BY- ANUBHAV SINGH

M.PHARM 1st Year

IPR, GLA UNIVERSITY

It is a standard for clinical studies or trials that encompasses the design, conduct, monitoring, termination, audit, analyses, reporting and documentation of the studies.

It ensures that the studies are implemented and reported in such a manner that there is public assurance that the data are credible, accurate and that the rights, integrity and confidentiality of the subjects are protected.

GCP aims to ensure that the studies are scientifically authentic and that the clinical properties of the “Investigational Product” are properly documented.

*To understand:

*The affect of Good Clinical Practices on institutions conducting Clinical Research

*To discuss:

*What is GCP

*Guidelines for GCP

*The history of Good Clinical Practices

*Basic principles

*Practices and strategy for staying compliant with Good Clinical Practices.

*GCP`s are mainly focused on the protection of human rights in clinical trial.

*Provide assurance of the safety of the newly developed compounds.

*Provide standards on how clinical trials should be conducted.

* Define the roles and responsibilities of clinical sponsors, clinical research investigators, Clinical Research Associates, and monitors.

*GCPs are generally accepted, international best practices for conducting clinical trials and device studies.

*They are defined as an international ethical and scientific standard for designing, conducting, recording and reporting trials that involve the participation of human subjects.

*Compliance with GCPs provide public assurance that the rights and safety of participants in human subject research are protected and that the data that arises from the study is credible

GCPs are generally accepted, international best practices for conducting clinical trials and device studies.

They are defined as an international ethical and scientific standard for designing, conducting, recording and reporting trials that involve the participation of human subjects.

Compliance with GCPs provide public assurance that the rights and safety of participants in human subject research are protected and that the data that arises from the study is credible

Good Clinical Laboratory Practices should be used by all laboratories where tests are done on biological specimens for diagnosis, patient care, disease control and research such as:

• Microbiology & Serology

• Hematology & Blood Banking

• Molecular Biology and Molecular Pathology

• Clinical Pathology

• Clinical Biochemistry

• Immunology (Immunohematology and Immuno biochemistry)

• Histopathology/Pathology and Cytology

Infrastructure of laboratories should be planned according to the services provided bythe laboratory. The basic infrastructure facilities include:

• Reception room/area where requisition forms are received and reports disbursed.• Specimen collection room/area, toilets, privacy for special purposes e.g. semen collection, facilities for disabled persons, toilet for staff.• Quality water supply for analytical purpose.• Uninterrupted power supply.• Analytical work area.• Specimen/Sample/slide storage facility including cold storage where applicable.• Record room/area.• Facility for cleaning of glassware, sterilization /disinfection.

About Laboratories

• Waste disposal facility including biomedical wastes

• Fire-safety equipment

• Ventilation, climate control and lighting arrangements

• Separate room/area for meetings/administrative work

• Separate facilities/area for staff for hand washing, eating and storing food,

drinks etc.

• Communication facility with referral centers

• Transport of specimen/samples to referral centers

• Additional infrastructure facilities may be added for special tasks as and when

needed.

Cont.

The laboratory should maintain a personal file of all the technical and nontechnical staff employed. Personal file should contain all information on:

•Personal bio-data including educational qualification and experience

•Copy of degree/diploma and registration with state authority if applicable

•Copy of appointment letter

•Duly verified health information (physical fitness including color blindness, immunizations received etc.) prepared at the time of employment and its regular updates

•Performance appraisal

•Training certificates, awards/recognition received

•Disciplinary action if any taken by the management

•Reference letter from previous employer if applicable

About Personnel's

• Each laboratory should prepare an exhaustive list of equipment and consumables required and available for general functioning of the laboratory and specialized equipment for special tests.

• Equipment should be suitably located in the laboratory so as to allow accessibility and sequential utilization thus minimizing the need for frequent movement of specimens or reagents.

• All equipment should be in good working condition at all times. Periodic inspection, cleaning, maintenance of equipment should be done. An equipment log book should be maintained for all major equipment. Laboratories should maintain necessary instructions for operation and maintenance of equipment in the form of Standard Operating Procedures (SOPs). A copy of SOP should be readily available.

About Equipment's

• Standard reagents of certified quality must be used for the purpose of analysis.

• The batch number of reagents must be recorded. The quality of the reagent viz. Annular grade, HPLC grade, etc. to be used for in-house procedures should be defined in SOP

• The reagents, chemicals and consumables should be stored under appropriate environmental conditions.

• Quality of newly purchased reagents should be validated against suitable control/reference material prior to use. Validation data should be properly documented. In-house prepared reagents should also be checked periodically for stability and a record of the same should be maintained.

