Trial Master File and essential document maintenance MCQs With Answer

Introduction: This blog presents a focused set of multiple-choice questions on Trial Master File (TMF) and essential document maintenance tailored for M.Pharm students studying Clinical Research (MPP 104T). The questions target core regulatory principles such as ICH-GCP requirements, TMF content and structure, electronic TMF (eTMF) practices, document control, retention and archiving, inspection readiness, and sponsor/site responsibilities. Each item is designed to deepen understanding of record-keeping needed to reconstruct and verify clinical trial conduct, prepare for inspections, and ensure data integrity. Answers are provided to help you self-assess and reinforce best practices for robust TMF management in regulated clinical research.

Q1. What is the primary purpose of the Trial Master File (TMF)?

• To store all signed patient consent forms only
• To provide a collection of essential documents that permits evaluation of the conduct of a trial and the quality of the data produced
• To act as a commercial archive for finalized study publications
• To hold solely financial records related to the study

Correct Answer: To provide a collection of essential documents that permits evaluation of the conduct of a trial and the quality of the data produced

Q2. Which guideline is most widely used as the reference for defining essential documents that should be included in the TMF?

• Good Laboratory Practice (GLP)
• ICH E6(R2) Good Clinical Practice (GCP)
• ICH Q10 Pharmaceutical Quality System
• Declaration of Helsinki

Correct Answer: ICH E6(R2) Good Clinical Practice (GCP)

Q3. Which of the following documents should ideally be included in the TMF before the first subject is enrolled?

• Final approved protocol, IRB/IEC approval of the protocol and informed consent form, signed investigator CVs and delegation log
• Final clinical study report and all subject files
• Marketing authorization for the investigational product
• Final study publication drafts

Correct Answer: Final approved protocol, IRB/IEC approval of the protocol and informed consent form, signed investigator CVs and delegation log

Q4. How does the Sponsor TMF differ from the Investigator Site File (ISF)?

• The Sponsor TMF includes site consent forms while the ISF only contains sponsor contracts
• The Sponsor TMF holds sponsor-level and study-wide documentation; the ISF contains site-specific documents maintained at the investigational site
• The ISF is used only for monitoring reports and not for regulatory inspections
• They are identical and interchangeable for inspection purposes

Correct Answer: The Sponsor TMF holds sponsor-level and study-wide documentation; the ISF contains site-specific documents maintained at the investigational site

Q5. According to ICH GCP, what is the minimum recommended retention period for TMF documents after the last approval of a marketing application in an ICH region?

• 6 months
• 2 years
• 20 years
• Until the end of patient follow-up only

Correct Answer: 2 years

Q6. Which of the following is a key advantage of an electronic TMF (eTMF) compared with a paper TMF?

• eTMF eliminates the need for any SOPs or governance
• eTMF provides improved searchability, automated audit trails, controlled access and easier remote inspection readiness
• eTMF replaces the need for certified copies of regulatory approvals
• eTMF makes version control unnecessary

Correct Answer: eTMF provides improved searchability, automated audit trails, controlled access and easier remote inspection readiness

Q7. Which metadata elements are essential for indexing documents in an eTMF to ensure traceability?

• Document title, author, creation date, version identifier, document type/study role and uploaded file name only
• Document title, author, creation date, version identifier, approver name/date and study role/document classification
• Only the document title and file size
• Only the upload timestamp and file extension

Correct Answer: Document title, author, creation date, version identifier, approver name/date and study role/document classification

Q8. Who holds primary responsibility for establishing and maintaining the TMF for a clinical trial?

• The investigator alone
• The sponsor
• The ethics committee
• The contract research organization (CRO) with no sponsor oversight

Correct Answer: The sponsor

Q9. Which practice best ensures TMF inspection readiness?

• Filing documents anywhere and relying on the monitor to find them
• Maintaining a complete, consistently indexed, up-to-date TMF with controlled versioning and a visible audit trail
• Retaining only electronic copies without any record of approvals
• Waiting until the end of the trial to compile the TMF

Correct Answer: Maintaining a complete, consistently indexed, up-to-date TMF with controlled versioning and a visible audit trail

Q10. Which document is used to record delegated responsibilities and authorized signatories at a study site?

