Globalization of the pharmaceutical supply chain has increased the challenges to FDA to ensure that drug products and ingredients
are not contaminated, counterfeited, or mislabeled (1, 2). To help in this effort, the agency has developed rapid screening
methods for pharmaceutical products and ingredients that can be deployed on portable instruments by field laboratories and
inspectors for the screening of dietary supplements, pharmaceutical ingredients, and finished products on site (e.g., at border
crossings, import centers, foreign manufacturing sites). Examples include detection of toxic and catalytic metals by X-ray
fluorescence, detection of weight-loss drugs in dietary supplements by ion mobility spectroscopy, detection of diethylene
glycol and ethylene glycol in glycerin, sorbitol or propylene glycol by Raman or near-infrared (NIR) spectroscopy (3–7). The
deployment of such instruments will allow FDA inspectors to screen a large number of ingredients and products at the site
of importation, in domestic commerce, or even at foreign drug manufacturing sites, and to determine which are suspect and
should be detained, sampled, and sent to laboratories for confirmatory testing by traditional methods such as US Pharmacopeial
testing. FDA is concerned about diversion into the legitimate supply chain of excipients that are unsuitable for use, as well
as the possibility of tampering with an excipient during transit.
During the past year, FDA's Division of Pharmaceutical Analysis (DPA) has developed a deeper understanding of the value and
limitations of library-based Raman and NIR spectral-correlation methods for rapid spectroscopic screening of pharmaceutical
ingredients (8–10). The division has developed procedures for transferring spectral libraries across instruments from different
vendors and platforms (e.g., laboratory, portable, and handheld).
DPA would now like to build an excipient library to be deployed on NIR and Raman portable instruments and used at points of
entry or storage. To ensure a robust library, DPA is partnering with the International Pharmaceutical Excipients Council (IPEC)
to reach out to manufacturers and distributors of common excipients to provide authentic samples to the agency to help build
these libraries. This article provides details on how to participate, and some anticipated questions and answers.
Benefits of participation
Development and deployment of an excipient library to monitor for possible contamination, adulteration, tampering, and diversion
into the qualified pharmaceutical supply chain will improve safety of the drug supply, and thus, patient safety. Additional
benefits include the following:
- An inspector can make an immediate determination as to whether laboratory analysis is necessary by performing a screening
test. This approach would reduce delays associated with sending samples to a laboratory.
- Knowledge that FDA is screening excipients and that excipients are receiving a higher level of scrutiny should provide deterrence
and add a layer of difficulty for anyone trying to infiltrate the supply chain.
- All parties can have an increased level of confidence that the material being identified is indeed from the qualified supplier.
- Materials that are different from the spectral reference standards can be flagged for additional investigation and, if warranted,
subsequently added to the library.
- All parties will have increased assurance that goods were not tampered with, substituted, or otherwise falsified with regard
to their origin during distribution.
- Screening and surveillance activities can enable rapid response to concerns of contamination, adulteration, and/or substitution
in the supply chain reported to or identified by FDA.
Creation of this library will provide added assurance that a given excipient is of the expected quality. Consumers will have
increased confidence in the quality of drug products based on this increased surveillance of the excipient supply chain.
Details of participation
Materials (i.e, excipient samples) would be shared with DPA in St. Louis using a Material Transfer Agreement (MTA). This agreement
would allow DPA to accept material from vendors and distributors and protect intellectual property. A copy of the MTA and
contact information can be obtained on the FDA's Office of Testing and Research website under Hot Topics, at
http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm136930.htm.
Manufacturers are asked to provide multiple lots (at least three) of approximately 2 g each of excipients with a Certificate
of Analysis for the lot. In the case where manufacturers do not supply directly to the US pharmaceutical industry, distributors
may submit the excipient samples. Material should be representative of the potential spectral variability that might be expected
in their product. Variables that might affect spectral variability would include the following:
- Manufacturing site
- Grade of material
- Expiration period
- Processing differences, including raw materials, operating conditions, and production equipment
- Time of year of harvest.
- Samples should be accompanied by the following information where applicable:
- Name of manufacturer
- Manufacture site
- Excipient name
- Trade name
- Compendial or excipient grade
- Lot designation
- Date of manufacture
- Special handling or packaging requirements.
Samples should conform to market standards and/or standards filed with the agency. DPA is ready to begin receiving excipient
samples for this project.
