GLP inspection

In Europe Directive 2004/9/EC, on the inspection and verification of good laboratory practice, lays down the obligation of the Member States to designate the authorities responsible for GLP inspections in their territory. 

Currently 23 Indian laboratories have been accredited by the Indian national GLP compliance monitoring authority as per the provisions of the OECD Principles of GLP to conduct nonclinical health and environmental safety studies. The Indian system of GLP inspection, accreditation, and monitoring of test facilities was started in 2004 (India GLP). 

A review of standards without an examination of the interpretation and enforcement of those standards would be of little value. In Chapter 7 therefore, the FDA s GLP inspection program is dissected and analyzed, reveahng the philosophy and approach of the regulators to GLP field interpretation. 

Although the GLP revisions of 1987 excluded animal feed and water from the definition of control article, it would appear that such common vehicles as saline solutions and carboxymethylcellulose solutions still fall within the definition. Such a strict definition of the term for such innocuous vehicles as saline solutions is quite burdensome when one considers the requirements for control articles that are found in other sections of the GLPs characterization [ 58.105(a)], stability testing [ 58.105(b)], sample retention [ 58.105(d)], and inventory [ 58.107(d)]. It does not appear that this comprehensive definition is enforced by FDA field investigators in the course of GLP inspections. 

If a facility conducts nonchnical laboratory studies, it is a testing facility and is subject to inspection by FDA to determine its GLP comphance status. If a facility conducts nonchnical laboratory studies as well as studies that do not meet the definition of nonchnical laboratory study, then only those portions of the facihty that conduct nonchnical laboratory studies are subject to a GLP inspection by FDA. The portions of the facihty that conduct studies other than nonchnical laboratory studies are not subject to inspection by FDA unless FDA has inspectional authority under some other set of regulations. 

The inspection authority of the FDA includes the right to copy records and to collect samples. It is discretionary with the inspected laboratory whether to charge for copies of records or to provide them to the inspector free of charge. The same is true with regard to the inspector s request for samples, although requests for samples are rare during GLP inspections. In most cases, laboratories wiU provide samples and copies of documents free of charge unless FDA requests for these are excessive. 

Before 1992 FDA normally provided at least 1 weekly advance notice of a GLP inspection except in the case of for-cause inspections, which usually occurred without advance... 

The requirement for adequate numbers of personnel was included in the GLP regulations as a result of FDA s pre-GLP inspection of a laboratory that had taken on more work than its employees could properly perform. The result, according to FDA, was poor-quahty or even fraudulent data. 

The FDA requires the name and address of the testing facihty to appear in the report so that when the report is submitted in support of a research or marketing permit the laboratory can be added to FDA s inventory of laboratories that are scheduled for GLP inspection. The name and address may also be used by FDA to estabhsh the site for any directed audit of the report. 

There are two types of GLP inspections. The first is the routine inspection, a periodic evaluation of a laboratory s compliance with the GLP regulations. To facilitate scheduling of... 

The second type of GLP inspection is the directed, or for-cause, inspection. The directed investigation is more comph-cated by its nature than the routine and is less frequently performed in the GLP program. These constitute only about 20% of the GLP investigations completed since the regulations were invoked. 

To validate critical studies, such as long-term and reproduction toxicity studies, submitted to INDs or NDAs. These studies are selected at each center from master schedules collected in the course of previous GLP inspections or from reviews prepared by the pharmacologist responsible for evaluating applications for research and marketing permits. 

Before concluding a GLP inspection, FDA officials meet with appropriate laboratory personnel to discuss any observed deviations from GLPs. If there are no departures from the GLP... 

Prior to December 1993, the classifications VAI-1, VAI-2, and VAI-3 were used to characterize the GLP comphance of an inspected facility. The category VAI means voluntary action indicated. The numerals 1, 2, and 3 formerly indicated degrees of failure to comply with the GLP regulations VAI-1 meant that the violations were minor and may have been corrected before the inspections was concluded, and VAI-2 indicated that minor procedural deficiencies were found that did not threaten to compromise the validity of any studies done under those circumstances. Those GLP inspections that were formerly classified VAI-1 and 2 are now termed VAI. 

As already mentioned, foreign GLP inspections are extremely expensive. To avoid incurring these costs, the FDA has made bilateral agreements with the drug regulatory agencies in several other countries. 

With all of the foregoing information on the GLP inspection procedures and the statistical evaluation of the completed inspections, one must stiU ask How have the GLP inspections impacted new drug evaluation ... 

First, the people responsible for FDA s bioresearch monitoring program are encouraged by the results of the GLP inspection seen in terms of industry s growing acceptance of the GLPs as a means of establishing a level of reliability for scientific testing. 

In addition to the development of the OECD Principles of GLP, the OECD Expert Group was given the responsibility of developing two additional guidance documents—one for the Implementation of OECD Principles of GLP and one as OECD Guidelines for National GLP Inspections and Study Audits. 

The OECD Guidelines for National GLP Inspections and Study Audits document serves as a companion document to the Principles and is intended to provide national authorities additional guidance in preparing and implementing their national GLP compliance programs. 

The second point is understanding the difference between a GLP audit, a data audit, and a technical audit. It is the industry position that these are three separate entities. All of these are legitimate EPA activities. We realize it s tempting for scientists to delve into the technical details of a particular study when conducting a GLP inspection. However, we believe this is the purview of other EPA activities and the GLP inspector should "stick to the knitting." On the other hand, we realize that one cannot be blind to discrepancies between raw and reported data, and technical... 

During a GLP inspection of a facility by the EPA, the inspectors usually examine SOPs and may check the items outlined below to determine the compliance status of the system. Commonly, inspectors request copies of SOPs to include them in the inspection report in support of their observations. 

The laboratory to be inspected will receive a letter approximately two weeks before the Agency inspection team arrives that specifies which studies will be audited and if a laboratory GLP inspection is to be included. Upon arrival, the inspector will present official credentials and a Notice of Inspection form. The GLP portion of the audit is now conducted as if GLPs for all types of studies were in effect. For those laboratories conducting non-GLP studies, this is done to give an idea of what to expect when, and if, the GLP regulations become law. The laboratory inspection aspects will be reviewed briefly and then the data audit portion will be discussed. 

Sponsor overview and proposed scope of work Brief contractor overview of company and services Discussion of GLP inspection history compliance issues Facility tour and document request during tour... 

OECD. No. 9 Guidance for the Preparation of GLP Inspection Reports, http // www.olis.oecd.org/olis/1995doc.nsf/LinkTo/ocde-gd(95)114... 

Koseisho (1988), Good Laboratory Practice Attachment GLP Inspection of Computerised Systems, Pharmaceutical Affairs Bureau, Japanese Ministry of Health and Welfare, Tokyo. 

With the enforcement of the revised Drug Organization Law in April 1994, the Drug Organization carries out a survey of GLP compliance. Confirmation of GLP compliance with domestic testing facilities is in principle done bcised on the results of the survey. When GLP studies are performed in foreign countries, the MHW may make a GLP inspection if necessary. 

Details of the GLPs and GLP inspections may be found on government-specific websites. Many are listed in the references below. Briefly, the FDA GLPs, define the scope of the regulation and have a detailed listing of definitions. If the FDA is to consider a nonclinical laboratory study in support of an application for a research or marketing permit, the testing facility, records and specimens must be available for inspection by an authorized employee of the FDA. 

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