Predetermined Change Control Plans for Antimicrobial Susceptibility Test Systems: Updating Breakpoints in Device Labeling

What You Need to Know? 👇

What is a Predetermined Change Control Plan (PCCP) for AST devices?

A PCCP is a protocol that allows AST device manufacturers to update breakpoints in device labeling without submitting a new 510(k). It must be reviewed and cleared by FDA as part of the original 510(k) submission and includes procedures to ensure updated breakpoints don’t significantly affect device performance.

Can legacy AST devices use breakpoint change protocols from other cleared devices?

Yes, FDA won’t object if sponsors use a cleared PCCP or breakpoint change protocol from their separate 510(k) for legacy AST devices, provided both devices have the same classification regulation, product code, intended use, and technological characteristics.

What breakpoints can be updated using a PCCP without new 510(k) submission?

Only breakpoints identical to those recognized by FDA on the STIC Website and falling within the drug concentration range previously reviewed and cleared by FDA can be updated using a PCCP without requiring a new 510(k) submission.

How should manufacturers document breakpoint updates made under a PCCP?

Manufacturers must document changes according to their quality system, including the 510(k) number containing the referenced PCCP, evaluation summary confirming protocol compliance, and determination that updates fall within FDA’s enforcement policy. Updated labeling should be sent to ASTDevices@fda.hhs.gov.

What happens if breakpoint updates deviate from the cleared PCCP?

Deviations from a cleared PCCP could significantly affect device safety or effectiveness. Such updates generally require a new 510(k) submission before updating device labeling, as the modified device would be considered adulterated and misbranded under FDA regulations.

Which AST devices are covered by this guidance for breakpoint updates?

The guidance covers devices classified under 21 CFR 866.1640, 866.1645, or 866.1650 with specific product codes including automated systems, manual test systems, susceptibility panels, test cards, and antifungal plates. It excludes antimicrobial susceptibility test discs under 21 CFR 866.1620.

---

What You Need to Do 👇

Recommended Actions

1. Submit a PCCP in any future 510(k) submission if no applicable PCCP exists
2. Include in PCCP:
   • Description of modifications and applicability
   • Specific procedures for data re-evaluation
   • Planned labeling updates
   • Performance criteria verification process
3. For legacy devices:
   • Evaluate if existing cleared PCCP can be utilized
   • Document changes and protocol use in quality system
   • Submit updated labeling to FDA’s designated inbox
4. For new 510(k) submissions:
   • Incorporate by reference any previously cleared PCCP
   • Include reference to prior submission number
5. Monitor STIC Website for breakpoint updates
6. Maintain documentation of all changes and evaluations in quality system
7. Contact FDA for additional guidance if needed through pre-submission process

Key Considerations

Clinical testing

• Re-evaluation of previously collected clinical data must demonstrate unchanged device performance with updated breakpoints
• Must meet prespecified performance criteria for category agreement, essential agreement, and error rates

Non-clinical testing

• Sufficient number of resistant isolates required based on microbiology activity spectrum and MIC distribution data
• Performance evaluation with updated breakpoints must be maintained compared to most recently cleared device

Labelling

• Must update device labeling to incorporate new breakpoint information
• Must update performance characteristics or limitations based on evaluation
• Updated labeling should be sent to FDA’s designated email inbox

Safety

• Changes must not reveal new risks or significantly modify existing risks
• Must document changes in accordance with quality system requirements

Other considerations

• PCCP must be reviewed and cleared as part of 510(k) submission
• Updates must be consistent with FDA-recognized breakpoints on STIC Website
• Breakpoints must fall within drug concentration range reviewed and cleared by FDA
• Changes must be documented in manufacturer’s quality system

---

Relevant Guidances 🔗

• Predetermined Change Control Plans for Medical Device Modifications (Draft)
• Quality System Information Requirements for Premarket Submissions
• Content and Decision-Making Process for 510k Submissions: Determining Substantial Equivalence

Related references and norms 📂

• 21 CFR 866.1640: Antimicrobial susceptibility test system
• 21 CFR 866.1645: Automated antimicrobial susceptibility test system
• 21 CFR 866.1650: Blood culture identification and susceptibility test system
• 21 CFR Part 820: Quality System Regulation

---

Original guidance

• Predetermined Change Control Plans for Antimicrobial Susceptibility Test Systems: Updating Breakpoints in Device Labeling
• HTML / PDF
• Issue date: 2023-09-29
• Last changed date: 2023-09-28
• Status: FINAL
• Official FDA topics: Medical Devices, Antimicrobial Resistance
• ReguVirta ID: 606f045ce5facf479fb8b4e3b4c64788