR interprets the Federal Food, Drug and Cosmetic Act and related statutes.  Section 21 of the CFR contains most regulations pertaining to food and drugs.  The regulations document the actions of drug sponsors that are required under Federal law. 

• 21 Code of Federal Regulations Part 210.  Current Good Manufacturing Practice in Manufacturing Processing, packing, or Holding of Drugs.

• 21 Code of Federal Regulations Part 211.  Current Good Manufacturing Practice for Finished Pharmaceuticals.

• Federal Register Notices for Proposed Changes and Final Changes to CGMP.  The Office of Compliance, Division of Manufacturing and Product Quality web page provides links to in-process changes in CGMP regulations announced in the Federal Register. 

Back to Top

Guidance Documents

Guidance documents represent the Agency's current thinking on a particular subject. These documents are prepared for FDA review staff and drug sponsors to provide guidelines for the processing, content, and evaluation of applications, and for the design, production, manufacturing, and testing of regulated products.  They also provide consistency in the Agency's regulation, inspection and enforcement procedures.  Because guidances are not regulations or laws, they are not enforceable.  An alternative approach may be used if it satisfies the requirements of the applicable statute, regulations, or both.

• Guideline on the Preparation of Investigational New Drug Products (Human and Animal) (Issued 11/1992, Posted 3/2/1998).  This guidance provides practices and procedures for preparing investigational new drug products that comply with certain section of the Current Good Manufacturing Practice (CGMP) regulations for finished pharmaceuticals (Title 21 of the Code of Federal Regulations, Parts 210 and 211.)

• Draft Guidance for Industry:  Investigating Out-of-Specification (OOS) Test Results for Pharmaceutical Production. 9/30/98   This guidance provides the Agency’s current thinking on how to evaluate suspect, or out of specification (OOS) test results. For purposes of this document, the term OOS results includes all suspect results that fall outside the specifications or acceptance criteria established in new drug applications.   

• Draft Guidance for Industry:  ANDAs: Blend Uniformity Analysis.  This guidance provides recommendations on when and how blend uniformity analysis should be performed. The recommendations apply to original ANDAs and supplemental ANDAs for formulation and process changes. The Federal Register notice for this draft is also available.

Back to Top

CDER Manual of Policies and Procedures (MaPPs)

MaPPs are approved instructions for internal practices and procedures followed by CDER staff to help standardize the new drug review process and other activities.  MaPPs define external activities as well.  All MaPPs are available for the public to review to get a better understanding of office policies, definitions, staff responsibilities and procedures.

• 4723.1  Standing Operating Procedures for NDA/ANDA Field Alert Reports. (Issued 10/30/1998, posted 11/02/1998).  This MaPP establishes a system for evaluating new drug application (NDA) and abbreviated new drug application (ANDA) Field Alert Reports and provides instructions to the responsible CDER units for handling those reports.

Back to Top

Compliance Policy Programs and Guidelines

• Compliance References.  This web site from the Office of Regulatory Affairs provides links to compliance policy guides, regulatory procedures manuals, and other compliance related information.  Chapter 4 of the Compliance Policy Guide covers human drugs.

• Compliance Program Guidance Manual.  These programs and instructions are for FDA field inspectors.

• Consistent Application of Current Good Manufacturing Practice Determinations.  FDA cannot approve applications to market new drugs from companies who have been cited for Current Good Manufacturing Practice violations.  Similarly, disapproval of any drug marketing application based upon CGMP deficiencies must also lead to regulatory and/or administrative action against other products produced under the same conditions.

Back to Top

Compliance Questions and Answers

• Human Drug Current Good Manufacturing Practice Notes.  These memos are intended to enhance field/headquarters communications on CGMP issues in a timely manner. The document is a forum to hear and address CGMP questions, provide updates on CGMP projects, and clarify and help apply existing policy to day-to-day activities of FDA staff.

  Back to Top        Back to Drug Applications      

FDA/Center for Drug Evaluation and Research
Last Updated: March 08, 2001
Originator: OTCOM/DML
HTML by  PKS, SJW