Users Club - General Quality / Compliance / Inspections
Download more than 500 documents: SOPs, examples, templates, checklists,
FDA waning letters, 483 inspectional observations, FDA and other official
guidelines, presentations/publications from FDA personnel.
The FDA requires that an investigation be conducted whenever an
Out-of-Specification (OOS) result is observed. This SOP defines the
requirements for dealing with OOS results. Even if a batch is rejected based
on an OOS result, the investigation is necessary to determine if the result
is associated with other batches of the same drug product or other products.
This SOP deals with results that fall outside the specifications or
acceptance criteria established in new drug applications, official
compendia, or by the manufacturer and suspect within test results. The SOP
applies to OOS as a result of analytical errors, process errors and
Defines responsibilities and how to specify training needs, training
techniques and how to document results.
FDA’s 21st CGMP initiative suggests risk-based inspections. Companies are
expected to document risks that the system has on product quality, product
safety and public health. Information is used, for example, to define the
extent of validation, to define the scope of 21 CFR Part 11 and to implement
controls such as electronic audit trail, electronic copies and archiving of
records. This procedure establishes a method for identifying, evaluating and
prioritizing the risks associated with the use of systems in applicable GxP
applications, specifically but not only where such systems are subject to
regulation under 21 CFR Part 11.
How to Respond to 483s and Warning Letters Related to OOS and Failure
Well-functioning and well-documented quality systems are important for
complying with Current Good Manufacturing Practice regulations and for
meeting business goals. Use this checklist to define gaps between a quality
system as required by the FDA and your actual system. use this information
to close the gap.
Use this checklist to audit your laboratory. It is also most useful to
learn what 3rd party auditors and regulatory inspectors will look at.
Elemental Impurity Control according to
During inspections the FDA verifies that companies procedures and
processes are in compliance with FDA GxP regulations such as Good Laboratory
Practices, Good Clinical Practices and Good Manufacturing Practices. If the
FDA inspections identify deviations from the regulations, they will issue
inspectional observations using a special form with number 483. These
reports are usually called 483’sor 483 inspectional observations. Depending
on the severity of deviation the companies may get a warning letter later
on. Such warning letter can have a significant impact on a company's
business and reputation. This articles gives recommendations on how to avoid
Published in BioPharm.
An agreement on the terminology is of utmost importance for a common
understanding of validation, calibration and qualification. It frequently
happens at validation symposia that different speakers used different terms
for the same thing and the same terms for different things. This article
elaborates on terms most frequently used in the area of validation,
calibration and qualification in analytical laboratories. Whenever
available, official terms are used together with a reference to the source.
Sia Chong Hock, Chairman of the ASEAN MRA taskforce on GMP
Inspection for Medical Products gave a presentation at the ISPE
conference in Singapore on June 1, 2009 about the history, status
and further plans for harmonizing GMP inspections.
For enforcement of laws Federal Agencies such as the FDA promulgate rules
or regulations. These are published as the Code of Federal Regulation (CFR)
in the Federal Register. FDA regulations are coded as 21 CFR Part xxx and
inform the public and industry how the laws are implemented. The most
well-known FDA regulations are the GLP and GMP regulations. GMP stands for
Good Manufacturing Practice, but there are many more. Sometimes these
regulations are also called “predicate rules”. A table with a list of the
most well-known FDA regulations can be downloaded from the 'regulations'
website of the users club section.
In many cases regulations are not detailed enough for inspectors and for
the industry. In this case the FDA develops guidance documents. They provide
assistance to the regulated industry by clarifying requirements imposed by
Congress or issued in regulations by the FDA and by explaining how industry
may comply with these statutory and regulatory requirements. They also
provide specific review and enforcement approaches to help ensure that the
FDA's employees implement the agency's mandate in an effective, fair and
consistent manner. FDA Guidance documents related to selected topics can be
be found on users club websites that are related to selected topics
Validation: General Principles and Practices
July 2001, The document is based on the PIC/S recommendations and has
been drafted in consultation with Member States Inspectors within the expert
group on Inspections and Control of Medicinal Products.
