GLP compliance

Laboratories wishing to claim GLP compliance are nonually registered with Competent Authorities who issue statements of compliance following successful periodic inspections of the premises to monitor compliance with the relevant legislation. In the UK compliance with the Good Laboratory Practice Regulations 1999 is audited by the Medicines Control Agency. 

Laboratories wishing to claim GLP compliance are normally registered with Competent Authorities who issue statements of compliance following successful periodic inspections of the premises. 

The form or format of the notebook is not as critical from a GLP compliance standpoint as the completion of the record in an accurate, timely, readable, and attributable manner. Company and PI conventions typically have evolved into cost-effective and very efficient data notebooks for field residue trials. These notebooks contain the actual raw data for the trial and once begun become extremely valuable legal parts of the study record. The notebooks should be audited by QA during the field phase of the study as well as at the end of the trial before the notebook is returned to the sponsor organization. The quality of the trial is easily refiected in the quality of the field notebook at the end of the season. 

For each regulatory study, a written plan must exist prior to initiation of the study. The study plan must be approved by dated signature of the Study Director and verified for GLP compliance by QA personnel. 

All phases of a multi-site regulatory study should be carried out in facilities that are members of the UK or a relevant national GLP compliance program. Pre-study test site inspections may be conducted if considered necessary. If an organization is considering using a particular test site, a copy of the test facility s current GLP certificate should be obtained and included in the QA multi-site file. 

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. 

Include a disclaimer or deviation in the Study Director GLP compliance statement. The disclaimer route can be used for a phase of a multi-site study but should generally not be used if the work in question is a critical phase, e.g., application. The remainder of the study must be conducted in accordance with the principles of GLP. This route may not be acceptable to overseas regulators and should be avoided if possible. 

Protocol deviations in the processing phase of the study must be reported to the Study Director without delay. The Study Director will determine any potential impact upon the study that would result from the protocol deviation and will advise the PPI how to proceed with the study. Regardless of the form of communication by which the Study Director is notified of the protocol deviation, a formal description of the protocol deviation must be written by the PPI and submitted to the Smdy Director for an assessment of impact on the study. The assessment of impact by the Study Director should address any scientific and GLP compliance issues. A signed copy of the deviation report is included with the raw data notebook. 

If the PPI determines that there may be an impact on the study, the Study Director must be consulted promptly to determine the proper course of action. Any impact on the scientific aspect of the study resulting from an SOP deviation may generate a protocol deviation. Any impact on the GLP compliance of the study resulting from an SOP or GLP deviation will at the very least need to be addressed in the GLP compliance statement from the processing facility which is included in the raw data notebook. 

Thereafter, the primary functions of the study QA specialist fell into two main headings. First, GLP compliance during the collection and documentation of commodity samples had to be assured. This was done via observation of several collections for different shops (collection incidents) at various geographic locations. In these audits, the study QA specialist examined specific items, such as (1) did the shopper follow the written instructions, (2) were the correct types and numbers of samples collected, (3) was the documentation maintained as required, (4) were the samples labeled and packaged correctly, and (5) were the samples delivered to the shipper as required Findings were communicated to study management and used as appropriate in subsequent shops. 

GLP compliance for electronic records does not differ from GLP compliance for paper records. The increased access and distribution of records and documents enabled by electronic systems provide compliance challenges. There are many new questions to answer for example, what is the difference between electronic approvals and electronic signatures The solutions to these challenges lie in ensuring that system validation and management processes are in place, such as SOPs or procedures... 

QA personnel who audit and monitor the GLP compliance of computerized systems should be familiar with and/or receive training on each system that is utilized in... 

The use of individual passwords increases software security. During a study inspection, QA should ensure that the person physically entering the data is the person that has logged on to the system. If not, this is a GLP compliance issue since the person entering the data will not be the person identified as such in the electronic data. QA personnel should have read-only access to the data in order to avoid any inadvertent changes. 

Problems with GLP compliance for a study always comes back to the Study Director... 

A test facility or an individual laboratory area within a test facility may be engaged in the conduct of both regulatory studies (GLP compliant) and other work (GLP not required). In such situations, measures must be taken to ensure that the GLP compliance of the regulatory studies is not compromised. The way to resolve this is for all of the work of the laboratory to be carried out to meet GLP requirements. 

Table 9.2 Some differences between GLP compliance and ISO/IEC 17025 accreditation...

Most of the information sought is similar to the FDA s IND requirements. One major difference is that a Qualihed Person has to certify that the investigational medicinal product (IMP) is manufactured according to GMP The Competent Authority has the right to inspect the manufacturing facility for GMP compliance, the preclinical facility for GLP compliance, and the clinical trial sites for GCP compliance. 

As a tool to make mutual acceptance of risk assessments possible, OECD has developed the concept of Good Laboratory Practice (GLP). The OECD Principles of GLP are an integral part of the 1981 OECD council decision on the Mutual Assessment of Data (MAD) in the Assessment of Chemicals (revised 1997, Section 2.2.2). MAD also harmonizes procedures of GLP compliance monitoring, ensuring that preclinical safety studies are carried out according to the principles of GLP and that countries can have conftdence in the quahty and rigor of safety tests. 

Written plan, verified for GLP compliance, approved by the study director and by the management... 

Haider SI (2002) Pharmaceutical Master Validation Plan The Ultimate Guide to FDA, GMP, and GLP Compliance. Informa Healthcare... 

The Government of India has established the National GLP Compliance Monitoring Authority (India GLP), adopting the OECD quality system of the principles of GLP, for inspection, monitoring, and accreditation of test facilities in India for conducting nonclinical and environmental safety studies. Currently, India enjoys the full member status of OECD for GLP. India is a member of the OECD Test Guidelines program. 

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). 

The FDA has made it clear that the duration of the study and the place where the study is conducted do not determine whether or not the study is GLP-regulated. Thus, the GLPs apply to short-term studies (e.g., median lethal dose studies and irritation studies) as well as long-term studies that meet all of the above criteria, and the GLPs apply to such studies whether conducted in a manufacturer s lahora-tories, in a university laboratory, or at a contract or subcontract facUity. The FDA expects GLP compliance for studies conducted in foreign countries as well as for those conducted within the United States. 

Even as increasingly sophisticated self-contained GLP compliance lab-in-a-box options become available, another countertrend is likely to result in fewer traditional labs as better... 

The pharmaceutical industry and its top management are confronted today with a period in which the demands for validation, GMP, and GLP compliance have never been greater. The validation procedures in the present environment must be designed to ensure regulatory compliance... 

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