Compliance with GLP

If the test facility claims to be GLP-compliant but is located in a country where there is no authorised body responsible for GLP monitoring, i.e., a national GLP compliance program, the Study Director needs to be assured that the facility (including the archive, if used) does operate in compliance with GLP principles. This can be achieved by conducting a pre-study QA test site inspection or by a review of documentary evidence, e.g., notice of adverse findings and subsequent responses, or Establishment Inspection reports. The Study Director should ideally discuss the above with QA personnel and send copies of any documentary evidence used to the Quality Assurance Unit (QAU) for inclusion in the QA multi-site study file. 

The Study Director is the pivotal person in any GLP study. The sponsor initiates the study and assigns a Study Director to act as the primary control point for all aspects of the study. The Processing Principle Investigator (PPI) acts as an agent of the Study Director and handles the processing phase of the study. The PPI reports directly to the Study Director, and quality assurance (QA) documents resulting from the processing phase are sent to the Study Director for approval. The Study Director has final say in all questions of compliance with GLP and interpretations of the protocol. The... 

Auditing data that have been captured, manipulated, transferred, and reported electronically has produced new challenges for QA personnel. In general, auditing electronically captured data from studies conducted in compliance with GLP should be approached no differently than performing any other data audit however, there are additional considerations. 

The responsibility of the QA unit should not be limited to in-process inspections and data and report audits. To be in full compliance with GLP, the QA unit should review all procedures for storing and archiving electronic as well as paper raw data. This review should include ensuring that back up and archiving procedures were performed as specified in the SOPs, that archiving was documented properly, and that long-term storage procedures were followed. 

Good laboratory practice (GLP) is a set of procedures within which the overall performance of a laboratory can be monitored. It is applicable to the organization and functioning of any laboratory but it is particularly relevant to the pharmaceutical industry. Compliance with GLP may be required for accreditation of a laboratory by an external regulating agency. 

EU Member States shall verify the compliance with GLP of any testing laboratory within their territory claiming to use GLP in the conduct of tests on chemicals... 

In the paragraph entitled "Applicability to studies performed under grants and contracts," the regulations state that whenever a sponsor utilizes the services of a consulting laboratory, contractor, or grantee to perform an analysis or other service, it shall notify this laboratory, contractor, or grantee that the service must be conducted in compliance with GLP. Hence, essen-... 

If the study was conducted in full compliance with GLP requirements, the conforming amendments statement will so indicate. If not, then the conforming amendments statement must contain a brief statement of the reason for the noncom-phance. 

As mentioned earlier, when estabhshing GLP standards in a non-GLP lab, the first decision is whether or not to implement the requirements across the entire organization or only in some technical areas. A key element of compliance with GLP is that adequate facilities and equipment are available for the projects, so the laboratory may face a chicken and egg dilemma, particularly when venturing into GLP projects for the first time. 

The principles of GLP require an independent quality assurance (QA) program to ensure that the study is being conducted in compliance with GLP. The QA personnel cannot overlap with those of the study because of the potential conflict of interest, but they may be part-time staff if the size of the study does not warrant a full-time QA section. The responsibilities of the QA unit are to maintain copies of plans, standard operating procedures, and in particular the master schedule of the study, and to verily, in writing, that these conform to GLP. The QA unit is responsible for inspections and audits, which must be documented and the results made available to the study director and the principal investigator. The QA unit also signs off on the final report. Any problems discovered or corrective action that is recommended by the unit must be documented and followed up. 

Ensure that the protocol meets the requirements for compliance with GLPs, and scientifically addresses guideline requirements. It 1s also Important to be aware that 1n some cases more recently published reporting addenda and standard evaluation procedures contain Information critical to proper study design, and therefore, protocol developement. If there 1s a question, check with the regulatory agency. 

Characterization of the vector batch used in non-clinical safety studies is also performed in compliance with GLPs. Care should be taken to ensure that adequate and appropriate processes are used to produce the batch(es) required, and the production process should be similar to that proposed for production of the vector for human clinical trials, or at least performed in such a way that adequate documentation of the production methods is available for comparative purposes. The GLP regulations state that the identity, purity, and composition of the vector batch (test article) used in a safety study must be known and documented. In addition, the stability of the vector preparation in the specific container used for the study must also be known prior to initiation of the study or acquired concomitantly with the study itself. These test article characterization experiments require that the researcher produce additional amounts of vector identical to the material used in... 

Q Does FDA reject nonclinical laboratory studies that have not been conducted in full compliance with GLPs ... 

Dose escalation studies in rodent and nonrodent These studies are generally the first time the test article is administered to a living system. They provide an initial indication of toxicity, organs involved, and doses that can be used in longer term studies. Many times these studies are not conducted in full compliance with GLPs. 

Supplementary or follow-up studies are more wide-ranging and cover cognitive function (learning, memory and attention), brain function (EEG) and dependence/abuse potential. Because of their complexity, there exist no standard protocols and there is no requirement that such studies be carried out in compliance with GLP. A more stringent requirement is that such procedures be carried out according to internationally accepted scientific standards of excellence. Protocols which we have found useful for evaluating such effects are also included below (Section 3). 

A declaration that each study subject to GLP regulations was performed in full compliance with GLPs or, if the study was not conducted in compliance with those regulations, a brief statement of the reason for the non-compliance and the sponsor s view on how such noncompliance might affect the interpretation of the findings. 

As we move into the twenty-first century, it is quite apparent that the industry will shrink as mergers and acquisitions take place, and, with this, the emergence of the now familiar CRO will become ever more popular in the conduct of non-clinical safety studies. It is, therefore, very important that, in this area, the sponsor has the assurance that these facilities are operating not only to the highest standard of science but also in compliance with GLP and that, as a subcontractor, the data they generate will be equally accepted as if the data were generated by the company itself. 

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