In 62 detailed slides James S. Cohen from the US FDA discusses and
presents the status and further FDA plans, for example: development of an
FDA Agency wide integrated risk based quality system standard, seven steps
to speed drug product availability, transfer of therapeutic products from
CBER to CDER, international collaborations, science based policies and
standards and experience with risk based system inspection
The presentation gives an overview on current thinking of process
validation. The presentation relates to FDA's 21 Century GMP Initiative. The
importance of validation master plans is emphasized.
Joseph Famulare, Deputy Director, Office of Compliance, Center for Drug
Evaluation & Research
Janet Woodcock, FDA's director for the Center for Drug Evaluation and
Update by Janet Woodcock, FDA's director for the Center for Drug
Evaluation and Research
Since the early 1970s, the FDA has operated the Drug Quality Reporting
System (DQRS), which encourages health care professionals to report observed
or suspected defects or quality problems with marketed drug products.
Juliaette Johnson of the FDA has developed a slide presentation with update
of the system. The presentation also includes contact information for
reporting, a chart with primary defects reported and links to a website with
Mark A. Elengold, Deputy Director, Operations, Center for Biologics
Evaluation and Research, PDA International Congress.
David Horowitz, Director, Office of Compliance, FDA CDER, gave an update
on current status, future plans and upcoming announcements on FDA's drug GMP
initiative at the joint FDA/PDA joint regulatory conference. Horowitz gave
specific examples for topics such as "Encouraging best manufacturing
practices", "Risk-based approaches", "Enhanced coordination", "Consistency",and
"Predictability and international collaboration". He also gavec an overview
of FDA's Steering Committee and 15 active working groups. They plan to
publish new White Papers and at least five new new Guidance Documents (some
final, some draft).
Introduction to CGMP: Current Good Manufacturing Practices
Electronic Source Documentation
in Clinical Investigations
Fred Blumenschein at the 2nd European GMP Conference, Organized by the
European Compliance Academy and the Unversity of Heidelberg.
Grace McNally, US FDA CDER, Athens, 2007
Explains the process and details of four lifecycle steps
Can Less Really Be More?
Source Documentation in Clinical Trials
Chris Joneckis, PhD, CBER
Starting from the 1987 guide Dr. Joneckis explains the evaluation of process
validation that ends with the lifecycle approach as recommended in the 2008
Barry Cherney, Ph.D. Deputy Director at CDER gave "A Product Reviewer's
Perspective" with examples for 483's and recommendations such as: Process
validation is an activity that should continue throughout the entire life
cycle of the product.
FDA’s Foreign Inspection Program
Susan Laska, Deputy Director Division Foreign Field Investigations
The presentation demonstrates the significant increase in foreign
inspections between 2003 and 2011.
Presented at the ISPE Conference 2012 in Singapore by Carmelo Rosa,
M.S.,Psy.D., Office of Compliance, FDA/CDER
Director Division of International Drug Quality, Office of Manufacturing and
update has been presented by Ilisa B.G. Bernstein and Connie T. Jung, RPh,
PhD, from CDER's Office of Compliance at the APhA Annual Meeting in New
Orleans, LA, on March 11. The objective of the presentation was to describe
FDA activities during the last year and to state how changes in FDA
regulations and actions will affect the conference participant’s. The
50-page slide presentation includes includes statistics on new drug
approvals and on applications of generic drugs. Quite interesting was the
information on drug product recalls from 2007 to 2012 . It shows an
increasing trend with a big jump in the first quarter of FY 2012
Mary Malarkey, Director, FDA Office of Compliance and Biologics Quality,
Joint PDA/FDA Meeting, 2008
With Citation Hitlist for Biological Products, intermediates, substances
Douglas A. Campbell inserted 5 slides about international inspection trends
in his presentation about “Regulatory Trends in Aseptic Processing”. Data
are from 2009 and 2010 . Besides a summary overview, detailed breakdowns are
presented for Europe, China and India. Laboratory control deviations rank
highest in the overview as well as in Europe and China.