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On Friday, August 17, 2007, FDA at least
temporarily dropped its ill-advised reorganization plan for their field
force.
Margaret Glavin, Associate Commissioner for Regulatory Affairs (ACRA),
and head of the agency field force, told employees that "To assure
our success and allow additional time to gather input, I am
cancelling plans for the rollout of all changes to our organizational
structure." Michigan Representative Bart Stupak said in response that
"If it had
been implemented, the FDA's plan could have put the American
public health at an even greater risk." There was major opposition to
FDA's reorganization plan in both the House and Senate, from both
political parties. It is possible that agency leaders will continue to
plan for a future reorganization. The agency has recently announced
that they are planning on outsourcing 322 jobs, a plan which has also
met with Congressional opposition. Reorganization
Details District offices that were to have been
closed or merged included New Jersey to Philadelphia, Detroit
to Cincinnati, San Juan, Puerto Rico to Florida, and Kansas City to
Denver. Regional offices that would have closed were in Atlanta,
Dallas, New York (Jamaica), Philadelphia, and San Francisco (Oakland).
If the plan
were
enacted, at least 260 FDA employees, including 200 lab analysts,
would have lost their jobs, unless they were willing to relocate or
apply for other open, agency positions. Field management was to have
been
centralized to
report to
the ACRA via two deputies: a Deputy for
Operations, and a Deputy for Policy and Risk Management. All field
staff were to have reported to the Deputy for Operations, the districts
via a new
Inspectorate and Compliance Directorate, and the remaining labs via a
new Science Directorate. Imports were also to have been reorganized to
report into a new Import Directorate. The surviving labs would have
been in Atlanta,
Cincinnati, Jefferson, AR, Los Angeles, New York City, and Seattle. Background Proposed bill Conclusion Immel Resources believes the real reason behind the proposed reorganization is deregulation, the desire of the Administration to reduce enforcement of the industry, and to allow the industry to self regulate. FDA is severely underfunded. FDA regulates 25 cents of every dollar spent in the U.S. on food, drugs, medical devices, biologics, animal foods and drugs, and cosmetics, with a budget of less than $2 billion U.S. and approximately 9,000 employees. FDA's budget is the same as that of a single, large school district in the U.S. In an era of significant consumer concern over food and drug safety, including melamine in pet food, antifreeze in toothpaste, E coli in spinach, salmonella in peanut butter, and contaminants in imported fish, not to mention concerns expressed about the approved drugs Vioxx, Ketek, and Avandia -- and the 2004 loss of half of the U.S. flu vaccine supply due to contamination -- this proposal is unconscionable. Let's hope FDA senior management once again remember that their primary mission is to protect the American people.
FDA No Longer
Enforcing GLPs for Devices * Historically, CDRH review divisions have
not required animal safety
studies to follow GLP Immel Resources LLC would like to remind readers that the U.S. GLP regulations must be followed during "nonclinical laboratory studies that support or are intended to support applications for research or marketing permits for products regulated by the Food and Drug Administration, including food and color additives, animal food additives, human and animal drugs, medical devices for human use, biological products, and electronic products." Compliance with the GLPs "is intended to assure the quality and integrity of the safety data." Although FDA can and does exercise enforcement discretion, until the existing regulation is modified or rescinded, it must be followed. Other world GLPs include OECD GLPs and Japanese GLPs; see also the Global Regulatory Links section below. Final cGMPs for Dietary Supplements A third controversial subject is that FDA recently published its final regulation for current, good manufacturing practices (cGMPs) for dietary supplements. A copy of the rule is shown below. The agency stated in its press release announcing the final rule that "to limit any disruption for dietary supplements produced by small businesses, the rule has a three-year phase-in for small businesses. Companies with more than 500 employees have until June 2008 to comply, companies with less than 500 employees have until June 2009 to comply, and companies with fewer than 20 employees have until June 2010 to comply with the regulations." At the same time, FDA published an