Showing posts with label US FDA. Show all posts
Showing posts with label US FDA. Show all posts

Thursday, May 9, 2019

Safe disposal of expired and unused medicines


It is the usual tendency to throw the unused and expired medicines in the household trash, which is then collected by the waste collector or thrown into vacant plots in the neighborhood or on the streets. But this is approach to drug disposal is hazardous to the environment and thence to life.

Through the waste (in the open or landfills), these medicines may pollute water sources and also enter the soil. There are chances of accidental exposure to these medicines for waste pickers or children. Then, there is the hypothetical risk of these drugs being recycled back into the market.

Unused and expired medicines are considered as “domestic hazardous waste” in India as per the Solid Waste Management Rules 2016. These new rules mandate segregation of waste at source into biodegradable, non-biodegradable (recyclable and combustible), sanitary waste and domestic hazardous wastes.

“direct waste generators not to litter i.e throw or dispose of any waste such as paper, water bottles, liquor bottles, soft drink cans, tetra packs, fruit peel, wrappers, etc., or burn or burry waste on streets, open public spaces, drains, waste bodies and to segregate the waste at source as prescribed under these rules and hand over the segregated waste to authorised the waste pickers or waste collectors authorised by the local body”

The rules also require the local authorities to ensure door to door collection of segregated solid waste from all households and transport it in covered vehicles to the processing or disposal facilities.

Biomedical Waste Management Rules, 2016 categorize Discarded or Expired Medicine Pharmaceutical waste like antibiotics, cytotoxic drugs including all items contaminated with cytotoxic drugs along with glass or plastic ampoules, vials etc. in the yellow category, which are to be discarded in the yellow coloured non-chlorinated Plastic Bags

The US FDA has listed three disposal methods for unused or expired medicines:

·         Medicine take-back options
·         Disposal in the household trash and
·         Flushing certain potentially dangerous medicines in the toilet

Medicine take-back option is the preferred option to safely dispose of most types of unneeded medicines. This can be done via temporary collection sites or authorized permanent collection sites, which may be available in may be in retail pharmacies, hospital or clinic pharmacies, and law enforcement facilities. 

The FDA has laid down simple steps when considering disposal in the household trash

·         Mix medicines (do not crush tablets or capsules) with an unpalatable substance such as dirt, cat litter, or used coffee grounds;
·         Place the mixture in a container such as a sealed plastic bag;
·         Throw the container in your household trash; and
·         Delete all personal information on the prescription label of empty pill bottles or medicine packaging, then dispose of the container.

Some medicines such as fentanyl patches, diazepam have specific instructions to immediately flush down the toilet when no longer needed and a take-back option is not readily available. The FDA has created a list of medicines recommended for disposal by flushing that are no longer needed and when take-back options are not readily available.

In an article published in 2017 in the journal Science of the Total Environment, the FDA examined the risks associated with the environmental release of 15 active pharmaceutical ingredients (APIs) currently on its "flush list”. The FDA concluded that most of these APIs present a negligible eco-toxicological risk, although some additional data would be helpful for confirming this finding for some of these medicines. And, all 15 APIs present negligible risk through ingestion of water and fish (Sci Total Environ. 2017 Dec 31;609:1023-1040).

It is important to be aware of the drug disposal methods to avoid potential harm to the community. Patients should be counselled about safe drug disposal.

India has the rules and regulations in place for safe drug disposal, but they need to be implemented strictly.



Dr KK Aggarwal
Padma Shri Awardee
President Elect Confederation of Medical Associations in Asia and Oceania   (CMAAO)
Group Editor-in-Chief IJCP Publications
President Heart Care Foundation of India
Past National President IMA


Wednesday, May 8, 2019

Biosimilars in India


Biosimilar is a biologic product, which is very similar to the reference product that has been FDA approved and does not differ much from the reference product with regard to safety and effectiveness.1 Only the indications and conditions of use that have been approved for the reference drug can be approved for the biosimilar

Biosimilars have been defined in various ways by regulating bodies around the world. Let’s take a look at some definitions:

· World Health Organization (WHO): A similar biotherapeutic product (SBP) is a “biotherapeutic product which is similar in terms of quality, safety and efficacy to an already licensed reference biotherapeutic product”. 2

·  US FDA: A biosimilar is a biological product that is highly similar to and has no clinically meaningful differences from an existing FDA-approved reference product”. 3 

o    In this definition, “no clinically meaningful differences” means that a manufacturer must also demonstrate that its proposed biosimilar product has no clinically meaningful differences from the reference product in terms of safety, purity, and potency (safety and effectiveness). 
o    “Highly similar” means that a manufacturer developing a proposed biosimilar demonstrates that its product is highly similar to the reference product by extensively analyzing (i.e., characterizing) the structure and function of both the reference product and the proposed biosimilar.

·  European Union: A biosimilar is a biological medicine highly similar to another biological medicine already approved in the EU (the so-called ‘reference medicine’). 4

· Health Canada: Biosimilar biologic drug is “a biologic drug that obtains market authorization subsequent to a version previously authorized in Canada and with demonstrable similarity to a reference biologic drug.” Biosimilars were previously referred to as Subsequent Entry Biologics (SEBs) in Canada. 5

· CDSCO: “A Similar Biologic product is a biological product/ drug produced by genetic engineering techniques and claimed to be “similar” in terms of safety, efficacy and quality to a reference biologic, which has been granted a marketing authorization in India by DCGI on the basis of a complete dossier, and with a history of safe use in India.” 6

Omnitrope, a somatropin biosimilar was the first biosimilar in Europe to be approved by the European Medicines Agency (EMA) in 2006. 7 However, the US FDA approval for the first biosimilar in the country came in 2015, when it approved the first biosimilar to filgrastim, a granulocyte colony-stimulating factor. 1

The first biosimilar in India was approved in 2000 for hepatitis B. Recently, Herceptin (active drug trastuzumab) became the first biosimilar manufactured in India to be FDA approved for certain breast and stomach cancer. 1

Biosimilars in India are listed in the Table below. 8

Biosimilar
Product Description
Adfrar
biosimilar adalimumab for the treatment of auto immune disorders
Toritz RA
Biosimilar rituximab
Reditux
Biosimilar rituximab (mAb targeting CD20)
Grafeel
Filgrastim (recombinant granulocyte-macrophage colony-stimulating factor, G-CSF)
Cresp
Darbepoetin alfa (recombinant erythropoietin)
Peg-grafeel
(pelfilgrastim)
Actorise
darbepoetin alfa in collaboration with Cipla
Neukine
Filgrastim (recombinant G-CSF)
Neupeg
PEGylated G-CSF
Intalfa
Recombinant human interferon alpha-2b
Epofit
Recombinant erythropoietin
Mbtas
Rituximab
Shanferon
Recombinant interferon alpha-2b
Shankinase
Recombinant streptokinase
Shanpoietin
Recombinant erythropoietin
ReliPoietin
Recombinant erythropoietin
ReliGrast
Recombinant G-CSF
ReliFeron
Recombinant interferon alpha-2b
Relibeta
Interferon beta-la
MIRel
Recombinant reteplase (tissue plasminogen activator)
Wepox
Recombinant erythropoietin
Wosulin
Recombinant insulin
Eripro
Recombinant human erythropoietin
Biomab
Biosimilar nimotuzumab (humanized mAb targeting epidermal growth factor receptor)
Nufil
Filgrastim, recombinant G-CSF
Myokinase
Recombinant streptokinase biosimilar
Insugen
Recombinant human insulin
Alzumab
Itolizumab
Basalog
Insulin glargine

References

1.     Meher BR, et al. Biosimilars in India; current status and future perspectives. J Pharm Bioallied Sci. 2019;11(1):12-15.

2.     Guidelines on evaluation of similar biotherapeutic products (SBPs), WHO 2009.

3.     Biological product definitions, US FDA 2017.

4.     Biosimilars in the EU. European Medicines Agency and the European Commission, 2017.

5.     Information and Submission Requirements for Biosimilar Biologic Drugs, Health Canada, 2016.

6.     Guidelines on similar biologic: Regulatory requirements for marketing authorization in India, 2012.

7.     Iughetti L, et al. Long-term safety and efficacy of Omnitrope®, a somatropin biosimilar, in children requiringgrowth hormone treatment: Italian interim analysis of the PATRO Children study. Ital J Pediatr. 2016;42(1):93.