About Reagents and Materials

• Laboratory data management includes recording details of the patient, findings of analysis, reporting of results and archiving the data for future reference.

• Recording data allows smooth functioning of the internal quality control measures, internal audit and external quality assessment. From the point of view of management, absence of record implies that the work was never done.

• The format of recording and reporting results should be described in the Standard Operating Procedures (SOPs).

• Data entry should begin as soon as registration number is assigned to the specimen. Further entries should be made in the accession list and worksheet.

• The final report should be recorded after approval/signature of the designated authority.

Data Management

• SOP is a document, which contains detailed, written instructions describing the stepwise process and technique of performing a test or procedure in the laboratory.

• SOP helps to ensure uniformity, consistency and control over the processes carried out. It ensures that the procedures are done in exactly the same way each time irrespective of the operator.

• SOP should contain information on who can perform the test, their qualification and training, how to carry out the test including pre-analytical, analytical and post-analytical stages of test/procedure, laboratory conditions required for the test/ procedure, routine care and maintenance of equipment, precautions and safety instructions, trouble shooting measures, waste disposal and linkage with reference laboratories.

• SOP should be simple and written in an easy to understand language.

• The procedure described in the SOP must be followed exactly by all staff members to ensure high quality results.

Standard Operating Procedures (SOP)

Where, GQP- Good Quality Practices GVP- Good Vigilance Practices PV- Pharmacovigilance GD- Guidance Documents

1 Clinical trials should be conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki, and that are consistent with GCP and the applicable regulatory requirements.

2 Before a trial is initiated, foreseeable risks and inconveniences should be weighed against the anticipated benefit for the individual trial subject and society. A trial should be initiated and continued only if the anticipated benefits justify the risks. 3 The rights, safety, and well-being of the trial subjects are the most important considerations and should prevail over interests of science and society. 4 The available non clinical and clinical information on an investigational product should be adequate to support the proposed clinical trial. 5 Clinical trials should be scientifically sound, and described in a clear, detailed protocol.

6 A trial should be conducted in compliance with the protocol that has received prior institutional review board (IRB)/independent ethics committee (IEC) approval/favorable opinion.

7 The medical care given to, and medical decisions made on behalf of, subjects should always be the responsibility of a qualified physician or, when appropriate, of a qualified dentist.

8 Each individual involved in conducting a trial should be qualified by education, training, and experience to perform his or her respective tasks.

9 Freely given informed consent should be obtained from every subject prior to clinical trial participation.

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

11 The confidentiality of records that could identify subjects should be protected, respecting the privacy and confidentiality rules in accordance with the applicable regulatory requirements.

12 Investigational products should be manufactured, handled, and stored in accordance with applicable good manufacturing practice (GMP). They should be used in accordance with the approved protocol. 13 Systems with procedures that assure the quality of every aspect of the trial should be implemented.

Cont.

*Prior to an actual set of guidelines to follow for good clinical practice, clinical studies were dangerous and could result in serous disease, or possibly death

*The Nuremburg Code of 1947* Experiments performed in Germany during WWII opened the eyes of the

world for guidance for clinical testing on humans.

* The code did set ethical guidelines, but it lacked legislation to back it up.

*Declaration of Helsinki* In 1964, the World Medical Association established

recommendations guiding medical doctors in biomedical research involving human subjects. These guidelines influenced national legislation, but there was no set standard between nations

The Good Clinical Practice Program is the focal point within FDA regarding issues in human research trials regulated by FDA. The Good Clinical Practice Program:

Coordinates FDA policies. Contributes to leadership and direction through participation

in FDA's Human Subject Protection/Bioresearch Monitoring Council.

Coordinates FDA's Bioresearch Monitoring program with respect to clinical trials, working together with FDA's Office of Regulatory Affairs (ORA).

Contributes to international Good Clinical Practice harmonization activities.

Plans and conducts training and outreach programs.

*The trials are conducted in 4 phases.

*Phase 1 trials are for determining dosing, document how a drug is metabolized and identify side effects.

*Phase 2 trials gather further safety data and evidence of the drug's efficacy.

*Phase 3 trials further tests the product's effectiveness on a greater number of participants, and monitors side effects.

*Phase 4 trials can be conducted after a product is already approved and on the market to find out more about the treatment's long-term risks

*It is estimated that only 5 in 5,000 compounds that enter preclinical testing make it to human testing, and only 1 of those 5 may be safe and effective enough to reach pharmacy shelves.