GXP is a general term for Good Practice quality guidelines and
regulations. The titles of these good practice guidelines usually begin with
"Good" and end in "Practice", with the specific practice
descriptor in between. A "c" is sometimes added to the front of the
acronym which stands for "current." Three most commonly-used GXPs in the
pharmaceutical industry are discussed below, including:
Laboratory Practices (GLP) Requirements
Objective of GLP
Good Laboratory Practice (GLP) deals
with the organization, process and conditions under which laboratory studies
are planned, performed, monitored, recorded and
reported. GLP practices are
intended to promote the quality and validity of test data. The objective is not
only quality of data but also traceability and integrity of data.
GLPs were established after FDA
inspected several research laboratories during the mid 1970s, which revealed
serious problems with the conduct of safety studies submitted to the agency.
In 1979, good laboratory practice (GLP) regulations became
effective under 21 Code of Federal Regulations (CFR) Part 58.
Subsequently, during 1979 and 1981, FDA published two critical
"Guidance for Industry" documents -- "Post Conference Report" and "Questions and Answers" -- to
proper and consistent interpretation of the regulations by the industry and FDA
Applicability and Relation to other Regulations
Typically research and drug discovery are not
regulated. GLP starts with preclinical development. Clinical trials are regulated
by good clinical practice regulations. Manufacturing is regulated through GMPs.
GLPs regulate all non-clinical
safety studies that support or are intended to support applications for
research or marketing permits for products regulated by the FDA.
GLP Key Requirements- Assignment of study directors
According to GLP principles, at a
minimum, GLP compliance requires the following:
- Establishment of a Quality Assurance Unit (QAU)
- Establishment of Standard Operating Procedures
- written protocol for each study
- Final report
GLP Inspections and
The FDA has the responsibility to
inspect GLP studies related to products that are marketed in the United States,
it does not matter where the products are developed or manufactured.
Two types of inspection programs
inspections should be conducted at least every second year. It
is an on-going evaluation of a laboratory’s compliance with GLP regulation.
cause inspections are less frequent, they constitute
only about 20% of all GLP inspections. Reasons for such inspections could be a
follow up of an inspection with serious deficiencies or when the FDA suspect
non-compliance when investigating NDA applications. It also may happen that the
FDA gets some hints from external sources about non-compliance in laboratories.
Deviations from GLP requirements are documented in
different ways: if the inspection team finds deviations, they write them in a
specific form 483. Then the lead inspector writes a full inspection report
which is called: establishment inspection report. Depending on the deviations
the inspector will or will not to write a warning letter. This letter is sent to
the company’s management. Within 14 days the company should respond with a
corrective action plan.
are complex and could be confusing at times. Besides the 21 CFR part 58, the
FDA has published guidance documents which consolidate all GLP
questions answered by the agency. Below are listed some suggested
resources for more information on Good Laboratory Practices:
Guidance for Industry
- Useful links
Manufacturing Practices (GMP) Requirements
cGMP refers to the Current Good Manufacturing Practice
regulations enforced by the US Food and Drug Administration (FDA). cGMPs
provide for systems that
assure proper design, monitoring, and control of
manufacturing processes and facilities. Adherence to the cGMP regulations
assures the identity, strength, quality,
and purity of drug products by requiring that
manufacturers of medications adequately control manufacturing operations.
Drug cGMP Requirements
cGMP requirements were established to be flexible in order to allow each manufacturer
to decide individually how to best implement the necessary controls by using
scientifically sound design, processing methods, and testing procedures. This
includes establishing strong quality management systems, obtaining appropriate
quality raw materials, establishing robust operating procedures, detecting and
investigating product quality deviations, and maintaining reliable testing
GMP Inspections and Enforcement
inspects pharmaceutical manufacturing facilities worldwide using scientifically
and cGMP- trained individuals whose job it is to evaluate whether the company
is following the cGMP regulations. FDA also relies upon reports of
potentially defective drug products from the public and the industry. FDA will
often use these reports to identify sites for which an inspection or
investigation is needed. Most companies that are inspected are found to
be fully compliant with the cGMP regulations.
If the failure to meet cGMPs results in
the distribution of a defective drug, the company may subsequently recall that
product. While FDA cannot force a company to recall a drug, companies will
usually recall voluntarily or at FDA’s request. If a company refuses to recall
a drug, FDA can warn the public and could seize the drugs that are on the
market. FDA can also bring a seizure or injunction case in court to address
cGMP violations. Both seizure and injunction cases often lead to court orders
that require companies to take many steps to correct cGMP violations.
Current Good Manufacturing Practices (cGMPs) for human
pharmaceuticals affect every American. Most people, however, are not aware of
cGMPs, or how FDA assures that drug manufacturing processes meet these basic
objectives. The following is some resources that may be helpful in
understanding how cGMPs establish the foundation for drug product quality:
- FDA regulation- Other education material about cGMP:
- FDA Guidance
Useful link for more information about cGMP:
Good Clinical Practices
Practice (GCP) is an international quality standard that is provided by
International Conference on Harmonization (ICH), an international body that
defines standards. It is an international ethical and scientific quality
standard for designing, conducting, recording, and reporting trials that
involve the participation of human subjects. Compliance to these standards
provides the health authorities as well as the general population with
assurance of the integrity of trial subjects and the validity of the data
The US FDA has collaborated and adopted
International GCP guidance for the conduct of clinical trials, which have been
in effect since the 1970s, addressing both
GCP (Good Clinical Practices) and HSP
(human subject protection).
Drug GCP Requirements
guideline specifies, in rather general terms, how to design, conduct, record
and report a clinical trial in accordance with GCP standards. In order to
comply with this, it is the responsibility of the sponsor, or
sponsor-investigator, to ensure that a set of standard operating procedures is
written and that the level and intensity of the GCP monitoring process is
specified by the sponsor according to the complexity of the study. Then the
monitoring process must be conducted and serves to document that the study
complies with GCP standards before the initiation of the study, during the
trial and after the trial is completed.
GCP Inspections and Enforcement
FDA maintains information about
clinical investigators who have and/or are participating in clinical trials of
pharmaceutical products. FDA’s bioresearch monitoring (BIMO) program conducts
on-site inspections of both clinical and nonclinical studies performed to
support research and marketing applications/submissions to the agency.
Regulatory correspondence and restrictions can be issued due to noncompliance
observed during bioresearch monitoring (BIMO) inspections. The following link
provides more information by the FDA about the BIMO program
and compliance and enforcement of GCP.
The FDA regulations and guidance documents related to GCP
are accessible through the following link.
- FDA regulation
- FDA Guidance
Other education material about cGMP: