failing to print not matched lines from second file

[Serafim]

First of all, the "l_few" (file with fewer lines) is file_1 according to the text, so I swapped the file names to change as little as possible in your original program.
Then I came up with this, hope it helps, note that I didn't change much, just enough to make it print what you need:

with open ('file_2','r') as l_few :
    f2=l_few.readlines()
sp23 = [s.split(',')[3].strip() for s in f2] # collect all the terms you need to compare
with open ('file_1','r') as f1:          
    for lf1 in f1:
        lf1=lf1.strip()
        sp1 = lf1.split(",")
        if sp1[3] in sp23:
            pass # here we have a match so print nothing
            # spL2=lf2.split(",")
            #print (" File 2 Line matched --> "+lf2)
            #break
        else :
            print (lf1) # print the non-matching line
            #break

Output:

Output:
03/28/2021,P,16,LINE1
03/28/2021,P,9,LINE3
03/28/2021,P,8,LINE5
03/28/2021,S,95,LINE6
03/28/2021,S,1,LINE7
03/28/2021,P,46,LINE8

So the error you made was to compare first with one term then with the other so, for each line you had at least one mismatch.
Further simplification:

with open ('file_2','r') as l_few :
    f2=l_few.readlines()
sp23 = [s.split(',')[3].strip() for s in f2] # collect all the terms you need to compare
with open ('file_1','r') as f1:          
    for lf1 in f1:
        lf1=lf1.strip()
        sp1 = lf1.split(",")
        if sp1[3] not in sp23:
            print (lf1) # print the non-matching line