Heparin sodium compliance to the new proposed usp monograph. Any lowmolecularmass heparin covered by a specific monograph complies with the requirements for. The us regulatory and pharmacopeia response to the global. It is to be administered by intravenous or deep subcutaneous routes. The most common impurity found in heparin sodium is dermatan sulfate ds which, like heparin, contains liduronic acid units. On the basis of comments received on the published and new methods submitted by the industry, it is proposed to. New usp standards for heparin includes new identity and. We have implemented and validated these challenging assays according to the usp monograph and they are ready to. Who monographs for heparin calcium and heparin sodium in. European pharmacopeia adopts revised heparin monographs. Heparin sodium sodium chloride 5,000 usp units 7 mg ph 5. Easytoread drug name and dosage strength to aid in identifying the right product.
Pharmaceutical grade heparin is derived from mucosal tissues of slaughtered meat animals such as porcine pig intestines or bovine cattle lungs. The style and presentation have also been updated in line with the current version of the style guide. Identification of heparin samples that contain impurities or. Heparin sodium injection 1 000 usp unitsml and 10 000 usp unitsml has indicated that early hemodialysis is of value in cases of multiple trauma. Jun 17, 2008 usp believes that both methods are needed to quickly allow for a qualified supply of heparin and to address the current adulteration of the heparin supply. Federal register heparincontaining medical devices and.
Question and answers about changes to the usp heparin. Elucidation of a minor structural modification responsible for a process dependent 2. Quantitative analysis of impurities in unfractionated heparin. Sugammadex bridion drug monograph updated august 2016 updated version may be found at. Dissolve or dilute an accurately measured quantity of heparin sodium in ph 8. Treatment and secondary prevention of venous thromboembolism dvt andor pe.
Food and drug administration fda have shown that heparin sodium, usp heparin made under the new united states pharmacopeia usp monograph. Report who working group on biological standardization of. The minutes of the who consultation on biological standardization of unfractionated heparin held on the 1718 june 1998 were approved by all members of the working group and adopted. Heparin sodium injection, usp is a sterile solution of heparin sodium derived from bovine lung tissue, standardized for anticoagulant activity. Usp endotoxin rs signal 1, h1 of idoa2s signal 2, the h2 of glcns signal usp heparin sodium for assays rs 3, and the methyl of glcnac signal 4 of heparin are present at 5. Heparin sodium injection, usp is available in the following concentrationsml. Aug 03, 2017 laboratory studies performed at the request of the u. Purified heparin produced in accordance with the guideline for monitoring crude heparin for quality. Usp statement on heparin potency unit assignment and. Strasbourg, france june 25the european pharmacopoeia commission epc adopted revised monographs for heparin calcium and heparin sodium to strengthen the level of testing required for quality control. The 1 h nuclear magnetic resonance nmr acceptance criteria in the new heparin us pharmacopeia usp monograph do not take into account potential structural modifications responsible for any extra signals observed in 1 h nmr spectra, some purified heparins may be noncompliant under the proposed new usp guidelines and incorrectly classified as unsuitable for pharmaceutical use.
A new usp heparin sodium reference standard rs lot f for assay has been selected and value assigned by subgroup analysis of data obtained using the proposed new usp monograph potency method antifactor iia antithrombin dependent assay. Due to the structural similarity and chemical affinity between ds and heparin, complete removal of ds impurity in heparin is difficult to achieve 9. Pharmacopeial usp convention announces that revised monographs for heparin sodium and heparin calcium in the united states pharmacopeia usp are now available and official on the usp. Changes in the usp heparin monograph and implications for. Morris explained, is the most rapid usp revision mechanism, and on june 18, 2008, the revised heparin sodium and heparin calcium monographs were published. New heparin standards recently adopted by the united states pharmacopeia usp include new tests to ensure the quality of the drug. Prescribing information heparin sodium injection usp sterile. Clinical pharmacology heparin inhibits reactions that lead to the clotting of blood and the formation of. Product monograph heparin sodium injection usp for intravenous or subcutaneous use usp units per ml 10 000 usp units per ml anticoagulant pfizer canada inc. Heparins, lowmolecularmass european pharmacopoeia 6. Hazard information carcinogen list substance iarc ntp osha heparin sodium not listed not listed not listed emergency overview heparin lock flush solution, usp, is a solution containing heparin sodium, a heterogenous group of straightchain anionic mucopolysaccharides, called glycosaminoglycans. The revised monographs are scheduled to become effective on aug.
The stage 1 monograph revisions of heparin sodium and heparin calcium incorporated fdas analytical methods for identifying oscs in heparin. The potency is determined by a biological assay using a usp reference standard based on units of heparin activity per milligram. Food and drug administration fda previously issued a public health alert to inform healthcare providers of a change to the united states pharmacopeia usp monograph for heparin, effective october 1, 2009. Identification of heparin samples that contain impurities. Usp encourages any manufacturers that have methods for consideration in stage 2 to submit them to dr. The clearance of rwarfarin is generally half that of swarfarin, thus as the volumes of distribution are similar, the halflife of rwarfarin is longer than that of swarfarin. Uspc laboratories validated these methods according to procedures outlined in general information chapter validation of compendial procedures 3. Heparin sodium and heparin calcium monographs uspnf. Question and answers about changes to the usp heparin monograph. Heparin sodium injection usp has also been used as an anticoagulant in blood transfusion samples, particularly when the presence ofcitrates, oxalates or fluorides might interfere with. Us pharmacopeia usp to be nmt 1% of several natural gag impurities. Product monograph heparin sodium injection usp for subcutaneous use 5000 usp units per 0.
