Extent, Preparation, Implementation, and Use - - Forside€¦ · Extent, Preparation, Implementation, and Use ... • General vs. trial specific SOPs • Extent • Template • Revision

Standard Operation Procedures Extent, Preparation,

Implementation, and Use

From a GCP point of view

Charlotte Calov, cand.med.vet., Head of the GCP Unit at Odense University Hospital

SOPs - Danish Biobank Netwoork Meeting 17th March 2016

Good Clinical Practice (GCP)

An international ethical and scientific quality standard for designing, conducting, recording and reporting trials (with medicinal products) that involve the participation of human subjects

Compliance with the standard will assure

• the rights, safety and well-being of trial subjects

• that the clinical trial data are credible


Agenda • Definition and Legal requirements (clinical trials)

• SOP system • General vs. trial specific SOPs

• Extent

• Template

• Revision

• SOP training and implementation

• The use of SOPs


SOPs are used in many companies


SOPs in Clinical Trials (ICH-GCP 1.55)

Detailed, written instructions to achieve uniformity of the performance of a specific function

→ Reliable data


Other Definitions e.g.

The documented processes that a company has in place to ensure services and/or products are delivered consistently every time

Established procedure to be followed in carrying out a given operation or in a given situation


7

13 Principals of GCP for Clinical Trials, e.g. 6: A trial should be conducted in compliance with the protocol 8: Each individual involved in conducting a trial should be qualified by education, training, and experience to perform his or her respective tasks

10: All clinical trial information should be recorded, handled, and stored in a way that allows its accurate reporting, interpretation and verification

13: Systems with procedures that assure the quality of every aspect of the trial should be implemented


Executive order on GCP (GCP-bekendtgørelsen)

Sec. 4, sub-sec. 1: The sponsor is responsible for implementing and maintaining quality assurance and quality control systems (with written SOPs) to ensure that trials are planned, conducted and data are generated, documented (recorded), and reported in compliance with the protocol, GCP, and the applicable regulatory requirement(s).

GXP should be followed – assisted by SOPs

GCP (Clinical) GDocP (Documentation) GDP (Distribution)

GLP (Laboratory) GMP (Manufacturing)


Laboratories must have SOPs ICH-GCP 5.2.1

A sponsor may transfer any or all of the sponsor's trial-related duties and functions to a CRO, but the ultimate responsibility for the quality and integrity of the trial data always resides with the sponsor. The CRO should implement quality assurance and quality control CRO = Contract Research Organisation


From Reflection paper for laboratories that perform the analysis or evaluation of clinical trial samples

6.19: Standard operating procedures or documented policies should cover all key activities; examples include, but are not limited to the following: • The way in which the analysis or evaluation of clinical trial

samples is performed and reported • Issues linked to patient safety and confidentiality such as

expedited reporting of results, issues associated with unblinding and blinding samples and procedures for dealing with the receipt of unexpected, unscheduled or poorly labelled samples

• Procedures for the receipt, storage and processing of samples and reference materials

• The retention of trial data and non trial-specific records • Staff training


http://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2012/05/WC500127124.pdf

http://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2012/05/WC500127124.pdf


http://www.google.dk/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwj-8Yuvh7TLAhXBO5oKHawpB0UQjRwIBw&url=http://www.takepart.com/sop&bvm=bv.116274245,d.ZWU&psig=AFQjCNHaPYEqcLeC4XkQLAVB3dw0Fvku-g&ust=1457628262617629

General SOPs e.g.

• Maintenance of equipment

• SOP training

• Preparation and approval of SOPs

• Preparation of trial specific SOPs

• Labelling of samples

• Storage of samples

• Draw up contracts (With template)


Trial Specific SOPs A supplement to the protocol - Description of items not decided at the time for protocol approval (Non-substantial only!) e.g. • Sampling (amount of blood, which glass tubes, time

limits, labelling, storage etc.)

• Reporting the results to investigator and sponsor e.g.

• Outliers, blinding, quality control of data registration

Must not conflict with protocol or sponsors SOP

Replaced by templates from general SOPs?


Building up a SOP system Set up a QA-team Identify all procedures Arrange in groups with subtopics: Name and number

1 – Samples 1.1 – Incoming samples 1.2 – Preparation of samples before freezing 1.3 – Labelling of samples 1.X – etc.

2 – Collaboration ……etc.

Never ending system – New SOPs may be necessary and old SOPs may be irrelevant and can be nullified


Responsibility

SOPs must be

• drawn up by people with sufficient knowledge and experience of the field involved

• approved by the person responsible for the QA-system (or delegated)

• Ensure no contradiction to other SOPs

• complied by relevant staff


Template for a SOP - Framework

• Identification - Name and number

• Version - Version Y, replaces version X

• Valid – Be in force from dd.mm.yyyy

• Approval

• Completed (or revised) by: Names or title of group

• Approved by: Name/title and date

• Table of contents (same main points in every SOP?)

• Pagination - Page x of y (in the footer)


Template for a SOP - Content • Apply for – when must it be used and followed

• Purpose – what must the SOP ensure

• Responsibilities – whom must do what

• Basis/foundation – legal basis and internal instructions

• Definitions of terms used in the SOP (if relevant)

• Description – what you must do (and don´t)

• Clear wording (same phrases in all SOPs)

• Logical structure (chronology often helps)

• Comprehensive but no unnecessary details


Template for a SOP – Content

• Filing - of the documents made following the SOP

• Log with substantial changes

• State the reason for revision

• Gives an overview of and revised parts of the SOP

• Will facilitate a focused training


Template for a SOP - Appendices • Clarification of parts of the description – to make the

SOP text more reader-friendly

• Templates for e.g. • CV

• Co-operation agreements

• Check form

• Deviation Reports

• Could be replaced by a separate document (versioning and approved) with reference to the SOP


SOP Revision As stated in the SOP for revision (and in the SOP) • Some SOPs may require more frequent revision than

other

• Make sure to have a system that will remind you

New legislation, new organization, new services, new equipment etc. • Impact on the SOPs?

• If no, document the evaluation

• If yes, speed up the revision


Training before implementation New version must be available in time before training

• Self study?

• A (exhaustive) survey of the text on a common meeting?

• Using examples to achieve a mutual understanding?

Documentation of training is mandatory - Training log

• Total overview

• Signature and date of the instructor (often the persons that draw up the SOP) and the trained


SOP Implementation

The old version must be withdrawn (keep the master) and the new version must be distributed (paper and electronical version)

Distribution system must be clear

• SOPs handed out to the staff? • “Illegal” copies?

• SOPs located by the equipment?


The daily use of SOPs

• Available at all times (paper and/or electronically)

• Must be read rather once too often than once too little • You think you remember what to do but often

you remember what was in a former version….

• Keep a log of observed errors and amendment for coming revision


SOP Deviation If you intend to deviate or all ready have deviated from a SOP by mistake it must be documented

• identify the deviation

• specify the root cause for the deviation

• valuate the consequence

• specify the corrective actions that will prevent the recurrence of the deviation

The deviation report must be signed and dated by the responsible person and filed


Reporting Deviations Reporting to sponsor (or/and investigator) may be necessary e.g. • The sample was not frozen within the time limit • The centrifuge was not inspected and calibrated

within the time limit stated in the instruction manual • The amount of sample material was less than

required Sponsor decides • whether the data can be used or not • if she must take action


SOPs - Danish Biobank Netwoork

Meeting 17th March 2016

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Extent, Preparation, Implementation, and Use - - Forside€¦ · Extent, Preparation, Implementation, and Use ... • General vs. trial specific SOPs • Extent • Template • Revision