Good
Manufacturing Practices:
[Top]
The FDA's "Pharmaceutical CGMPS for the 21st Century - A Risk Based
Approach"
This
is the final report, dated September 2004, is the culmination of FDA’s
efforts that began in August 2002, to modernize the regulation of
pharmaceutical manufacturing and product quality. The basis for this
new direction is risk-based decision making throughout the manufacturing
process.
21 CFR Parts
210, and 211. "Current Good Manufacturing Practice In Manufacturing,
Processing, Packing, Or Holding Of Drugs; Current Good Manufacturing
Practice For Finished Pharmaceuticals" Critical part of the CFR
addressing requirements for manufacturing practice and the facilities or
controls to be used for, the manufacture, processing, packing, or holding of
a drug to assure that such drug meets the requirements of the act as to
safety and quality.
Current Good Manufacturing Practices In Manufacturing, Packaging, or holding
Human Food Straight from the U.S. Food and Drug Administration, this is
an Adobe Acrobat version of
the federal regulations for manufacturing, packaging and holding of human
food.
Version 2 of the Good Manufacturing Practices (GMP) Guidelines 2002 Edition
Written by the Health Products and Food Branch Inspectorate of the Canadian
government, this document provides excellent guidelines for manufacturing.
"This document replaces Version 1 of the GMP Guidelines 2002 Edition issued
on December 1st, 2002, and the modification related to personnel published
on May 23, 2002. This version also reflects changes made to Regulations as a
result of the publication of Schedule 1247 on October 23, 2002."
World Health Organization: Annex 4 - Good Manufacturing Practices for
Pharmaceutical Products: Main Principles
"...outlines the general concepts of quality assurance as well as the
principal components or subsystems of GMP, which are joint responsibilities
of top management and of production and quality control management."
Good Laboratory Practices: [Top]
Good Laboratory Practice for Non-Clinical Lab Studies (21 CFR part 58)
Largely based on the GMP, with a focus on the pre- or non-clinical stage of
the drug development process, that is, one that involves non-human research.
Good Laboratory Practice for Nonclinical Laboratory Studies, (21 CFR
part 58)
Straight from the U.S. Food and Drug Administration, this is
an Adobe Acrobat version of the federal
regulations for laboratory
practices.
Good Clinical Practices:
[Top]
A
quick tutorial on GCP from the National Health Council on Ethics in Human
Research.
This is an introduction to the international ethical and scientific quality
standard for designing, conducting, recording and reporting trials that
involve the participation of human subjects. A glossary of terms commonly
used during this stage of drug development is also included and is
searchable alphabetically.
Protection Of Human Subjects (21 CFR part 50) This is one of a number of
sections of the CFR that collectively make up the GCPs or Good Clinical
Practices. Specifically, this section addresses requirements and precautions
to be taken when conducting drug studies on human subjects.
Financial Disclosure By Clinical Investigators (21 CFR part 54)
Also a section that makes up the GCPs, this part of the CFR addresses
requirements for clinical trial investigators (or physicians), to disclose
their financial compensation and arrangements with the trial sponsors to
ensure that financial compensation for participating in the clinical trial
does not unfairly affect the results.
Institutional Review Boards (IRBs)
(21 CFR part 56) Another slice of the GCP pie, this section sets forth the
responsibilities of the IRB or Institutional Review Boards in clinical
trials. These IRBs are in large part responsible for the safety of human
subjects in clinical trials.
\_
IRBMED Home Page
(University of Michigan Medical School)
Investigational New Drug Application (21 CFR part 312) A critical part
of the GCPs, this section lays out the requirements for packaging, labeling
and distribution of clinical trial materials (experimental drugs) across
state lines, for use in human studies.
Applications For FDA Approval To Market A New Drug (21 CFR part 314) The
final section making up the GCPs represents the last stage of human studies,
that is, once human studies have been completed and data evaluated, the
sponsor (drug company), must formally apply to the FDA to secure permission
to market its new drug. This section details the requirements for this new
drug application (NDA) process.
Electronic Record,
Electronic Signature [Part 11]
[Top]
Code of Federal Regulations
and Updates (21 CFR Part 11) A good starting point for this topic,
this document is the regulation itself. There is a link at the bottom of
this page entitled ‘Final Rule’ that points to the regulation along with the
preamble, which contains industry comments as well as FDA’s response to
those comments. This is a valuable resource for gaining insight into FDA’s
thinking around compliance with this regulation.
