British Association of Research Quality Assurance

Transcription

1 British Association of Research Quality Assurance DISCUSSION PAPER NUMBER 6 IN A SERIES PRODUCED BY THE GLP COMMITTEE THE APPLICATION OF GLP PRINCIPLES TO FIELD STUDIES REPORTING AND ARCHIVING Author(s) Produced by the Field Studies Committee in 2004 and updated by members of the GLP Committee The British Association of Research Quality Assurance 2012 This paper may be freely transmitted, copied and used provided that the text is not altered and the attribution of BARQA remains clear Revised July 2012 Page 1 of 9

2 1 INTRODUCTION 1.1 The information in this paper gives advice on the requirements for reporting and archiving all types of Good Laboratory Practice (GLP) field studies as defined in Paper Number 1 of this series 1-5. The guidance and recommendations included in this paper, based on the knowledge and experience of Committee members, is provided purely on an advisory basis to assist in the interpretation of the current GLP regulations to field studies. 2 REPORTING 2.1 The OECD GLP Principles 6 define the way in which studies should be reported and are very prescriptive about what should be contained within a report. However, the principles are written in such a way that they cover all types of studies that are required to be conducted to GLP, and are not very specific about field trial reports. In addition, the OECD Consensus Document on the Application of the GLP Principles to Field Trials 7 gives very little further guidance. 2.2 This paper will provide advice on the contents of a final report and how Principal Investigator contributions for multi-site studies should be handled. 2.3 General Considerations The Study Director has the ultimate responsibility for ensuring the accuracy of the final report and the GLP compliance statement relating to the entire study. However, for many field studies the Principal Investigator (PI) may also be responsible for providing a report of his/her phase to the Study Director (SD) for inclusion into the final report. Alternatively, it is acceptable in most countries for the Principal Investigator to return the raw data for his/her phase to the Study Director, who will then write that part of the study into the final report. For each study, a study being defined by the Study Plan, a final report should be produced by the Study Director. For multi-site studies there are several ways in which preparation of the report can be approached: i) All raw data, compliance statements and QA statements are sent to the Study Director from each PI. The Study Director will then take these and prepare the final report. ii) iii) An audited report from the PI for his/her phase of the study is sent to the Study Director for inclusion, either in its entirety (preferred option) or is abstracted into the final report. It should be noted that this option is insisted upon by some Monitoring Authorities. A combination of the above. 2.4 In circumstances where option (ii) is applied, the report can take two forms. A summary report containing sufficient information for the Study Director to write the relevant parts of the final report, or, more usually, a complete report of the phase which can be added as Revised July 2012 Page 2 of 9

3 an appendix to the final report. statements. This fuller report would also contain PI and QA 2.5 To take account of page numbering issues when including the PI report, it is acceptable for the final report to run from page x to y with a contents page listing appendices (including the PI report) as having n pages. 2.6 The format of reports in submission dossiers may vary due to the requirements of specific countries. Such requirements should be taken into consideration when preparing reports. It should be noted that reformatting of reports is acceptable following issue but it is suggested that an internationally acceptable format be adopted wherever possible. Formatting should be agreed between the Study Director and Principal Investigator at the outset. 2.7 Content of a Final Report Many of the elements required to be in the report are self explanatory. However, there are a number of issues that need to be considered more carefully for field study reports. The following GLP elements are required for a field study report: a descriptive title This should be the same as the title of the Study Plan (or subsequent amendments). If there is a Principal Investigator report then the title of that report should also indicate the phase of the study to which the report relates. study number There can only be one study number, regardless of the number of phases involved and the study number for multi-site studies should be the same as that on the study plan. In multi-site studies it is common to find reference numbers or other identifiers relating to the work done at test sites. Such reference numbers should also be included in any reports from these sites, but the study number must always be clear in these reports. name and address of Test Facility and Sites The name and address of the Test Facility and all test sites should be included. For field studies there may be trial sites or locations (e.g. hired farmland; moorland) which do not fully meet the definition of a test site. All such locations should also be included and referred to as trial sites. Study Director compliance statement A GLP compliance statement signed and dated by the Study Director indicating the extent of compliance of the study with GLP is required. This statement will declare that the study has been conducted in compliance with GLP or, if not, Revised July 2012 Page 3 of 9

