The Indian Pharmacopoeia Commission (IPC) will soon amend the heparin sodium monograph in IP 2018 following an appeal from stakeholders.
The decision to this effect was taken by the IPC at a meeting held on September 23, 2020. The meet was attended by IPC officials— Dr Jai Prakash, senior secretary-cum-scientific director, Dr M Kalaivani, senior scientific officer, Dr Gaurav Pratap Singh, senior scientific officer, Anubhuti Goyal, scientific assistant, Sargam Verma, technical associate, Rajesh Verma, assistant drugs controller (biological) at CDSCO, National Institute of Biologicals (NIB) officials, Central Drug Testing Laboratory (CDTL), Mumbai officials, and Dr Ranjeet Ajmani, chief executive officer, PlasmaGen Biosciences, Bengaluru.
Heparin, a common anti-coagulant drug (that reduces blood clots from forming in the body), is used in treating C-19 patients. It is included in the “Guidelines on Clinical management of C-19”, released by the directorate general of health services, ministry of health & family welfare. The blood-thinning drug has reduced hospitalisation rates, improved recovery rates, and even reduced the rate of sudden deaths by 90 per cent.
At the meet, stakeholders requested for amendment only in heparin sodium monograph not in heparin injection monograph of IP 2018, as amendment in potency value of the bulk does not have any impact on usual strength of injection.
Currently, there are two potency value of heparin sodium mentioned in its monograph in IP 2018 i.e. a potency of not less than 180 IU per mg in parenteral preparations containing heparin sodium and a potency of not less than 120 IU per mg in non-parenteral preparations containing heparin sodium.
With the proposed amendment to heparin sodium monograph in IP 2018, a potency of not less than 150 IU per mg in parenteral preparations containing heparin sodium will be included in the monograph.
The data/supporting documents (certificate of analysis Brazilian manufacturers) submitted by Biological E Ltd and Bacto Chem. Lab. supports the potency value of not less than 150 IU/mg.
The manufacturers have expressed difficulty in achieving the potency value of not less than 180 IU/mg in parenteral preparations comprising heparin sodium, said a senior scientific official at IPC.
At present, heparin sodium monograph in IP 2018 mentions that heparin sodium intended for use in the manufacture of parenteral preparation contains not less than 180 IU per mg and heparin sodium not intended for the use in the parenteral preparation contains not less than 120 IU per mg, calculated on the dried basis.
Once the proposed amendment is introduced to heparin sodium monograph, it will read as follows, “Heparin sodium intended for use in the manufacture of parenteral preparation contains not less than 180 IU per mg for Heparin obtained from the intestinal mucosa or other suitable tissues of domestic mammals used for food by man except bovine source. Heparin sodium intended for use in the manufacture of parenteral preparation contains not less than 150 IU per mg obtained from the intestinal mucosa or other suitable tissues of bovine and heparin sodium not intended for the use in the parenteral preparation contains not less than 120 IU per mg, calculated on the dried basis.”
At present heparin sodium monograph mentions method A to perform assay test to the bulk drug obtained from porcine/ bovine sources.
With the proposed amendment, method B will be reintroduced to the monograph of heparin sodium in IP 2018 to perform assay test to the bulk drug obtained from bovine source. Thus assay using method A or B can be performed on heparin sodium obtained from bovine source. For heparin sodium obtained from porcine source, assay using method A is required to be performed.
Earlier heparin sodium monograph in IP 2014 contained method B to perform assay test to the bulk drug, it was not included in IP 2018 following stakeholders’ request.
The method B comprises assay, method of assay such as test solution, reference solution, preparation of plasma etc.
As per the assay mentioned in method B, the potency of heparin sodium can be determined by comparing the concentration necessary to prevent the clotting of sheep or goat or human plasma with the concentration of the reference solution of heparin sodium necessary to give the same effect.
The proposed amendment will be introduced to heparin sodium monograph in IP 2018 after receiving suggestions from the industry stakeholder, stated the senior scientific official.
The stakeholder is required to submit comparative data of chromogenic method and clotting method for at least 25 batches within three months to IPC for further discussion, the official said.
Three out of four manufacturers of heparin sodium bulk drug are manufacturing from bovine source in India. Five importers are importing porcine heparin sodium from other countries. The dependency on China is more for importing heparin sodium.