interim final rule allowing manufacturers to petition the agency to not perform 100% identity testing of their ingredients. A copy of the interim final rule is shown below. The interim final rule includes instructions on how to submit comments to FDA and possibly affect the outcome of the interim final rule. If your organization is involved in manufacturing dietary supplements, we also highly recommend reading the preamble to the regulation (the opening section), which discusses comments the agency received and their thinking regarding the comments. Many people believe that the final rule is a watered down version of the proposed rule. The final rule does not require a quality control unit (even though the proposed rule did), and does not require that all batches of finished product be tested to ensure that they conform to specifications before the batch is released (in the weaker, final rule, a subset of finished batches may be tested instead). It is hard to see how this rule will ensure the quality and safety of dietary supplements. Interim final rule Proposed rule Backgrounder We all must
remain current with FDA trends
and industry
practice. To avoid compliance problems with FDA and world regulatory
agencies, call us today,
toll-free at (866) 778-7222 in the Benefits:
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Audits
P.S. Call
us today! All participants in our
training classes receive a wealth
of resource materials, including pertinent regulations and guidance
documents, and copies of our well-respected articles. Thank you very
much, and we look forward to serving you. CAPA systems
are an area of intense FDA scrutiny. More than 50% of FDA Form 483
observations and warning letters cite CAPA deficiencies. When FDA
inspectors identify problems with a CAPA system, they will inevitably
target the organization's entire quality system. In partnership with FDAnews, Immel Resources is
presenting four sessions of our Conducting Bulletproof CAPA
Investigations class this year:
Second Annual FDA Inspections Summit  Mark your calendars -- the next FDA Inspections Summit will be held October 22-24, 2007 at the Marriott Bethesda North Hotel and Conference Center. The conference is being hosted by FDAnews. Last year's inaugural conference drew a stellar group of participants from many pharmaceutical, biologics, and medical device companies worldwide -- and a stellar list of speakers, many of them current and former FDA. The conference features three tracks: drugs and biologics, medical devices, and clinical trials. Barbara Immel, president of Immel Resources LLC, has been asked to serve as conference chairperson once again, and is delighted to be planning the conference with Jeff Grizzel, Craig Rotzler, and James Culp of FDAnews. We hope that you can join us. Free Sample Issue of Immel Report The Immel Report provides advice and guidance for managers in FDA-regulated industries, and is edited by an industry insider with 25 years of hands-on, industry experience. Here’s how we can help:
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The following are our latest articles in the
trade press: "Compliance Briefing: Increased International Requirements and FDA Cuts," BioPharm International, February 2007 This article discusses new, international regulatory requirements for biologic products sold in Canada, Japan, and Europe. Article also briefly discusses FDA's inadequate funding and two advocacy groups that have formed to request sufficient funding from Congress, FDA Alliance (www.strengthenFDA.org) and Coaltion for a Stronger FDA (www.fdacoalition.org). Clinical Trials (Device Emphasis) "Building Quality into Device Clinical Trials, Part 1," Medical Device & Diagnostic Industry, July 2006 "Building Quality into Device Clinical Trials, Part 2," Medical Device & Diagnostic Industry, October 2006 These articles were written in collaboration with FDA's Bioresearch Monitoring experts in their Center for Devices and Radiological Health, and are based on an earlier FDLI/Clinical Device Group webinar in which FDA speakers presented on this topic.The first article discusses how to better ensure human subject protection and strengthen the sponsor-IRB relationship. It includes deficiencies found during FDA inspections of sponsors, clinical investigators, and institutional review boards. The second article discusses sponsor responsibilities in detail, including tips on selecting investigators, training and re-training, developing the protocol and preventing protocol violations, recordkeeping, and ensuring compliance. Also covered are tips on organizing a submission to expedite FDA review. Investigational Drugs and Biologics "Chipping Away at the GMPs: FDA's Phase 1 