• Fifth Annual FDA Inspections Summit is a Success
• ADVANCED Bulletproof CAPA Investigations Class
• MedCon Conference for Medical Devices
  
• Free Articles
• Global Regulatory Links
• Free Compliance Resources
• FDA Revises Pharma GMPs
• FDA Exempts Most Phase 1 Clinical Material from Pharmaceutical GMP Regulation
  
• Final cGMPs for Dietary Supplements

Fifth Annual FDA Inspections Summit is a Success

The Fifth Annual FDA Inspections Summit was just held November 3-5, 2010, at the Marriott Bethesda North Hotel and Conference Center in Bethesda, MD. Hosted by FDAnews, the conference offers three tracks: drugs and biologics, medical devices, and clinical trials. The purpose of the conference is to help organizations better prepare for FDA inspections, to better comply with FDA regulations, and to better protect patients and consumers. Barbara Immel has been fortunate to serve as conference chairperson since the conference's inception. Seventy-five percent of participants are directors, vice presidents and managers. FDA speakers this fall included:

* Deb Autor, Director, Office of Compliance, CDER
* Eric Blumberg, Deputy Chief Counsel for Litigation, Office of Chief Counsel
* Lori Lawless, Consumer Safety Officer, Medical Device Specialist, Baltimore District Office, Office of Regulatory Affairs
* Mary Malarkey, Director, Office of Compliance and Biologics Quality, CBER
* Michael Marcarelli, Director of Bioresearch Monitoring, CDRH
* Ann Meeker-O'Connell, Division of Scientific Investigations, Office of Compliance, CDER
* Stephanie Shapley, Bioresearch Monitoring Specialist, Office of Regulatory Affairs
* Larry Spears, Deputy Director for Regulatory Affairs, CDRH

Former FDAers who spoke this fall included:

* Mark Brown, Partner, King & Spalding
* Dave Chesney, Vice President of Strategic Compliance Services, PAREXEL Consulting
* John Godshalk, Senior Consultant, Biologics Consulting Group, Inc.
* Seth Mailhot, Counsel, Nixon Peabody
* Steve Niedelman, Senior Consultant, Crowell & Moring LLP
* Edwin Rivera-Martinez, Vice President, Technical, PAREXEL Consulting
* Vicky Stoakes, President, IntegRx, Inc.
* Monica Wilkins, Senior Director, Corporate Quality Assurance and Compliance, Abbott Laboratories

ADVANCED Conducting Bulletproof CAPA Investigations Class

For many years running, CAPA and investigations have been among the top FDA Form 483 deficiencies of drug, device, and biologic manufacturers. In partnership with FDAnews, Immel Resources is presenting an advanced version of our Conducting Bulletproof CAPA Investigations class. Three courses are scheduled for 2011: April 13-14 in Raleigh, NC; July 13-14 in Chicago, IL; and September 14-15 in Boston, MA.

Topics include FDA regulatory requirements and expectations, how FDA inspects CAPA systems and a firm's investigations, managing CAPA, tips on selecting and training people who conduct investigations, CAPA best practices, a refresher on how to conduct an investigation (problem investigation toolkit), root cause analysis, report writing, interviewing techniques, required FDA notifications, the importance of good surveillance systems (including auditing, customer complaints, supplier controls, and management reviews), preventive action, and risk management as it applies to CAPA. This class has been offered repeatedly throughout the United States over the past few years in Boston, Chicago, Minneapolis, Philadelphia, Raleigh, San Diego, San Francisco Bay Area, and San Juan, Puerto Rico. Immel Resources has been teaching classes on CAPA, investigations, root cause analysis, and writing reports for deviations and failure investigations, for nearly a decade.

Curious about what we discuss in class? Links to two of our articles on CAPA, published in Medical Device & Diagnostic Industry, are shown below, along with a recent blog entry on CAPA Basics that Carl Anderson asked us to write (Carl's Blog on FDA and GxP stuff). Also linked below is a recent presentation Barbara Immel gave on CAPA and investigations at the inaugural MedCon 2010 Conference. If you'd prefer to offer the class on site, and tailor it for your employees, please give us a call at (707) 778-7222.

