The Move to 100% Testing of Incoming Raw Material. Ravi Kalyanaraman, Ph.D. Global Analytical Technology Bristol-Myers Squibb

Transcription

1 The Move to 100% Testing of Incoming Raw Material Ravi Kalyanaraman, Ph.D. Global Analytical Technology Bristol-Myers Squibb

2 Current Situation Current procedure in pharmaceutical industry is to obtain a composite sample of each lot for identity and full release testing Full testing on each lot performed on statistically pooled samples Raw material vendors are qualified which results in skip lot testing Identity verification and other tests are performed in laboratory

3 Why 100% Identity Testing Outsourcing and global procurement of raw materials from countries not well regulated To reduce cost, improve testing efficiency and increase productivity Health authority and regulatory requirements

4 Regulatory Requirement FDA: The Current Good Manufacturing Practice (CGMP) regulations address component sampling and testing primarily at 21 CFR These regulations require representative samples ([N + 1] 1/2 ) of each shipment of each lot of active and inactive component (or raw materials) to be tested to confirm the identity of the component as labeled prior to release for use in drug product manufacturing Canadian GMP Guidelines 2009 edition, ver. 02 : Raw Material Testing: C and C : 6.1: Each container of a lot of a raw material is tested for the identity of its contents using a specifically discriminating identity test Europe requires 100% testing: FDA requires 100% testing for Neutraceutical industry Some South American countries require 100% testing

5 Raw Material Testing Workflow SAP Receiving Area/Warehouse Sampling Area Sampleng for ID and Full testing Schedule of the Analysis by QC Full Testing QC Lab Analysis Data Review Supervisor Approval QA Release 100 % ID at reception in Warehouse Testing by Portable Spectrometer Print and Sync reports/ereports into LIMS Report

6 Vibrational Spectroscopy Raman and Near-Infrared (NIR) spectral signatures are used as fingerprints to identify and verify raw materials Energy Scattered Radiation Excitation laser 2 nd overtone 1 st overtone Combination: Two Fundamental vibrations Raw material fingerprint Inter-nuclear distance 6

7 What is Raman Spectroscopy? Raman spectroscopy is a spectroscopic technique used to study vibration, rotational, and other low-frequency modes in a system. Is commonly used in chemistry, since vibration information is specific to the chemical bonds and symmetry of molecules. Therefore, it provides a unique fingerprint by which the molecule can be identified. It can be used for raw materials verification without opening their packaging due the ability of penetrate glass, plastic and other materials using proper wavelength for the incident excitation laser. 7

8 Portable Raman Technology: How Material ID Works Measured spectrum Reference spectrum (stored in instrument) Raman/NIR Spectrum Does measured spectrum match reference spectrum? Raman/NIR Spectrum YES NO PASS Suspect

9 Instrument Use Select Method Log in lactose Mcc API etc Scan Barcode Scan Sample Through Bag Read Result (Pass/Fail) Sync w/ host computer (at end of day)

10 Summary Due to increasing regulatory requirements and to cut cost, time and to improve productivity, pharmaceutical industry is moving towards 100% testing identity of raw materials Portable Raman spectrometer is an excellent alternative to traditional incoming raw material verification by HPLC, TLC and other wet chemistry techniques The technique brings the lab to the warehouse and storage area and is non-destructive with no sample handling or preparation required Raw materials are analyzed directly through packaging, such as plastic bags, glass and other primary and secondary packaging materials Pharmaceutical and neutraceutical industry are currently using this technology and are cutting cost and improving efficiency in raw material verification and identification