8.     Rushvi P, et al. Biosimilars: an emerging market opportunities in India. Pharmaceut Reg Affairs.2016;5:165. 


Dr KK Aggarwal
Padma Shri Awardee
President Elect Confederation of Medical Associations in Asia and Oceania   (CMAAO)
Group Editor-in-Chief IJCP Publications
President Heart Care Foundation of India
Past National President IMA

Thursday, May 2, 2019

US FDA clears heat-not-burn tobacco device for sale


The US Food and Drug Administration has cleared a heat-not-burn tobacco device designed as an alternative to conventional cigarettes, for sale in the United States.

The product consists of a tube that gently heats up sticks of tobacco instead of burning them, making what is inhaled less harmful than conventional cigarette smoke.

The FDA said the marketing of the devices is “appropriate” for public health because “the products produce fewer or lower levels of some toxins than combustible cigarettes.” The agency also said it has placed stringent marketing restrictions on the products in an effort to prevent minors from using the device.

The review, which took almost 2 years, took into consideration the risks and benefits to the population as a whole. It included how the products may impact youth use of nicotine and tobacco, and the potential for the products to completely move adult smokers away from use of combustible cigarettes.

By using heat instead of flame the device eliminates 90-95% of toxic compounds in cigarette smoke.

Dr KK Aggarwal
Padma Shri Awardee
President Elect Confederation of Medical Associations in Asia and Oceania   (CMAAO)
Group Editor-in-Chief IJCP Publications
President Heart Care Foundation of India
Past National President IMA


Thursday, April 11, 2019

Tafenoquine, a new drug to prevent relapse of vivax malaria


A new drug, tafenoquine was approved this year by US FDA as a single-dose treatment to prevent relapse (radical cure) of Plasmodium vivax malaria.

Tafenoquine is a new 8-aminoquinoline antimalarial drug. It is a synthetic analog of primaquine with an elimination half-life of 15 days. It acts on all stages of malaria (Antimicrob Agents Chemother. 2007 Aug;51(8):2709-15), including the quiescent liver stage, the hypnozoite. Hence, it is used for the radical cure or prevention of relapse of Plasmodium vivax infections.

The effectiveness of tafenoquine as an anti-relapse agent has been demonstrated in two studies published in the New England Journal of Medicine this year.

In a trial conducted in Ethiopia, Peru, Brazil, Cambodia, Thailand and the Philippines, single-dose tafenoquine significantly reduced the risk of P. vivax recurrence in patients with phenotypically normal G6PD activity. The percentage of patients who were free from recurrence at 6 months was 62.4% in the tafenoquine group, 27.7% in the placebo group and 69.6% in the primaquine group (N Engl J Med. 2019 Jan 17;380(3):215-22).

 In another trial of patients with confirmed P. vivax parasitemia, which compared compared tafenoquine with primaquine, tafenoquine (single 300 mg dose) was shown to be not inferior to primaquine (15 mg once daily x 14 days). In the patient-level meta-analysis, the percentage of patients who were free from recurrence at 6 months was 67.0% in the tafenoquine-treated group and 72.8% in the primaquine-treated group. Among patients with normal G6PD enzyme activity, the decline in hemoglobin level with tafenoquine was not significantly different from that with primaquine. (N Engl J Med. 2019 Jan 17;380(3):229-241).


These trials show tafenoquine as an effective and convenient alternative to primaquine as anti-relapse therapy for adult patient with P. vivax infection. A word of caution, the patient must be tested for G6PD deficiency as tafenoquine can cause hemolysis in individuals with G6PD enzyme activity less than 70%.


                  
Dr KK Aggarwal
Padma Shri Awardee
President Elect Confederation of Medical Associations in Asia and Oceania   (CMAAO)
Group Editor-in-Chief IJCP Publications
President Heart Care Foundation of India
Past National President IMA