Good Clinical Practice (GCP): how does a laboratory that supports a clinical trial ensure compliance with these Regulations

Transcription

1 Good Clinical Practice (GCP): how does a laboratory that supports a clinical trial ensure compliance with these Regulations 9th edition of Synevo Clinical Research Symposium. 17 th November 2017 Bucharest. Tim Stiles info@qualogy.co.uk Qualogy Training & Development

2 Clinical Trial Laboratories Laboratories that support clinical trials and provide results from the analysis of clinical samples are numerous and varied. These laboratories include: Pharmaceutical companies; Hospital laboratories; Contract Research Central Laboratories; GLP Laboratories; Research laboratories.

3 Clinical Trial Laboratories Given that these results contribute significantly to the interpretation of a trial, what quality standards should we expect be present in the way the work is performed and the level of Good Clinical Practice (GCP) Compliance. How can we ensure the reliability and integrity of data produced from such laboratories and the degree to which patient safety is assured. The presentation examines the role of Good Clinical Laboratory Practice can play in ensure compliance with GCP.

4 Introduction Good Clinical Practice Regulations (GCP) are written into Law across Europe and the majority of other countries around the world. What are these GCP Regulations and how does GCP impact upon the Quality System of a Laboratory that assays samples from a clinical trial. What do we need to do in the laboratory to meet the challenge of GCP. Qualogy Training & Development

5 GCP Guidelines ICH Good Clinical Practice Guidelines (ICH International committee on Harmonisation) An International ethical and scientific quality standard Standard for designing, conducting, recording and reporting trials Originally effective 1997

6 ICH GCP Regulations Updated ICH Guideline for Good Clinical Practice E6(R2) Comes into effect June 2017) This guideline has been amended to encourage implementation of improved and more efficient approaches to clinical trial design, conduct, oversight, recording and reporting while continuing to ensure human subject protection and data integrity.

7 ICH GCP Guidelines Designed to protect the involvement of Subjects/Patients in the Trial Adopted globally as the GCP standard ICH is not a receiving authority, nor an Inspectorate ICH also produces other guidance

8 NEW European GCP Regulations Regulation (EU) No.536/2014 of the European Parliament and of the Council of 16th April 2014 on clinical trials on medicinal products for human use, and repealing Directive 2001/20/EC

9 What does ICH GCP say about clinicaltrial laboratories 2.13 Systems with procedures that assure the quality of every aspect of the trial should be implemented Essential Documents: Medical/Laboratory/Technical procedures/tests -certification or accreditation or established quality control and /or external quality assessment or other validation (where required) Qualogy Training & Development

10 Expected standards in a GCP clinical laboratory A quality system which: Produces accurate and reliable results Satisfies the GCP regulations and expectations Encompasses the entire process not just the laboratory Enables the reconstruction of the systems and procedures. Protects the subjects rights and confidentiality GCP does not define the standards laboratories should follow. GLP will not ensure compliance with GCP regulations Qualogy Training & Development

11 Clinical Trial process Clinical Protocol Regulatory Approval (Could be more than one) Ethics approval (Could be more than one) Investigator and site selection Data management Sample collection and assay Conduct of the trial Patient recruitment Archive Report Submit report to Receiving Authority Production of IMP to GMP

12 Good Clinical Laboratory Practice (GCLP) GCLP is a quality system which when applied in the clinical laboratory should meet the requirements of GCP. GCLP is a standard which is now being adopted globally in all types of laboratories that assay samples from clinical trials. Qualogy Training & Development

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14 Reflection paper on guidance for laboratories that perform the analysis or evaluation of clinical trials samples. 2012

15 Research and Discovery Good Laboratory Practice (GLP) Good Clinical Practice (GCP) Good Manufacture Practice (GMP) Pharmacovigilance (PV) RQA Good Clinical Laboratory Practice (GCLP) EMA Reflection paper on clinical laboratories Good Distribution Practice (GDP) 15 ISO Standards 9001:

16 Good Clinical Practice (GCP) RQA Good Clinical Laboratory Practice (GCLP) EMA Reflection paper Discussion document available ISO Standards ISO 9001:2015 Quality Management Systems ISO Medical Laboratories Particular requirements for Quality and Competence ISO General requirements for the Competence of Testing and Calibration Laboratories 16

17 Types of Laboratories that assay Clinical Samples This includes the following types: Pharmaceutical companies; Hospital laboratories; Contract Research Central Laboratories (CROs); Central labs Specialised labs GLP Laboratories; Research laboratories.

