Major League Baseball and the Major League Baseball Players Association agreed Friday on significant enhancements to the Joint Drug Prevention and Treatment Program, including more frequent testing and harsher penalties for players who intentionally use performance-enhancing substances.

The changes are the most extensive since 2006 and come just more than a year after MLB and the MLBPA added blood testing for human growth hormone, extended testing to the offseason and established a baseline for testosterone levels at the Owners Meetings in January 2013.

"Although we had the strongest program in professional sports before these changes, I am committed to constantly finding ways to improve the program in order to eradicate performance-enhancing drugs from the game and for MLB to serve as a model for other drug programs," Commissioner Bud Selig said in a statement. "I want to express my appreciation to the players for being proactive and showing remarkable leadership in producing the new agreement. I commend them for both their foresight and their creativity throughout this process, and for strongly sharing our desire to improve what is already the toughest drug program in sports."

Said Tony Clark, executive director of the Players Association: "Experience proves that increased penalties alone are not sufficient; that's why the players pushed for a dramatic increase in the frequency and sophistication of our tests, as well as comprehensive changes in a number of other areas of the program that will serve as a deterrent. Make no mistake, this agreement underscores the undisputed reality that the players put forward many of the most significant changes reached in these negotiations because they want a fair and clean game."

The revisions address three primary areas:

INCREASED TESTING

Beginning immediately, the number of in-season random urine collections will more than double from 1,400 to 3,200 and the frequency of offseason collections has been raised from 250 to 350. That's in addition to the mandatory tests that every player undergoes during Spring Training and the regular season.

Blood collections for HGH detection, already the most thorough in American professional sports, will increase to 400 both in and out of season. Again, that's in addition to the 1,200 samples taken in Spring Training.

Any player who's suspended for violating the program will be subject to six additional urine tests and three additional blood tests per season for the rest of his career.

The list of banned substances has been expanded. Use of dehydroepiandrosterone (DHEA) in 2014 will result in follow-up testing for a first violation; a 25-game suspension for a second violation; an 80-game suspension for a third violation; and up to a permanent suspension for a fourth violation. MLB and the MLBPA are still finalizing other additions to the prohibited substance list, which are expected to be completed by next week.

Carbon Isotope Ratio Mass Spectrometry (IRMS) will be randomly performed on at least one specimen from every player in addition to any IRMS test that the Montreal laboratory conducts as a result of the parties' longitudinal profiling program (which was implemented prior to the 2013 season) and the World Anti-Doping Agency (WADA) guidelines for conducting IRMS.

PENALTIES

A first-time offender will receive an 80-game suspension, up from the previous 50 games. A second violation will result in a 162-game suspension and a loss of an entire season (183 days) of pay, up from 100 games. A third violation will lead to permanent banishment.

Any player disciplined for a violation involving performance-enhancing substances will not be allowed to participate in the postseason and will not be eligible for an automatic playoff share.

PLAYER BENEFITS

The Arbitration Panel has been given the right to reduce a player's suspension if he proves at a hearing that the use was not intended to improve his performance.

The panel may not reduce the first-time penalty to fewer than 40 games, the second offense to fewer than 80 games or change the permanent suspension for a third-time violator at all. The panel will have no authority to reduce a penalty if the positive test result was for testosterone; human growth hormone (HGH); gonadotropins; selective estrogen receptor modulators; anti-estrogens, boldenone; nandrolone; and stanozolol.

A program has been established which will give players year-round access to supplements that will not cause positive test results as well as additional technological resources to provide information regarding supplements and prescription or over-the-counter medications.

Improvements will be made in both home and visitor's weight rooms based on recommendations by a joint committee chaired by Tim Maxey, the Joint Strength and Conditioning Coordinator.

The confidentiality provisions of the program also have been strengthened.