Proposals," BioProcess International, September 2006 (free registration required) This article provides compelling reasons why the agency's proposal to exempt phase 1 investigational drug and biologics from the CGMP regulation was flawed. Because of significant adverse comment received from the public, FDA withdrew their direct final rule. For more information, please see the article above and the section below, FDA Withdraws Phase 1 Direct Final Rule. FDA Inspection Trends and Compliance Tips "Current Trends in FDA Inspection Findings and How to Avoid Compliance Pitfalls," BioPharm International Global Compliance Supplement, September 2006 This article provides current FDA inspection trends (common deficiencies cited on FDA Form 483s) concerning good laboratory practices, good clinical practices, and good manufacturing practices for drugs, biologics, medical devices, and active pharmaceutical ingredients. Article also provides tips on internal auditing and recommended training ideas, and has a thorough reference list of recommended FDA compliance resources. CAPA "Best Practices: Managing a CAPA System," Medical Device & Diagnostic Industry, June 2006 Article discusses how to establish and maintain a robust corrective and preventive action system, including tips on selecting data sources, analyzing data regularly, investing in necessary resources, handling investigations and taking appropriate action, documenting and implementing CAPA, and communicating the CAPA. It also includes key practices and 20 tips on training employees how to conduct a problem investigation. Problem Investigations On Problem Investigations, Part 1, BioProcess International, April 2003 (article search and free registration required) On Problem Investigations, Part 2, BioProcess International, May 2003 (article search and free registration required) Part 1 explains when an investigation is warranted, and provides root cause analysis basics, required timelines for investigations, and ideas for investigation procedures. Part 2 discusses how to analyze, research, and document a problem investigation. Article provides tips on conducting problem investigations and provides recommendations from our well-received workshops on conducting investigations. Electronic Records "Part 11: New Guidance Provides Little Guidance," Medical Device & Diagnostic Industry, January 2004 Article discusses FDA's current approach to 21 CFR Part 11, Electronic Records, Electronic Signatures, including their use of enforcement discretion. Article has a checklist on how to implement Part 11 (a Part 11 plan), as well as inventory form ideas and recommended resources on Part 11. For more information on Part 11, please see the article above and the Electronic Records Implementation page in the Library/Resources section of this website. The regulation and recent FDA guidance narrowing the scope of the rule are available below under Global Regulatory Links. FDA Withdraws Phase 1 Direct Final Rule As you may know, the U.S. Food and Drug Administration withdrew their direct final rule to exempt phase 1 material from the CGMP regulation in Spring 2006. FDA withdrew the rule because they received significant adverse comment. Under FDA's direct final rule procedures, the receipt of any significant adverse comment will result in the withdrawal of the direct final rule. Had FDA not received significant adverse comment, the rule would have gone into effect, and phase 1 material would have been exempted from the CGMP regulation. FDA has said that comments that they have received regarding the withdrawn rule will be considered in developing a final rule using the usual notice-and-comment procedures. The proposed rule and the draft guidance, INDs -- Approaches to Complying with CGMP During Phase 1, have not been withdrawn. Immel Resources hopes that the agency will use the comments received to develop proposed GMPs for investigational drugs, as the agency had always considered doing. The CGMP regulation, 21 CFR 210/211, is legally binding and must be followed during the manufacture of clinical (phases I-IV) and commercial drug and therapeutic biologic products intended for use in the United States. Guidance documents are not legally binding, and offer guidance only. Links to the FDA documents are shown below, with a link to a tutorial that we presented in Spring 2006 at the GMP Conference at the University of Georgia, prior to the withdrawal of the rule. Also provided is a link to one of our most popular articles, "A Brief History of the GMPs: The Power of Storytelling." BioProcess International ran an article based on our comments to FDA concerning their proposal to exempt phase 1 investigational material from the CGMP regulation in their