June 2005 Meeting

Progress from Stable-Isotopic Authentication to Process Analytical Chemistry

The June 2005 CSSC meeting will be held at Bristol Myers Squibb in Wallingford, CT.

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Since 1999, there has been an incremental transition in the use of stable-isotopic analysis from pharmaceutical authentication to preliminary assessment for Process Analytical Chemistry (PAC). By way of background, the stable-isotopic compositions of such materials are a function of two variables: the initial stable-isotopic composition of the intermediates and reagents used in synthesis and the isotopic fractionation that occurs during manufacturing processes. This transformation follows the characteristic progress from observational science (pharmaceutical authentication) to mechanistic science (PAC). There have been five major steps in this transformation:

• The observation of batch-to-batch stable-isotopic composition of two over-the-counter analgesic drugs, performed with Micromass UK (Jasper et al., 2003, FIRMS Newsletter 1(3):4-5; Jasper et al., 2004, Pharm. Technol. 28(8):60-67);
• The ability to distinguish six manufacturers of a single Active Pharmaceutical Ingredients (API), Naproxen, in a blind study performed for the FDA-DPA (Jasper et al., 2003, FIRMS Newsletter 2(1):3; Wokovich et al., J. Pharm. Biomed. Anal., submitted);
• The ability to distinguish individual manufacturers and batches of four APIs produced by nine manufacturers also in a blind study performed for the FDA-DPA (Jasper et al., J. Pharm. Biomed. Anal., 2004, 35:21-30);
• A preliminary study with Johnson & Johnson to distinguish three synthetic pathways of one API, Topiramate, performed on archive samples in which the stable-isotopic composition of the reagent raw-materials was not isotopically controlled (Jasper et al., 2004, FIRMS Newsletter 2(2):8-9; Jasper et al., J. Pharm. Biomed. Anal., submitted); and,
• Fully-controlled studies are presently underway to constrain the major variables (i.e., the raw materials and synthetic pathways) that determine the isotopic composition of pharmaceutical materials. With that, the isotopic composition of pharmaceutical products can be predicted and synthetic processes plausibly monitored, finding useful application in the R&D laboratory as well as in pharmaceutical manufacturing and authentication. 

The principles of stable-isotopic authentication of pharmaceutical materials (Jasper, 2004,Tablets and Capsules 2(3):37-42) have been widely accepted in the pharmaceutical and regulatory communities. This presentation will be summarized in an invited article entitled “Progress from Stable-Isotopic Authentication to Process Analytical Chemistry” to be published in the May, 2005 edition of Pharmaceutical Manufacturing. The article will be co-authored by J. P. Jasper, R. C. Lyon (FDA-CDER-DPQR, Rockville, MD), and L. E. Weaner (J&J, Spring House, PA). 

PDF copies of the preceding and other papers can be found here. 

Dr. John P. Jasper

Presently, Chief Scientific Officer of Molecular Isotope Technologies 
(of Niantic, Connecticut).

The focus of Molecular Isotope Technologies is on
pharmaceutical authentication of both products and processes 
by their naturally-existing stable-isotopic compositions.

Brief biography:

• B.A., Geophysical Sciences and Biology, The University of Chicago.
• Ph.D., 1988, in Marine Organic and Isotope Chemistry
• Jointly granted by both M.I.T. and Woods Hole Oceanographic Institution.
• Scientist and postdoctoral fellow in Stable Isotope Chemistry, 
• Indiana University’s Department of Chemistry, in Bloomington, Indiana.

With ten years in the pharmaceutical industry as an analytical organic- and stable-isotope chemist, with:

• Pfizer-Cultor,
• Drumbeat Dimensions, and 
• Molecular Isotope Technologies. 

Bristol-Myers Squibb Company
Pharmaceutical Research Institute
5 Research Parkway
Wallingford, CT 06492

 From the South (New York)

I-95 Northbound to Exit 48 in New Haven which is the beginning of I-91 North. Get off Exit 15 from I-91 and take right at the traffic light onto Route 68 East. Take a left at the first traffic light onto Research Parkway, which is about 3/10 of a mile from the exit. The Wallingford facility is the first building on the right.

From the North

I-91 Southbound to Exit 15. Take left at light at end of ramp. Take left at second traffic light (approximately 1/2 mile) onto Research Parkway. The Wallingford facility is the first building on the right.

Via Route 15 (Hutchinson River/Merritt/Wilber Cross Parkways)

Exit 66 in Wallingford. Turn left at light at the end of the ramp onto Route 5 Southbound. Stay on Route 5 for approximately 1/2 mile and make left onto the access road for Route 68. Turn left at light onto Route 68 (Eastbound). Follow Route 68 East past the Courtyard Hotel on the left and continue past the entrances to I-91.Turn left at the first traffic light past I-91 (not including the entrance to I-91 Northbound) onto Research Parkway. Bristol-Myers Squibb is the first building on the right.

Via I-95 (New England Expressway)