18 Key Elements The following are some of the key elements of GCLP which must be addressed by your quality systems: Informed Patient/Subject consent Patent Confidentiality Patent safety Expedited reporting Serious breach of GCP Study Blinding

19 Content of GCLP Definitions The specific use of terms, such as "Analytical Plan" and Analytical Project Manager, are intended to identify specific documents, individuals or activities. The use of such terms is not mandatory but the activities or responsibilities associated with a specific item, as defined within the guidance, should be followed and adherence is expected.

20 Content of GCLP Laboratory Facilities Those areas of the laboratory which are operated in accordance with GCLP should be clearly identified and documented. The laboratory should be of suitable size, construction and location to meet the requirements of the trial and minimise any disturbances that might interfere with the validity of the trial or its results.

21 Content of GCLP Organisation and Personnel Defined responsibilities for: Laboratory Management Analytical Project Manager Laboratory Staff

22 Content of GCLP Standard Operating Procedures A laboratory should have documented Standard Operating Procedures approved by Laboratory Management that are intended to ensure the quality and integrity of the work performed and the data generated. Standard Operating Procedures should be periodically reviewed to ensure that they remain current and up to date.

23 Content of GCLP Equipment Equipment used in the analysis of trial samples and operation of the laboratory should be suitably located and of appropriate design and adequate capacity. Equipment used should be periodically inspected, cleaned, maintained, and calibrated. Calibration and maintenance frequency will be determined by Laboratory Management and should be designed to ensure that all equipment remains fit for purpose.

24 Content of GCLP Analytical Plan For each trial a written analytical plan should be produced by the laboratory prior to initiation of the work. The analytical plan should describe the work to be performed by the laboratory and be available to the staff. This plan should be an exact reflection of the requirements of the clinical protocol and only include work that is covered by the informed consent given by the trial subjects. This plan should be agreed by the dated signature of the Analytical Project Manager and Sponsor.

25 Content of GCLP Trial Samples Procedures for the receipt, handling, storage, retrieval and management of trial samples should be designed to prevent mix-ups and maintain their integrity. Samples should be transported in such a way that their integrity and viability remains unaffected. Trial samples should be checked on receipt to confirm their identification. Records of identity, source, date of arrival, and condition on arrival should be maintained.

26 Content of GCLP Logistics (Sample kit preparation) When a laboratory prepares sample kits or materials used for the collection of trial samples, the systems used for the preparation, distribution, sample collection and return of such materials to the laboratory must be documented and the systems and procedures used should be validated.

27 Content of GCLP Conduct of the work The work should be conducted in accordance with the clinical protocol and the analytical plan. Method validation Repeat analysis Additionalwork

28 Content of GCLP Sub-Contracting No analytical or other study related work should be subcontracted by the laboratory without the prior approval of the Sponsor.

29 Content of GCLP Reporting Results It is acceptable to report analytical results in a number of different ways. The analytical plan or Laboratory SOPs should indicate the type of reporting mechanism to be followed and the time scale for issue. Regardless of how data is reported it must be complete and accurately reflect the results obtained and the raw data.

30 Content of GCLP Quality Control The laboratory should operate appropriate Quality Control (QC) procedures to ensure the quality and accuracy of all aspects of the work performed and reported. Documenting and trending of QC sample results to indicate drift in the analytical performance should be maintained where appropriate.

31 Content of GCLP Quality Audit Independent auditing of the laboratory should be conducted to assure patient safety, patient confidentiality, data integrity and compliance with GCP. This includes confirmation that the clinical protocol, analytical plan, SOPs and these guidelines are being complied with.

32 Content of GCLP Storage and Retention (Archive Facilities) Records need to be retained for the reconstruction of the laboratory work. Space should be provided for the safe and secure archive storage of data, reports, samples and specimens.

33 Content of GCLP Patient safety The need to expedite reporting of results or events that could adversely impact on patient safety. Patent confidentiality Procedures for the handling of trial samples, collection of data and reporting of results should be designed to maintain subject confidentiality Blinding of samples The laboratory should be aware of any blinding and unblinding conditions that apply to a trial and take care not to inadvertently un-blind a trial. Patient Safety The safety of trial subjects takes precedence over any other aspect of the trial. Serious Breach of GCP No laboratory events has occurred on the study/trial that could be classed as a serious breaches of GCP prompting reporting to the Sponsor.

34 GCLP Simplicity GCLP is written in a language that can be easily understood. Too often we assume greater understanding in Regulatory requirements than actually exists. Many of the laboratories have little experience of regulatory expectation In the end we need to comply with the GCP Regulations GCLP is a Quality System that can be easily applied and understood

35 GCLP Accreditation Schemes GCLP Accreditation Scheme operated by Qualogy Ltd. Assessment of laboratories GCLP Compliance Scheme operates globally Provides independent assessment of you quality system. Qualogy Training & Development

36 Thank you Any questions Please

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