One approach to prevent PDs consists of physical-chemical optimization of the PCR system, i.e. changing the concentrations of primers, magnesium chloride, nucleotides, ionic strength and temperature of the reaction. This method is somewhat limited by the physical-chemical characteristics that also determine  the efficiency of amplification of the target sequence in the PCR. Therefore, reducing PDs formation may also result in reduced PCR efficiency. To overcome this limitation, other methods aim to reduce the formation of PDs only, including primer design, and use of different PCR enzyme systems or reagents.