4 identify the areas of non-compliance. Examples of exemptions from the claim for GLP compliance could include: The use of a test site which is not part of a national GLP programme. Weather data may have been generated by a Station which is not GLP compliant. Farmers records may often not be generated in accordance with GLP. When auditing the report QA should check that such exclusions have been included on the statement as appropriate. The statement should also identify the GLP regulations/guidelines against which the study is being claimed. It is common in multi-site field studies for phases to be conducted in different countries and thus compliance against each country s national regulation may be cited if this is required by the respective national Monitoring Authority. However, if the study is being conducted according to OECD GLP Principles then it is recommended that these are referenced to ensure the study is recognised internationally. National GLP legislation should be quoted also, with at least a general statement confirming that the requirements have been met, when a number of countries are involved. Principal Investigator statement For multi-site studies, where a Principal Investigator(s) has been appointed, it is important that the PI produces a similar GLP compliance statement, confirming the extent of GLP compliance for his/her phase. If a PI report is produced it would normally include such a statement. If the Principal Investigator has not produced a report for his/her phase, it is not necessary for the PI GLP compliance statements to be included in the final report. These must however, be provided to the Study Director with the raw data to assure him/her that each phase was conducted to GLP. Before signing the Compliance Statement, the Study Director should review the report to ensure that all contributions from PIs and contributing scientists have been accurately incorporated and that GLP compliance for the whole study can be claimed. QA audit and inspection statement In multi-site field studies it is the responsibility of Lead QA to ensure that all phases of the study have been adequately covered. Test site QA are responsible for ensuring that the phase of the study conducted at their site has been subject to inspection. Thus, suitable statements should be produced to indicate the extent of QA monitoring for the entire study. Revised July 2012 Page 4 of 9

5 There are two situations which could arise in multi-site field studies: i) The appointment of a single QA function to oversee all the phases of the study. In this case a single QA statement would be prepared to cover all phases inspected. ii) The appointment of a Lead QA function by Test Facility management, normally where the Study Director is located, to oversee the phase(s) conducted at that location and to ensure that all phases at test sites are adequately monitored by test site QA personnel. In this case the Lead QA function could either: a) produce one statement which gives details, provided by all QA personnel, of all procedures inspected on the study, signed and dated by the Lead QA. This should make it clear which phase was inspected by which QA function and that the information was transcribed from test site QA statements. or b) produce a QA statement with details of the phase(s) inspected by Lead QA. Test site QA would then produce separate QA statements for the phase(s) that they covered which can then be included in the final report. However, more usually, such test site QA statements are included with the Principal Investigator report, if issued. Option b) in either form is preferred. The UK GLP Monitoring Authority has produced guidance on their expected content of a QA Statement 9. For the sake of simplicity it is easier if QA audit reports are distributed to all recipients on the same day, to avoid the need for the inclusion of columns to show when QA findings were reported to test site and test facility personnel. Electronic pdf copies of audit reports issued as attachments are now commonplace. other signatories to the report It should be noted that some countries require other functions to sign the report such as the Sponsor and Management. As with the report format issue, facilities should determine when other signatories are required and format the report accordingly. dates Study and experimental start and completion dates should be included. The paper on Study Planning, Paper Number 4 in this series 4, clarifies how these dates should be determined. Revised July 2012 Page 5 of 9

6 tables/appendices It can sometimes be useful to include summary tables to illustrate the details of each trial at each test site. It may be sufficient to summarise weather condition details in the text of the report rather than include copies of the weather data, although full details may be requested by the Sponsor in an Appendix to the report. Such details should include the source of the data and it may be useful to include long-term averages for comparison, whenever possible. Copies of trial layouts are often requested and it is standard practice to include any map references. data manipulation Descriptions of calculations and data transformation techniques should be included. It may be sufficient just to reference the source of the techniques for some countries, e.g. UK. However, other countries may need the report to clearly specify the calculations used, on a step by step basis. location of data, samples and specimens The storage location of all raw data (paper and electronic) generated on the study, including any samples or specimens that have been retained, should be specified. If test and reference items and specimens are not retained, the report should indicate this and justify the disposal. If some data are being archived at other sites/facilities these should also be stated. It is sufficient to give the facility name and location. This will enable a Regulatory Authority to identify where data are being held, should it be necessary to perform an audit of the study. Some Monitoring Authorities require that a sample of test item is retained at each test site involved in the study. If this is the case then it should be clearly stated. The UK GLPM Monitoring Authority has produced some guidance on their requirement to retain data at test facilities or test sites for at least one inspection cycle 10. Use of contract QA The use of contract QA for the audit of field phase reports is likely to be more common than for other study types or phases, because of the seasonal nature of the work. Peaks may be handled by the use of contract QA. The UK GLP Monitoring Authority has produced guidance on the use of such QA personnel 11. Revised July 2012 Page 6 of 9

