GXPs
 

GXP
BASIC RESEARCH
PRECLINICAL
CLINICAL
FDA FILING/APPROVAL


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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:


Good Laboratory Practices (GLP) Requirements

 

Introduction and 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.

History of GLP
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 

ensure proper and consistent interpretation of the regulations by the industry and FDA field investigators.

Applicability and Relation to other Regulations
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.

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.

GLP Key Requirements
According to GLP principles, at a minimum, GLP compliance requires the following:

- Assignment of study directors
- Establishment of a Quality Assurance Unit (QAU)
- Establishment of Standard Operating Procedures
- written protocol for each study
- Final report

GLP Inspections and Enforcement
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

Routine inspections should be conducted at least every second year. It is an on-going evaluation of a laboratory’s compliance with GLP regulation.

For 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.

- Enforcement

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.

Helpful Resources
GLPs 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:

- FDA regulation

- FDA Guidance for Industry

- Useful links

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Good Manufacturing Practices (GMP) Requirements

 


GMP Overview
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
The 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 laboratories.

GMP Inspections and Enforcement
FDA 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.

Helpful Resources
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 for Industry

- Useful link for more information about cGMP:

 

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Good Clinical Practices (GCP) Requirements

 

GCP Introduction
Good Clinical 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 generated.

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
The ICH-GCP 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.

Helpful Resources
The FDA regulations and guidance documents related to GCP are accessible through the following link. 

- FDA regulation

- FDA Guidance for Industry

- Other education material about cGMP:

 

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