Converting CAPA to an Advantage

Global Regulatory Links

European Union

Pharmaceutical GMPs

Medical Device Standards (see links on left for Active Implantable, In Vitro Diagnostic, and Medical Device Directives)

Canada

Japan

          Drug GMPs (Ministerial Ordinance on GMP)

          Device GMPs (Ministerial Ordinance on QMS)

          Pharmaceuticals and Medical Devices Agency Japan (English index)

          Ministry of Health, Labor and Welfare (English index)

World Health Organization

WHO GMPs

Australia

          Australian Regulatory Guidelines for Medical Devices (ARGMD)

United States

Drug cGMPs

Preparation of investigational materials
All clinical material for the U.S. must be produced according to current good manufacturing practices. See also the Phase 1 Final Guidance for FDA suggestions concerning the production of phase 1 clinical material. Please also see the brief discussion on FDA Exempts Most Phase 1 Clinical Material from Pharmaceutical GMP Regulation below. You may also wish to see FDA's original guidance on the subject, Guideline on the Preparation of Investigational Drug Products (Human and Animal).

Aseptic Processing Guidance

Final Guidance: Investigating Out-of-Specification (OOS) Test Results for Pharmaceutical Production

Process Validation: General Principles and Practices (draft)

Guideline on General Principles of Process Validation (previous)

CPG on Validation

FDA Compliance Program Guidance Manual on Drug Manufacturing Inspections

FDA Compliance Program Guidance Manual on Inspections of Licensed, Therapeutic Biological Drugs

FDA Compliance Program Guidance Manual on Inspections of Biological Drug Products (vaccines, etc.)

Biotechnology Inspection Guide

Medical Device CGMPs

Blood Product CGMPs

          Blood and blood components

Cosmetics   

Food CGMPs

Veterinary Biologics

Human Tissue

Medical Gases

Part 11 Electronic Records, Electronic Signatures

          U.S. GLPs

          FDA Compliance Program Guidance Manual on GLPs

          OECD GLPs and Guidance Documents

          Japanese GLPs (Ordinance on GLP)

Good Clinical Practices (GCPs)

ICH Guidelines

On September 8, 2008, FDA issued a final rule changing the pharmaceutical GMPs (21 CFR 210 and 211), with the changes becoming effective December 8, 2008. Key changes included requiring the validation of all aseptic processes and also of depyrogenation processes (the validation of all sterilization processes was already required). In addition, if an automated system is used to perform a critical step such as adding materials to the batch, weighing, measuring or subdividing components, determining calculation of yield, verifying the cleaning or maintenance of equipment, and verifying each critical step on the batch record, a sole, human verifier (rather than a two-person double-check) is now required, after the automated step performs the function. Fortunately, the agency did not put through the proposed elimination of required water testing of source or feed water (40 CFR 141), which states required testing and maximum contaminant levels for coliforms (E coli), nitrates, selenium, fluorides, radium, and turbidity. This means that rigorous testing of source or feed water is still required.

If you intend to implement a sole, human verifier (rather than a two-person double-check), Immel Resources recommends that you ensure that the individual performing the sole check is a highly experienced, trained employee, and that the computerized system is validated and remains in a validated state. Using a sole, human verifier is only allowed for the specific GMP tasks discussed above. The final rule, along with comments submitted by Immel Resources re: the proposed rule, are shown below. Pharmaceutical Technology asked Barb to write an article on the proposed changes. "FDA's Direct Final Rule to Change the Pharmaceutical GMPs" was published in June 2008. We believe that this article and our comments were taken into consideration by the agency in developing their final rule. If you would like a copy of the article, please call or write us at (707) 778-7222 or immel@immel.com and we will send you one.

Final Rule

Comments Submitted by Immel Resources LLC

FDA Exempts Most (but not all) Phase 1 Clinical Material from Pharmaceutical GMPs (21 CFR 210/211)

Despite receiving significant adverse comment, on July 15, 2008, FDA issued a final rule exempting most phase 1 clinical material -- the first time people are exposed to a new drug or biologic compound -- from the pharmaceutical GMP regulation (21 CFR 210/211). The exemption became effective September 15, 2008. If the compound is already in use in a phase 2 or phase 3 trial, or if the compound is already marketed, the clinical material must be manufactured following the GMP regulation, 21 CFR 210/211. If , however, an organization is manufacturing a drug compound for use in a phase 1 trial for the first time, the organization does not need to follow the GMP regulation (21 CFR 210/211) when manufacturing the material, although they must follow some standard of GMP in that manufacture (all drugs must be manufactured per the GMPs, per the U.S. Federal Food, Drug and Cosmetic Act.)

FDA has issued a final guidance document with their recommendations on GMPs to follow when manufacturing a compound for use in a phase 1 trial for the first time (see below). Links to the final rule, the final guidance, and our article on the proposed rule, Chipping Away at the GMPs, are shown below, along with a GMP history article written by Barb Immel (A Brief History of the GMPs), submitted with our comments to the agency.

Final Rule

cGMP regulation