Table 3.

Good clinical practice inspection regulatory references

Deficiency areas category/sub-categories	ICH E6 (R1) Section/CPMP/ICH/ 135/95	FDA code of federal regulations, Title 21 Part 312, 50, 56
Trial management
Data management	Specifically requires that the data changes are documented and that there is no deletion of entered data (i.e., maintain an audit trail, data trail, edit trail) (5.5)	Has general language that a sponsor is required to select qualified clinical investigators (312.50), who are required to prepare and maintain adequate and accurate case histories (312.62)
Monitoring	Has specific requirements concerning the purpose of monitoring; the selection and qualifications of monitors; extent and nature of monitoring Monitor’s responsibilities; monitoring procedures, monitoring report and monitoring plan (5.18) The sponsor may consider establishing an independent data monitoring committee, to assess the progress of a clinical trial, including the safety data and the critical efficacy endpoints at intervals, and to recommend to the sponsor whether to continue, modify, or stop a trial. The independent data monitoring committee should have written operating procedures and maintain written records of all its meetings (5.5.2)	Has general language that the sponsor shall select a monitor qualified by training and experience to monitor the progress of the investigation (312.53); and is responsible for ensuring proper monitoring of the investigation(s) (312.56)
		No requirements for the use of data monitoring committee in trials except research studies in emergency settings in which the informed consent requirement is excepted (50.24)
Document control	Specific requirements of document identification and version history [8]	No specific requirement of version history
Audit	Gives detailed guidance on how sponsors should conduct site quality assurance audits	No specific requirements. However, many sponsors obtain independent audits/data verifications to determine the compliance with clinical trial sops and FDA regulations and verify the accuracy of the case reports
Documentation
Essential documents	Trial Master File includes documents, for examples: • Insurance Statement • Subject Screening Log • Signature Sheet (to document signatures/initials of persons authorized to make CRF entries and corrections) • Pretrial and trial initiation monitoring report from sites • Subject screening and enrollment log/subject identification code list ICH specifically requires filing essential documents in a timely manner [8]	no specifics as Trial Master File but has different requirements of essential documents
Qualification and training	Requires documentation of GCP training The investigator(s) should be qualified by education, training, and experience to assume responsibility for the proper conduct of the trial, should meet all the qualifications specified by the applicable regulatory requirement(s), and should provide evidence of such qualifications through up-to-date curriculum vitae and/or other relevant documentation requested by the sponsor, the IRB/IEC, and/or the regulatory authority(ies) The investigator should be aware of, and should comply with, GCP and the applicable regulatory requirements (4.1)	Has similar requirements but does not require GCP training (312.53)
Standard operating procedures	The sponsor is responsible for implementing and maintaining quality assurance and quality control systems with written standard operating procedures Requires Monitoring procedures (Monitor Plan) and auditing procedures (5.18)	No specific requirements of standard operating procedures
Organization and personnel	Requires maintaining a delegation log. The investigator should maintain a list of appropriately qualified persons to whom the investigator has delegated significant trial-related duties (4.1.5)	The investigator is responsible for supervising any individual or party to whom the investigator delegates trial-related duties and functions conducted at the trial site; but documentation only requires a list of the names of the sub-investigators (312.53)
Contracts and agreements	ICH has specific requirement for signatures of documents (8.2.6)	Similar requirements in writing for transferred obligations but no specific mentioning of signatures (312.52)
Study drug
Supplying/storage/retrieving/destruction	Investigational products should be manufactured, handled, and stored in accordance with applicable good manufacturing practice	A sponsor shall maintain adequate records showing the receipt, shipment, or other disposition of the investigational drug (312.57)
	Sponsor should determine for investigational medicinal product acceptable storage, temperatures, conditions during shipment The sponsor should have written procedures including adequate, safe receipt and handling
	The sponsor should ensure that written procedures include instructions that the investigator/institution should follow for the handling and storage of investigational product(s) for the trial and documentation thereof. The procedures should address adequate and safe receipt, handling, storage, dispensing, retrieval of unused product from subjects, and return of unused investigational product(s) to the sponsor (or alternative disposition if authorized by the sponsor and in compliance with the applicable regulatory requirement(s)) (5.14)
Informed consent
Informed consent process/informed consent form	The written informed consent form should be signed and personally dated by the subject	Informed consent shall be documented by the use of a written consent form approved by the IRB and signed and dated by the subject or the subject's legally authorized representative at the time of consent (50.27) Allows to use the short form written consent document to be signed by the subject or the representative; a witness to the oral presentation sign both the short form and a copy of the summary; the person who conducted the informed consent discussion sign a copy of the summary (50.27)
	Or by the subject’s legally acceptable representative, and by the person who conducted the informed consent discussion prior to a subject’s participation in the trial (4.8.8., 4.8.9)
	Requires that the subject receive a signed and dated copy of the written informed consent (4.8.11)	Requires that a copy be given to the subject but does not state that it must be a signed copy (50.27)
	Detailed specific explanations are required to give to study subjects during the informed consent discussion such as: Trial treatments and probability of random assignment The anticipated prorated payment, if any, to the subject for participating in the trial	Requires notifying subject that clinical trial information has been or will be submitted for inclusion in the clinical trial registry and need to contain the Clinical Trial registry language (50.25)
	access of medical records by monitor(s), the auditor(s), the IRB/IEC, and the regulatory authority(ies) to the subject's original medical records (4.8)	Requires stating the possibility that the Food and Drug Administration may inspect the records (50.25)
Institutional review boards/independent ethics committees
Opinion/amendments/notifications to the Institutional Review Boards/Independent Ethics Committees	The investigator should not implement any deviation from, or changes of the protocol without agreement by the sponsor and prior review and documented approval/favorable opinion from the Institutional Review Boards/Independent Ethics Committees of an amendment, except where necessary to eliminate an immediate hazard(s) to trial subjects, or when the change(s) involves only logistical or administrative aspects of the trial (e.g., change in monitor(s), change of telephone number(s)) (3, 4.5)	The investigator shall also assure that he or she will promptly report to the Institutional Review Board all changes in the research activity and all unanticipated problems involving risk to human subjects or others, and that he or she will not make any changes in the research without Institutional Review Board approval, except where necessary to eliminate apparent immediate hazards to human subjects. (56.109, 312.66)

Table 3 shows the good clinical practice inspection regulatory differences of ICH E6 (R1) and FDA Code of Federal Regulations, Title 21 Part 312, 50, 56 for the study period of 2009–2015. CPMP Committee for Proprietary Medicinal Products, which was replaced by the current name Committee for Medicinal Products for Human Use (CHMP) in May 2004