• Site Master File
• Trial Master Index
• Delegation of Authority Log (Delegation Log)
• Financial Disclosure Form

Correct Answer: Delegation of Authority Log (Delegation Log)

Q11. When should monitoring visit reports be filed in the TMF following a monitoring visit?

• Only at the end of the trial
• As soon as they are finalized—promptly after each monitoring visit—because they are essential documents
• Only if there is a major protocol deviation
• Never; monitoring reports belong exclusively in the ISF

Correct Answer: As soon as they are finalized—promptly after each monitoring visit—because they are essential documents

Q12. In regulatory practice, what is a “certified copy” in the context of TMF documents?

• An uncertified photocopy of an original
• A copy verified to be a true copy of the original, acceptable to replace the original for filing
• A handwritten summary of the original document
• A scanned image without any verification

Correct Answer: A copy verified to be a true copy of the original, acceptable to replace the original for filing

Q13. Which approach best supports robust version control of TMF documents?

• Overwriting files without tracking changes
• Assigning unique version identifiers, recording change history, effective date and approver for each version
• Keeping only the latest file with no archive of prior versions
• Using date-only filenames with no change log

Correct Answer: Assigning unique version identifiers, recording change history, effective date and approver for each version

Q14. Which TMF document provides evidence that serious adverse events (SAEs) and SUSARs were reported according to required timelines?

• Final clinical study report only
• Serious adverse event (SAE) reports, SUSAR notification records and safety reporting tracker/log
• Investigator brochure without safety updates
• Standard laboratory normal ranges

Correct Answer: Serious adverse event (SAE) reports, SUSAR notification records and safety reporting tracker/log

Q15. Who is responsible for determining the long-term archive arrangement and location for the TMF after study close-out?

• The local ethics committee
• The sponsor, who may delegate to an archive vendor but retains overall responsibility
• The trial monitor only
• The investigational site without sponsor involvement

Correct Answer: The sponsor, who may delegate to an archive vendor but retains overall responsibility

Q16. Which TMF document maps blinded subject identifiers to actual subject identities for audit or inspection, while protecting confidentiality?

• Investigator Financial Disclosure
• Subject Identification Code List
• Source document for each visit
• Case report form (CRF) only

Correct Answer: Subject Identification Code List

Q17. When a protocol amendment is implemented, what is the correct TMF filing practice?

• File only the original protocol and destroy amendment documents
• File the finalized approved amendment, associated approvals (regulatory/IRB), and the amendment notification letters in the TMF; site-specific approvals filed in the ISF
• Keep amendments only in email folders and not in TMF
• Record amendments verbally with no supporting documents

Correct Answer: File the finalized approved amendment, associated approvals (regulatory/IRB), and the amendment notification letters in the TMF; site-specific approvals filed in the ISF

Q18. Which of the following would NOT typically be considered an essential TMF document?

• Investigator Brochure
• Internal company training material unrelated to the specific study procedures
• Regulatory authority approval letters
• Signed informed consent forms and approved versions of the informed consent document

Correct Answer: Internal company training material unrelated to the specific study procedures

Q19. What regulatory consequences can result from poorly maintained or incomplete TMF documentation?

• Inspection findings, potential regulatory actions, trial holds, and compromised ability to verify study conduct and data integrity
• No impact as TMF is optional
• Only minor administrative notices without consequences
• Automatic extension of the trial without review

Correct Answer: Inspection findings, potential regulatory actions, trial holds, and compromised ability to verify study conduct and data integrity

Q20. Which resource is recommended as a standard for consistent TMF document classification and indexing across studies?

• The ICH eTMF Reference Model
• Investigator’s personal filing system
• Random folder names chosen by monitors
• The journal submission guidelines

Correct Answer: The ICH eTMF Reference Model

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