Regulation of combination products MCQs With Answer

Regulation of combination products MCQs With Answer is designed for M. Pharm students taking Regulatory Affairs (MPH 104T). Combination products merge drugs, devices, and/or biologics into a single therapy, creating unique regulatory challenges across classification, submission strategy, quality systems, and postmarket oversight. This quiz focuses on core principles such as Primary Mode of Action (PMOA), FDA’s Office of Combination Products (OCP) processes, 21 CFR Parts 3 and 4, EU MDR Article 117, and global nuances. You will test your understanding of Requests for Designation (RFD), cGMP/QSR integration, human factors, safety reporting, and lifecycle change control. Use these MCQs to sharpen exam readiness and develop a structured approach to real-world combination product development and compliance.

Q1. Which U.S. regulation defines “combination product” and outlines the designation process?

• 21 CFR Part 3
• 21 CFR Part 4
• 21 CFR Part 820
• ICH Q10

Correct Answer: 21 CFR Part 3

Q2. What is the primary function of FDA’s Office of Combination Products (OCP)?

• Issue Certificates of Pharmaceutical Product (CPPs)
• Assign the FDA lead center based on PMOA and coordinate inter-center review
• Conduct GCP inspections at clinical trial sites
• Approve all PMAs and BLAs

Correct Answer: Assign the FDA lead center based on PMOA and coordinate inter-center review

Q3. Which set correctly lists the three FDA-recognized categories of combination products?

• Single-entity, co-packaged, and cross-labeled
• Standalone drug, standalone device, and IVD
• NDA-led, BLA-led, and PMA-led
• Premarket, postmarket, and lifecycle

Correct Answer: Single-entity, co-packaged, and cross-labeled

Q4. Primary Mode of Action (PMOA) is best defined as:

• The mechanism producing the fastest onset
• The mode of action expected to make the greatest contribution to the product’s overall intended therapeutic effect
• The device mechanism that delivers the drug
• The most novel mechanism requiring the highest evidence

Correct Answer: The mode of action expected to make the greatest contribution to the product’s overall intended therapeutic effect

Q5. If PMOA cannot be determined with reasonable certainty, FDA assigns the lead center using:

• A default rule to CDER for all borderline cases
• The center with the lowest user fee
• A tie-breaker algorithm focusing on the center best able to address the most significant safety and effectiveness questions
• A lottery across centers

Correct Answer: A tie-breaker algorithm focusing on the center best able to address the most significant safety and effectiveness questions

Q6. Under 21 CFR Part 3, FDA’s response timeline for a formal Request for Designation (RFD) is:

• 15 calendar days
• 30 calendar days
• 60 calendar days
• 90 calendar days

Correct Answer: 60 calendar days

Q7. U.S. current good manufacturing practice (cGMP) requirements for combination products are codified in:

• 21 CFR Part 11
• 21 CFR Part 210/211 only
• 21 CFR Part 820 only
• 21 CFR Part 4

Correct Answer: 21 CFR Part 4

Q8. Which statement best reflects FDA’s “streamlined” cGMP approach under 21 CFR Part 4?

• Firms must fully comply with both drug cGMP and device QSR in their entirety
• Compliance with a base (drug or device) system plus specified provisions from the other system, as applicable to the constituent parts
• Device QSR applies only during clinical development
• Drug cGMP applies only after approval

Correct Answer: Compliance with a base (drug or device) system plus specified provisions from the other system, as applicable to the constituent parts

Q9. In the EU, which legal provision requires inclusion of a Notified Body opinion in the MA dossier for a medicinal product with an integral device that is a medical device?

• Annex XXI of EU MDR 2017/745
• Article 117 of EU MDR 2017/745
• Article 120 of EU MDR 2017/745
• ISO 14971:2019

Correct Answer: Article 117 of EU MDR 2017/745

Q10. In the EU, a device incorporating an ancillary medicinal substance (e.g., drug-eluting stent) is typically:

• Regulated as a medicinal product with EMA as lead
• Regulated as a device; the Notified Body seeks a scientific opinion from a medicines authority
• Regulated as an in vitro diagnostic
• Unregulated until the drug receives an MA

Correct Answer: Regulated as a device; the Notified Body seeks a scientific opinion from a medicines authority