September 2006 issue. Special thanks to Anne Montgomery, editor of BioProcess International, for asking to reprint our comments. That article may be accessed here (free registration required) or above under Latest Articles. Tutorial Chipping Away at the GMPs: Understanding FDA's Proposal to Exempt Material for Phase 1 Clinical Trials from CGMP Regulations, and new Draft Guidance A Brief History of the GMPs: The Power of Storytelling (pdf) Current Good Manufacturing Practice Regulation and Investigational New Drugs; Direct Final Rule Proposed Rule Current Good Manufacturing Practice Regulation and Investigational New Drugs; Companion Document to Direct Final Rule Draft Guidance INDs -- Approaches to Complying with CGMP During Phase I (pdf) European Union Medical
Device Directives Canada Drug GMPs
GMP 2002 (html) GMP 2002 (PDF) Device Requirements Medical Device Regulations ISO 13485/ISO 13488 Information Japan
Ministry of Health, Labor and
Welfare (English index) MHLW Ministerial Ordinances on GQP and GMP 2005, and Pharmaceutical Affairs Law, Enforcement Ordinance and Enforcement Regulations 2005/07 In hard copy: Balogh International Online/electronic: Jouhou Koukai Pharmaceutical GMPs in a CD-ROM with other international pharmaceutical requirements: Drumbeat Dimensions World Health Organization
Australia
United States For human and animal drugs,
therapeutic biologics,
and as guide to active pharmaceutical ingredients
Revision of
Certain Labeling Controls Preparation
of investigational materials Final Guidance:
Investigating
Out-of-Specification (OOS) Test Results for Pharmaceutical Production Guideline on General
Principles of Process Validation FDA
Compliance Program Guidance Manual on Drug Manufacturing Inspections FDA Compliance
Program Guidance Manual on
Inspections of Licensed, Therapeutic Biologics Quality System Regulation
FDA Guide to Inspections of Quality Systems (QSIT Manual) FDA CGMP/Quality Systems Guidances FDA Design Control Guidance FDA Medical Device Quality Systems Manual FDA General Principles of Software Validation Guidance Global Harmonization Task Force Guidances Risk management principles Process validation guidance AdvaMed Points to Consider CAPA Design Controls Management Controls Blood and blood components
Cosmetics
Facility requirements for
licensed veterinary biologics
Dietary Supplement cGMPs For a discussion of the new rule, see also the top of this page. Good tissue practice (final rule)
GMP draft guidance
Part 11
Electronic Records, Electronic Signatures Good Laboratory Practices (GLPs) FDA
Compliance Program Guidance Manual on GLPs Good Clinical Practices (GCPs) FDA regulations re: Clinical
Trials
European Clinical Trials Directive information ICH Harmonized Tripartite Guideline for Good Clinical Practice E6 FDA Guidance for Industry: E6 Good Clinical Practice: Consolidated Guidance FDA Compliance Program Guidance Manual, Clinical Investigators FDA Compliance Program Guidance Manual, Sponsors, CROs, and Monitors FDA Compliance Program Guidance Manual, IRBs HIPAA Regulations Other Useful Guidances (a partial list) Active Pharmaceutical Ingredients ICH Harmonized
Tripartite Guidance
Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients Q7 FDA Guidance for Industry: Q7A Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients FDA Compliance Program Guidance Manual on APIs Although we recommend all of the above resources, some of our other favorite FDA resources include the following: FDA Enforcement Story Issued annually, this document contains excellent information to include in a senior management compliance briefing or advanced CGMP training class. FDA Compliance Program Guidance Manual (CPGM) The CPGM provides instructions for FDA staff, and contain questions that you may be asked in your next inspection. Sections are available for foods, cosmetics, biologics, bioresearch monitoring (GLP/GCP compliance), drugs, veterinary medicine and devices. FDA Warning Letters FDA posts warning letters on their web site; they can be searched by company, subject, date, issuing office, or regulation citation, and are great training tools. FDA Frequently Requested 483s FDA posts frequently requested 483s or inspectional observations on their web site. Most are for GMP issues; however, several concern GLP and GCP violations. FDA Enforcement Report Issued twice a month, this publication contains information on recent recalls reported to, and classified by, FDA. FDA Investigations Operations Manual (IOM) This is FDA's primary document on inspection policy and procedures for FDA investigators. It covers sampling, inspections, investigations, regulatory actions and recall activities. |
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