Q.01

What does FDA PMA mean for medical devices?

PMA stands for premarket approval. It is the FDA marketing application that most class III medical devices, the highest-risk class, need under section 515 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 360e) [1][2]. To get a PMA, the applicant must show that there is reasonable assurance the device is safe and effective under the conditions of use in its proposed labeling [3].

Where PMA sits among FDA's routes to market

  • Risk tiers: Devices are placed in class I, II or III, with more controls at each step up. Most class I devices are exempt from a 510(k). Class II devices need a 510(k) unless a regulation exempts them. Class III devices need a PMA [2].
  • PMA versus 510(k): A 510(k) shows the device is "substantially equivalent" to a device already legally on the market. A PMA needs valid scientific evidence that the device is safe and effective for its intended use [2].
  • What makes a device class III: General or special controls can't give enough assurance of safety and effectiveness. These are usually devices that support or sustain life, are of substantial importance in preventing impairment of health, or present a potential unreasonable risk of illness or injury [4].
  • Exception: A limited number of class III devices that are equivalent to devices sold before the 1976 Medical Device Amendments can still go through the 510(k) route. That lasts until FDA publishes a requirement for that device type to submit PMA data [4].
  • How a device ends up in class III: FDA can classify or reclassify a device type into class III by regulation or order. A new type of device with no predicate is also automatically class III by law (section 513(f)(1)). Those new devices can use the De Novo process to ask for class I or II instead of going through a PMA [5].

What counts as evidence

  • The data should consist mainly of well-controlled investigations or other valid scientific evidence as defined in 21 CFR 860.7 [3].
  • Valid scientific evidence can include partially controlled studies, well-documented case histories and reports of significant human experience. Isolated case reports and unsupported opinions don't count [3].
  • FDA weighs the probable benefit to health against the probable risk of injury or illness [3].

After approval

  • Under 21 CFR 814.39(a), changes that affect safety or effectiveness need a PMA supplement. A new indication for use is one example [6].
  • Depending on the change, the submission can be a panel-track, 180-day, real-time or special (changes being effected) supplement, a 30-day notice, a manufacturing site change supplement or a periodic report [1].
  • Both CDRH and CBER review PMAs [1].

FDA's PMA decisions database lists each original approval and supplement under a P-number. For example, P850006 is Edwards Lifesciences' Duromedics bileaflet mechanical heart valve, with a decision date of 08/29/1986 [7].

Approach: I used FDA CDRH guidance documents on PMA, 510(k), De Novo and IVD topics, and the CDRH PMA decisions database. These guidance documents are nonbinding; the binding rules are section 515 of the FD&C Act and 21 CFR Part 814, which I've cited only as the guidance quotes them.

Q.02