7 2.8 Report Amendments Once the final report has been produced any changes or corrections should be made in the form of a formal report amendment. These normally take the form of a document detailing the correction/change made, the reason for the change and should be signed by the Study Director and subject to audit and signature by QA. In some circumstances it may be necessary to re-issue a new version of the report. If this is the case then it should be clear in the re-issued report that a previous version has been withdrawn. However, copies of both versions must be retained in the archive. 3 ARCHIVING OF STUDY DATA, TEST ITEMS AND SPECIMENS 3.1 General There are two issues associated with the retention of raw data, test items, samples and specimens. The first relates to the temporary storage of these at the test sites where they are generated. The second relates to the long-term retention of data. Document Number 15 in the OECD GLP Series 8 archiving expectations than earlier gives more detailed guidance on 3.2 Temporary Retention The retention of records at field facilities can be an issue at small sites where the provision of secure storage would be expensive, relative to the small number of studies conducted. Some Monitoring Authorities have insisted on fire resistant cabinets, even for short-term storage. However, as a minimum, data from studies should be kept in a lockable facility, whether this be a purpose built facility or just a cupboard at the test site. The decision to have a temporary or permanent archive at field facilities will be dependent on the circumstances. 3.3 Long-Term Retention In field studies where many sites are involved it is a challenge to ensure that ALL data and material are archived appropriately. It is also important that the Study Director is aware of the location of data pertaining to his/her study and that the report accurately reflects where the data is being archived. This is not a problem if all the study related data is returned to the Study Director. However, facility records for each test site will also need to be archived. 3.4 Records and Data to be Held at the Test Site Raw data from the phase of the study conducted at the test site would be archived according to test site SOPs or in line with the intent specified in individual Study Plans. Supporting data such as facility records (e.g. training records, calibration and equipment records/historical SOPs etc) would also be expected to be held by test site management at their test facility. Facility Management for the study may need to know where the records from all test sites have been archived. If original study data is being sent to the Study Director, it is strongly advisable to retain a copy at test sites since national Monitoring Revised July 2012 Page 7 of 9

8 Authorities need to access their chosen studies during inspections. A period of retention of at least one inspection cycle for the original or copy study data is recommended by the UK GLP Monitoring Authority Records and Data to be Held at the Test Facility Raw data from the phase of the study conducted at the test facility and facility records would be archived according to Test Facility SOPs unless details are stated in the Study Plan. The Archivist at the test facility (usually where the Study Director based) must maintain a listing of where all the data for a particular study are held. The Study Director should also check that other test sites are retaining the data in a GLP archive. It has become more and more common for the Study Director to request all original study data, so that it is all retained at a single location. If data from a test site is returned to either the Study Director s facility or the Sponsor, a record of this should be maintained by the Archivist. If study data is returned to a Sponsor soon after study completion, most Monitoring Authorities may expect to see retention of copies of data, at least till the next inspection. Thus, is it advisable to take copies of all data before transfer. 3.6 Retention of Test and Reference Items and Specimens In addition to study records, retention of test and reference items and specimens is specified 'for as long as the quality of the preparation permits evaluation' in the OECD GLP and Compliance Monitoring document 6. It is generally accepted that test and reference items need to be retained until expiry date, and specimens until after the completion of a study at a minimum. 3.7 Retention periods The requirement for the duration of archive storage of study raw data is not clear. A fixed period of retention, usually of between 10 and 15 years, has been specified by a few national GLP authorities. Sponsor company policy is likely to be to retain data for as long as a product is in commercial production. Contract research organisations normally retain for an agreed fixed period only, before returning data to the Sponsor. 3.8 Electronic Archiving 4 CONCLUSION More and more field study data is being captured electronically. Where this is the case it is important to understand that such data should be stored with the same level of access control, indexing and expedient retrieval as other types of data. The different options that exist include permanent storage of data on long-term storage media and storage on local servers. In conclusion, it is important in field and multi-site studies that the Study Director ensures that all data pertaining to the study is collated, reported and retained to enable full reconstruction of study. Revised July 2012 Page 8 of 9

9 It is emphasised that the Study Director retains the responsibility for the reporting of the whole study, including any contributions from the Principal Investigator(s) and should ensure that test facility and test site managements have adequate systems in place for the archiving of all data and records and that the report clearly states where all the data are being retained. 5 REFERENCES BARQA discussion papers: The Application of GLP Principles to Field Studies Series 1 Discussion Paper No 1: Introduction to the Field Studies Papers 2 Discussion Paper No 2: Personnel, Facilities and Equipment 3 Discussion Paper No 3: Test, Reference and Control Items 4 Discussion Paper No 4: Study Planning 5 Discussion Paper No 5: Study Conduct Other references 6 OECD Series on Principles of Good Laboratory Practice and Compliance Monitoring. Number 1: OECD Principles on Good Laboratory Practice (as revised in 1997). ENV/MC/CHEM(98)17. Jan OECD Series on Principles of Good Laboratory Practice and Compliance Monitoring. Number 6 (Revised): Consensus Document: The Application of the GLP Principles to Field Studies. ENV/JM/MONO(99)22. Sept OECD series on Principles of Good Laboratory Practice and Compliance Monitoring. Number 15: Advisory Document of the Working Group on Good Laboratory Practice: Establishment and Control of Archives that Operate in Compliance with the Principles of GLP ENV/JM/MONO(2007)10 June UK Medicines & Healthcare products Regulatory Agency Guidance Note: The Quality Assurance Statement. July UK Medicines & Healthcare products Regulatory Agency Guidance: Retention of study data and supporting records for inspection purposes. March UK Medicines & Healthcare products Regulatory Agency Guidance: GLPMA expectations when using a contract Quality Assurance service. December 2006 Revised July 2012 Page 9 of 9