biological or biopharmaceuticals are drugs produced from living cells through the biological process , and mimic natural biological substances such as hormones .
biosimilars are copy drugs similar to biological drugs that has already been authorized ( the biological reference medicine ) , hence similar but not identical .
indian guidelines define a  similar biologics  as a biological product / drug produced by genetic engineering techniques and claimed to be  similar  in terms of safety , efficacy and quality to a reference biologics , which has been authorized by drug controller general of india ( dcgi ) for safe use in india .
the active substance of biosimilar medicine is similar to one of the biological reference medicine and used in general at the same dosage to treat the same disease .
biosimilars are entity based ( including product - process ) , regulatory based ( under an abbreviated testing ) , and market based ( same manufactures , different trade name ) .
biosimilars also known as similar biological products , follow - up biologics , subsequent entry biological , second entry biological , biogenerics , multisource products , and off - patent biotech products as synonyms .
general public and insurance companies prefer economic alternatives , the long - term economic consequence of using biosimilars have not been studied
biosimilars are a new class of drugs intended to offer comparable safety and efficacy to the reference , off - patent biological .
the active protein structure of biologicals makes them more prone to induce an acute and chronic immune response .
the overall risk is modest with biosimilars , but regulatory pathways are required because of structural complexity , manufacturing process and risk for immunogenicity .
the problems / limitations with biosimilar are that , the two biosimilar have a different origin , the two biosimilars may have same therapeutic effect , may have different side - effects and hence require thorough testing .
the main reason of biosimilar drug development is the expiry of patent protection for many biological medicines [ table 1 ] .
patent expiration of biological / biopharmaceuticals * biopharmaceuticals are different from the conventional small molecule drugs because of the size and complexity of the active substance and nature of the manufacturing process .
even minor change in the process can lead to the fatal outcome ( process is product ) , safety , and efficacy issues .
for epoietin ( erythropoietin ) , minor change in the packaging process caused pure red cell aplasia .
european medicines agency ( emea ) and committee for the medicinal product for human use ( chmp ) raised the objection that marvel insulin and reference human insulin were not comparable .
, withdrew its application as they were unable to meet the standards set by chmp , but biosimilar insulin continues to flood indian market .
hence , legal and regulatory principals applicable to generic drugs can not be applied to biosimilars .
emea - chmp has published product specific guidelines to establish the similarity in terms of safety , efficacy and quality of biosimilar product . according to these guidelines
moreover , in order to support pharmacovigilance monitoring , the specific product given to the patient should be clearly identified .
the active substance of the biosimilar product must be similar in molecular and biological terms to the active substance of the reference medicinal product , and the same reference product throughout the comparability program .
the pharmaceutical form , doses and route of administration of the biosimilar and the reference product should be the same .
if the reference product has more than one indication , the safety and efficacy for all indications have to be justified or demonstrated for each indication separately .
the issue of immunogenicity should always be addressed , and its long - term monitoring is necessary .
fda was given the authority to approve biosimilars , including interchangeable , to maintain safety , efficacy , and quality of biosimilar product .
 abbreviated pathway  for approval of biologics that are  biosimilar  to already approved products .
the abbreviated pathway will eliminate unnecessary and unethical testing of biosimilars in animal and human .
the patient protection and affordable care act of 2010 ( usa ) also supports this .
the new india guidelines  draft guidelines on similar biologics : regulatory requirements for marketing authorization in india ,  were announced in june 2012 , by department of biotechnology ( dbt ) .
the indian guidelines on similar biologics address the pre - marketing and post - marketing regulatory requirement ( i.e. ,  comparability exercise  ) , and also address the requirements related to manufacturing process and quality control .
as such these indian guidelines on similar biologics are comparable in many respects to biosimilar guidelines of usa and eu .
india has adopted a  sequential approach  ( like  stepwise approach  - us and eu ) to market biosimilar products .
the review committee on genetic manipulation of the genetic engineering approval committee ( geac ) with the permission of dcgi , approve clinical trials to be conducted in india related to biosimilar therapeutic products .
the biosimilar has to demonstrate comparable data of non - clinical studies viz . , pharmacokinetics and toxicology ( safety pharmacology , reproduction toxicology , mutagenecity and carcinogenicity ) and clinical studies ( efficacy and tolerability for each indication ) before it gets approval for all indication of the reference medicine .
biosimilars in india consist primarily of vaccine , monoclonal antibodies , recombinant proteins and diagnostics , insulin ( wosulin , insugen , recosulin ) , erythropoietin ( hemax , epofer , wepox , ceriton , epofit ) , hepatitis b vaccine ( shanvac b , revac b , enivac b , biovac b , genevac b , bevac ) , granulocyte colony stimulating factor ( g - csf  grastim , neukine ) , streptokinase ( indikinase , shankinase , stpase ) , interferon alpha-2b ( shanferon ) , rituxinab ( mab ) , epidermal growth factor receptor ( anti - egfr ) ( mab)(reditux , biomab - egfr ) .
status of similar biologics in india there are about 100 biopharmaceutical companies actively involved in research and development , manufacturing and marketing of biosimilar therapeutic products in india .
there were 14 therapeutic drugs ( similar biologics ) available in 50 brands in 2005 ; the number has increased to 20 therapeutic drugs in 250 brands in 2011 .
biosimilar therapeutic products include insulin , erthropoietin , chorionic gonadotropin , streptokinase , interferon and heparin .
the growing biosimilars market offers huge potential for companies involved in manufacturing , research and development .
pharmacovigilance is more important for biosimilar drugs because these are not reference medicine as such , and are from different manufacturer from the reference products .
many adverse effects may appear only after a biosimilar drug is used more extensively , for a longer period of time , in a greater number of patients .
both manufacturers and prescriber should be aware of the importance of post marketing vigilance , and careful on patients taking biosimilar .
biosimilar are not generic ; biologics are larger and more complicated than chemical drugs , due to the complexity of biological / biotechnology derived products the generic approach is scientifically not appropriate for biosimilar products .
the challenge with biosimilars is to know the differences which matter clinically . the specific product given to the patient
 biologic products are being developed over the past three decades . 
 the expiry of patent protection for many biological medicines has led to the development of biosimilars in uk or follow on biologics in usa . 
 this article reviews the literature on biosimilar drugs that covers the therapeutic status and regulatory guidelines . 
 appraisal of published articles from peer reviewed journals for english language publications , search from pubmed , and guidelines from european medicines agency , us food drug administration ( fda ) and india were used to identify data for review . 
 literature suggest that biosimilars are similar biological products , i.e. , comparable but not identical to the reference product , are not generic version of innovator product and do not ensure therapeutic equivalence . 
 biosimilars present more challenges than conventional generics and marketing approval is also more complicated . to improve access , 
 us congress passed the biologics price competition and innovation act 2009 and us fda allowed  abbreviated pathway  for their approval . 
 u.s law has defined new standards and terms and ema scientific guidelines have also set detailed approval standards . 
 india being one of the most preferred manufacturing destinations of biosimilars , there is a need for stringent safety and regulatory guidelines . the new india guidelines  draft guidelines on similar biologics were announced in june 2012 , by department of biotechnology at boston bio and available online . 