Q11. For a drug-led combination product with a novel device constituent in the U.S., the typical premarket route is:

• Separate PMA for the device and separate NDA/BLA for the drug
• A single NDA/BLA including device data; no separate PMA/510(k) is typically required
• Device 510(k) only
• De Novo for both constituents

Correct Answer: A single NDA/BLA including device data; no separate PMA/510(k) is typically required

Q12. A cross-labeled combination product generally involves:

• A single-entity product with drug and device physically combined
• A kit co-packaging unrelated products
• Two separately marketed products whose labeling requires that they be used together to achieve the intended effect
• An IVD and a general laboratory instrument

Correct Answer: Two separately marketed products whose labeling requires that they be used together to achieve the intended effect

Q13. Regarding human factors and usability for combination products, which statement is most accurate?

• Human factors are optional if the device is CE marked
• Summative usability validation is generally expected when the user interface is critical to safe and effective use
• Only formative studies are needed for home-use products
• Human factors do not apply to prefilled syringes

Correct Answer: Summative usability validation is generally expected when the user interface is critical to safe and effective use

Q14. The 2016 FDA final rule on postmarket safety reporting for combination products primarily enables:

• Elimination of adverse event reporting for device-led products
• Single, application-based reporting to the lead center with cross-compliance to combination product requirements in 21 CFR Part 4 Subpart B
• Reporting only to FAERS for all products
• Annual cumulative reporting in lieu of individual case safety reports

Correct Answer: Single, application-based reporting to the lead center with cross-compliance to combination product requirements in 21 CFR Part 4 Subpart B

Q15. Which statement about identifiers for U.S. combination products is most accurate?

• All combination products must carry a UDI only
• All combination products must carry an NDC only
• Drug-led single-entity products generally use an NDC; UDI applies when a device constituent is distributed as a device (e.g., separately)
• No identifiers are required if packaged for hospitals

Correct Answer: Drug-led single-entity products generally use an NDC; UDI applies when a device constituent is distributed as a device (e.g., separately)

Q16. For a significant design change to the device constituent of an NDA-led single-entity combination product, the appropriate U.S. regulatory action is typically:

• Submit a new 510(k) to CDRH separate from the NDA
• File a Prior Approval Supplement to the NDA including design change documentation consistent with Part 4 expectations
• No filing is required if performance testing passes
• Submit only an annual report to the NDA

Correct Answer: File a Prior Approval Supplement to the NDA including design change documentation consistent with Part 4 expectations

Q17. In India, which statement best reflects classification practice for drug–device combinations such as prefilled syringes or pens?

• They are always regulated as medical devices under CDSCO’s Medical Device Rules
• They are typically regulated as drugs when the primary intended action is pharmacological, with the device as an integral delivery system
• They are unregulated if imported
• They require only ISO 13485 certification

Correct Answer: They are typically regulated as drugs when the primary intended action is pharmacological, with the device as an integral delivery system

Q18. During development, how are U.S. investigational submissions commonly handled for combination products?

• Separate IDE and IND are always required and cannot be combined
• A single investigational application (e.g., an IND) may be used when appropriate, coordinated by the lead center, with cross-center input
• No investigational submissions are needed if the device is non-significant risk
• Only an IDE is required for all combination products

Correct Answer: A single investigational application (e.g., an IND) may be used when appropriate, coordinated by the lead center, with cross-center input

Q19. Regarding companion diagnostics (CDx) and therapeutics, which statement is correct in the context of combination product regulation?

• A therapy and its CDx are always a combination product
• They are never a combination product
• They are a combination product only when co-packaged or cross-labeled for required use together to achieve the intended therapeutic effect
• They are always regulated as drugs

Correct Answer: They are a combination product only when co-packaged or cross-labeled for required use together to achieve the intended therapeutic effect

Q20. Which scenario best exemplifies a cross-labeled combination product?

• A drug-eluting stent with drug coating integrated onto the device
• A prefilled syringe containing a biologic
• A photosensitizing drug whose labeling requires a specific light-activation device marketed by a different firm
• A co-packaged kit containing an antibiotic vial and a general-purpose syringe

Correct Answer: A photosensitizing drug whose labeling requires a specific light-activation device marketed by a different firm

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