The unit for antifactor xa activity is defined by the usp heparin sodium reference standard and change to read. Intravenous solutions with heparin sodium injection 12,500 usp heparin units250 ml, 25,000 usp heparin units500 ml, or 25,000 usp heparin units250 ml of heparin sodium in 0. Product monograph heparin sodium injection usp pdf. Note on the monograph this monograph has been thoroughly revised further to the contamination events in 2008 to ensure appropriate quality control for unfractionated heparin. Usp believes that both methods are needed to quickly allow for a qualified supply of heparin and to address the current adulteration of the heparin supply. Jul 10, 2008 strasbourg, france june 25the european pharmacopoeia commission epc adopted revised monographs for heparin calcium and heparin sodium to strengthen the level of testing required for quality control. Revised monographs in the european pharmacopoeia on heparin sodium 0333 and heparin calcium 0332 are in force from january 1st, 2015. These monographs include chromogenic antifactor iia and antifactor xa assays. Revision bulletin heparin 1 official june 18, 2008 heparin sodium tive units are not equivalent see general notices. Heparin sodium is the sodium salt of sulfatedpackaging and storagepreserve in tight con.
As part of the stage 2 revisions to the heparin sodium monograph, usp has adopted a new potency assay for heparin, the chromogenic antifactor iia test. Because of the suspected serious adverse events associated with the contamination of heparin with oversulfated chondroitin sulfate, usp has further revised the usp heparin sodium monograph. Heparin and change in usp monograph possible potency variation the u. Prlovenox, manufacturers standard, manufacturers standard. Heparin sodium injection, usp sagent pharmaceuticals. Because of the content of benzyl alcohol, lovenox, when using multiple dose vials, must not be given to newborns or premature neonates see warnings and precautions, under special populations, pregnant women. We have implemented and validated these challenging assays according to the usp monograph and they are. Us pharmacopeia announces revised heparin monographs and. In addition, uspc proposed appropriate system suitability criteria and.
Laboratory studies performed at the request of the u. Heparin sodium usp method introduction heparin is a highly sulfated glycosaminoglycan widely used as an injectable anticoagulant. Heparin sodium injection, usp is a sterile solution of heparin sodium derived from porcine intestinal mucosa, standardized for anticoagulant activity. Jun 09, 2016 a monograph for heparin entered the usp in 1950, with tests for identity, strength, quality, purity and potency 5. Structural formula of heparin sodium representative subunits heparin sodium injection, usp is a sterile solution of heparin sodium derived from porcine. The concentration of oversulfated chondroitin sulfate in the. Usps validation of these two tools led to the incorporation of capillary electrophoresis and proton nmr into the heparin sodium monograph, published as a revision bulletin, and met the immediate need to prevent contaminated heparin from entering the u. Standard solutions dilute an accurately measured volume of usp heparin sodium rs with ph 8.
Food and drug administration fda has alerted healthcare professionals to changes in the united states pharmacopeia usp monograph for heparin products, effective october 1, 2009. The united states pharmacopeia usp drug substance monograph for heparin sodium, and drug product monographs for heparin lock flush solution and heparin sodium injection, recently have undergone several revisions following serious and fatal events related to. Mi relative molecular mass corresponding to fraction i. Heparin sodium injection usp is a sterile, p yrogenfree solution of a highly purified sodium salt of heparin, a high molecular weight. Heparin sodium injection usp is a sterile, p yrogenfree solution of a highly purified sodium salt of heparin, a high molecular weight polysaccharide derived from porcine intestinal muc osa. January 25th, 2008 boucherville, qc, canada j4b 7k8. Usp statement on heparin potency unit assignment and harmonization with the international standard for unfractionated heparin. For composition, see the dosage forms, composition and packaging section of the product monograph. Heparin sodium injection 1 000 usp unitsml and 10 000 usp unitsml prescribing information heparin sodium injection usp 1 000 and 10 000 usp unitsml sterile anticoagulant sandoz canada inc. Coumadin tablets warfarin sodium tablets, usp crystalline.
Dr thomas reminded the wg that there are three major issues to be discussed in. In response to the heparin adulteration crisis of 20072008, usp has worked swiftly to improve the standards for unfractionated heparin ufh in order to secure the supply of safe heparin and heparin products in the us. Request pdf heparin sodium compliance to the new proposed usp monograph. A monograph for heparin entered the usp in 1950, with tests for identity, strength, quality, purity and potency 5. Low molecular weight heparin for bioassays united states.
The usp heparin sodium monograph lists impurities with specifications developed for porcine derived products. These stage 1 revisions to the monographs are accompanied by two new and two existing usp reference standards see the heparin hot topics page for complete information. This pharmacopeia standard was one of several elements in the multitiered safety net that helped assure practitioners they were administering, and patients they were receiving, good quality, safe and effective heparin drug products. Americancollegeofcardiology,americanheartassociation. The revisions to the usp heparin monograph, which became official on october 1, were made in response to incidents in 20072008 where heparin was intentionally adulterated with oversulfated chondroitin sulfate oscs during the manufacturing process. Heparin sodium injection is a sterile solution of heparin sodium in water for injection.
Heparin sodium injection, usp is a sterile solution of heparin sodium derived from porcine intestinal mucosa, standardized for anticoagulant activity, in water for injection. The usp monograph for heparin sodium had been updated previously. The terminal halflife of warfarin after a single dose is approximately 1 week. Due to the prevalence of contaminated heparin products, usp has revised its monographs for heparin sodium and heparin calcium. Low molecular weight heparin for bioassays united states pharmacopeia usp reference standard.831 256 46 862 1094 579 711 891 710 1462 693 1064 854 957 289 1041 1292 1502 1122 556 1002 276 1437 2 809 1149 1006 1243 191 117 760