1. Purpose
To define the process to be used for the frequency and audit of critical phases within a non-clinical safety study.
2. Scope and Applicability
This procedure may be applicable for all R&D GLP QA staff and will be used in the compilation of a program to identify audits to be undertaken for non-clinical safety studies and study parts for which compliance with GLP is claimed.
3. Definitions
3.1 Critical Phase: A study specific procedure, during the experimental phase of, a non-clinical safety study that has been identified for QA involvement. Critical phases are defined in Appendix 1.
3.2 Study based audit: The audit performed on a critical phase during the conduct of a specific study.
3.3 Study Part: The defined set of activities on a study for which a Principal Investigator is responsible.
3.4 Study type: Non-clinical safety studies grouped by scientific discipline or resource group. Study types are defined in Appendix 1.
4. Responsibilities
4.1 GLP QA Head
Head of GLP QA is responsible for ensuring that adequate study based audits are conducted to assure management that GLP compliance is being maintained.
4.2 QA Advisor
Any trained member of GLP QA may undertake study based audits. Advisors are responsible for the planning/scheduling, conduct, reporting and follow-up of an audit, and for maintaining QA records.
5. Procedure
5.1 Frequency of audits
All critical phases listed in Appendix 1, will be audited every 3 months, when they are being conducted. For all study types, critical phases ongoing at the same time as dosing will also be audited at that time. Dosing will be audited every3 months for long-term studies. Any phase that is non-routine, e g non-routine analysis, non-routine formulation and planned on a study but is not defined in Appendix 1 will be audited per study.
The minimum number and type of critical phases to be audited per study type is as follows:
– General Toxicology
– Dosing will be audited for each study.
– Necropsy will be audited every 3 months for a single dose study, a MTD study and a repeat dose study.
– Reproductive Toxicology
– Dosing & Necropsy (including fatal examination) will be audited for each study.
– Genetic Toxicology in-vivo
– Dosing or Scoring/Assessment will be audited for each study.
– Genetic Toxicology in-vitro=
– Formulation preparation (if prepared by Genetic Toxicology) or Dosing or Scoring/Assessment will be audited for each study.
– Safety Pharmacology in-vivo
– Dosing will be audited for each study.
– Safety Pharmacology in-vitro
– Formulation preparation (if prepared by Safety Pharmacology) or Dosing will be audited for each study.
– Development DMPK& Bioanalysis
– Formulation preparation or Dosing will be audited for each study.
5.2 Conduct of audit
Study audits will be made announced or unannounced. Arrangements with the responsible study staff to visit the area at the time of day when the procedure is to be carried out can be made.
When entering an area to be audited, any safety or quarantine requirements specified in the study plan and/or SOP or locally displayed must be followed.
Audit of a study involves visual audit of work, audit of raw data and advice where appropriate. The procedures are checked for SOP, study plan (with amendments) and GLP compliance.
A copy of the study plan and any amendments, the previous QA report, where relevant and pertinent SOPs shall be read before or during the audit.
All GLP and related issues will be discussed with the personnel undertaking the procedure at the end of the audit. It may be necessary to further clarify audit comments with the appropriate ability staff or Study Director or Principal Investigator prior to reporting. The advisor may also check that actions arising from relevant previous audits have been dealt with satisfactorily.
5.3 Checklist
Checklists are available as a general guide and do not form part of the audit records.
5.4 QA Report
A QA report will be generated according to the International Procedure for GLPQA reporting.
6. Appendix 1
Study Types and their Critical Phases
– General Toxicology
– Body weight
– Clinical Observation
– Dosing
– ECG
– Biological Fluids Sampling
– Necropsy
– Food consumption
– Water consumption
– Ophthalmology
– Impactor/filter sampling (inhalation studies)
– Reproductive Toxicology
– Body weight
– Clinical Observations
– Dosing
– Biological Fluids Sampling
– Necropsy
– Food consumption
– Water consumption
– Foetal examination
– Skeletal examination
– Vaginal smears
– Genetic Toxicology
– In vivo studies
– Dosing
– Cell harvesting
– Scoring/assessment
– In vitro studies
– Formulation preparation/Dosing
– Cell harvesting
– Scoring/assessment
– Safety Pharmacology
– In vivo studies
– Body weight
– Dosing
– Biological Fluids Sampling
– Clinical Observation or Study specific observations, as applicable
– Necropsy – gastric emptying and intestinal motility studies (UK only)
– In vitro studiesFormulation preparation/Dosing
– Development DMPK& Bioanalysis
– Formulation preparation (14C studies)
– Formulation Analysis (14C studies)
– Dosing
– Biological Fluids Sampling
– Biological Sample Collection
Sample Analysis
* Sample Receipt
* Sample Preparation
* Sample Analysis
(*) = only used at test sites where process audits are not conducted for these phases.