Heparin Supply Chain Integrity
The heparin supply chain is a complex process, involving multiple facilities in multiple countries, with a rigorous set of safety standards incorporated at each stage. Fresenius Kabi USA, LLC has effectively managed the supply chain to ensure the safe supply of Fresenius Kabi USA, LLC's heparin products. The following section includes a detailed overview of each of the steps involved in the production of this life-saving medicine.
Cycle through the slides below to learn more about each stage in the production of heparin.
Fresenius Kabi USA, LLC receives Active Pharmaceutical Ingredient (API) from suppliers
Crude material is refined and processed to make the Active Pharmaceutical Ingredient (API) of heparin.
Crude product is obtained from producers through a meticulous process, which makes certain that Good Manufacturing Practice standards are met, and provides a mechanism to trace the source of a problem should one occur. Fresenius Kabi USA, LLC's suppliers of API receive the crude material for heparin from designated providers that are audited and follow strict regulations. Fresenius Kabi USA, LLC also conducts regular quality assurance audits of our API suppliers, both in the United States and in China. Fresenius Kabi USA, LLC only works with FDA-approved facilities.
Suppliers conduct multiple quality testing procedures on the API before it is shipped to Fresenius Kabi USA, LLC , including methods required by the FDA to verify that no contaminants are present. Fresenius Kabi USA, LLC conducts additional tests when the API is received.
API placed into quarantine for quality and purity tests
When the API arrives at Fresenius Kabi USA, LLC's manufacturing facilities, it immediately is placed into quarantine for extensive testing to evaluate the purity and quality of the API.
A full spectrum of microbial and chemistry tests are performed to determine if any contaminants are present. Among the tests Fresenius Kabi USA, LLC conducts are Nuclear Magnetic Resonance Spectroscopy (NMR) and Capillary Electrophoresis (CE). The FDA now requires these sophisticated techniques of all suppliers and manufacturers of heparin. In addition to testing all new lots of heparin raw material, APP recently completed testing on all lots of heparin raw material dating back to January 2006, all of which have been found to be contaminate-free. The FDA has also tested select material and has completed their review of the analytical testing, therefore confirming the results. Testing procedures for all heparin that Fresenius Kabi USA, LLC manufactures meet the standards set by the United States Pharmacopeia (USP).
API goes into production to formulate heparin
Once the testing is complete and the quality of the API has been validated, it is ready to be produced into heparin. Samples are also sent to the lab at this stage for chemistry tests on pH, particulates and color before being filled into the vials.
Heparin is filled into vials
An additional series of tests are conducted throughout the filling stage. These include a filter integrity check to make sure the product will be filtered correctly; a volume check to ensure the correct volume goes into the container; and confirmation that the vial is stoppered and sealed correctly. Additional lab tests are also performed, including an analysis of sterility, confirmation no endotoxins or particulates are present, and a check for correct color and volume. The sterility test alone takes approximately 14-15 days.
Every vial is inspected
Every vial of heparin is inspected thoroughly before being packaged and labeled to confirm the solution color is right, the fill volume is accurate, the cap colors are correct, and that there are no issues with the container.
Product is labeled and packaged
The label design is intended to assist healthcare professionals in identifying the right drug and ultimately in administering the proper dose. The label includes unique cap and label colors for each strength, bar codes for the individual unit-of-use, and new bolder and larger typefaces and notations of total unit strength and volume to help clearly differentiate Heparin Sodium Injection, USP, from other heparin products (including Heparin Lock Flush Solution, USP).
Final check to ensure all policies and procedures followed
All paperwork is reviewed to ensure all standard operating procedures were followed without deviation before heparin is released to the distribution facility.
Heparin sent to Fresenius Kabi USA, LLC distribution centers
Heparin is sent to Fresenius Kabi USA, LLC's distribution centers. Orders by hospitals and clinics are processed and delivered, and ultimately used by healthcare professionals to treat patients in critical life-saving situations such as open heart surgeries and dialysis settings. During the recent supply shortage crisis, APP implemented an allocation distribution process, shipping directly to hospitals. Now that supply has returned to normal levels, Fresenius Kabi USA, LLC is again distributing to wholesalers and specialty distributors as well as hospitals and clinics.