21 CFR Part 11 has been Amended: A final rule regarding required records under the Public Health Security Act and Bioterrorism Preparedness and Response Act of 2002. It amends the scope to 21 CFR Parts 1 and 11.
Guidance for
Industry: Part 11, Electronic Records; Electronic Signatures — Scope and
Application. The official FDA guidance document released in September
2003.
Discovery Automation: The
Benefits of 21 CFR Part 11 Compliance — Even if the FDA Never Asks for Your
Records, written by Patrick Coffey, Ph.D. Excellent document on
writing solid compliant software applications, a must read!
Executive Summary
on New FDA Part 11 Guidance
The title says it all... this document is an executive summary of the April
2003 FDA Guidance on 21 CFR Part 11.
Meeting the FDA’s Requirements for 21 CFR Part 11 For reference
purposes only, this white paper provides one company’s perspective of
meeting Part 11’s security requirements.
This, like the previous link, provides an overview and interpretation of Part 11 from a perspective of how best to meet the security requirements of 21 CFR Part 11. It is by no means endorsed by this site.
Information Technology / Data Center (Validation and Qualification)
[Top]"What is a good definition of "Validation" as it pertains to validating a system?" Answer: "An on-going process to establish documented, objective evidence which provides a high degree of assurance that a system will consistently meet its predetermined specifications, and will perform repeatedly as intended."
Qualification of
Computer Networks and Infrastructure
In this paper, the authors "discuss some terms and definitions, the scope of
the regulations and some recent regulatory actions and finally outline some
approaches to aid qualification of computer networks and the associated
infrastructure."
Guidance for Industry, FDA
Reviewers and Compliance on Off-The-Shelf Software Use in Medical Devices
Published in 1997 by CDRH, this guidance document demonstrated some staying
power and continues to be an effective reference not only for medical
devices but other FDA-regulated areas as well. Since most software solutions
implemented at major companies fit into the category know as COTS or
Commercial Off-the-Shelf, this document is a good starting point.
General Principles of Software
Validation; Final Guidance for Industry and FDA Staff Another CDRH
publication (2002), that provides some insight into what FDA is expecting to
see in terms software validation deliverables for computer systems used to
automate manual processes. As with the previous reference, a lot of good
information can be gleaned from this document and applied to areas other
than medical devices.
Risk Management Guide for
Information Technology Systems This particular guidance developed by the
National Institute of Standards and Technology (under the U.S. Department of
Commerce) reflects the direction that the FDA seems to be headed in at the
moment, that is, Risk Management. Essentially, this guidance documents
introduces the reader to the risk-based approach for developing computer
systems. Typically, employing the risk-based approach in development of
anything yields a more streamlined, efficient product or process.
Medical Devices:
[Top]
Quality System Regulation (21 CFR part 820) Simply put, this is the “GMP
for Medical Devices”. FDA regulation that is quite similar to the cGMP
(Parts 210 and 211), with an added bonus… a section on process validation.
Exemptions From Federal Preemption Of State And Local Medical Device
Requirements (21 CFR part 808)
A useful read for anyone working in the medical device arena, this
regulation prohibits state or local governments’ inability from imposing
additional/more stringent requirements on those entities producing medical
devices that are intended for human use.
Medical Device Reporting (21 CFR part 803) This part of the CFR contains
requirements for reporting serious injury or death caused by medical
devices.
Medical Devices; Reports Of Corrections And Removals (21 CFR part 806)
Another part of the CFR focused on patient safety as it pertains to medical
devices. It lays out the reporting requirements for device manufacturers as
well as requirements for the repair or removal of a device from a patient.
Pre-market Approval of Medical Devices (21 CFR part 814) This regulation
is the rough equivalent of a New Drug Application (NDA) (in the
pharmaceutical arena) and lays out the requirements that must be met before
a medical device can be granted approval by the FDA as a marketable product.
New Drugs (21 CFR part 310) Written by CDRH, this regulation
specifically applies to the packaging, labeling and handling of radiological
drugs.
New Animal Drugs 21 (CFR part 510) Essentially, this regulation sets
forth the requirements for record keeping, labeling and reporting on animal
medicines, feeds and other animal products.
New Animal Drug Applications (21 CFR part 514) As the name indicates,
this part of the CFR pertains to requirements for completing and submitting
an application to market a new animal medicine.
New Animal Drugs For Investigational Use (21 CFR part 511) This
regulation lays out the requirements for handling, distribution and labeling
of animal medicines to be used for research purposes.
A Sample FDA Warning
Letter
FDA Warning letters are public documents and are available via
searchable database at
http://www.fda.gov/foi/warning.htm