Is there basis or regulations for the use of the chiral compounds regarding its isomeric form L, D or the racemic form DL in the pharmaceutical industry? Is there a general rule or it can be taken case by case according to the nature of the material?
See thalidomide.
From my experience, all stereoisomers of an API must be investigated to satisfy regulatory agencies. Diastereomers of APIs tend to have different biological profiles than expected or intended.
This additional scrutiny on chiral APIs is why most compounds that come through med chem factories are achiral (also for ease of synthetic control).
The FDA guidance's for the Development of New Stereoisomeric Drugs are given in the first link.
The second link is an good review on Chiral Drugs.
My take (as a peptide chemist):
As an example, take a biologically active 10 amino acid residue peptide which has 1024 possible stereoisomers. Which of these possible stereoisomers would you not want to own the patent for? I would want the patent on all of them; while the all "L" isomer is most likely the one that was screened for, inversion or racemization at one or several residues could potentially yield a better (more potent, with less side effects) candidate. 1024 stereoisomers is a lot of compounds to make, purify, characterize and test! How many of these stereoisomers do you want to submit and IND for? Due to costs I would only want submit one IND for one of the stereoisomers; possibly with one or two of the other stereoisomers as backup candidates. The racemic mixture, with all 1024 isomers present, would undoubtedly be of lower specific activity and possess highest amount of toxic side effects.
http://www.fda.gov/drugs/guidancecomplianceregulatoryinformation/guidances/ucm122883.htm
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3614593/pdf/IJBS-2-85.pdf
The biologically active stereoisomer is to be synthesized and it has to met pharmacopia specfications like USP and BP/EP. For example pregabalin. only one stereoisomer is active biologically so other undesired stereoisomer is recovered, converted into racemic and then resolution to get desired stereoisomer.
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